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University of Iowa
Iowa Research Online
Theses and Dissertations
Spring 2014
Hippocampal contributions to language: an
examination of referential processing and narrative
in amnesia
Jake Christopher Kurczek
University of Iowa
Copyright 2014 Jake C. Kurczek
This dissertation is available at Iowa Research Online: http://ir.uiowa.edu/etd/4672
Recommended Citation
Kurczek, Jake Christopher. "Hippocampal contributions to language: an examination of referential processing and narrative in
amnesia." PhD (Doctor of Philosophy) thesis, University of Iowa, 2014.
http://ir.uiowa.edu/etd/4672.
Follow this and additional works at: http://ir.uiowa.edu/etd
Part of the Neuroscience and Neurobiology Commons
HIPPOCAMPAL CONTRIBUTIONS TO LANGUAGE: AN EXAMINATION OF
REFERENTIAL PROCESSING AND NARRATIVE IN AMNESIA
by
Jake Christopher Kurczek
A thesis submitted in partial fulfillment
of the requirements for the Doctor of
Philosophy degree in Neuroscience
in the Graduate College of
The University of Iowa
May 2014
Thesis Supervisor: Assistant Professor Melissa C. Duff
Graduate College
The University of Iowa
Iowa City, Iowa
CERTIFICATE OF APPROVAL
_______________________
PH.D. THESIS
_______________
This is to certify that the Ph.D. thesis of
Jake Christopher Kurczek
has been approved by the Examining Committee
for the thesis requirement for the Doctor of Philosophy
degree in Neuroscience at the May 2014 graduation.
Thesis Committee: ___________________________________
Melissa C. Duff, Thesis Supervisor
___________________________________
Steven Anderson
___________________________________
Neal Cohen
___________________________________
Daniel Tranel
___________________________________
Michelle Voss
___________________________________
Kristine Williams
The story is one that you and I will construct together in your memory. If the story means
anything to you at all, then when you remember it afterward, think of it, not as something
I created, but rather as something that we made together.
Orson Scott Card
Ender’s Game
ii
ACKNOWLEDGMENTS
I am extremely grateful to all of the people without whom this research would not
be possible. First and foremost, I’m grateful to the research participants and their families
for donating their time and effort. In the last five years, I have learned so much from
these amazing and interesting people, and I want to thank them for sharing their time,
stories and lives with me. Secondly, I would like to thank my mentor Melissa Duff, who
has done much more than “throw me a bone” as I requested in our first meeting. She has
done everything possible in order to help me succeed as a scientist, educator and mentor
in the past five years and I wouldn’t be any where near the person/scientist/teacher that I
am today without her. I would also like to thank the members of my thesis committee,
Daniel Tranel, Neal Cohen, Steven Anderson, Michelle Voss and Kristine Williams for
their helpful contributions to shaping this work in particular.
I’d like to thank my friends in colleagues who have contributed to my education
at Iowa and my ability to be a researcher in neuroscience. I’d like to thank Ruth Henson
and Keary Saul for their work scheduling participants and reminding me how to be a
good person and researcher. Thank you to Joel Bruss and Nick Jones for helping me to
understand computers and technology better and for our always helpful conversations.
Without the help of Isabelle Hardy, Linda Hurst, Anita Kafer and Dan Tranel, navigating
the road of being a graduate student would be much more difficult. I also want to thank
the many members of the Communication and Memory Lab for their help transcribing,
coding and testing, especially, Samantha Shune, Laura Savicki, Margaret Miller, Sarah
Kirk, Janelle Beadle, Samantha Crooks, and in particular for this dissertation Allison
Alpers and Roxanne Calderwood.
I’d also like to thank some of the people that have contributed to my graduate
education more broadly. I’d like to thank Mitchell Kelly, Mike Baker, Dan Lehn and
Wendy Dunn for all that they have done to help me become a better educator. I’d like to
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thank Dave Warren for his helping me to become a more sophisticated thinker and a
better scientific programmer. I’d like to thank the Obermann Center for Advanced
Studies and Iowa Campus Compact for their work bringing research, scholarship and the
community together. I’d also like to acknowledge and thank my fellow students in the
neuroscience program for their guidance, help, and support especially Bradley TaberThomas, Rupa Gupta Gordon, and Erik Asp.
Finally, I want to thank my family for their love and support. I am extremely
thankful to my wife Kameko Halfmann who helps to keep me grounded and whose
patience, understanding and thoughtfulness has been much appreciated throughout
graduate school and life.
iv
ABSTRACT
Language production is characterized by an unlimited expressive capacity and
creative flexibility that allows speakers to rapidly generate novel and complex utterances.
In turn, listeners interpret language “on-line”, incrementally integrating diverse
representations to create meaning in real-time. A challenge for theories of language has
been to understand how speakers generate, integrate, and maintain representations in
service of language use and processing and how this is accomplished in the brain. Much
of this work has focused prefrontal cortex mechanisms such as “working memory”. The
goal of this dissertation is to understand the role of the hippocampal declarative memory
system (HDMS) in language use and processing, specifically in referential processing and
narrative construction.
To test the role of the hippocampus in referential processing, healthy
comparisons, brain damaged comparisons (BDC), individuals with bilateral hippocampal
damage participated in an eyetracking experiment in which individuals viewed scenes
and listened to short stories. The amount of time participants spent looking at the
characters after a pronoun reference was recorded. Healthy comparisons and BDC
participants preferentially targeted the first mentioned character while participants with
hippocampal damage did not to the same degree, suggesting that the hippocampus plays a
role in maintaining and integrating information, even in short discourse history.
In a second experiment, participants with bilateral hippocampal damage and
healthy comparisons told narratives multiple times over the course of a month. The
narratives were analyzed for the number of words, the number of episodic details, the
number of semantic details, the number of editorials and the consistency of details over
the multiple tellings. The patients with hippocampal damage told stories that were
significantly shorter, more semanticized and less consistent from telling to telling than
healthy comparisons.
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The final goal of this study was to understand the effects of unilateral
hippocampal damage on language processing. Individuals with unilateral hippocampal
damage participated in all of the previous experiments. It was predicted that individuals
with left hippocampal damage would perform worse than individuals with right
hippocampal damage, though there was a trend towards a deficit their performance was
not significantly impaired across measures. This suggests that the left hippocampus may
be particularly important for processing linguistic material outside of even verbal
memory.
This dissertation enters a line of work demonstrating the contributions of the
hippocampus to cognition outside memory. We are beginning to see the mark of the
hippocampus across all areas of cognition, both early and continuously. This and other
evidence appears to suggest that the processing capacities of the hippocampus are called
upon and used by many (most) other neural structures in the formation and establishment
of complex human behavior including language processing.
vi
TABLE OF CONTENTS
LIST OF TABLES ............................................................................................................. ix
LIST OF FIGURES ............................................................................................................X
CHAPTER 1: SIGNIFICANCE AND SPECIFIC AIMS....................................................1!
CHAPTER 2: NEUROPSYCHOLOGICAL INVESTIGATION INTO
LANGUAGE AND MEMORY .......................................................................6
2.1. Neuropsychology overview .......................................................................6!
2.2. Language..................................................................................................10!
2.2.1. Language processes .......................................................................10!
2.2.2. Neural substrates ...........................................................................12!
2.2.3. Language interim summary ...........................................................18!
2.3. Memory....................................................................................................18!
2.3.1. Memory processes .........................................................................18!
2.3.2. Neural substrates ...........................................................................20!
2.3.3. Cognitive processes and theories...................................................28!
2.4. Memory and Language ............................................................................32!
2.4.1. Connecting the hippocampus, declarative memory, and
language ...................................................................................................33!
2.4.2. Hippocampal Declarative (Relational) Memory System:
Contributions to Language ......................................................................37!
CHAPTER 3: GENERAL METHODOLOGY .................................................................43
3.1 Participants ...............................................................................................43!
3.2. Statistical Approach .................................................................................44!
CHAPTER 4: REFERENTIAL PROCESSING - FACILITATING PRONOUN
COMPREHENSION IN INDIVIDUALS WITH PROFOUND
MEMORY IMPAIRMENT ............................................................................45
4.1. Background/Rationale .............................................................................45!
4.2. Specific Aims and Hypotheses ................................................................50!
4.3. Methods ...................................................................................................51!
4.3.1. Participants ....................................................................................51!
4.3.2. Materials ........................................................................................52!
4.3.3. Procedure .......................................................................................53!
4.3.4. Analysis .........................................................................................54!
4.4. Results......................................................................................................55!
4.4.1. Offline Data. ..................................................................................55!
4.4.2. Eye-movement Data. .....................................................................56!
4.5. Discussion ................................................................................................58
vii
!
CHAPTER 5: NARRATIVE IN AMNESIA: THE EFFECTS OF REPEATED
TELLINGS ON NARRATIVE CONSTRUCTION ......................................68
5.1. Background/Rationale .............................................................................68!
5.2. Specific Aims and Hypotheses ................................................................75!
5.3. Methods ...................................................................................................76!
5.3.1. Participants ....................................................................................76!
5.3.2. Materials ........................................................................................76!
5.3.3. Procedure .......................................................................................77!
5.3.4. Analysis .........................................................................................78!
5.4. Results......................................................................................................79!
5.4.1. Multiple Tellings Autobiographical Memory Interview
Analysis (Condition 1) ............................................................................79!
5.4.2. Multiple Tellings Consistency Analysis for hippocampal
amnesics and their comparisons ..............................................................80!
5.4.3. Self Ratings of Multiple Tellings for hippocampal amnesics
and their comparisons ..............................................................................80!
5.4.4. War of the Ghosts Analysis (Condition 2) ....................................81!
5.5. Discussion ................................................................................................81!
CHAPTER 6: HIPPOCAMPAL LATERALITY: THE EFFECT OF
UNILATERAL HIPPOCAMPAL DAMAGE ON LANGUAGE USE .......100!
6.1. Background ............................................................................................100!
6.2. Specific Aims and Hypotheses ..............................................................103!
6.3. Methods .................................................................................................104!
6.3.1. Participants ..................................................................................104!
6.3.2. Experimental protocol .................................................................104!
6.4. Results....................................................................................................105!
6.4.1. Referential processing .................................................................105!
6.4.2. Narrative construction analysis for patients with unilateral
hippocampal damage .............................................................................108!
6.5. Discussion ..............................................................................................110!
CHAPTER 7: CONCLUSIONS ......................................................................................121!
APPENDIX: THE WAR OF THE GHOSTS ..................................................................127!
REFERENCES ................................................................................................................128!
viii
LIST OF TABLES
Table 1. Demographic and neuropsychological characteristics of hippocampal
amnesic and BDC participants..................................................................................64!
Table 2. Study 1: On-line referential processing experimental conditions. .......................65!
Table 3. Demographic and neuropsychological characteristics of hippocampal
amnesic participants..................................................................................................90!
Table 4. Comparison of amnesic and healthy comparison narratives over time. ..............94!
Table 5. Comparison of hippocampal amnesic and healthy comparison performance
on War of the Ghosts retelling. .................................................................................98!
Table 6. Demographic characteristics of patients with unilateral hippocampal
damage. ...................................................................................................................114!
Table 7. Neuropsychological characteristics of patients with unilateral hippocampal
damage. ...................................................................................................................115!
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LIST OF FIGURES
Figure 1. Offline judgments of story-picture match for hippocampal amnesics,
BDC and comparison participants. ...........................................................................66!
Figure 2. Time course of fixation preferences for hippocampal amnesics, BDC
participants and healthy comparison participants. ....................................................67!
Figure 3. Memory ratings for condition 1, multiple tellings..............................................91!
Figure 4. Internal to overall ratio across multiple tellings for hippocampal amnesics
and healthy comparison participants.........................................................................92!
Figure 5. Consistency data for multiple tellings for hippocampal amnesics and the
healthy comparison participants. ..............................................................................93!
Figure 6. Self Ratings for multiple tellings for hippocampal amnesics and their
healthy comparisons .................................................................................................96!
Figure 7. War of the Ghosts accuracy data for hippocampal amnesics and their
healthy comparisons. ................................................................................................97!
Figure 8. Off-line performance for unilateral hippocampal patients. ..............................117!
Figure 9. Time course of fixation preference data for unilateral hippocampal
patients. ...................................................................................................................118!
Figure 10. Internal details across multiple tellings for unilateral hippocampal
patients. ...................................................................................................................119!
Figure 11. Consistency data for unilateral hippocampal patients in the multiple
telling. .....................................................................................................................120
x
1
CHAPTER 1: SIGNIFICANCE AND SPECIFIC AIMS
This thesis brings together the study of two quintessential human capacities,
memory and language, by examining the role of the hippocampal declarative memory
system (HDMS) in language processing and use. At the heart of this proposal is the idea
that the same processes by which the HDMS contributes to the formation of new
memories, and maintains representations on-line to be used in service of complex
behavior, are the same processes for using and processing language (Duff & BrownSchmidt, 2012). Evidence in support of this proposal comes from work demonstrating
that patients with hippocampal damage and declarative memory impairment have deficits
in a variety of linguistic and discursive abilities (e.g., Duff, Hengst, Tranel & Cohen,
2008; MacKay, Stewart & Burke, 1998). The proposed work here extends this proposal
by expanding the scope of the potential HDMS contribution to two language phenomena
that are ubiquitous in everyday uses of language, referential processing and narrative
construction.
Informed by theories of language processing and use and cognitive neuroscience
theories of memory, the research approach capitalizes on a compelling opportunity to
combine neuropsychological methods with eye-tracking and behavioral measures.
Performance of patients with hippocampal amnesia, who have bilateral hippocampal
damage and severe and selective impairments in declarative memory will be compared to
healthy comparison participants.
The proposed work is significant theoretically and has potential clinical
implications. Defining and characterizing the cognitive and neural systems that support
language is a key goal in the neuroscience of language. Although the HDMS has received
2
little consideration as a key neural/cognitive system for language use and processing
(outside of lexical acquisition/consolidation), preliminary and anticipated findings from
the proposed studies fit with increasing evidence that the language network extends
beyond the traditional structures of the left perisylvian areas to include the hippocampus
and declarative memory (Duff & Brown-Schmidt, 2012). Recent research demonstrating
that the hippocampus also plays a critical role in the generation and use of on-line
representations created during ongoing information processing to support behavioral
performance positions the hippocampus, for the first time, as a candidate neural system
for supporting language (Rubin, Brown-Schmidt, Duff, Tranel, & Cohen, 2011). In the
memory literature, there is increasing evidence that the hippocampus plays a critical role
in cognitive abilities beyond its traditional role in memory (e.g., perception (Warren,
Duff, Tranel & Cohen, 2010; 2011), creativity (Duff, Kurczek, Rubin, Tranel & Cohen
2013). The interdisciplinary and integrated approach taken here to studying the memorylanguage interface is timely as it dovetails with recent trends in the neuroscience
literature of examining the coordination of cognitive and neural systems in the production
of complex behavior. Finally, linking deficits in language to HDMS impairment offers a
more fine-grained characterization of the underlying mechanisms of the observed nonaphasic language deficits common in neurological and psychiatric diseases where HDMS
deficits are prominent (e.g., TBI; Alzheimer’s disease, schizophrenia).
3
Aim 1: To define and characterize the role of the hippocampal dependent
declarative memory system (HDMS) in on-line referential processing.
Efficient and successful language processing relies on the ability to establish and
maintain reference (e.g., proper nouns, pronouns) as most of what we talk about involves
referring to things in the world. Using reference places a demand on the ability to both
track information across time and bind information and representations from potentially
rich contexts. It is hypothesized that the HDMS contributes to on-line referential
processing. It is predicted that patients with damage to the HDMS will be impaired
compared to healthy participants in the ability to form and maintain the representations
necessary for successful referential processing in the moment in contexts where referents
are established with minimal representation.
Specifically, combing neuropsychological and eyetracking methods, participants
will view images while listening to narratives. In Aim 1 with an eye towards
rehabilitation, I attempt to recover performance of the participants with amnesia by
providing more context in the discourse to firmly establish the target character. It is
predicted that participants with hippocampal amnesia will benefit from increased
representation information and preferentially view the target character.
Aim 2: To define and characterize the role of the HDMS in narrative
construction.
Personal narrative allows one to use language to give life events a temporal order,
to demystify them, and to establish coherence across a life lived, living and yet to be
lived (Ochs & Capps, 2001). Recent work on the functions of the hippocampus suggest it
is engaged in behaviors outside of (re)constructing memories for the past (and future),
4
and may potentially by necessary for any behavior that requires the flexible generation,
and subsequent (re)combination of perceptually distant and distinct mental
representations on-line and in response to novel contexts (Shohamy & Turk-Brown,
2013).
It is hypothesized that the HDMS plays a critical role in the generation and
flexible use of representations that compose narratives. In Aim 2, I will investigate the
impact of hippocampal damage on the repeated tellings of either episodic or semantic
narratives over time. In healthy populations, participants have been shown to become less
detailed (i.e., less words/details) in their tellings of semantic narratives while they
become more detailed in their telling of their own episodic narratives. It is predicted that
patients with hippocampal amnesia will not be able to narrate the semantic stories while
performance on the episodic narratives will be impaired because hippocampal damage
will cause greater variability in the reproduction of narratives (i.e. inconsistent telling of
details) over time.
Specific Aim #3: To investigate the contribution of left versus right damage
to the hippocampus on referential processing and narrative construction.
Functional lateralization of the brain has indicated that the left hemisphere is
primarily responsible for processing language while the right hemisphere is responsible
for processing spatial information. After unilateral damage to the temporal lobe, mild
deficits in material specific recall as been observed (Milner 1968; 1990; Naugle, 1992)
with damage to the left hemisphere causing problems in verbal recall and damage to the
right hemisphere causing deficits in spatial recall. However there is a question of whether
these deficits are deficits due to damage to the hippocampus or a loss of connection to the
5
other cortical areas. In other words are the deficits observed after unilateral damage to the
hippocampus due to a loss of hippocampal functioning or the loss of the ability to
connect to higher cortical areas.
It is hypothesized that damage to the left hippocampus will disrupt hippocampal
functioning and language processing capacities of the hippocampus to a greater extent
than right hippocampal damage. Therefore, it is predicted that patients with left
hippocampal damage will perform significantly worse than patients with right
hippocampal damage on both the referential processing and narrative construction
experimental measures.
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CHAPTER 2: NEUROPSYCHOLOGICAL INVESTIGATION INTO
LANGUAGE AND MEMORY
2.1. Neuropsychology overview
Language (Hauser, Chomsky, & Fitch, 2002; Pinker & Jackendoff, 2003; Ujhelyi,
1996) and episodic memory (Roberts & Feeney, 2009; Suddendorf, 1994; Tulving &
Markowitsch, 1998) are two cognitive abilities that are thought to separate mankind from
the rest of the animal kingdom. In the history of mankind’s investigations into the inner
workings of his brain, through disciplines such as philosophy, psychology, and more
recently neuroscience, the prevailing notion has been to study each type cognitive ability
and each brain area separately, before attempting to study them together (Fodor, 1983).
While the history of brain-behavior relationships stretches back to the dawn of
mankind (e.g. Egyptian physicians performing trepanation; Arnott, Finger & Smith,
2003; Hippocrates’ work with Greek gladiators; Hippocrates, 460 BCE), its modern
investigation can only be traced back to the 19th century. Franz Gall, inspired or perhaps
limited by faculty psychology, hypothesized that the brain consisted of a number of
separate organs, each responsible for a basic trait. Further, he reasoned that skill or
capacity of various traits would increase the size of that brain area and affect the size of
the skull (Gall, 1825). This set of hypotheses, termed phrenology, formed the early basis
for the localization theory of brain function.
A number of reports in the middle of the century helped to lend credence to the
idea of localized brain functions. The first, occurred in 1848, when a railroad foreman
suffered a brain injury to the frontal lobe caused by a tamping iron (Harlow, 1868).
Phineas Gage had been described as an adept, mild-mannered and well-respected
7
foreman of the railroad before his injury, and as fitful, irreverent, profane and impatient,
while on the whole largely intact in all other mental capacities after (Harlow, 1868). The
description of Phineas Gage is one of the first to account for a circumscribed lesion and
its resulting loss of a specific set of abilities. However, one of the most famous cases of
cognitive deficit localizability in lesion damage occurred in 1861 when Paul Broca
announced the most well known breakthroughs in localization of higher cognitive
functioning, noting that motor speech was specifically located in the posterior, inferior
region of the left frontal lobe (Broca, 1861a, 1861b). It has been noted that this was one
of the first indications that specific locations in the brain support specific functions and
also that the left and right hemispheres separate their contributions to various functions
(Zillmer, Spiers & Culbertson, 2008). A decade later, Carl Wernicke announced that
understanding of speech was located in the superior, posterior temporal lobe, when he
discovered patients who had fluent speech but were unable to understand speech
(Wernicke, 1874). In a different cognitive domain, memory, it wasn’t until the early
1950s that we found evidence for the localizability of memory in patient H.M. (Scoville
& Milner, 1957). These three sets of patients provided a foundation in the support of
particular cognitive functions being supported by distinct areas of the brain.
While localization received much attention, not all of it was in support. A number
of investigators criticized the idea of localization, including Sigmund Freud who
questioned how to explain partial and mixed aphasias through Broca’s and Wernicke’s
understanding (Freud, 1891). Others including Pierre Flourens (who popularized
equipotentiality) and later Pierre Marie (Marie, 1906) and Karl Lashley (whose beliefs
were more tempered than Flourens, by advocating, multipotentiality and mass action, as
8
well as localization of basic functions; Lashley, 1929) were proponents of a more
distributed view of cognitive abilities. As the debate between localization and
equipotentiality waged on, evidence continued to mount on the side of localized cognitive
functions. John Hughlings Jackson, however, suggested a combination of the two views
in which behavior results from the interaction among all the areas of the brain. Jackson’s
idea was further adapted by Alexander Luria, who proposed that behavior arises from the
interaction of three functional units (e.g. arousal/muscle tone; reception, integration and
analysis of sensory information; planning, executing and verifying behavior; Luria, 1964;
1966).
While all behavior is represented by the brain as a whole, each brain area has a
specific role in shaping behavior. In the fifty years since Luria published his accounts on
behavior, the fields of neuropsychology, neuroscience, and cognitive psychology have
continued to enhance our understanding of brain functioning by delineating the
contributions of various brain areas to particular cognitive functions. While more modern
investigation and research techniques have provided a more detailed list of cognitive
functions and the brain areas that are both necessary and sufficient for those functions,
less is known about how coordinated activity across the brain creates behavior.
This history of neuropsychology provides the perfect backdrop for the
investigation at hand. Localization of function has provided the opportunity for
uncovering a vast number of brain areas and their associated cognitive functions.
However, sometimes, when a particular cognitive function becomes attributed to a
certain area, research has been focused on that particular relationship, rather than on the
contribution of that area to other cognitive functions, or conversely, the contribution of
9
multiple brain structures to a particular function. Of interest to the current investigation
are the views that two prominent language scientists held in regard to the contribution of
memory to language. Broca (1865) and Wernicke (1874) thought that that language
production and comprehension were achieved via separate stages involving units and
processes that were dissociable from memory storage and retrieval, meaning that
problems in language could be independent of memory disorders. The principles of
multipotentiality or pluripotentiality are fundamental to the current investigation. The
historical roots of brain behavior relationship in localization of function has largely
resulted in the study of cognitive capacities, including memory and language, in isolation.
For the past sixty years, researchers have investigated and delineated the contribution of
the hippocampus to declarative memory, while perisylvian structures have been probed
for close to 150 years in their relationship to language. However, new research is
beginning to describe the hippocampus in broader terms outside of memory processing,
as contributing more fundamental processing immediately and continually while the
language network has been expanding beyond the perisylvian cortical structures of the
left hemisphere. This thesis will continue the trend of investigations which have strayed
away from the contribution of the hippocampus solely to memory, and will investigate
the more recent conceptualization of memory and language functioning which sees those
systems as interactive and interdependent, and specifically investigate the contribution of
the hippocampus to language processing. What follows is a summary of the work on the
localization of language and memory and a framework for examining the
interaction/interdependencies of language and memory.
10
2.2. Language
2.2.1. Language processes
Language is so pervasive in our lives that it has become an axiom of the human
experience. Language is the principle mechanism by which human beings communicate
and bond with one another. Language allows us to provide instructions, note our needs
and desires and work collaboratively. Through oral traditions and writing, language
allows us to connect to our present, our past and the future; it provides continuity to the
human experience. Because of the seeming ease by which we speak and understand
speech, people often take their language ability for granted.
All human languages share a set of fundamental properties including arbitrary
relations, incremental processing, generativity, and multi-modality. The language system
is composed of a set of arbitrary relations in that, with some limited exceptions,
conceptual information cannot be derived from the acoustic signal itself. This is
demonstrated by the fact that there are few, if any words across languages that mean the
same thing. While some point to onomatopoeic words such as “meow” or “bark” as
counter examples to arbitrariness, even these examples rarely hold up across languages
where for example in Spanish, the sound dogs make is “guau.” Language is learned over
time in a series of presentations between form and a meaning selected randomly with
noise involved in both the form (what/how someone says something) and meaning (there
are many unique items that combine to form the meaning exemplar; Gasser, 2004).
Language processing is incremental, meaning that it occurs over time, at a rate of
about 150-200 words per minute (Levelt, 1989; Tauroza & Alison, 1990). The meaning
11
of many words are ambiguous (e.g. lexically, Allopenna, Magnuson, & Tannenhaus,
1998; referentially, Hanna, Tanenhaus, & Trueswell, 2003; and syntactically, Tanenhaus,
Spivey-Knowlton, Eberhard, & Sedivy, 1995) until later in the sentence, when multiple
sources of information must be generated, integrated, and maintained in real-time to
create meaning. In its most strict interpretation, incremental processing means that
information is fully integrated with previously processed material as soon as it is
available. At the level of syntax, incrementality would mean that each word is integrated
into a syntactic structure immediately. As a result of this property, speakers are
constantly integrating information and making predictions (Federmeier & Ktuas, 1999;
Federmeier, 2007) based on the scenes they are within (Altmann & Kamide, 2007), past
scenes (Altmann & Kamide, 2009), the subject (Kamide, Altmann & Haywood, 2003)
and the speaker (Van Berkum, Van den Brink, Tesink, Kos, & Haagort, 2008). With this
continual building of representations, listeners and speakers are constantly binding
representations into rules (e.g. grammar, syntax, semantic, pragmatic) and forming
understanding of what is being communicated.
Attempts to identify what separates human language capacities from other
creatures in the animal kingdom have long pointed to the generative capacity of human
language and communication (Chomsky, 1957). Language use is flexible and creative
meaning that the symbols of language can be combined and recombined in new and
unusual ways to convey meaning. Indeed, particular words can mean very different things
in different contexts and to different listeners (Tannen, 1989). Speakers recreate,
repurpose and re-contextualize language over time and settings (Bakhtin, 1986; Prior,
2001) in order to convey different meanings.
12
Finally, language use is multi-modal encompassing far more than a stream of
spoken words. Language and communication combines words with changes in the body
either in the face such as gaze (Meyer, Sleiderink, & Levelt 1998), or in the rest of the
body in the case of gesture (Wagner Cook & Tanenhaus, 2009). Language can even
extend to objects outside of the person including the way objects in the environment are
used (Olson, 1970).
While there is some dispute as to the number of properties that are considered to
be fundamental to language, which can vary from as few as four to as many as sixteen,
what is important in regard to this thesis is the contribution of brain to language
processing (Hockett, 1958). So while these fundamental properties of language are
considered universal and are accomplished rapidly and with seemingly little effort, how
they are accomplished in the brain is not fully understood and much of the work in
neuroscience, psycholinguistics and other fields is dedicated to understand the cognitive
and neural bases of language.
2.2.2. Neural substrates
2.2.2.1. Left hemisphere language network
One hundred and fifty years ago, Paul Broca introduced a revolutionary paper
emphasizing the importance of cerebral localization (Broca, 1861a, 1861b) and research
regarding language has been under intense study since. However, Broca wasn’t the first
to note the role of the left hemisphere in language. Hippocrates (460 BCE) noted that the
loss of speech was often accompanied by a loss of movement on the right side. So while
this relationship had been noted for 2000 years, its further description began in the 19th
13
century. Marc Dax (1865) was one of the first to indicate the left hemisphere (or
hemisphere opposite the dominant hand) was important to language. Although, Dax’s
paper is published four years after Broca’s, his findings were originally presented in
1836. The “classic language model” which combines the research of Broca (and Dax)
with other neuropsychologists’ findings from aphasic patients has long been the standard
bearer in our understanding of language processing. This model proposes frontal motor
area for speech production (Broca, 1861a; 1861b) and posterior receptive area for speech
understanding (Wernicke, 1874). The connection of these two language areas within the
brain formed the basis of the understanding of language as being supported by the
perisylvian (i.e., around the sylvian or lateral fissure) structures of the left hemisphere
(Catani, Jones, & Ffytche, 2005). These early findings in aphasic patients were
fundamental to our early understanding of the localization of cognitive functions and
provided a shift in a major debate occurring at the time, which revolved around the idea
about whether cognitive functions were localized or processed by the brain as a whole.
With the evidence from the aphasics, the prevailing notion of the 19th century came to
understand the left hemisphere as the “major” hemisphere, dominant, verbal, analytic and
intelligent, while the “minor” right hemisphere was described as nondominant,
nonverbal, visuospatial, holistic and creative (Harrington, 1987).
Further investigation of language using new technologies has both confirmed and
extended the classic language model. Penfield and Roberts (1959) mapped sites in the left
hemisphere where electrical stimulation interfered with speech. The conceptualization of
language that was formed by lesion investigation continued until the 1960s as more
evidence about language localization and lateralization was gathered with a new
14
technique using patients with a different type of brain lesion. A new technique emerged
in the 1960s with the use of patients who had undergone copus callosotomy, in which the
corpus callosum is sectioned leaving little communication between the hemispheres.
Roger Sperry (1961) confirmed the laterality findings that had been demonstrated in the
lesion patients, however, they also revealed the involvement of the right hemisphere in
language processing. Another advancement in technology, with the development of
functional imaging, has begun to reveal more intricacies in the language processing
system. Early studies used positron imaging technology (PET) to image the language
related images of the left hemisphere while subjects viewed words, listened to words,
spoke and generated word associations (Petersen, Fox, Posner, Mintun, Raichle, 1988;
Demonet et al., 1992). Another new technology, functional magnetic resonance imaging
(fMRI), followed PET, and with it we were able to view dynamic changes in brain
activation during language processing (Hinke, Hu, Stillman, Kim, Merkle, Salmi, &
Ugurbil, 1993; McCarthy, Blamire, Rothman, Gruetter, & Shulman, 1993; Rueckert,
Appollonio, Grafman, Jezzard, Johnson, Le Bihan, & Turner, 1994; Binder, Rao,
Hammeke, Frost, Bandettini, Jesmanowicz, & Hyde, 1995; Demb, Desmond, Wagner,
Vaidya, Glover, & Gabrieli, 1995; Shaywitz, Pugh, Constable, Shaywitz, Bronen,
Fulbright, Shankweiler, et al., 1995; Binder, Frost, Hammeke, Cox, Rao, & Prieto,1997).
With these new techniques our understanding of language processing beyond the “classic
language model” is becoming more and more complicated, especially our understandings
of the right hemisphere’s contribution.
15
2.2.2.2. Right hemisphere Language Network
While the “classic language model” became the foundation of our understanding
of language, even Broca (1865) added caveats to his first description, noting that while
the left hemisphere is more efficient language processor, it may not be the exclusive
center of language processing. Following this notion, John Hughlings Jackson (1868)
proposed an alternative to the “classic language model.” Jackson proposed that Broca’s
findings supported the role of the left hemisphere in speech production, not language as a
whole. Jackson proposed that right hemisphere shares a role in language processing with
the left, however despite his findings, the conceptualization of the “dominant” left
hemisphere persisted.
Sperry (1961) challenged the exclusivity of language processing in the left
hemisphere with their work using split-brain patients, where he found intact language
abilities in the left-hemisphere if not always expressive language abilities. Indeed, the
right hemisphere is unable to produce language in over 95% of the population (Loring,
Meador, Lee, Murro, Smith, Flanigin, et al., 1990). Although the right hemisphere
appears to be less able to produce language, researchers have hypothesized the anatomy
of the right hemisphere to mirror that of the left, with more anterior portions involved in
motor components and more posterior and inferior portions involved in semantics and
comprehension. Further, investigators have more thoroughly investigated the language
functioning of right hemisphere brain damaged patients with the list of deficits including
both the linguistic and extralinguistic domains. Deficits include: difficulty generating
inferences, comprehending/producing central themes, reduced sensitivity to
16
communicative context (Myers, 1999), integrating context (Hough, 1990), word fluency,
comprehension (Myers & Mackisack, 1990), and understanding non-literal language due
to impulsivity, inefficiency and egocentricity (Blake, 2007). Taken together, the language
network was understood to be the connection between Broca’s and Wernicke’s areas on
(primarily) the left hemisphere with complementary support of extra- and para-linguistic
functions on the right hemisphere.
2.2.2.3. Frontal Lobes
The frontal lobes are one of the most controversial areas of the human brain in
terms of assigning cognitive abilities. Lesions to the frontal lobes often produce a variety
of symptoms. Outside the contribution of Broca’s area in the frontal lobe to language
production, other subdivisions of the frontal lobes have also been implicated in language
processes. Lesions of the anterior and medial left frontal lobe have been implicated in a
communication disorder that involves formulation of language and other characteristics
of “frontal lobe syndrome” (Benson, 1988). Large lesions of the right frontal hemisphere
including areas analogous to Broca’s area and extending into DLPFC have been
demonstrated to critically contribute to pragmatic abilities such as communicating
coherently (Delis, Wapner, Gardner, & Moses, 1983; Joanette, Goulet, Ska, &
Nespoulous, 1986) and avoiding tangential or irrelevant comments (Weylman, Brownell,
& Gardner, 1988). Kaczmarek (1984) found in an investigation of 105 patients with
frontal lobe lesions that the dorsolateral prefrontal cortex was involved with sequencing
the pattern of an utterance, where the orbital cortex was involved with the development
of a narrative. Additionally, implications from Baddely and Hitch’s theory of working
17
memory (1974) suggest that deficits in working memory (and thus a deficit in the frontal
lobe) would impair language learning. Evidence to support this claim comes from
children with specific language impairment who have both a difficulty learning language
and an impairment in digit span (Baddely, Papagno, & Vallar, 1998; Gathercole &
Baddely, 1990).
2.2.2.4. Subcortical structures
Both Wernicke (1874) and Marie (1906) suggested that subcortical structures
contributed to language processing. Stimulation of different subcortical structures led to
various behavioral performances, where stimulation of the globus pallidus produced a
deficit in the ability to produce language (Hermann, Turner, Gillingham, & Gaze, 1966),
stimulation of the head of the caudate produced a deficit in the ability to produce
comprehensible language (Van Buren, 1963). Although the precise role of the thalamus
and basal ganglia in language processing remains unclear, there are clues from patients
with subcortical lesions (Nadeau & Crosson, 1997), Parkinson’s disease (Copland, 2003;
Copland, Chenery, & Murdoch, 2001), schizophrenia, (Titone, Levy, & Holzman, 2000)
and Tourette’s syndrome (Legg, Penn, Temlett, & Sonnenberg, 2005). Broadly, the
thalamus has been suggested to play a role in semantic processing (Kraut, Kremen, Moo,
Segal, Calhoun, & Hart 2002), while the basal ganglia has been implicated in language
control (Friederici, 2006) and grammatical processing (Grossman, Lee, Morris, Stern, &
Hurtig, 2002; Ullman, 2001). Evidence from functional imaging has implicated the basal
ganglia in syntactic computation (Friederici, Ruschemeyer, Hahne, & Fiebach, 2003;
Moro, Tettamanti, Perani, Donati, Cappa, & Fazio 2001).
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2.2.3. Language interim summary
Language processing requires a complicated coordination of a number of topdown and bottom-up processes. Regardless of whether you hear or see a word or
sentence, both are going to be built of small pieces of information (phonemes and
graphemes respectively) which are combined in some sort of orderly fashion (grammar)
made into something meaningful (semantics). The speed with which this occurs, makes
language processing seem almost automatic, to the point where we take for granted the
complex processing and interactions occurring in order to craft understandable discourse
and comprehend the communications of others. The fundamental processing
requirements of the language system, arbitrary relations, incremental processing,
generativity, and multi-modality, on their face appear complicated and demanding
enough to require support from other cognitive systems. Following is a discussion of
memory and later a discussion of recent findings indicating that the hippocampal
declarative memory system is capable of many of the processing requirements of the
language system and is able to contribute on a time-scale necessitated by language.
2.3. Memory
2.3.1. Memory processes
Over the centuries, many metaphors have been used to describe memory. An
ancient Egyptian legend describes Mnemosyne, the god of memory who gave a wax
tablet, in which our perceptions and impressions are stamped into. Since then, a series of
metaphors has been proposed for the mechanisms of memory, each working within the
confines of the technology of the time. The metaphor of a dovecote or aviary was long
used, where memories, like birds would fly in and out of our minds. In the Middle Ages,
19
a more technologically advanced version of the wax tablet, the book, provided an
understanding of the functioning of memory (this metaphor is still prevalent to describe
our knowledge for words, where the lexicon is imagined to be the brain’s dictionary). In
the nineteenth century, the progress of technology led to a series of metaphors about
machines including photography (e.g., photographic memory), the telephone system, and
the phonograph (which used wax covered cylinders). Even today, our colloquial
understanding of memory uses the metaphor of the computer.
It is argued that memory is the most basic and important operation of the brain in
that many cognitive processes such as language, planning, and problem-solving rely on
memory for effective operation (Tranel & Damasio, 2002). But what is memory? An easy
why is to describe it is by the processes or mechanisms that memory performs, where
memory refers to knowledge that is stored in the brain and to the processes associated
with acquiring, encoding, storing, and retrieving this information. Another understanding
of memory is to understand what memory is for. Memory holds onto the details of
everyday life, what time is the meeting, where did I park my car. But memory is also for
holding onto information for a short period of time, attempting mental math or
remembering the phone number you just received from someone (when you don’t have
your cell phone on you). Memory is also for remembering the aspects of our lives
particular to us, the events and people and things particular to each individual, the facts
and statistics available to everyone, but also for learning the associations and procedures
between common occurrences in life, like the particular rigmarole of each social situation
(e.g., the procedures for a proper seminar include arriving early for the snacks, attentively
listening and after the lecturer finishes, asking difficult questions; Cohen & Banich,
20
2003). While memory was once thought of as a unitary function (Lashley, 1950), one of
the most important developments was the recognition that there is more than one kind of
memory supported by different structures of the brain (Cohen, 1984; Tulving, 1985).
2.3.2. Neural substrates
2.3.2.1. Hippocampus and the Medial Temporal Lobe
Karl Lashley spent a considerable amount of time looking for the “engram” the
structure in the brain where memories could be found or stored. In lesioning the brains of
animals across the cortex and in varying amounts with subsequent behavioral tests, he
was unable to impair memory performance, leading him to conclude that it may be
impossible to locate the “engram” (Lashley, 1950). However, years before, the first hint
that the medial temporal lobe plays a critical role in human memory occurred in 1899
when a Russian physician demonstrated the brain of a patient with softened uncus,
hippocampus and medial temporal cortex, who had shown a severe memory impairment
(Bekhterev, 1899). Moving forward approximately 50 years to 1953, the case of HM
marks the seminal case linking the hippocampus and declarative memory. Interestingly,
this was just three years after Lashley (1950) declared it impossible to localize the
memory trace after being unable to find the memory trace in his search for the engram.
HM’s case is often described as serendipitous as his case was one of more than a dozen
cases at the time undergoing experimental surgical procedures to treat a number of
ailments including epilepsy and psychiatric illness, but because of confounding variables,
HM’s neuropsychological profile appeared to be the cleanest of the group (Scoville,
1954; Scoville & Milner, 1957). Before the systematic investigation of HM, memory was
21
once thought to be a unitary faculty (i.e the “engram”), however, the study of HM and
other patients with memory impairments has provided evidence that memory is
manifested across multiple systems that are supported by functionally and anatomically
distinct brain systems and that memory is a fundamental property and natural outcome of
the brain’s ongoing processing (Eichenbaum & Cohen, 2001; Gabrieli, 1998; Ranganath
& Paller, 1999; Squire & Wixted, 2011).
Investigation of HM’s abilities revealed that the hippocampus and medial
temporal lobe structures (MTL) were necessary in the consolidation (but not storage) of
memories and critical for forming new memories (Scoville & Milner, 1957). Over the
next 50 years of investigation, HM demonstrated a number of distinctions in memory
systems including a split between declarative (including episodic – specific personal
experiences; and semantic – general facts and knowledge; Cohen & Squire, 1980) and
non-declarative (e.g. skills, priming, habituation, simple classical conditioning) memory
in that the hippocampus is critical for processing declarative but not non-declarative
memory (Cohen & Squire, 1980) and a distinction between long-term and short-term
memory where the hippocampus is critical for long-term memory, but not short term
memory (Baddeley & Warrington, 1970; Warrington & Baddeley, 1974). Despite the
severe deficit in declarative memory, HM demonstrated that memory could be
distinguished from other cognitive abilities and had intact perceptual, motor, and
cognitive functions, immediate memory, and even spared remote memory, and that
selective impairments in memory itself could teased apart (Eichenbaum & Cohen, 2001).
Recent work in neuroimaging has also implicated the hippocampus in memory
processing. Early investigations into the functioning of the hippocampus using functional
22
imaging focused on the role of the hippocampus during encoding and retrieval and found
that activity of the hippocampus was similar during encoding and retrieval (Small, Nava,
Perera, DeLaPaz, Mayeux, & Stern, 2001) and activity during encoding could predict the
success of retrieval (Stark & Okado, 2003). The hippocampus is active in relation to both
visual and spatial memory (Bellgowan, Saad, & Bandettini, 2003) Hippocampal
activation has been observed when participants recollect a studied event (Eldridge,
Knowlton, Furmanski, Bookheimer, & Engle, 2000), remember the source of an item
(Casino, Maquet, Dolan, & Rugg, 2002; Davachi, Mitchell, & Wagner, 2003) and
remember the associations amongst items (Giovanello, Schnyer, & Verfaellie, 2004).
2.3.2.2. Extended MTL
A number of medial temporal lobe structures beyond the hippocampus including
perirhinal cortex, parahippocampal cortex and entorhinal cortex have been implicated in
various memory functions. While the hippocampus has been primarily implicated in
recollection, familiarity has been suggested to depend on adjacent cortex (Brown &
Aggleton, 2001; Rugg & Yonelinas, 2003). Another subdivision of memory contributions
within the medial temporal lobe has been between relational and item memory, where
relational memory depends primarily on the hippocampus, the perirhinal cortex and other
regions neighboring hippocampus support item memory (i.e., the binding of inflexible
relations; Cohen, Poldrack, Eichenbaum, 1997). Several functional imaging studies have
suggested that the hippocampus and parahippocampal cortex is active in both the retrieval
of associations and also recollective memory (Davachi et al., 2003; Kirwan & Stark,
2004; Ranganath, Yonelinas, Cohen, Dy, Tom, & D’Esposito, 2003), but many studies
23
have found evidence for activation of the entorhinal and perirhinal cortices (Dobbins,
Rice, Wagner, & Schacter, 2002; Davachi et al., 2003) and parahippocampal cortex
(Kirwan & Stark, 2004) in familiarity based memory.
2.3.2.3. Frontal Lobes
While hippocampal damage impairs long-term memory, it has traditionally been
thought to leave short-term or working memory intact. The first well known patient with
a deficit was KF whose left tempo-parietal lesion impaired his ability to hold onto even
short strings of words or digits despite long-term memory (Shallice & Warrington, 1970).
Other deficits have been thought to be linked to various aspects of language processing,
comprehension versus production (Caramazza, Miceli, Silveri, & Laudanna, 1985), or the
visuospatial workpad (Baddely, 1986) in the case of visual verbal working memory
impairments. Evidence from the animal literature has suggested that working memory
can be linked to the dorsolateral prefrontal cortex (DLPFC) as lesions in monkeys
impairs their ability to find rewards in a delayed-response task with delays as short as
even one second (Goldman-Rakic, 1988; Goldman-Rakic, 1995). Converging
methodology in human imaging has also indicated the importance of the DLPFC in
holding information on-line about spatial location (Smith & Jonides, 1999).
The frontal lobes have also been implicated in encoding memories. Ventrolateral
regions of the frontal lobes are activated during acquisition and encoding of information
(Buckner, 1996; Buckner & Koustaal, 1998; Kelley, Miezin, McDermott, Buckner,
Raichel, Cohen, Ollinger, et al., 1998; Poldrack & Gabrieli, 1998). The prefrontal cortex
has also been implicated in retrieval as patients with damage to this area, who have
24
problems organizing and monitoring memory retrieval tend to confabulate (Moscovitch
& Winocur, 1995) and have problems in recognition tasks where they disproportionate
amount of false positives (Schacter, Reiman, Uecker, Polster, Yun, & Cooper, 1995).
Other portions of the frontal lobes including the DLPFC have been implicated in retrieval
(Buckner, 1996; McDermott, Buckner, Petersen, Kelley, & Sanders 1999; Nyberg,
Cabeza, & Tulving, 1996; Wagner, Desmond, Glover, Gabrieli, 1998).
Complimentary findings from functional imaging have implicated frontal
contributions to memory such as when individuals are asked to maintain information over
short delay (Courtney. Ungerleider, Keil, & Haxby, 1997; Zarahn, Aguirre, &
D’Esposito, 1999). Activation of the frontal lobes during encoding (Cabeza & Nyberg,
2000; Kim, Daselaar, & Cabeza, 2010) and retrieval (Shimamura, 1995; Blumenfeld &
Ranganath, 2007; Blumenfeld, Parks, Yonelinas, & Ranganath, 2011) have also been
observed.
2.3.2.4. Lateral Temporal Lobe
Semantic memory (conceptual knowledge) is the memory of general knowledge,
word meanings, facts and people, without personal connection to place or time (Tulving,
1985). Conceptual knowledge is largely accessible across persons in a culture (although
the scope depends on the individual), while episodic memory ties a particular experience
to specific times and places. While the interest in how a concept is represented in the
brain has been of interest for centuries, the ability to study its representation in the brain
has only emerged recently. Early reports on the loss of specific categories of conceptual
knowledge relied on reports from patients with widespread damage, such as demented
25
patients or patients with Herpes Simplex Encephalitis (Warrington & Shallice, 1984).
More specific brain localization relied on patients with focal brain damage and category
specific loss of semantic representation. A report by Damasio and colleagues (1996) used
a combination of PET imaging in normal subjects and lesion overlap analysis in
neuropsychological patients to investigate lexical retrieval, finding that the normal
process of retrieving concrete words depends on distinct regions of the left hemisphere
outside of the classic language area.
While some work has focused on the theoretical organization of conceptual
knowledge, four theories have focused on the neuroanatomical organization. Work with
neuropsychological patients has shaped Damasio and colleagues hypotheses of the
conceptual system (Damasio et al, 1996; Tranel, Damasio, & Damasio, 1997).
Conceptual knowledge is organized in multiple convergence/divergence sites, which
direct the reconstruction of explicit pieces of the concept in the relevant sensory cortices
(which is essential for conscious processing of the concept). Intermediary regions
(distinct regions of the temporal cortex) promote the activation of sensorimotor
representations and serve as a flexible feedback/feedforward projection site (Tranel et al.,
1997). These intermediary regions are activated by preferential physical characteristics
and contexts of entities, which leads to the possibility of neurally distinct, category
specific loss of conceptual knowledge.
While Damasio and colleagues’ account of conceptual processing appeals to brain
areas outside of the classical language network, Jung-Beeman’s bilateral activation,
integration, selection (BIAS) theory proposes a framework of multiple bilateral processes
to construct meaning (Jung-Beeman, 2005) within the classic language network. The
26
framework assumes three distinct but interactive components representing the activation
(posterior middle and superior temporal gyri), integration (anterior superior temporal
gyrus, superior temporal sulcus, middle temporal gyrus) and selection (inferior frontal
gyrus) of semantic information (Jung-Beeman, 2005). Further, the semantic processes
occur bilaterally with each hemisphere contributing a different level of processing of the
information, with the right hemisphere providing coarse semantic coding and the left
hemisphere providing fine semantic coding (Jung-Beeman, 2005). A third theory of
concrete conceptual representation appears to be combine aspects of the previous two.
Just and colleagues (2010) present a neurosemantic theory of concrete noun
representation in which semantic factors (manipulation, shelter and eating) underpin the
representation of concrete noun and are represented in neurally distinct areas (anterior
superior parietal, posterior temporal, and posterior lateral frontal respectively; Just et al.,
2010). The final theory envisions the organization of the semantic system as a “hub-andspoke” in which semantic information is represented in both modality-dependent cortices
(“spokes”) and the anterior temporal lobes convergence zone (an amodal hub; Patterson,
Nestor & Rogers, 2007).
2.3.2.5. Parietal Cortex
The most recent addition to the neural network of structures underlying memory
is the lateral parietal lobe (PL). Typically the PL has been associated with functions such
as visuospatial attention and visually-guided reaching. Research into the role of PL
regions in memory has grown following Wagner and colleagues (2005) review of the
functional neuroimaging literature, which highlighted how PL responses, in particular on
27
the left, are closely linked with episodic retrieval success. A meta-analysis by Simons et
al. (2008) identified that PL regions may be consistently activated during recollection
than core episodic memory regions (i.e. MTL) and has been echoed in other meta
analyses including Skinner and Fernandes (2007). Patient studies have indicated that
while the patients with damage to the PL are not amnesic, their memory may not be quite
normal on tasks of autobiographical memory (Berryhill, Phuong, Picasso, Cabeza, &
Olson, 2007) or recognition (Davidson, Anaki, Ciaramelli, Cohn, Kim, Murphy, Troyer,
et al., 2008).
2.3.2.6. Striatum
While hippocampal damage impairs declarative memory, it has traditionally been
thought to leave non-declarative memory intact, lending thought to the double
dissociation between the hippocampus and declarative memory and non-declarative
memory and striatal structures (Knowlton, Squire, & Gluck, 1994). Evidence from
studies of patients with Parkinson’s disease and Huntington’s disease suggests that the
striatum is critical to non-declarative learning. In one task, patients were unable to
perform the rotary pursuit task in which a participant tracks a target spinning in a circle
with a handheld stylus. Generally, individuals improve their ability to track the target
over time, but the patients with striatal damage were unable to (Gabrieli, 1995).
Converging methodology from functional imaging has indicated activation in the striatum
with learning on this task (Grafton, Nazzuitta, Presty, Friston, Frackowwiak, & Phelps,
1992). In another example of a more cognitive non-declarative task, the serial reaction
time task, in which an individual presses certain buttons in response to spatial locations
28
of a target. Unbeknownst to the participant, there is a pattern that is repeated within the
trials, that in healthy people is accomplished faster over time. In patients with damage to
the striatum, this effect is not observed (Willingham & Koroshetz, 1993; Ferraro, Balota,
& Conor, 1993; Pascual-Leone, Grafman, Clark, Stewart, Massaquoi, Lou, et al., 1993).
Again, converging evidence from functional imaging reveals activation of the striatum
during learning on this (Grafton, Hazeltine, & Ivry, 1995) and similar tasks (Seitz,
Roland, Bohm, Greitz, & Stone-Elander, 1990; Seitz & Roland, 1992). More recent
literature from neuroimaging has also implicated the striatum in nondeclarative/procedural memory (Kumari, Gray, Honey, Soni, Bullmore, Williams, Ng, et
al., 2002; Martis, Wright, McMullin, Shin, & Rauch, 2004; Rauch, Walen, Savage,
Curran, Kendrick, Brown, Bush, et al 1997; Zedkova, Woodward, Harding, Tibbo, &
Purdon, 2006).
2.3.3. Cognitive processes and theories
2.3.3.1. Declarative memory
The relative impairment of episodic and semantic memory by neurological
disorders has implications for theories of long-term memory. How we conceptualize the
processing and functioning of the hippocampus has significant effects on what cognitive
capacities we understand the hippocampus can contribute to. The traditional view of the
functioning of the hippocampus comes from our understanding of amnestic disorders. In
1881, Ribot proposed that there is a time gradient in retrograde amnesia where the most
recent memories are the most likely to be lost. The ‘standard model’ of memory
consolidation (e.g. Squire, 1992) proposes that both episodic and semantic information
29
becomes independent of the hippocampus after consolidation. Hippocampal damage
should, therefore, lead to a temporal gradient for both episodic and semantic information
with greater sparing of remote than recent information. This view fits well into the
understanding of the hippocampus and its critical contribution to long-term memory,
where the hippocampus is responsible for both storing memories early and later retrieving
memories that have been consolidated in the cortex.
Other theories in contrast, for example, the Multiple Trace Theory (MTT;
Moscovitch, Rosenbaum, Gilboa, Addis, Westmacott, Grady, & McAndrews, et al. 2005)
suggests that semantic but not episodic memory becomes independent of the
hippocampus over time. According to MTT, medial temporal lobe damage should lead to
a temporally extended impairment of episodic memory; for semantic memory, MTT, like
the consolidation model, predicts a standard temporal gradient. Examination of patients
with medial temporal lobe damage has produced mixed results; some studies favor the
standard consolidation model (e.g. Bayley, Frascino, & Squire, 2005; Kirwan, Wixted &
Squire, 2008), and others MTT (e.g. Steinvorth, Levine & Corkin, 2005; Poreh, Winocur,
Moscovitch, Backon, Goshen, Ram & Feldman, 2006; Rosenbaum, Moscovitch, Foster,
Schnyer, Gao, Kovacevic, Verfaellie, et al., 2008). Previous studies have confirmed the
occurrence of remote memory deficits in patients with dysfunctional temporal lobes but
have differed on their precise nature.
Some studies have revealed an impairment in autobiographical memory
throughout the entire life span (e.g. Viskontas, McAndrews, & Moscovitch, 2000;
Noulhiane, Piolino, Hasboun, Clemenceau, Baulac, & Samson, 2007), whereas in others
the deficit extends back as little as 5 years (Kapur, Millar, Colbourn, Abbott, Kennedy, &
30
Docherty, 1997). Viskontas et al. (2000) found autobiographical memory deficits with
intact personal semantics, while others have reported deficits in both autobiographical
memory and semantic memory for public events with intact personal semantic memory
(Lucchelli & Spinnler, 1998; Voltzenlogel Despres, Vignal, Steinhoff, Kehrli,
& Manning, 2006) or disproportionate loss of public semantics compared to
autobiographical memory (Barr, Goldberg, Wasserstein, & Novelly, 1990; Manning et
al., 2005). This evidence is consistent with the dissociations observed between
components of remote memory in other contexts (e.g. O’Connor, Butters, Miliotis,
Eslinger, & Cermak, 1992; Graham & Hodges, 1997) suggesting there is at least partial
independence between these processes (Kapur, 1999). This suggestion converges with
neuroimaging evidence that shows neural overlap between components of remote
memory as well as unique contributions corresponding to the specific properties of the
retrieved memories (e.g. Graham, Lee, Brett, & Patterson, 2003; Levine, Turner,
Tisserand, Hevenor, Graham, & McIntosh, 2004; Svoboda, McKinnon & Levine, 2006;
Burianova & Grady, 2007). However, the conceptualization of the functioning of the
hippocampus in either the standard model or MTT limits its processing capabilities to the
domain of declarative memory.
2.3.3.2. Relational memory
The critical role of the hippocampus and related medial temporal lobe regions in
the formation and subsequent retrieval of new enduring memories (i.e., long-term
memory) is incontrovertible as demonstrated by decades of neuroscience and cognitive
neuroscience research (Cohen, 1984; Cohen & Eichenbaum, 1993; Eichenbaum &
31
Cohen, 2001; Gabrieli, 1998; Squire, 1987; 1992). Cohen and Eichenbaum (1993)
hypothesize that the hippocampal system, is critical for learning and forming new
declarative memories because of its processing capacities. Damage to the hippocampus
selectively impairs the ability to acquire new declarative memories while non-declarative
(procedural) memory remains intact. Declarative representations supported by the
hippocampus are uniquely flexible (which stands in stark contrast to the relatively static
and inflexible memory representations supported by other brain regions), permitting rapid
integration with other representations. These representations are then accessible to other
processing systems (as when a rich, multisensory autobiographical memory is evoked by
the sight of a familiar face or the sound of a familiar song), and permitting
representations to be used in novel contexts (Cohen, 1984; Dusek & Eichenbaum, 1997;
Eichenbaum & Cohen, 2001; O’Keefe & Nadel, 1978; Squire, 1992).
Rather than serve as the storage site of declarative memories, the hippocampus
serves to bind together and interact with representations between various neocortical
processors (e.g., language processors, spatial processors, face processors) forming
relational representations. Further, the hippocampus supports the creation and integration
of representations for events including information about the co- occurrences of people,
places, and things, and the ability to link the spatial, temporal and interactional relations
among them across time (e.g., a word and its meaning; a pronoun and its referent; a
narrative and a specific speaker) (Cohen & Banich, 2003; Davachi, 2006; Eichenbaum &
Cohen, 2001; Giovanello, Verfaellie, & Keane, 2003; Konkel, Warren, Duff, Tranel, &
Cohen, 2008). These cortical processors thus act as the storage sites of memory with each
processor storing the particular elements/attributes of the experience or event that it
32
processed (i.e., linguistic elements are stored in language processors; visual
representations are stored in or near primary visual cortex).
The view of the hippocampus in relational memory theory, where its processing
capacities allow for the rapid and on-going access and manipulation of cortically bound
representations, allows for a more flexible understanding of the processing capacities of
the hippocampus. Rather than just limited to memory processing, the hippocampus is able
to flexibly contribute to cognition more generally where a rapid, on-going manipulation
of representations is required. This thesis is grounded in this theory as its
conceptualization of the hippocampus allows the hippocampus to promiscuously
contribute to its fundamental processing capacities to a number of cognitive processes.
Below, I discuss how the processing demands of language and the processing capabilities
of the hippocampus overlap to a great extent and that the hippocampus may be a critical
neural substrate of language capacities that rely on the processing contributions of the
hippocampus.
2.4. Memory and Language
There have been longstanding efforts to link language to cognitive and neural
systems outside of the “traditional language network.” The idea that language relies on
other cognitive domains is not new. In healthy and disordered populations the effective
use of language has been linked to executive functioning (e.g., Coelho, 2002; Novick,
Trueswell, & Thompson-Schill, 2005) and attention (e.g., McNeil, Odell, & Tseng, 1991;
Murray, Holland & Beeson, 1998) to name a few. The relationship between memory and
language has been of special interest and specific hypotheses have been made regarding
33
the mapping of particular language components (e.g. phonology, lexicon, grammar) and
processes (e.g. production, comprehension) to multiple forms of memory (e.g. working
memory, declarative memory, procedural memory; e.g., Caplan & Waters, 1998;
Crosson, 1992; Gathercole & Baddeley, 1993; Gupta & MacWhinney, 1997; Just &
Carpenter, 1992; Ullman, 2004). With the exception of vocabulary acquisition and the
role of explicit remembering on extended discourse and text production/processing, the
contribution of declarative memory to the processing and use of language has received
little attention. Instead, the bulk of work directed at linking language to an aspect of
memory has focused on a relationship with working memory (e.g., Caplan & Waters,
1998; Just & Carpenter, 1992). This has been true even in clinical populations for whom
profound declarative memory impairments are a hallmark such as traumatic brain injury
and Alzheimer’s disease (e.g., Bayles, 2003; Dijkstra, Bourgeouis, Allen, & Burgio,
2004; Youse & Coelho, 2005).
2.4.1. Connecting the hippocampus, declarative memory,
and language
Although the relationship between memory and language has received a lot of
attention, outside of word learning, the hippocampal declarative memory system has
received little attention. For example, one model that has received some attention in
terms of the differential contribution of memory systems to language is the
declarative/procedural model proposed by Ullman and colleagues (Ullman, 2001;
Ullman, 2004; Ullman, Corkin, Coppola, Hickok, Growdon, Koroshetz, & Pinker 1997)
which argues that language depends directly on the same brain structures that also
34
subserve memory. In this model Ullman (2001, 2004) argues that temporal lobe
structures and the declarative memory system subserve the mental lexicon of memorized
word-specific knowledge. In contrast, a network of frontal, basal ganglia and cerebellar
structures, underlying procedural memory are responsible for mental grammar, the rulegoverned combination of lexical items into complex representation.
The declarative/procedural model has mapped onto the spared and intact abilities
following amnesia. Kensinger, Ullman, and Corkin, (2001) found that the lexical and
grammatical knowledge that the amnesic patient H.M. acquired during his childhood and
prior to his surgery did not differ from normal age- and education-matched control
subjects, while, Gabrieli and colleagues (1988) found that H.M. was unable to acquire
new lexical information (i.e., words and their definitions) following his amnesia. In an
investigation of procedural knowledge following hippocampal damage, Knowlton,
Ramus, and Squire (1992) found that 13 amnesic participants performed as well as
comparison participants on an artificial grammar task suggesting that learning novel
grammatical structures can be supported by nondeclarative memory systems, which are
intact in amnesia.
The declarative/procedural model of language easily maps onto the standard
model of memory, where the hippocampus serves to store and retrieve long-term
memories, in this case, words. However, what if we view the capacities of the
hippocampus through the relational memory theory, are there other language abilities that
the hippocampus may contribute to? Much of our understanding of the contribution (and
perceived lack there of) of declarative memory to language stems from the study of the
famous neurological patient H.M. In the earliest descriptions of his profile (Milner,
35
Corkin, & Teuber, 1968; Scoville & Milner, 1957), the researchers were struck by the
severity and selectiveness of the deficit of his ability to form new long term memories,
indicating that he had many intact abilities including intelligence and perceptual abilities.
The integrity of language in amnesia has been controversial and of great interest since the
beginning of H.M.’s formal testing. There are many opinions on the nature of H.M.’s
language deficits and whether language deficits exist at all; some claimed H.M. had a
pure memory deficit and that language comprehension was undisturbed (Milner, Corkin,
and Teuber, 1968).
Neuropsychological testing of the language abilities of individuals with amnesia
has revealed that they do not have aphasia and furthermore, the ability of amnesic
individuals to engage in sophisticated conversations (MacKay, Burke, & Stewart, 1998)
has lead to the assumption that language production abilities were intact. However,
despite the assertion of normal language, Ogden and Corkin (1991) noted that while
H.M.’s was able to discuss the current topic, his language often became markedly
tangential and at other times rote and repetitious.
As early as 1974, researchers began to more closely examine his language
following the thinking that his lack of deficits in language functioning could be due to the
lack of probing of the full capacity of language (Lackner, 1974). Lackner (1974) found
that while H.M.’s ability to detect ambiguity appeared intact, his performance in
segmenting ongoing perceptual speech is not. Further investigation however have
indicated that H.M.’s ability has remained intact in a number of language abilities
including, lexical retrieval (Skotko, Rubin, & Tupler, 2008), phonology, morphology,
direct references, phatic function, conative response, metalinguistic abilities, poetic
36
abilities and extended narrative ability among others (Skotko, Andrews, & Einstein,
2005) syntax (Corkin, 1984; Skotko, Andrews, & Einstein, 2005), semantics (Schmolck,
Kensigner, Corkin, & Squire, 2002; Skotko, Andrews, & Einstein, 2005) or lexical and
grammatical processing (Kensigner, Ullman, & Corkin, 2001).
While others have called into question the language performance of H.M. (c.f.
MacKay, Burke & Stewart, 1998; MacKay & James, 2001), and others have criticized the
work with H.M. because of extended pathologies (e.g., cerebellar damage), complicating
factors (age, long-term medication usage, and seizure disorder) and a lack of contact with
current memory theories (Squire, 2011) few of these investigations of H.M.’s language
performance finely probe abilities that place high demand on the creative and flexible
manipulation of multiple representations. It appears when an individual with amnesia is
required to balance, match or compare multiple representations, whether they be time
(e.g. the past and present or present and future in reporting speech or describing an
event), person (e.g. that he refers to the boy and not the police man), or item (e.g. that the
game refers to a game we both have access to and knowledge of), deficits in the ability to
narrate those instances becomes more difficult.
If individuals with amnesia and hippocampal damage do indeed show deficits on
language tasks that probe the processing demands of language that overlap with the
processing capacities of the hippocampus, they may provide evidence that the
hippocampus plays a more fundamental role in cognition besides contributing to the
storage and retrieval of declarative memories and rather serves to generate and
relationally bind together representations that can be used in service of multiple cognitive
abilities (Cohen & Eichenbaum, 1993; Eichenbaum & Cohen, 2001) including
37
declarative memory, perception (Warren et al., 2010), creativity (Duff, et al., 2013), and
language.
2.4.2. Hippocampal Declarative (Relational) Memory
System: Contributions to Language
The demands of language production and comprehension are immense.
Fundamental to all human languages is an unlimited expressive capacity and a creative
flexibility that allow speakers to rapidly generate novel and complex utterances, but a
challenge for theories of language processing has been to understand how listeners
generate, maintain and integrate representations while interpreting language rapidly,
incrementally and in real time. Much of the focus on working memory has been due to its
purported ability to maintain information on line. However, given the recent discovery of
the functionality of the hippocampal declarative memory system (i.e., its generativity and
flexibility) and the implication emerging work that new hippocampal-dependent
representations are available rapidly enough to influence ongoing processing (e.g.,
Warren et al., 2010), this form of memory seems uniquely suited to meet the demands of
understanding and using language.
The processing demands of language, arbitrary relations, processing incrementally
over time, being flexible/creative and having multi-modal characteristics are the same
processing capacities that are brought to bear in the hippocampus’ contribution to
declarative memory. For example, the in language we are required to bind arbitrary
speech sounds to meanings and evidence has shown that the hippocampus engages in
arbitrary bindings. Subsequently, patients with hippocampal damage are impaired at
38
learning arbitrary word pairs (Gabrieli et al., 1988; Winocur & Weiskrantz, 1976).
Another processing demand of language, incremental processing has also been
demonstrated as a function of the hippocampus, where the hippocampus is engaged over
short time courses (Cabeza, Dolcos, Graham, & Nyberg, 2002; Öztekin, McElree,
Staresina, & Davachi, 2009; Ranganath, Cohen, & Brozinsky, 2005; Ranganath &
D'Esposito, 2001). Accordingly, when individuals with amnesia are asked to maintain
representations over short-time courses their performance is impaired compared to
healthy performance (Hannula et al., 2006; Warren et al., 2010). Flexibility and creativity
are yet more processing demands of language that have been demonstrated as capacities
of the hippocampus (Duff et al., accepted). Again, when patients are assessed for their
ability to be flexible and creative with their language, their performance is impaired
compared to healthy performance (Duff, Hengst, Tranel & Cohen, 2009). A final
processing demand of language, multi-modality, meaning that a word and its meaning
includes the physical, visual, auditory and other physical sensations as well as how it is
expressed with in the body and environmental context, is yet another processing capacity
of the hippocampus (Damasio, Graff-Radford, Eslinger, Damasio & Kassell, 1985). In a
tightly controlled series of experiments, participants were asked to identify material that
had been altered across spatial, sequential (temporal) and associative (co-occurrence) and
found that individuals with amnesia were deficient across all tests of relations (Konkel et
al., 2008). Thus, there are compelling reasons to predict that disruptions in hippocampal
functioning would be revealed in language use (see MacKay et al., 1998 for an alternative
account).
39
Indeed, Duff and colleagues, grounding their work in the relational memory
theory, have shown that hippocampal amnesia impairs various aspects of everyday
language use, when the language use demands the processing capacities of the
hippocampus, including disruptions in collaborative referencing (Duff et al., 2008),
verbal play (Duff et al., 2009), procedural discourse (Duff, Hengst, Tengshe, Krema,
Tranel, & Cohen 2008), reported speech (Duff, Hengst, Tranel, & Cohen, 2007),
cohesion and coherence (Kurczek & Duff, 2011) and definite references such as “the
dissertation” as opposed to “a dissertation” (Duff, Gupta, Hengst, Tranel & Cohen, 2011;
Duff, Hengst, Gupta, Tranel, & Cohen, 2011).
Recently, this work has been extended to examine the role of hippocampaldependent declarative memory in perspective-taking processes using on-line language
measures (e.g., eye tracking), revealing striking failures in amnesia patients to integrate
self- versus other-perspective information into on-line ambiguity resolution processes
(Rubin et al., 2011). Rubin, et al. (2011) asked eye-tracked amnesic patients and healthy
comparison participants to interpret definite references such as “the duck” in scenes
containing two ducks, one of which was known to a discourse partner, and one of which
was not. When the identity of the shared duck was visually marked in the scene or
mentioned in an immediately preceding discourse, amnesic patients, like healthy
comparisons were largely successful at looking to the shared duck. By contrast, when a
40s unrelated delay was introduced between identifying the shared duck and
subsequently referring to it, amnesic patients (but not comparisons) were unable to
identify the shared duck. These findings suggest potential deficits in referential
processing when processing of the referential expression requires maintaining a
40
representation of a previous discourse across an intervening unrelated delay (Rubin et al.,
2011).
Kurczek and colleagues (2013) investigated the contributions of the hippocampus
to on-line referential processing. Using a visual real world paradigm, they monitored eye
movements of individuals with hippocampal amnesia, brain-damaged comparisons and
healthy comparisons while they viewed a scene and listened to a brief, two-sentence
narrative. They found that individuals with amnesia experienced difficulty in integrating
and maintaining information about the discourse even over a very short discourse history
(Kurczek, Brown-Schmidt & Duff, 2013). This work not only extended the cognitive
contributions of the hippocampus to referential processing during comprehension but also
provided further evidence for the contribution of the hippocampus to on-line processing.
While the notion that the language abilities of H.M. and other patients with
hippocampal damage are fully intact has been challenged (e.g., Duff et al., 2007;
MacKay, Stewart, & Burke, 1998; Park, St-Laurent, McAndrews, & Moscovitch, 2011),
these studies all used off-line methodologies that tapped the final, ultimate
interpretation/production of an utterance. Thus, little is known about the time-course of
language processing in amnesia—that is, how impairments to the processes provided by
the hippocampus affect processing as it unfolds in real time, leading to the possibility that
these patients exhibit even more subtle deficits in the time-course with which they access
and process linguistic information, even in cases where they are ultimately successful.
For example, consider the amnesic patients’ performance on the Token Test (see Table
1), a standardized neuropsychological assessment of language comprehension where
subjects are asked to “Point to a circle” or “Pick up the small yellow circle and the large
41
black square” when presented with small and large squares and circles of different colors.
This test was designed to capture the more deleterious language impairments associated
with aphasia, and thus amnesia patients are nearly all at ceiling levels of performance.
Yet, the results of the present study raises the possibility that even though the patients are
ultimately successful at performing the command they may be challenged in the
incremental processing of the unfolding utterance with respect to the context (e.g., small
yellow circle). If so, such disruptions, which are not evident in the end-state of
performance (i.e., picking up the right object), may be revealed using the type of on-line
assessment deployed here. Indeed, such a pattern of behavioral accuracy and disrupted
language processing as measured by participant eye movements has been shown in
adolescents with specific language impairment (McMurray, Samelson, Lee, & Tomblin,
2010).
Building on the work that has investigated the contributions of the hippocampus
to language, this thesis expands that work and investigates how the hippocampus may
contribute to other aspects of language processing not previously explored. The
traditional view of hippocampal amnesia has been as a pure memory deficit, leaving
language (and other cognitive) capacities unaffected. However, the repeated observations
demonstrating disruptions of language, however, suggests that the same processes by
which the hippocampus creates and integrates representations in the formation of new
memories, and maintaining representations on-line to be evaluated and used in service of
behavioral performance, could be the same processes necessary for the on-line processing
and use of language.
42
I have chosen the lesion method because, despite advances in imaging and other
functional methodology, it remains a fundamental and indispensable scientific approach
in cognitive neuroscience (Chatterjee, 2004; Fellows, Heberlein, Morales, Shivde,
Waller, & Wu, 2005; Fellows, Stark, Berg, & Chatterjee, 2008; Poldrack, 2006; Rorden
& Karnath, 2004). It is often the first source of evidence for brain-behavior relationships,
has been provided by lesion studies (including the importance of the hippocampus to new
learning and recent memory from observations of patient H.M.). These results, in fact, are
often used to validate the use of newer functional methodologies, which are then used as
complementary evidence for the lesion studies. Unlike neuroimaging methodology, the
lesion method provides a critical test of whether a particular structure is
actually necessary for one or another cognitive process or behavioral performance. In this
dissertation, I will use lesion methodology to provide a critical test of the necessity of the
hippocampus to referential processing and narrative construction.
This dissertation focuses on the role of hippocampal dependent declarative
memory in the processing and use of language. More specifically, I propose that this form
of memory plays a critical role in the creation, maintenance, updating, and use of
representations necessary for the processing, use, and understanding of language
including in referential processing and in narrative construction. I propose, and aim to
test in the experiments below, that on-line linguistic representations depend critically on
processing capacities of the hippocampal declarative memory system and that damage to
the hippocampal declarative memory system will disrupt referential processing and
narrative construction.
43
CHAPTER 3: GENERAL METHODOLOGY
3.1 Participants
The participant sample will include a participant group with bilateral hippocampal
damage (AM), a brain damaged comparison (BDC) group of individuals with brain
damage outside of the hippocampus and medial temporal lobes (specifically, the
ventromedial prefrontal cortex), a group of individuals with unilateral temporal lobe
damage (TL) and a healthy non-brain injured comparison group (NC). Participants with
brain damage were selected from the Iowa Patient Registry of the Department of
Neurology at the University of Iowa. The registry serves as a database of participants
with focal brain damage and specified behavioral deficits. All of the patients are in the
chronic epoch (greater than three months post onset of lesion) and are well characterized
neuroanatomically and neuropsychologically according to the standard protocols of the
Benton Neuropsychology Laboratory (Frank, Damasio & Grabowski, 1997; Tranel,
2007) and the Laboratory of Brain Imaging and Cognitive Neuroscience (Damasio, 1995,
Damasio & Damasio, 1989). Inclusion criteria include normal or corrected vision and
hearing, negative history of language impairment or premorbid learning disabilities, and
monolingual English speakers. Additionally, patients in this study had a negative history
of language impairment as indicated by normal scores on the Boston Naming Test and
Token Test, and WAIS-III or WAIS-IV scores greater than 80. Patients with a history of
psychiatric disorders, mental retardation/intellectual disability, dementia, psychiatric
disease, drug/alcohol abuse, or other neurological illness were excluded. Additionally, for
44
participants to be diagnosed with amnesia their WMS-III GMI were at least 25 points
below their WAIS-III /IV IQ.
3.2. Statistical Approach
Across all analyses the participant groups were compared using the appropriate
test (e.g. T-test, ANOVA, Linear mixed effects modeling). In Aim 1, each patient group
(AM and BDC) were compared separately to the healthy comparison group. For all
ANOVA tests performed, if there was any violation of the underlying assumptions, the
appropriate kluge was applied (e.g., for unequal variances the Greenhouse-Geisser
correction was applied). For all tests in which multiple comparisons were performed,
the Šidák correction was applied.
45
CHAPTER 4: REFERENTIAL PROCESSING - FACILITATING
PRONOUN COMPREHENSION IN INDIVIDUALS WITH
PROFOUND MEMORY IMPAIRMENT
4.1. Background/Rationale
Efficient and successful language processing relies on the ability to establish and
maintain reference as most of what we talk about involves referring to things in the
world. Using reference places a demand on the ability to both track information across
time and bind information and representations from potentially rich contexts. When
interpreting pronouns such as she, it, or him, the addressee must bind features of the
pronoun (gender, animacy, etc.) with representations of the salience of relevant discourse
referents. However, while this process appears to be quite complex, this process occurs
rapidly, with evidence from eye-tracking tasks demonstrating that healthy adults
preferentially fixate on salient referents in ambiguous discourse within 200-400ms of the
onset of a pronoun like she (Arnold et al., 2000).
In terms of the neural systems that could support these abilities, there are a
number of reasons to consider the hippocampal declarative memory system. This system
supports the creation of representations for successive events including information about
the co-occurrences of people, places, and things and the ability to link the spatial,
temporal and interactional relations among them across time. Referential processing
requires maintaining a representation of unfolding discourse history and potential
referents, and integration of information about binding representations together, for
example, referential form and context. Research indicating that HDMS representations
are available rapidly enough to influence ongoing processing suggests HDMS
46
involvement in integrating distant and immediately available information necessary for
referential processing.
Discursive cohesion and coherence gives our communication continuity (Ferstle
& von Cramon, 2001). One way to study referential processing is to look at cohesion,
how speakers use references and pronouns to link ideas within language (the boy….
He….; Halliday & Hasan, 1976). Another way we can examine referential processing is
through coherence, the effect that those cohesive links have on how well the story flows
or how connected one utterance is to another (Gloser & Deser, 1991).
Three preliminary studies have been completed that support the hypothesis that
the HDMS contributes to referential processing. In two studies I looked at discourse
production and examined the ability of patients with hippocampal damage (Kurczek &
Duff, 2011), patients with vmPFC damage (and no hippocampal damage or declarative
memory impairment; Kurczek & Duff, 2012) and healthy comparison participants
(Kurczek & Duff, 2011; 2012) while in preliminary study 3 I investigated discourse
comprehension in patients with hippocampal damage, patients with vmPFC damage and
healthy comparisons (Kurczek, Brown-Schmidt & Duff, 2013).
In preliminary study 1 participants were asked to produce language across a
number of discourse settings including conversation, story-telling, picture description and
procedural discourse. These language samples were then analyzed for two linguistic
resources, one that investigated how cohesive the language tied together within the
sample while the other looked at how coherent the language was within the sample. In
comparison to healthy participants amnesia participants (1) produced fewer cohesive ties
across all discourse types; (2) the adequacy of their ties were judged to be incomplete
47
more often, and (3) and the ratings of their local coherence were consistently lower. This
finding suggests that the hippocampal declarative memory system critically contributes to
referential processing as measured by discursive production of cohesion and coherence.
In preliminary study 2 I replicated the procedures from preliminary study 1 with a
group of patients with damage to the frontal lobes, an area of the brain that was thought
to be important for the linguistic resources I had demonstrated to critically rely on the
hippocampus. I found that bilateral frontal lobe damage does not impair cohesion
and coherence in spoken discourse. This study provides insights into the neural systems
that provide critical contributions to referential processing. This study further strengthens
the potential of hippocampal specificity within referential processing by ruling out brain
injury in general and the prefrontal cortex specifically, where much of the previous work
has attempted to make the link between neural systems and referential processing
(Kurczek & Duff, 2011; 2012).
The first two preliminary studies point to the critical contribution of the
hippocampus in reference production. Little is known about the real-time languageprocessing abilities of individuals with amnesia, as most previous work has used off-line
measures or explicit judgments (e.g., Kurczek & Duff, 2011; MacKay, Burke, & Stewart,
1998). Here I examine the time course with which participants with hippocampal amnesia
interpret discourse in real-time during comprehension. In preliminary study 3, by
tracking participants’ eye movements as they process language in real-time, I provide
novel insights into if and how hippocampal declarative memory contributes to on-line
processing.
48
In preliminary study 3, (Kurczek, Brown-Schmidt, & Duff, 2013), I find support
for the hypothesis that the HDMS contributes to referential processing on-line, during
comprehension. This study investigated referential comprehension and examined the
ability of patients with hippocampal damage), patients with frontal damage (and no
hippocampal damage or declarative memory impairment) and healthy comparison
participants. Participants were asked to listen to a short narrative and decide whether the
narrative matched a picture they saw or not while being eyetracked. Patients with
hippocampal damage did not track the referents of the discourse in the same way as the
other comparison groups (i.e., they did not look at the correct characters at the correct
times) indicating the critical and selective contribution of the hippocampus to on-line
referential processing during comprehension.
Consistent with previous work, analysis of eye-gaze showed that healthy
comparison participants rapidly identified the intended referent of the pronoun when
gender uniquely identified the referent, and when it did not, they showed a preference to
interpret the pronoun as referring to the first-mentioned character. By contrast,
hippocampal patients, while exhibiting a similar gender effect, were significantly
impaired in their ability to use information about which character had been mentioned
first to interpret the pronoun. This finding suggests that the hippocampus plays a role in
maintaining and integrating information even over a very short discourse history. These
observed disruptions in referential processing demonstrate how promiscuously the
hallmark processing features of the hippocampus are used in service of a variety of
cognitive domains including language.
49
In preliminary study 3, the results demonstrated a striking impairment in the
ability to identify referents in discourse. The goals of this study are to better understand
the time course and extent of the observed deficit in study 1 and to test efforts to facilitate
pronoun compression with an eye towards informing rehabilitative efforts.
Communicating with individuals with memory impairments offers many challenges.
Rehabilitation efforts in memory training also prove difficult as a recent meta-analysis
revealed no significant effects of treatment (Rohling, Faust, Beverly, & Demakis, 2009).
However there is significant evidence that language treatments, especially in individuals
with aphasia, are effective (Rohling et al., 2009). Communication and social interaction
are intimately intertwined and positive social interactions provide a number of benefits
(Clark, 1993). In amnesia, the experience of emotion outlasts the memory of the
experience, which means that even after the memory of an interaction is gone, the
positive benefits of that social interaction will exist (Feinstein, Duff & Tranel, 2010).
However in individuals with amnesia, there are a number of impairments in language that
may make communication more difficult (Duff et al., 2007, 2008, 2009), but this also
makes attempts at rehabilitation in language that more important. In other literatures,
researchers have targeted improving communication as a way to improve social
interaction (Williams & Hummert, 2004) and cognitive decline (Williams, 2010). The
potential for recovering performance in language in the presence of a memory disorder
holds important implications in the ability to improve the quality of life after a brain
injury.
In this experiment I explored the integrity and stability of discourse
representations by using ambiguous same-gender scenes and manipulating the degree to
50
which the pronoun is clearly established across the discourse. In one condition, additional
discourse context is provided in an attempt to improve amnesic performance from
baseline (of potential therapeutic benefit) while in a second condition, there is no
additional context (similar to preliminary study 3). The repetition of the target character
is meant to bolster the representation of the referent by drawing increased attention to the
referent and allowing for more time to integrate the discourse information. Participants
with brain damage outside of the hippocampus and MTL were included to investigate
whether the results we find in the hippocampal amnesics are specific to damage to the
hippocampus or a result of brain damage in general. If the performance of individuals
with amnesia is improved in this study compared to preliminary study 3, it will be
evidence that altering how we communicate with individuals with memory disorders can
facilitate their ability to follow a conversation. It will also open an opportunity to
investigate other avenues of research in areas of language that individuals with memory
disorders have performed disadvantageously. An important aspect to note is that if the
performance of the individuals with amnesia is improved in this study, it will not indicate
that we should undertake lines of rehabilitative or therapeutic interventions with
individuals with memory disorders, but rather that we should pursue interventions with
familiar communication partners in order to devise communication strategies that reduce
demands on hippocampal processing.
4.2. Specific Aims and Hypotheses
Aim #1: To define and characterize the role of the hippocampal dependent
declarative memory system in referential processing. It is hypothesized that the
51
HDMS critically contributes to referential processing and it is predicted that individuals
with damage to the hippocampus will be impaired at maintaining a representation of ongoing discourse in the no additional context condition. It is predicted that additional
context will aid patients with hippocampal amnesia allowing them to correctly direct their
gaze after the pronoun.
4.3. Methods
4.3.1. Participants
At the time of data collection, the four amnesic participants were in the chronic
epoch of amnesia, with time-post-onset ranging from 14 to 21 years, were, on average,
56.5 years old (range 51 – 59 years), and had, on average, 16.5 years of education (range
14 – 18 years). Etiologies of participants with amnesia included anoxia/hypoxia (1846,
2363, 2563), resulting in bilateral hippocampal damage, and herpes simplex encephalitis
(HSE) (2308), resulting in more extensive bilateral medial temporal lobe damage
affecting hippocampus, amygdala, and surrounding cortices. Four brain damaged
comparison (BDC) subjects with brain damage outside of the hippocampus and medial
temporal lobes (damage had the greatest overlap within the ventromedial prefrontal
cortex (vmPFC)) and no declarative memory impairment also participated. These BDC
participants were significantly older (p = 0.019) with higher IQ (p = 0.034) and WMSGMI (p < 0.001) scores than the bilateral hippocampal amnesic patients. Table 1 presents
the demographic and neuroanatomical information for each of the amnesic and BDC
participants. Ten non-brain injured comparison participants were matched to the
participants with hippocampal amnesia on age, sex, educations, and handedness and
52
recruited from the Iowa City and surrounding community through existing participant
registries in the Department of Neurology. As there was no effect of age in preliminary
study 3, the same healthy comparison group will be used for comparison to both the
amnesia and BDC groups.
4.3.2. Materials
Items consisted of pictures and narratives (that were a subset of the materials from
preliminary study 3 – the same gender trials); the participants’ task was to decide if the
picture and narrative matched or not. Picture stimuli, which were prepared in Adobe
Photoshop, used scenes with known Disney cartoon characters (e.g. Mickey Mouse and
Donald Duck; see Table 2). Before the experiment, I confirmed that participants were
familiar with the Disney characters, and had three practice items that introduced all of the
characters by name. The critical stimuli consisted of 32 target items for which the
narrative always matched the picture. There were four variants of each target item that
manipulated a) the integrity of discourse representation (no set-up versus 2 clause set-up
– i.e. repetition of the target character) and b) order of mention (1st versus 2nd mentioned
character). These variables were manipulated within-subject and within-item, creating
128 critical trials, plus 32 filler items for a total of 160 total trials per participant. For
each critical item, the narrative had two sentences, consisting of multiple clauses (see
Table 2). The first clause mentioned the two characters (e.g. Minnie is playing violin for
Daisy), and was used to establish their relative salience (i.e., Minnie is more salient
because she was mentioned first). The second clause manipulated the integrity of
representation, (i.e. nothing vs increased integrity - repetition). The third clause was a
53
distracting phrase that mentioned some other object in the picture (e.g. as the sun is
shining overhead.), and was designed to shift eye-gaze away from the characters and to
an unrelated image in the scene. The fourth clause asked a question with the critical
pronoun referring to one character or the other (e.g. And what is she wearing?). The next
clause was then used to disambiguate the reference, the point at which the sentence
uniquely identified which character was the intended referent (e.g., Look, she’s wearing a
yellow/purple bracelet) in the present example both characters wore a bracelet, but only
the target referent wore a yellow/purple bracelet; see Table 2). The final clause provided
concluding information without mentioning either character individually (e.g. and it looks
like the song is being played well). Practice trials introduced all four characters and then
established the structure of the narratives, allowing participants to get used to comparing
the narratives and pictures. Filler trials were designed to have a similar structure to
critical trials, but did not contain ambiguous pronouns. In order to create situations in
which the answer to the narrative-picture comparison task was “no match”, 24 of the
filler narratives did not match the picture and thus required participants to indicate a lack
of match.
4.3.3. Procedure
Participants' eye movements were recorded while they viewed a scene and
listened to a narrative describing the picture. A drift check preceded each stimulus. After
advancing to the picture, participants explored the picture for four seconds before the
narrative began. When the narrative finished playing, participants indicated whether the
narratives were consistent with the picture by pressing `match' or `mismatch' on the
54
screen at the end of the story. After confirming knowledge of the characters and
completing the three practice items (2 `match', 1 `mismatch' answers), participants
completed the 128 critical trials (always `match' answers), interspersed with the 32 fillers
trials (8 `match', 24 `mismatch'). The critical and filler trials were presented in the same
randomized order to all participants. All healthy comparison participants completed one
session of all trials, while all participants with brain damage completed two sessions of
all trials. Due to scheduling constraints, one individual with amnesia (2363) completed
just one session. Additionally 1 and 1/3 sessions of comparison data were lost to
technical error.
4.3.4. Analysis
Following Kurczek et al., (2013) our measure of interest was the eye-fixations
participants made following the onset of the pronoun. For each stimulus, I identified
visual regions of interest where the participant was fixating: target (the referent of the
pronoun), competitor (the other character), other (something else in or off the picture).
The time-regions for the analysis were offset by 200ms to account for the time needed to
program and launch an eye movement (Hallett, 1986). Fixations were binned into three
critical time regions, baseline (-200 to 200 ms), immediately following pronoun onset
(200-1000ms), and late (1000 to 1800 ms following pronoun onset), and were analyzed
with mixed-effects models with a maximal random effects structure for both subjects and
items using R’s lmer function (see Jaeger, 2008; Barr, Levy, Scheepers, & Tily, 2013).
Fixed effects of repetition and order-of-mention were entered with orthogonal
contrast codes; the time-regions were entered as a fixed effect with the baseline region as
55
the reference category (i.e., 0, 1, 2). The dependent measure was the empirical logit of the
ratio of the proportion of fixations to the target over the proportion of fixations to the
competitor, calculated separately for each trial. By calculating this target preference score
on a trial-by-trial basis, I was able to include both subjects and items as crossed random
effects. To handle trials on which the proportion of fixations to the competitor was zero,
and the ratio is undefined, 0.05 was added to both numerator and denominator (see
similar empirical logit approach in Barr, 2008; Fine & Jaeger, 2013; Heller, Grodner, &
Tanenhaus, 2008). Fixed effects were considered significant if the t-statistic reached 2.0
or higher.
4.4. Results
4.4.1. Offline Data.
The participants were asked at the end of the narrative to decide whether the
narrative matched the story or not. The critical items were all designed so that they all
matched, but the offline data represent the participants’ ultimate interpretation of the
pronoun. If they decide the narrative and picture did not match, then they interpreted the
competitor referent as the target. Here in the ambiguous same-gender stories, we should
expect lower endorsement rates when the pronoun refers to the 2nd mentioned character.
Analysis of the response to the judgment task (whether the picture matched the narrative)
revealed that both participants with hippocampal damage and BDC participants
performed differently than comparison subjects, but in different ways. Comparing
amnesia to healthy comparison participants revealed significant effects of repetition (z=2.70, p<.01), order of mention (z=-9.07, p<.0001) and a order of mention*group
56
interaction (z=-4.24, p<.0001; see Figure 1) where amnesic subjects indicated more
matches in the second character conditions than comparison subjects. As expected
comparison participants interpreted the first mentioned character as the target in the firstmentioned conditions and had a lower endorsement rate for the picture matching in the
second-mentioned character condition. Amnesia participants show a similar pattern, but
did not interpret the narrative as mismatching the scene to the same degree as comparison
participants in the second-mentioned condition. Comparing BDC participants and healthy
comparison participants revealed an effect of order of mention (z=-7.63, p<.0001) and a
three-way interaction of group, repetition and order of mention (z=9.21, p<.0001). The
BDC participants had the same interpretation for the no repetition conditions but
responded in the opposite way for the repeated conditions.
4.4.2. Eye-movement Data.
Analyses of the eye movements made during interpretation of the pronoun are
used to test for group differences in the use of discourse context (order of mention and
repetition) to interpret a potentially ambiguous pronoun (as all characters were the same
gender) in real time. We compared eye-fixations for the amnesic patients and the healthy
comparison participants in one analysis, and the BDC participants and the comparison
participants in a second analysis. These analyses included repetition, order of mention
and participant group (patient vs. comparison) as orthogonal factors, as well as timewindow, with the baseline window coded as reference.
The first analysis compared amnesic patients to the healthy comparison
participants. During the pronoun region there was a significant order of mention (t = -
57
7.25, p < 0.001), an order of mention by repetition (t = -6.38, p < 0.001) interaction and
an order of mention by group interaction (t = -2.92, p < 0.001) demonstrating that the
amnesic patients and comparison participants were differentially sensitive to the order of
mention cue, where comparison participants had a stronger order of mention (t = -25.81,
p < 0.001) and order of mention by repetition effect (t = -6.16, p < 0.001) than amnesia
participants, (t = -7.50, p < 0.001; (t = -2.59, p = 0.01; respectively). This effect
continued into the late region, where there was a significant order of mention (t = -7.45, p
< 0.001), an order of mention by repetition interaction (t = -3.88, p < 0.001) and an order
of mention by group interaction (t = -2.84, p < 0.001) demonstrating that the amnesic
patients and comparison participants were differentially sensitive to the order of mention
cue, where comparison participants had a stronger order of mention (t = -27.11, p <
0.001) and order of mention by repetition effect (t = -3.54, p < 0.001) than amnesia
participants, (t = -10.66, p < 0.001; t = -1.78, p = 0.07; respectively). Thus, while both
comparison and amnesia participants were affected by the order in which the characters
were mentioned, comparison participants had a stronger effect (looked at the target at a
higher proportion) and only the comparison participants benefited from the repetition (in
the first mentioned condition).
Comparison of the healthy comparison participants and BDC participants during
the pronoun window revealed a significant of order of mention (t = -39.36, p < 0.001), an
order of mention by repetition interaction (t = -6.61, p < 0.001) and an order of mention
by repetition by group interaction (t = -2.59, p < 0.001), where comparison (t = -6.16, p <
0.001) participants had a larger order of mention by repetition effect than BDC
participants (t = -2.95, p = 0.003). The effect continued into the late window. A
58
significant of order of mention (t = -39.85, p < 0.001), an order of mention by repetition
(t = -3.00, p < 0.001) interaction and an order of mention by repetition by group
interaction (t = -2.61, p < 0.001) was observed, where comparison participants had an
order of mention by repetition interaction (t = -3.54, p < 0.001), but BDC participants did
not (t = -0.23, p = 0.818). Although like the amnesia participants, the BDC participants
performed differently than comparison participants, their difference was not in the
strength of their target preference depending on order of mention, but rather because of a
lack of a boost in performance from the repetition of the target.
4.5. Discussion
The results from the no repetition condition replicate the findings from the initial
investigation (Kurczek et al., 2013) where healthy individuals and BDC participants were
drawn to look at the first mentioned character. In the first study, amnesic participants
were impaired in their ability to preferentially view the target character (i.e., no order of
mention effect), but in this study, amnesia participants did show an order of mention
effect. However, the goal of this study was to improve the performance of patients with
bilateral hippocampal damage who did not preferentially view the target character
regardless of condition in the first study. By repeating the mention of the target character,
the goal was to increase the saliency and robustness of the character representation and
improve performance (i.e., increase gaze to target). Our findings however, demonstrated
that amnesic patients experienced difficulty in integrating and maintaining information
even over a very short discourse history and did not benefit from the repetition (i.e.,
increasing the saliency/representation) of the target character. Amnesic patients were
59
significantly impaired in their ability to use information about the relative salience of two
very recently mentioned discourse referents to disambiguate a pronoun. By contrast,
healthy adults and brain-damaged comparison (BDC) participants, recruited this
information, and used it to begin guiding the on-line interpretation of the pronoun within
the first second of pronoun onset. That amnesic patients performed significantly worse
than the BDCs suggests a strong link between the functionality of the hippocampus and
demands of referential processing rather than a general consequence of brain damage.
The observed disruption in referential comprehension in amnesia, but not in frontal lobe
patients is consistent with previous work on language production (e.g., Kurczek & Duff,
2011, 2012; Kurczek, et al., 2013).
Importantly, however, unlike in preliminary study 3, amnesic participants did
exhibit an order of mention effect, even if they did not exhibit a boost from repetition of
the target character. Although, this negative finding of repetition on the performance of
individuals with amnesia should be qualified by the repetition by order of mention
interaction found in the healthy comparisons where repetition only boosted performance
in first mentioned character condition. Perhaps in healthy participants, there was not a
main effect of repetition because a 40-60% target advantage is near ceiling. While the
repetition of information may have helped healthy participants (in one condition), it may
have been the case that in the presence of a damaged hippocampal declarative memory
system, the extra representations did nothing to integrate into the representation and
guide subsequent behavior.
The BDC off-line judgment data are also pause for concern as theses participants
behaved differently in the repeated conditions than the non-repeated conditions compared
60
to healthy comparisons. Although they did benefit from the repetition in the first
mentioned condition (only during the pronoun window), the magnitude of their order of
mention affect was similar to healthy comparisons and may have suffered from the same
potential ceiling effect.
The results here suggest that repetition can influence the behavior of both healthy
individuals and individuals with brain damage outside of the medial temporal lobes.
Repetition however did not improve the performance of individuals with hippocampal
amnesia. This finding speaks to the important theoretical underpinnings that should guide
rehabilitative efforts. Others have investigated the effect of repetition on behavior
(Verfaellie, Rajaram, Fossum, & Williams, 2008) and concluded that repetition of
information in varied contexts, enhances recollection of individuals with intact memory
but only affects familiarity in patients with severe amnesia. Others have taken the
benefits of repetition and implemented it into errorless learning paradigms. Although
errorless learning may provide a benefit over errorful learning (Wilson, Baddeley, Evans
& Shiel, 1994), the effect appears to be highly context specific.
The small benefit of repetition on healthy performance and even smaller benefit
on the performance of individuals with brain damage outside of the medial temporal
lobes may be sign to rethink the use of repetition in rehabilitation. Others have suggested
rethinking verbatim repetition in rehabilitation (Hengst, Duff, & Dettmer, 2010) and that
sentiment is echoed in the results here. Hengst and colleagues (2010) suggest repeated
engagement rather than context specific repetition be a greater benefit to improving realworld behavior. Perhaps the repetition of information in a specific context with little
61
opportunity to act on or engage with the material in this task did not allow for patients
with hippocampal amnesia to benefit from repetition.
The benefit of engagement over repetition has been demonstrated in amnesia
previously. Duff and colleagues (2006) asked individuals with amnesia to work with a
familiar communication partner to collaboratively place tangrams on a board in a certain
order. When the patients were able to generate the labels themselves in collaboration and
coordination with their communication partner they showed a learning rate similar to
healthy comparisons. However, when they attempted to learn arbitrary labels for the
tangrams, they showed no learning at all (Duff et al., 2006). The repeated engagement
with the materials in a rich, purpose driven context allowed patients to leverage intact
neural and cognitive systems to successfully navigate the task. As Verfaellie and
colleagues (2008) demonstrated in their investigation of repetition, varied contexts aid
learning. Future rehabilitative efforts should focus on the engagement of the individual
within a purposeful task rather than drilling or repeating within a contextless task. In this
task, we may have focused on just two characters (e.g., Mickey and Donald) and looked
to build representations over two very different characters over the course of the task
(i.e., Mickey as the “good” character and Donald as the “bad”). By establishing different
contexts of the characters across a variety of situations, perhaps over the course of the
experiment, attempts to bias performance with repetition within a single context could be
achieved.
However, while this and other work may suggest engagement as a good practice
for rehabilitative efforts for individuals with amnesia, previous attempts to rehabilitate
performance in amnesia have proven both slow and difficult (Squires, Hunkin, & Parkin,
62
1997) and the results from this experiment may extend those findings. While we were
able to find an order of mention effect in this experiment, as opposed to the previous
version of the experiment, there were twice as many opportunities to observe the effect
within the same trial condition and even yet, the order of mention effect is attenuated in
amnesia (i.e., so even though there is a difference within amnesia, the effect is still not
the same as in healthy comparisons and brain damaged comparisons). These findings
may indicate the robust difficulties in attempting rehabilitative efforts in patients with
declarative memory impairments.
Recommendations for speaking with individuals with memory disorders suggests
using a number of strategies as a communication partner, from speaking more slowly and
using close ended questions to make communication more successful (Tappen, WilliamsBurgess, Edelstein, Touhy, Fisherman, 1997). However, these findings paint a dim
outlook for even rehabilitative strategies that are contained within the environment rather
than the individual for people with memory disorders. While the participants with
amnesia did improve one aspect of their performance, it was not to the same degree as
other participants and still lacked another important effect. These findings here suggest
that even techniques that attempt to alter the environment of individuals with memory
disorders don’t help much or have limited benefits. Previous rehabilitation efforts have
attempted to place interventions within the domains of (supposedly) intact cognitive
domains.
However this and other studies are demonstrating the promiscuity of the
hippocampus and its ubiquitous contribution across cognitive domains, early and
continuously. Attempts to place demand on (supposedly) intact neural structures or
63
cognitive abilities, may simply be placing demands on the hippocampal declarative
memory system at different time points in cognition, or in different, less overt ways. One
of the most popular ways to attempt to teach individuals with memory impairments new
information has been to leverage the procedural/non-declarative memory system (Squires
et al., 1997), but recent evidence has implicated the hippocampus in even non-declarative
processes (Foerde, Race, Verfaellie, & Shohamy, 2013), so rehabilitation efforts like
errorless learning or adding gesture may not work. Future research within this area may
try to replace the pronouns used to increase access with the proper names, but this and
other potential augmentations may dramatically decrease the real-world application or
similarity (as we often don’t repeat a proper name after it has been established, though
individuals with amnesia do, see Kurczek & Duff, 2011).
64
Table 1. Demographic and neuropsychological characteristics of hippocampal amnesic
and BDC participants.
Sex
Ed
Age Etiology
HC
Vol
Patient
Intelligence Memory
Language
WAIS-III
WMS-III Token BNT
FSIQ
GMI
Test
1846
F
14
51
Anoxia
-4.23 84
57
41
43
2308
M
18
58
HSE
N/A
98
45
44
52
2363
M
18
58
Anoxia
-2.64 98
73
44
58
2563
M
16
59
Anoxia
N/A
94
63
44
52
AM
16.5 56.5 N/A
-3.4
93.5
59.5
43.3
51.3
Summary
±1.9 ±3.7
±1.1
±6.6
±11.7
±1.5
±6.2
318
M
14
71
MR
N/A
143
109
44
60
2025
F
16
63
ACoA
N/A
115
114
44
59
2352
F
14
62
SaH;
N/A
106
109
44
54
MR
N/A
109
132
43
57
14.3 65.3 N/A
N/A
118.3
116.0
43.8
57.5
ACoA
2391
BDC
F
13
65
Summary
±1.3 ± 4.0
±16.9
±10.9
±0.5 ±2.7
Difference t-val 1.91 3.05
2.62
6.30
0.62 1.81
p-val 0.097 0.019
0.034
0.001
0.550 0.112
Note. AM = Hippocampal amnesic participants; BDC = Brain damaged comparison; t-val
= T-statistic value; p-val = p-value; F = Female; M = Male; HC = Hippocampus; Ed =
Education; HSE = Herpes simplex encephalitis; MR = Meningioma Resection; ACoA =
Anterior communicating artery aneurysm; HC Vol = Hippocampal Volume;
Hippocampal z-scores represent the combined (left and right hemisphere) studentised
residuals of hippocampal volume relative to a group of comparison subjects (Allen et al.,
2006; Buchanan et al., 2005). WAIS-III = Wechsler Adult Intelligence Scale; FSIQ =
Full Scale Intelligence Quotient, WMS-III GMI = Wechsler Memory Scale-III; GMI =
General Memory Index; CFT = Complex Figure test BN = Boston Naming Test
65
Table 2. Study 1: On-line referential processing experimental conditions.
Narrative
Sentences of Narrative
Conditions
Establish
Mickey is painting a portrait of
Characters
Donald,
C1 – Limited
…
accessibility
C2 – Greater
He’s trying really hard to get the
increase in
portrait just right, because he wants to
accessibility
be a famous artist someday
Redirect gaze and some paint is spilling on the floor
Critical
And what is he wearing
Concluding
Look, he’s wearing red shoes and it
information
looks like they’re having fun
Note. C = condition.
Picture Stimulus
66
Percent "Match" Response
Figure 1. Offline judgments of story-picture match for hippocampal amnesics, BDC and
comparison participants.
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
1s0
1s3
2s0
2s3
Condition
Comparison!
Amnesia!
BDC!
Note: Error bars indicate one standard error. 1 = First mentioned character as target; 2 =
second mentioned character as target; 0 = no repetition; 3 = repetition of target.
67
Figure 2. Time course of fixation preferences for hippocampal amnesics, BDC
participants and healthy comparison participants.
Note: Plotted as the difference between target and competitor fixations (proportion target
minus proportion competitor) at each point in time. Data plotted separately by condition
and group. Positive values indicate target preference. 0ms= pronoun onset. Panel A =
healthy comparison participants matched to amnesia patients; Panel B = brain-damaged
comparison participants; Panel C = amnesia participants; 1 = First mentioned character as
target; 2 = second mentioned character as target; 0 = no repetition; 3 = repetition of
target.
68
CHAPTER 5: NARRATIVE IN AMNESIA: THE EFFECTS OF
REPEATED TELLINGS ON NARRATIVE CONSTRUCTION
5.1. Background/Rationale
Narratives are connected events and are an important aspect of culture and
communication (Flanagan, 1993). Personal narrative allows one to use language to give
life events a temporal order, to demystify them and to establish coherence across a life
lived, living and yet to be lived (Ochs & Capps, 2001). Autobiographical memories
influence how we tell and interpret narratives. However, the relationship between
narrative and memory is bidirectional, as autobiographical memory provides the building
blocks upon which narratives are crafted, while narrative practices in turn, influence how
we encode, retain and revise experiences in memory. Beyond the cognitive relationship
between narrative and memory, recent evidence suggests a common neural instantiation.
Recent evidence suggests that the hippocampus is engaged in basic functions
(flexible and relational binding) immediately and continuously with the hippocampus
maintaining representations on-line (Hannula, Tranel & Cohen, 2006; Warren, Duff,
Jensen, Tranel, & Cohen, 2012). These functions together, suggest that the hippocampus
can contribute to behaviors outside of (re)constructing memories for the past (and future),
and may potentially including any behavior that requires the flexible generation, and
subsequent (re)combination of perceptually distant and distinct mental representations
on-line and in response to novel contexts. Examples of such behaviors include perception
(Warren et al., 2011), creativity (Duff, Hengst, Tranel & Cohen, 2009) and language
(Duff & Brown-Schmidt, 2012; MacKay, Stewart, & Burke, 1998). Together, these
69
results suggest that the role of the hippocampal dependent declarative memory system
may extend beyond memory to broadly include generating and binding together
representations regardless of memory demands on the hippocampal system. The
implications of this view see the hippocampus as playing a fundamental role in the
earliest phases of cognition, generating and binding together, on-line, representations that
can be used in service of a number of cognitive capacities including its traditional roles in
memory/future thinking, but also extending to other capacities such language.
Narrative construction appears to be one capacity that places high demands on the
processing capacities of the HDMS, particularly representational flexibility, as speakers
creatively (re)construct events and chose what information and details to represent or
omit in response to contextual and audience cues. While creative thinking has been
examined in hippocampal amnesia, with patients with hippocampal damage showing
impairments in imagining events (Hassabis, Kumaran, Vann, & Maguire, 2007) in the
creative use of language (Duff et al., 2009) and in creativity (broadly defined; Duff et al.,
2013), I propose that the processing features of the hippocampus that support aspects of
creativity, will accordingly, critically contribute to the flexible and creative manipulation
of representations that are bound together in order to construct a narrative. While there is
some evidence that creative aspects of linguistic behavior are disrupted in amnesia, the
role of HDMS in narrative construction is an open question.
Disentangling memory from language is difficult to do because we generally
assess episodic memories by asking individuals to tell us their memories. While the
literature is full of examples of deficits in individuals with amnesia’s ability to include
episodic details in their narrations, there is an on-going debate as to whether those
70
deficits are a confined impairment within the memory system or a more basic impairment
in cognitive functioning outside of memory. An on-going debate in the field is the
whether deficits in the production of narrative elements across either personal stories or
picture descriptions/narratives represent solely an impairment in memory or a more basic
impairment in cognitive functioning outside of memory. Evidence for a more basic
impairment come from a relationship between deficits in narrative construction and
future thinking impairments in older adults (Gaesser, Sacchetti, Addis, & Schacter, 2011)
and deficits in amnesics ability to narrate pictures and real-life settings (Zeman, Beschin,
Dewar, & Della Sala, 2012). However, Race and colleagues (2011; 2013) investigated the
contribution of the hippocampus to 1) memory/future thinking and 2) picture narrative
construction, and found only a deficit in narratives that placed a demand memory/future
thinking and not in narratives cued by a picture as indicated by the number and type of
details from both types of narrative.
In a preliminary study, I find support for the hypothesis that the HDMS
contributes to narrative construction. I examined the role of the hippocampus (with 6
individuals with amnesia and their matched comparison participants) in the active and
flexible manipulation of acquired declarative memory representations to be used in
service of thinking about and telling narratives across constructed events (past events,
imagined past events, imagined present events, future events), personal past events and
pictures. Results indicate that regardless of the type of narrative produced, amnesic
participants were impaired on both memory and language analyses when compared to
normal healthy participants. Assaying memory and language has long been conflated. In
order to assess someone’s memory, one has asked them to construct a memory about a
71
personal past episode or imagine a fictional episode, while assaying someone’s language
again one may ask them to construct a narrative about a personal past episode or describe
a picture. By using both memory and language tasks and analyses I am able to assess the
fundamental capacities that underlie narrative construction (Duff & Kurczek, 2013)
Individuals with hippocampal damage were impaired across measures, both
memory and language compared to comparison participants. This indicates that the
hippocampus is engaging in a similar, fundamental mechanism when constructing
narratives regardless of the demand on memory, per se. These results suggest that the
hippocampus is necessary for generating, manipulating and combining representations
that later consist of the elements of the narrative and the linguistic/grammatical
combination of those elements.
In the preliminary study, I found disruptions in narrative construction after
hippocampal damage as measured by both language and memory analyses, here in study
2 I address narrative from another perspective. A critical aspect of our memories is that
they are constructed, which means that not only do they change over time, but we can
actively change them by emphasizing or leaving out details based on the demands of the
moment. In other words, episodic memory is the result of ongoing encoding within a
highly contextualized and dynamically changing environment (Tulving 1983; 2002;
Suddendorf and Busby 2005). The goal of study 2 is to investigate the effect of
hippocampal damage on the repeated recall of memories over time.
The consolidation view of memory over time inherently assumes that memories
over time remain a faithful record of the original event (Squire, Cohen, & Nadel, 1984).
The view was challenged as early as 1932 when Bartlett demonstrated that memory was a
72
constructive process and not just a reply of the past. Using the “War of the Ghosts” story
and mask drawing task, he demonstrated that repeated production of the story typically
led to a shorted, more stereotyped version of it, with details, changed, removed, or in
cases added. Further investigation of the effect has produced mixed results. Ahlberg and
Sharps (2010) were able to replicate Bartlett’s broader conclusions with both older and
younger adults reconfiguring stories and recall diminished over time. Bergman and
Roediger (1999) were also able to replicate Bartlett’s findings with subjects forgetting
more over time and changed the story (with rationalizations and distortions) as the
interval increased. In contrast, Carbon & Albrecht (2012) in a series of experiments
testing potential retrieval biases in the portrait d’homme reproductions were unable to
reproduce Bartlett’s findings although, the did find that each of the reproductions
changed over time, indicating the general effect of reconstruction, however, not the
specific effect of schematic rationalization over time. Wheeler and Roediger (1992)
found that when the interval distribution of the recall was changed, there were differences
in the recall of the stories. When the intervals were short, there was improvement
between the tests, while when the intervals were long, forgetting occurred (Wheeler &
Roediger, 1992). In summary, these results appear to indicate that in the retelling on nonpersonal or non-episodic stories, individuals recall and retell fewer details overtime. The
hallmark characteristic of amnesia, a significantly decreased ability to learn new
declarative memory, would suggest that individuals with amnesia would be able to recall
little to no details from the story after just 30 minutes.
However, the tests in Bartlett’s studies required learning new material and then
attempting to reproduce over time, what happens when you ask someone to reproduce
73
autobiographical memories over time? Wynn and Logie (1998) asked students in three
different groups to recall a description of a room over varying amounts of time and found
no differences in the amount or type of words produced over time. Neisser (1981) was
able to probe the memory of John Dean (counsel to President Richard Nixon) and
compare it to his Watergate testimony from years earlier. Neisser (1981) found that
Dean’s memory reflected distortions in some instances (e.g. seeing himself more central
to the case), and errors (e.g. recall of conversations) but was overall fairly accurate in the
general happenings. Moscovitch and colleagues have investigated the recall of
autobiographical information over time using both behavioral and functional imaging
techniques in order to test the Multiple Trace Theory (MTT; Nadal & Moscovitch, 1997)
that suggests repeated recall of information should strengthen the storage of a memory.
Nadal and colleagues (2007) asked participants to tell 24 memories and repeatedly told
12 of them 3 times over the course of a month. Two days after the last retelling,
participants told the 12 stories only told once, the 12 stories that were repeated and 12
new stories. Results showed that the repeated memories were retrieved faster and became
longer over time and more consistent. Imaging results showed greater cortical activation
in episodic memory networks which was interpreted as increased reconsolidation as is
suggested by MTT (Nadal et al., 2007). In a follow-up study Campbell and colleagues
(2011) asked 8 of the 12 participants from Nadal et al., (2007) to recall their narratives
approximately 1.4 years later. They found that, in contrast to Bartlett’s (1932) findings,
the autobiographical memories became more detailed and longer over time (Campbell et
al., 2011). In summary, these results indicate that individuals retelling personal or
74
episodic stories, in general, tell roughly the same story, but may retell more details over
time.
How does amnesia and damage to the hippocampus effect the telling of narratives
over time? The only evidence to date comes from patients with depression (who have
been suggested to have memory impairments, c.f., Williams, Barnhofer, Crane, Hermans,
Raes, Watkins, & Dalgleish, 2007; King, Macdougall, Gerris, Levine, Macqueen &
McKinnon, 2010; Sumner, Griffth, & Mineka, 2010). Using the Columbia
Autobiographical Memory Interview – Short Form administered over a two month or six
month interval, found that while all participants were less consistent in the follow-up,
only the patients still exhibiting depressive symptoms had significantly lower scores than
remitters on episodic information (Semkovska et al., 2012). This may suggest that
patients with hippocampal damage when retrieving memories repeatedly over time may
be less consistent and variable in all aspects of performance. However, I have also been
struck by some patients’ “riffs”, their short, highly repetitive sentences that are often
offered after a break in conversation or topic. These “riffs” appear to ground the
conversation in something in which the patient with hippocampal damage is confortable
or an expert. Thus, one hypothesis may be that severe cases of amnesia will lead to rote
retellings of the same narratives, in other words demonstrate no variability and tell the
same, story or riff time after time, while another hypothesis for the effect of hippocampal
damage on the repeated telling of autobiographical memories may be that patients will
demonstrate variability from telling to telling as was demonstrated by the patients with
depression (Semkovska et al., 2012). A reconciled view of these two opposing
hypotheses may be that we see a distinction in the performance of individuals with less
75
(anoxic) and more (herpes simplex encephalitis) hippocampal damage, where individuals
with less hippocampal damage become more variable (i.e., the number of words/details
and/or type of details may increase or decrease on subsequent tellings) in their
performance compared to healthy comparisons (who will show a consistent trend of
increasing the number of details over time), while individuals with more hippocampal
damage become less variable compared to healthy comparisons (i.e., they tell the same
rote story every time).
Here participants will be asked to undergo two conditions of story re-telling. In
the first condition, the semantic condition, participants will be asked to read through the
“War of the Ghosts” story twice and then recall it at four time intervals, fifteen minutes
later, one hour later, one week later and one month later. In the second condition,
participants will tell six personal episodic memories and recall them along the same time
intervals.
5.2. Specific Aims and Hypotheses
Aim #2: To define and characterize the role of the HDMS in narrative
construction.
It is hypothesized that the HDMS plays a critical role in the generation and
flexible use of representations critical to the construction of narratives. It is predicted that
the individuals with damage to the hippocampus will be significantly impaired at
recalling and retelling the “War of the Ghosts” story and impaired at generating
representations necessary for constructing narratives from their own lives. More
specifically, it is predicted that patients with bilateral hippocampal damage will produce
76
narratives that will be shorter, more semanticized and less consistent than healthy
comparisons over multiple tellings of the narratives.
5.3. Methods
5.3.1. Participants
At the time of data collection, five amnesic participants were in the chronic epoch
of amnesia, with time-post-onset ranging from 14 to 34 years, were, on average, 57.6
years old (range 51 – 62 years), and had, on average, 16.4 years of education (range 14 –
18 years). Etiologies of participants with amnesia included anoxia/hypoxia (1846, 2363,
2563), resulting in bilateral hippocampal damage, and herpes simplex encephalitis (HSE)
(1951, 2308), resulting in more extensive bilateral medial temporal lobe damage affecting
hippocampus, amygdala, and surrounding cortices. Table 3 presents the demographic and
neuroanatomical information for each of the amnesic participants. Ten non-brain injured
comparison participants were matched to the participants with hippocampal amnesia on
age, sex, educations, and handedness and were recruited from the Iowa City and
surrounding community through existing participant registries in the Department of
Neurology.
5.3.2. Materials
In condition one, a list of typical life events from Levine et al., (2002), such as
“your first job” or “falling in love” was used to generate memory prompting cues for the
memory retrieval sessions. For each memory, the event was required to have occurred
before they were 25 years old, have occurred in a specific time and place and have
77
happened only once. Participants were instructed to visualize the details of the event,
playing the event out as if it were a scene in a movie and describe all the details that you
can remember. Those details could have included what happened, who was there, where
you were, the time of day, and the physical details of the scene. After the participant
completed each recall, they were asked to rate the memory on several scales (Figure 3).
In condition two, participants read “The War of the Ghosts” (Appendix).
5.3.3. Procedure
In condition one, during the initial retrieval session, participants were asked to
generate six different memories. After each memory, they were asked to rate the memory
on two likert scales, for six questions they used a 5-point scale (from 1-not at all to 5extremely) and for one question they used a 7-point scale (from -3-very negative to 3very positive; see Figure 3). Participants were then asked to recall the memories three
more times over various time intervals including 1 hours, 1 week, and 1 month. In each
subsequent interview, participants were instructed to recall each memory in a randomized
order and subsequently rate each memory again.
In condition two, participants read through “The War of the Ghosts” twice at their
own reading pace. They were then asked to recall the story at four time intervals, fifteen
minutes later, one hour later, one week later and one month later. In subsequent
retellings, participants were prompted by being asked to retell “The War of the Ghosts”
story. Due to scheduling constraints two participants with amnesia were unable to
participate in the “War of the Ghosts” condition (1846, 2563), and due to a recording
failure, one comparison participant’s second telling of the “War of the Ghosts” was lost.
78
For condition one, the telling of personal stories, one participant with amnesia was unable
to participate in the third and fourth follow-ups of the multiple tellings (2563), one
participant with amnesia was unable to provide six stories and instead talked about three
stories but did not provide ratings for the stories (2308), and one comparison participant
was unable to participate in the third telling of the multiple tellings.
5.3.4. Analysis
Audio recordings of each of the retrieval sessions were transcribed for analysis.
Following Levine et al., (2002) and Nadel and colleagues (2007) each memory was
subjected to autobiographical memory analysis and the memories were divided into
different detail types including internal (i.e., episodic), external (i.e., semantic) and
editorial (details that reflected uncertainty – e.g., I think it was). For each retrieval session
after the first, the number of details that were consistent from the previous retrieval
session (i.e., comparing session 2 to 1, 3 to 2 and 4 to 3) were measured and expressed as
a proportion of the session’s total details. Details that were changed (e.g., Session 1 – We
got married at the Baptist Church; Session 2 – We got married at the Presbyterian
Church) were measured and expressed as a proportion of the session’s total details.
Details that were new or completely different (e.g. Session 1 – I flew to the hospital;
Session 2 – I flew to the hospital and died on the ride) were also measured and expressed
as a proportion of the session’s total details. The total number of words spoken by the
participant for each narrative were obtained using the word counting function of
Microsoft Word. The War of the Ghosts stories were scored using Mandler and Johnson’s
parsing (1977). Details that were correctly produced were scored as a one, while details
79
that were close were scored as a half (e.g., two braves instead of two young men) and
details that were missing were scored a zero. Summing the score and dividing by 43 (the
total number of parsed details) provided an accuracy measure for recall of the story.
5.4. Results
5.4.1. Multiple Tellings Autobiographical Memory
Interview Analysis (Condition 1)
We used the Autobiographical Memory Interview scoring method to score the
narratives of participants own personal life stories to calculate a ratio of internal details to
overall details, which is used to capture the “autobiographicalness” of narratives without
being influenced by length, as there was a significant difference (F(1,11) = 8.59, p =
0.014, in the length of the narratives, where comparison participants (mean = 280.38; SD
= 64.22) produced narratives with twice as many words that amnesia participants (mean
= 119.75; SD = 38.24). A 2 X 4 (group – AM, CP; time – first telling, second telling,
third telling, fourth telling) ANOVA on the internal to overall details revealed a main
effect of group, F(1, 11) = 8.34, p = 0.015, with a significant effect of time elicitation,
F(3, 33) = 5.67, p = 0.003, but no group by time interaction, F(3, 33) = 2.72, p = 0.06,
indicating that the amensic participants had a lower ratio of internal details to overall
details (mean = 0.60, SD = 0.04) than comparison participants (0.76, SD = 0.04), and
thus a lower “episodic re-experiencing” across all time retellings (see Figure 4). Followup comparisons of the time periods revealed no significant differences between the time
periods.
80
5.4.2. Multiple Tellings Consistency Analysis for
hippocampal amnesics and their comparisons
Analysis of the consistency of story details revealed a main effect of group on
both repeated, F(1, 11) = 29.08, p < 0.001, and added details, F(1, 11) = 57.78, p < 0.001.
There was no effect of time on either repeated, F(2, 22) = 1.95, p = 0.166, or added
details, F(2, 22) = 1.69, p = 0.208, nor any group by time interactions for either repeated,
F(2, 22) = 0.08, p = 0.927, or added details, F(2, 22) = 0.13, p < 0.883 (see Figure 5;
Table 4). This indicates that comparison participants were much more consistent in the
telling of the details of their stories from the current telling to the proceeding, while
participants with amnesia told very different stories from telling to telling (meaning that
even with one hour separating the telling of the stories, participants with amnesia were
telling narratives that were very different from the one told an hour earlier).
5.4.3. Self Ratings of Multiple Tellings for hippocampal
amnesics and their comparisons
Analysis of the seven ratings of the narratives after each telling revealed
significant group differences in two of the ratings, how important the event was at the
time, F(1, 10) = 4.90, p = 0.017, and how emotional the event was at the time, F(1, 10) =
6.47, p = 0.027, with comparison participants having higher ratings (i.e., more important
and more emotional) than amnesia participants across all tellings (see Figure 6).
Significant group*time interactions were revealed for how vivid their recall, F(3, 30) =
3.062, p = 0.043, was and how positive or negative the event was, F(3, 30) = 3.591, p =
0.025, where comparison participants rated the vividness of their recall as significantly
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higher than amnesia participants for all but the final retelling (ps < 0.05) and anmnesia
participants rated their final retelling as significantly more positive than other retellings
while comparison participants ratings stayed the same. Additional analysis of the
variability of the ratings from telling to telling revealed a significant difference in the
importance at the time, F(1, 10) = 19.36, p < 0.001, where amnesic participants were
much more variable in their ratings from telling to telling.
5.4.4. War of the Ghosts Analysis (Condition 2)
Scheduling issues prevented two participants (1846, 2563) from participating.
Further, two of the three participants (1951, 2308) with amnesia who participated were
unable to recall any details from the story after the first fifteen-minute break.
Accordingly, all statistical tests revealed profound impairments of the individuals with
amnesia to tell the story compared to comparison participants. Amnesia participants told
significantly shorter (mean = 14.67; SD = 17.4) and less accurate (mean = 1.0; SD = 2.0)
narratives than comparison participants (mean = 247.78; SD = 15.9; F(1,10) = 34.75; p <
0.001; mean = 36.37; SD = 3.0; F(1,10) = 106.13; p < 0.001; respectively; see Figure 7;
Table 5). The only within subject comparison to reach statistical significance was the
accuracy of the stories, F(3, 30) = 6.36, p = 0.017, with follow-up comparisons revealing
that the second retelling was told more accurately than the fourth (p = 0.038), indicating
that increases in the demands on declarative memory in healthy subjects led to a
decrement in performance.
5.5. Discussion
I examined the role of the hippocampus in active and flexible manipulation of
acquired declarative memory representations to be used in service of thinking about and
82
telling narratives across multiple tellings. I have previously reported deficits in
individuals with amnesia to tell narratives across time (i.e., past, present, and future),
imagination (i.e., real vs imagined) and type (i.e., personal stories vs picture narratives) in
both their “episodicness” (i.e., how many details of the stories are related to a specific
time and place) and in language measures (i.e., how cohesive and coherent the narratives
are). The current study investigates the telling of semantic (e.g., “War of the Ghosts”)
personal narratives over time. Results indicate that regardless of the time of follow-up of
the narrative produced, amnesic participants were impaired in their episodic telling of the
stories and how consistent their story stayed from telling to telling.
Through the lens of relational memory theory, this pattern of impairment across
all time conditions is easily understood (Cohen & Eichenbaum, 1993; Eichenbaum &
Cohen, 2001). In this view of declarative memory there are two hallmark features or
properties, which are critical to the instantiation of autobiographical memory and the
construction of mental representations. First, declarative memory supports flexible
expression of memory (Bunsey & Eichenbaum, 1996; Cohen, 1984; Cohen &
Eichenbaum, 1993; Dusek & Eichenbaum, 1997; Eichenbaum & Cohen, 2001; O’Keefe
& Nadel, 1978; Squire, 1992). The representational flexibility permits accessibility across
processing systems and can be used in novel situations. Second, is the importance of the
relational (associative) binding that the hippocampus engages in. Hippocampus encodes
into long-term memories the co-occurrences of the elements that constitute memories
along with the relations (e.g. spatial, temporal, and interactional) among them (see
Konkel et al., 2008; Konkel & Cohen, 2009). The hippocampus also encodes
83
representations of relationships among events, providing the basis for the larger record of
one’s experience.
Thus in retelling narratives, a lot demand is placed on these two properties. Not
only are the representations of the narrative activated and brought together, but how they
are brought together, and how they have been brought together in the past (i.e., as a part
of the larger record of one’s experience), and this plays an important role in how the
narratives are told. Healthy comparisons in telling their own narratives were able to
activate the experiences of the narrative itself as well as the previous experiences of
having told that narrative in the past. The interaction of those episodes drove how they
told the narratives in the subsequent retellings. Individuals with hippocampal amnesia not
only had a difficult time of generating and binding the representations particular to the
experience from the time that it occurred, but were unable to generate the experiences of
having told the narrative in the past, which did not allow them to tell the narratives in the
same way as healthy comparisons.
A particularly interesting result from past investigations has been that despite
amnesia, patients with focal hippocampal or MTL damage display relatively intact
remote past memories (Squire et al., 2010; Kirwan et al., 2008; Bayley, Gold, Hopkins, &
Squire, 2005; Bayley, Hopkins, & Squire, 2006; Maguire et al., 2010). In contrast,
patients with more widespread damage (Rosenbaum, McKinnon, Levine & Moscovitch,
2004; Rosenbaum, Moscovitch, Foster, Schnyer, Gao, Kovacevic, Verfaellie, et al., 2008)
and developmental damage (Kwan et al., 2010) have been reported to have more deficits
in remote past memory. However, while a prevailing notion of amnesia is the presence of
intact remote memories, different methodological approaches and recent advances in our
84
understanding of the declarative memory system have suggested that remote memories in
amnesia may be different. While individuals with amnesia can report remote memories
these memories appear to be different than healthy comparisons. Particularly relevant to
the experiment reported here are the social aspects of telling memories.
Memories are told for social benefits and the sharing of memories may help build
a sense of self (Bluck, Alea, & Habermas, 2005). The ability to recognize what and how
you have told a story in the past will shape how you tell the story in the future. The
healthy comparisons in this task tended to tell fairly consistent stories over time that
trended towards becoming more concise with time. The individuals with amnesia on the
other hand did not perform like the healthy comparisons. They told stories that were less
consistent (to the point of being different stories) that did not have a sense of continuity
to previous tellings. The social implications of this deficit are profound. The ability to
tailor your narrative to the person and the context allow you to shape the interaction and
the experience. The presence of intact declarative memory systems in the healthy
comparison participants allowed for them to shape their stories in a certain way from
telling to telling. The individuals with amnesia, were unable to recover the previous
episodes and thus unable to shape their stories in a socially beneficial way.
One particularly striking example of the difference in how individuals with
amnesia tell stories multiple times over time to the same communication partner is
provided in Table 4. Just one hour after telling his story, “Being Burglarized” about a
bike being stolen during his childhood, participant 2363 was unable to recover the
previous interaction and told a completely different story of his car being stolen in his
early 20s. The social ramifications for this difference in how stories are told over time
85
could be profound. This is yet another demonstration of the contribution of the
hippocampal declarative memory system to cognition outside of memory. How, where
and why we tell stories matter because our lives narratives often form the glue that binds
us together. It would be extremely difficult to navigate social interactions without the
ability to know when, if or how you had spoken about different events or topics, it would
be quite maladaptive to have memories that were fragmented, devoid of detail or were
confused over time. The damaged hippocampus may be particularly affected by the
present causing lability in their performance of telling stories. The inability to recover
past experience decreases the ability to live or experience or recover the continuity of
life.
Different contexts may drive or require the telling of different details. Take the
telling of your wedding day. After telling the story many times, you may have a cut and
dried version that you can tell at anytime, but imagine how you would tell the story to
your significant other, an individual from the wedding party, a co-worker that just
became engaged and a researcher from a psychology lab. Each one of those individuals
will have certain specific knowledge of you, weddings and a particular social relation to
you, and the combination and interaction of those relationships and knowledge will alter
how you tell the story. However, difficulty in generating the representations of the
wedding day itself as well as how and what your communication knows about you and
weddings will create problems in how you shape the narrative to the demands of the
current context.
Although the narratives of amnesic participants were highly variable in their
content, there were not many significant differences in the comparison of their ratings of
86
their events compared to healthy participants ratings of their own events. Interestingly,
the amensic participants rated the importance and emotion of the event at the time
significantly lower than comparison participants. Perhaps the decrease in “episodicness”
of their memories did not allow them to accurately assess their subjective feeling at the
time of the event or dampened the phenomenological experience during recall and reexperience. This disconnect between telling very different stories (e.g., patient 2363
telling of his bike being stolen at age 8 versus car being stolen at age 22) yet rating the
stories similarly may provide evidence for a lack of autonoetic experience when telling
these past remote memories. Reexperiencing in the moment, may allow for more episodic
details to be recovered and shared, but may also guide accurate assessment of the feeling
at the time.
This lability in performance is similar to findings from decision making in
patients with hippocampal damage, where they were impaired on the Iowa Gambling
Task. Their performance was impaired as they were not performing advantageously (like
healthy participants) or disadvantageously (like patients with frontal lobe damage; Gupta,
Duff, Denburg, Cohen, Bechara, & Tranel, 2009). Rather their performance was
seemingly random and changed drastically from event to event. We see similar
performance in the telling of these narratives, where past experience does not guide
present behavior. Where healthy comparisons appeared to censure themselves and tell
roughly the same story from telling to telling, individuals with amnesia told drastically
different stories from time to time.
The deficits we observe in active and flexible manipulation of acquired
declarative memory representations being used in service of thinking about and telling
87
narratives across time conditions appears obvious when viewing the issue from the
relational memory standpoint. The role of the hippocampus is flexibly bind together the
co-experiences of particular events and moments. One of these pieces of information is
time, however, the system is not then ordered by time. Thus, damage to the hippocampus
should affect the ability to flexibly and dynamically pull together mental representations
of memory will thinking about narratives regardless of time. The current results paired
with past investigations reveal the importance of the hippocampal declarative memory
system in shaping future advantageous performance. In the decision-making literature, an
intact hippocampal declarative memory system allows one to make advantageous
decisions, while in narratives an intact hippocampal declarative memory system allows
one to tell narratives tuned to the particular demands of the interaction, allowing one to
leverage narratives to the social demands of the moment.
An interesting point raised by Squire et al. (2011) is the issue of experimentally
measuring the hippocampus’ role in recollecting past and imaging future events is that it
depends on spoken narrative. A problem with this method is that hippocampal or other
brain damage may contribute to problems in language or narrative abilities. Perhaps using
complementary methods such as functional imaging we can ask individuals to think of or
imagine stories without telling them and look for activation of hippocampal and other
brain areas activation without relying on the actual narration of the stories.
Contrary to previous findings for the retelling of autobiographical memory we did
not see an increase in the length or repetition of story details from telling to telling across
the healthy comparisons (Campbell, Nadel, Duke & Ryan, 2011; Nadel, Campbell, &
Ryan, 2007). For the “War of the Ghosts” stories I demonstrated the main finding in
88
amnesia that individuals with amnesia are profoundly impaired in their ability to learn
new declarative information. The comparison subjects showed the general trend found in
previous investigations of the “War if the Ghosts” where they became less accurate over
time, however, there was no significant effect of time on repeated details, indicating that
they were fairly consistent in keeping the few accurate (or inaccurate) details from telling
to telling (Bartlett, 1932).
An interesting future investigation of the “War of the Ghosts” narratives from the
healthy comparisons may be to look into language measures such as cohesion and
coherence which has previously been demonstrated to rely on declarative memory
(Kurczek & Duff, 2011) and see if those measures decrease over time (i.e., as demand on
declarative memory increases). While we were unable to investigate the impact of
deficits in declarative memory within this task with patients with hippocampal amnesia,
increasing demands on declarative memory within healthy participants may reveal similar
effects as we observed within the tellings of personal stories.
Another interesting potential future investigation is into audience design in
patients with amnesia. While narrative production appears to place high demands on the
HDMS, particularly representational flexibility, as speakers creatively (re)construct
events and chose what information and details to represent or omit in response to
contextual and audience cues (e.g., healthy comparisons telling similar stories to the same
experimenter four times in the present experiment). While there is some evidence that
creative aspects of linguistic behavior are disrupted in amnesia, the role of HDMS in the
social aspects of narrative construction is a fairly open question.
89
To better understand how speakers use contextual and audience cues to tailor
narratives, we could ask participants to look at two stimuli (paintings produced by an
adult or child) and construct a narrative to be told to either a child or adult. Comparing
lexical and syntactic characteristics as well as subjective ratings, we could focus on the
ability of the speaker to use context and audience information to create distinct and
appropriate narratives.
Traditionally, patients with hippocampal amnesia have been described as having a
severe and selective memory impairment with other cognitive abilities left intact. Here, I
begin to explore the interactions and interdependencies of multiple cognitive functions.
Specifically, I provide evidence of the early and fundamental role of the declarative
memory underlying other cognitive processes such as language and social interaction.
Without an intact declarative memory system, patients with hippocampal amnesia tell
narratives in a fundamentally different way across time. This indicates that individuals
with hippocampal amnesia may not be able to flexibly adapt to different contexts or
perform advantageous in multiple contexts.
90
Table 3. Demographic and neuropsychological characteristics of hippocampal amnesic
participants.
Sex Ed Age Etiology
HC
Intelligence Memory
Language
Volume
Patient
WAIS-III WMS-III Token BNT
FSIQ
GMI
Test
1846
F
14
51
Anoxia
-4.23
84
57
41
43
1951
M
16
62
HSE
-8.1
106
57
44
49
2308
M
18
58
HSE
N/A
98
45
44
52
2363
M
18
58
Anoxia
-2.64
98
73
44
58
2563
M
16
59
Anoxia
N/A
94
63
44
52
N/A
-5.0
96.0
59.0
43.4
50.8
±2.8
±8.0
±10.2
±1.3 ±5.4
AM
16.4 57.6
Summary
±1.7 ±4.0
Note. AM = Hippocampal amnesic participants; F = Female; M = Male; Ed = Education;
HSE = Herpes simplex encephalitis; HC Volume = Hippocampal z-scores represent the
combined (left and right hemisphere) studentised residuals of hippocampal volume
relative to a group of comparison subjects (Allen et al., 2006; Buchanan et al., 2005).
WAIS-III = Wechsler Adult Intelligence Scale; FSIQ = Full Scale Intelligence Quotient,
WMS-III GMI = Wechsler Memory Scale-III; GMI = General Memory Index; CFT =
Complex Figure test BN = Boston Naming Test
91
Figure 3. Memory ratings for condition 1, multiple tellings.
Please use the following scale to rate the questions below:
1
2
3
4
Not at all
Somewhat
Moderately Very
5
Extremely
1) The importance of the event at the time it occurred?
2) The importance of the event currently?
3) The emotionality of the event at the time it occurred?
4) The emotionality of the event currently?
5) How vividly was your memory recalled?
6) What was your overall arousal or energy level at the time of the event?
7) How positive or negative was the event at the time it occurred
-3
-2
Very
Somewhat
Negative
Negative
-1
0
Neutral
+1
+2
+3
Somewhat
Very
Positive
Positive
92
Figure 4. Internal to overall ratio across multiple tellings for hippocampal amnesics and
healthy comparison participants.
1
Internal to Overall Detail Ratio
0.9
0.8
*
*
*
*
0.7
0.6
0.5
Comparison
0.4
Amnesia
0.3
0.2
0.1
0
1
2
3
Time
Note. * indicates significant at p<0.05 level.
4
*
Note. * indicates significant at p<0.05 level.
*
*
*
*
*
Figure 5. Consistency data for multiple tellings for hippocampal amnesics and the healthy comparison participants.
93
93
94
Table 4. Comparison of amnesic and healthy comparison narratives over time.
Telling
Number Comparison
Well I was about four or five uh
1
years old um and I was la-and
my parents were leaving for
some reason anyway I needed a
babysitter the next door
neighbor kid young girl or girl
much older than I at the time
anyway was coming to babysit
me and I recall she was coming
over to the house and I was
outside and I greeted her and I
went to uh open the door and in
those days the milk man came
you got deliveries of milk and
they left em in this case on your
porch and it was a metal box
and uh and I wasn’t tall enough
to reach the door- handle to
open the door so I stood up on
this box and while I did I caught
my shin on corner of one of
these milk boxes and ripped
open my leg uh a big gash on it
and I had to be taken to the
doctor and-and uh I-I just reremember this excruciating pain
while my mom and dad were
holdin me down while the
doctor stuck this long needle
inside my gash, inside the
wound and it just remem- it hurt
like crazy and I and I have – I
still- I have a very long scar on
that shin to this day and it was
just rather traumatizing. So uh
pain is what I remember from
that.
Amnesia - 2363
Job interview uh okay which job interview
do you want me to tell you about? Um well
let’s do the Texaco interview. Thy had me
over to Houston ‘cause I was livin’ in
Beaumont at the time and the uh they had
me over and they had me talk to five
different people and one turned out to be
my boss and the other four were her
members of the team that was developing
this probe to use for oil exploration and it
was a dielectric energy level and- or
dielectric measurement device and it was
used to tell the uh dielectric properties of
the water in the ground and by telling that
you could tell between saltwater and uh
freshwater, ‘cause freshwater is very- is
very uh dielectric- or the dielectric level isis very high the resistance is very high and
the uh saltwater is very low so it makes a
good demarcation point when you look for
oil in the ground and I built a probe that
was- consisted of four circuit boards, you
know there were four circuit boards and
circuitry on each one of ‘em. They were
about ’bout two inches wide- I mean two
inches wide and uh ‘bout four inches long
and there were multiples of those ‘cause
we had to put it in a tube that was about
roughly one and a half inches wide- or one
and a half- two and a half- it woulda been
two and a half inches wide and the uh we
had to mount those in a string to make the
whole circuitry and the uh mm let’s see uh
I forgot uh what I was talking about ’boutoh I made the probe but I forgot what the
question was job interview okay that’sthat’s what the job was that I interviewed
for. Twenty- one I guess.
95
Table 4. Continued.
Details
2
Details
Words = 235
Internal = 15
External = 10
IOR = 0.6
That’s a story of uh I was a little kid and
um I had the next door neighbor girl was
gonna babysit me for some reason um
and so I met her outside or close to
house and I was gonna let her in and in
those days we got milk delivered to us
by a milkman and that was front porch
they had this milk box it was a square
box and I was too little I couldn’t reach
the d- handle of the door so I went to let
her in I was being nice I was let her in I
tried st- I stood up on the milk box and I
caught the edge corner of uh the lid and
it just ripped a gash right into my left
shin all the way up and it was nasty it
went in and uh parents had to take me to
the doctors and I just recall them one
holdin my arms the other one holdin my
legs and the doctor- Doctor Block that
was his name Doctor Block and uh j-just
pour- or uh big needle right into the
wound and just give me a shot right intointo the wound uh ya know it was
horrifying at that being four years old or
fi- ya know little like that and uh hurt it
hurt and uh so that was that.
Words = 130
Internal = 15
External = 0
IOR = 1.0
Editorials = 0
Repeated = 40.9%
Changed = 22.7%
Added = 36.4%
Words = 311
Internal = 4
External = 26
IOR = 0.13
Okay ya want me to repeat it?
Okay the job interview at
Texaco was conducted at the
facility the uh I got to meet the
various people in the lab I’d be
working in. The uh they
showed me around, took me out
to dinner- or lunch I mean and
then uh asked me various
questions about my training and
uh that was about it. I was
twenty-one or twenty-two at the
time.
Words = 102
Internal =7
External = 1
IOR = 0.7
Editorials = 2
Repeated =0.0%
Changed =0.0%
Added = 100.0%
Note. Panel A) How important was the event at the time B) How emotional was the event at the time C) How positive or negative was
the event at the time D) How vivid is your memory for the event
Figure 6. Self Ratings for multiple tellings for hippocampal amnesics and their healthy comparisons
96
96
97
Figure 7. War of the Ghosts accuracy data for hippocampal amnesics and their healthy
comparisons.
0.5
0.45
0.4
*
*
*
*
Accuracy
0.35
0.3
0.25
Comparison
0.2
Amnesia
0.15
0.1
0.05
0
1
2
3
Time
4
98
Table 5. Comparison of hippocampal amnesic and healthy comparison performance on
War of the Ghosts retelling.
Telling
Comparison
Amnesia - 2363
Uh there were two uh m- or I dunno men or boys
The war of the ghost
went down to the river they were from Ergulac and story. Okay it um
they went down and um they were wanting to hunt talked about two young
seals and they heard um war cries and they saw
men that went out
some canoes and one came to the side of the river
hunting and they heard
where they were at and said uh what do you think
some noise off in the
come with us we’re going up river to war on some distance and it was
people. And one of ’em said um well I might get
another tribe that was
killed and I don’t have any arrows and they said
apparently- or that waswell there’s arrows in the canoe and then he said
they th- they thought
he didn’t want to go but he told the other guy that
was a tribe and they got
he could go with them so the one went back home
into a fight and the one
and the other got in the canoe and went with them
of them was killed and
and um, um they went up to- starts with a K,
the other one paddled
Komoldone or something like that and uh anyway
back to shore and told
they uh started fighting and some of ‘em there
the villages that he had
were people killed and some of them were killed
been attacked by ghosts
and then he heard one of ‘em say um let’s get out
and that that the other
of here the Indian’s been hit and uh so he didn’t
one had been killed the
think he had been shot but anyway they went back other member who him
home and uh let’s see. He went and built a fire and and his friend one of
then he uh said to the others that uh uh they said
whom had been killed
so that’s it.
I’d been hit but I didn’t think I had been and so
then overnight they said um black stuff started
coming out of his mouth and his face was
contorted and they said he’s dead. And I forget the
about he said about the ghost but
Words = 279
Words = 103
Details Accuracy = 51.2%
Accuracy = 11.9%
1
99
Table 5. Continued.
Telling
Comparison
Oh the war of the ghost story okay. There were
two uh guys I donno if they were boys from
Ergulac and they went down to the river to hunt
for seals and when they were down on the river
um they heard war cries and they saw in the
distance um well it was foggy and uh they
heard war cries and they saw these canoes out
in the distance and they one of the canoes came
to the side of the river where they were at and
uh said they said one of the guys said what do
you think and do you wanna come with us
we’re going up to um I donno Kamalon or
something like that uh to uh war on this
neighboring village um uh one of the guys said
well I am afraid I’ll get killed and I don’t have
any arrows and they said well we have arrows
in the canoe. He said well I don’t really wanna
go so he told the other boy or guy that hey you
can go with them I’m gonna go back to the
village so the one went back to the village and
then the other one got into the canoe with the
men and um I think there were five of them in
the canoe and they went up and stared way with
this village um there were people killed on their
side and on our side um and then one of the- on
of the people the guys that said hey let’s get out
of here the Indians have been hit and uh the guy
said you know they were talking about me that
had been shot but I didn’t think I had been shot
um so anyway we went back um when I got
home I went and started a fire and uh went in
the tent and uh told the people that he had been
thought he had been with ghosts and uh
overnight dark things- black things started
coming out of his mouth and he had a contorted
face and one of the people in the village yelled
he’s dead.
Words = 360
Details Accuracy = 51.2%
Repeated Details = 52.3%
Added Details = 31.8%
2
Amnesia - 2363
Oh let’s see the war of the
ghost story oh boy had
something to do with uh
two Indians and they were
expecting an attack from dfrom a different tribe or
something and they uh one
went back to warn the
people the people and the
other one went ahead to
spot them or- or find out
their position or where
they were that’s pretty
much all I can remember
right now.
Words = 73
Accuracy = 6.0%
Repeated Details = 33.3%
Added Details = 50.0%
100
CHAPTER 6: HIPPOCAMPAL LATERALITY: THE EFFECT OF
UNILATERAL HIPPOCAMPAL DAMAGE ON LANGUAGE USE
6.1. Background
While individuals with bilateral hippocampal damage have demonstrated deficits
in multiple domains of language use (Kurczek, et al., 2013; MacKay, Stewart, & Burke,
1998; Park et al., 2011), an open question is whether there are differential contributions
in the material processing of either the left or right hippocampus. While the left
hemisphere has been implicated in many language processes (see Chapter 2) and the right
hemisphere often associated with the processing of visuospatial information (Giovagnoli,
Casazza & Avanzini, 1995; Gleibner, Helmstaedter, & Elger, 1998), it is an open
question whether the deficits in language observed after bilateral damage to the
hippocampus would be differentially expressed after unilateral hippocampal damage.
In the 50 years since HM underwent surgery to relieve complications from
epilepsy there has been a concerted effort to understand the cognitive processing of
structures in the medial temporal lobe in order to avoid the same consequences suffered
by HM after his surgery. Almost all cases of temporal lobe epilepsy are associated with
some degree of memory impairment (Fisher, Vickery, Gibson, Hermann, Penovich,
Scherer, et al., 2000) and the predominant understanding of the contribution of each
hemisphere has been that of material specificity, where the left and right hemispheres
process different types of information (Milner, 1970). While global amnestic syndromes
are rare (Van Buren, 1987; Walczak, Radtke, McNamara, Lewis, Luther, Thompson,
Wilson, et al., 1990), milder deficits after unilateral damage occur in material specific
101
recall (Milner 1968; 1990; Naugle, 1992). The left hemisphere is thought to process
verbal material (Mungas, Ehlers, Walton, & McClutchen, 1985; Ojeman & Dodrill, 1985;
Rausch & Babb, 1993; Sass, Spencer, Kim, Westerveld, Novelly, & Lencz, 1990), while
the right hemisphere is thought to process non-verbal material (Abrahams, Pickering,
Polkey, & Morris, 1997; Barr, Chelune, Hermann, Loring, Perrine, Strauss, Trenerry, et
al., 1997; Giovagnoli, et al., 1995; Jones-Gotman, 1986; Smith & Milner, 1981; Taylor,
1969; Feigenbaum, Polkey & Morris, 1996), although the findings are less consistent
than those found in the left hemisphere (Giovagnoli, et al., 1995; Pigott & Milner, 1993;
Smith & Milner, 1981). These conflicting reports have led some to argue that the material
specificity hypothesis is too simple and that neural structures in the medial temporal lobe
outside of the hippocampus including the perirhinal cortex are part of a more extensive
network of structures both within the medial temporal lobe and outside including the
hemispheres at large, that contribute to the deficits observed after unilateral damage to
the MTL (Saling, 2009). Similarly, Weber and colleagues (2005) suggest that because of
the multiple reciprocal connections of the hippocampus to cortical systems and the neural
metabolic disturbances observed in more lateral portions of the temporal lobe in epilepsy
(Hammers, Koepp, Labbe, Brooks, Thom, Cunningham, et al., 2001), the observed
deficits after unilateral MTL damage may be a consequence of dysfunction of the entire
hemisphere instead of just the hippocampus.
Further complications in the material specificity hypothesis include atypical
language lateralization, functional reorganization and bilateral representation of verbal
and spatial representations. Although left hemisphere language processing is present in
the overwhelming majority of subjects, upwards of 6% of people show atypical language
102
activation in recent functional neuroimaging (Springer, Binder, Hammeke, Swanson,
Frost, Brewer, Perry, et al., 1999). However, in temporal lobe epilepsy, atypical language
lateralization is more common with rates observed as high as 30% (Helmstaedter,
Kurthen, Linke, & Elger, 1997; Rasmussen, & Milner, 1977; Springer, Binder,
Hammeke, Swanson, Frost, Bellgowan, Brewer, et al., 1999; Tanriverdi, Al Hinai, Mok,
Klein, Poulin, & Olivier, 2009) with some suggesting that epileptic activity (Janszky,
Jokeit, Heinemann, Schulz, Woermann, & Ebner, 2003; Janszky, Mertens, Janszky,
Ebner, & Woermann, 2006) or hippocampal sclerosis may drive shifts in language
lateralization (Brazdil, Chlebus, Mikl, Pazourkova, Krupa, & Rektor, 2005; Brazdil,
Zakopcan, Kuba, Fanfrdlova, & Rektor, 2003; Cousin, Baciu, Pichat, Kahane, & Le Bas,
2008).
Further, a study by Sass and colleagues (1992) investigated the relationship
between hippocampal neuron loss and cognitive performance, finding that only memory
correlated with left hippocampal neuron loss, but not language competency or general
intellectual ability even in light of worse performance on the Boston Naming task
compared to patients with right hippocampal damage. In a similar line of investigation,
intracranial recordings have revealed activity in medial temporal lobe neurons in both
hemispheres during a verbal paired associates task (Cameron, Yashar, Wilson, & Fried,
2001), while fMRI in patients with left hippocampal pathology show right medial
temporal lobe activation during a verbal memory task (Richardson, Strange, Duncan, &
Dolan, 2003). It is thought that, similar to the language reorganization observed in
developmental cases of amnesia (Vargha-Khadem, Issacs, & Muter, 1994), adults may be
103
capable of neural reorganization that allows homologous structures opposite the damaged
side to overtake cognitive processing once subserved by the damaged structures.
Others have suggested that the material-specificity effect observed after unilateral
MTL damage may be attributable to interactions with neural structures outside the MTL
including the frontal lobes and lateral temporal lobes (Pillon, Bazin, Deweer, Ehrle,
Baulac, & Dubois, 1999). A functional imaging study by Kelley and colleagues (1998)
found differences in the lateralization of activation for words (left), faces (right) and
nameable objects (bilateral) in both the frontal and medial temporal lobes. Interestingly,
the left MTL was activated by all material types (both verbal and nonverbal), showing the
strongest activation for the namable objects, suggesting to them, that the left MTL is not
specialized for processing particular stimulus types (Kelley et al., 1998). Similarly Golby
and colleagues (2001) found symmetrical activation for scenes and faces in both the
frontal and medial temporal lobes. In summary, although there has been some conflicting
evidence, a majority of the unilateral contribution of the hippocampus to memory appears
to suggest similar contributions observed in the hemispheres at large, with the left
hemisphere contributing to language processing and the right hemisphere contributing to
spatial processing.
6.2. Specific Aims and Hypotheses
Aim #3: To investigate the contribution of left versus right damage to the
hippocampus on referential processing and narrative construction. It is hypothesized
that damage to the left hippocampus will make a larger, more significant or
disproportionate contribution to language processing. Therefore, it is predicted that
104
patients with left hippocampal damage will perform significantly worse than patients
with right hippocampal damage in both referential processing and narrative construction.
6.3. Methods
6.3.1. Participants
Six people participated in this study, 3 individuals with left temporal lobe (TL)
damage and 3 people with right temporal lobe damage. Participants were recruited from
the Neurological Patient Registry at the University of Iowa. Inclusion criteria were the
same as listed in Chapter 4 for all previous participant groups. Additionally, patients
where excluded if their damage included frontal or occipital cortices or if
neuropsychological testing revealed significant impairments in language. All six TL
participants participated in the Referential Processing (Aim #1) and Narrative (Aim #2)
tasks. Demographic and neuropsychological information are listed in Table 6 and Table
7.
6.3.2. Experimental protocol
The TL participants participated in all of the experiments previously described in
Chapters 4 and 5. For Aim #1 the Referential processing experiment was performed as
described in preliminary study 3 (Kurczek, et al., 2013) was conducted (for details about
the procedure and analysis see Chapter 4 – the only difference in procedure is in one of
the fixed effects – gender (this experiment) versus repetition (Chapter 4); the same
analysis approach was used here). For Aim #2, the narrative experiment was also
105
performed just as described in the hippocampal amnesic experiment was conducted (see
Chapter 5).
Initial analyses compared the patients with unilateral left and right hippocampal
damage. Secondary analyses compared the patients with unilateral hippocampal damage
to patients with bilateral hippocampal damage and their comparison participants.
6.4. Results
6.4.1. Referential processing
6.4.1.1. Offline Data for patients with unilateral hippocampal damage
The offline data speak to the participants’ ultimate interpretation of the pronoun;
if we were successful in establishing the first-mentioned character as more prominent in
the story, we would expect lower endorsement rates in the same-gender condition when
the pronoun refers to the 2nd mentioned character. Analysis of the response to the
judgment task (whether the picture matched the narrative) revealed that there were no
group differences between left and right hippocampal patients as both were highly likely
to endorse the picture as matching the story across three conditions (D1 = M = 97.4%,
96.4%; SD = 1.8%, 1.8%; D2 = M = 87.5%, 93.8%; SD = 9.0%; 4.1% ; S1 =M = 95.8%,
92.2%; SD = 3.3% , 8.3%; left and right respectively), with lower endorsement in the S2
condition (M = 28.1%, 31.3%; SD = 12.2, 13.9%). The analysis revealed that effects of
order of mention (OOM) and gender were qualified by a significant gender by OOM
interaction (z=-3.32, p<.001; see Figure 8), due to the low endorsement rates in the S2
condition (see Figure 7). This result is consistent with previous findings (Arnold, et al.,
2000, Experiment 2; Kurczek et al., 2013) where participants (i.e., healthy undergraduate
106
participants, healthy older adults and individuals with brain damage outside the medial
temporal lobes) had high endorsement of agreement in all conditions except the same
gender, second-mentioned condition.
6.4.1.2. Eye-movement data for patients with unilateral hippocampal damage
Analyses of the eye movements made during interpretation of the pronoun are
used to test for group differences in the use of discourse context to interpret a potentially
ambiguous pronoun in real time. We directly compared eye-fixations for the left and right
hippocampal patients in one analysis which included gender, order of mention and
participant group (left vs. right) as orthogonal factors, as well as time-window, with the
baseline window coded as reference.
The first analysis compared left and right hippocampal patients and found that the
groups performed comparably. At baseline there were no significant effects (ts<1.4)
indicating no anticipatory effects or group differences. Analysis of the pronoun region
revealed significant effects of gender (t=-4.61, p<.05; see Figure 9) and order of mention
(t=-3.69, p<.05) that was qualified by a significant gender by order of mention
interaction (t=-3.83, p<.05) which is similar to the performance of undergraduates,
healthy older comparisons and individuals with brain damage outside of the hippocampus
(Kurczek et al., 2013). However, there were no effects of group or group interactions,
indicating that L and R TL groups performed similarly during the pronoun region. In the
final region, there were significant effects of gender (t=-5.77, p<.05) and order of
mention (t=-6.40, p<.05) that was qualified by a significant gender by order of mention
107
interaction (t=-4.85, p<.05), additionally there was a significant effect of group (t=-2.06,
p<.05),
The participants with right hippocampal damage during interpretation of the
pronoun had a larger target preference when the characters were of different gender
(t=4.48, p<.01), and when the target was the first-mentioned character (t=4.99, p<.05). In
addition, there was a significant gender*order interaction (t=-3.35, p<.05).
Participant with left hippocampal during interpretation of the pronoun had a larger
target preference when characters were of different gender (t=3.17, p<.01), and when the
target was the first-mentioned character (t=2.50, p<.05). In addition, there was a
significant gender*order interaction (t=-2.50, p<.05).
Comparing the performance of patients with unilateral hippocampal damage to
patients with bilateral hippocampal damage and healthy comparisons revealed differential
performance between each unilateral patient group, where patients with damage to the
left hippocampus perform much more similarly to the bilateral hippocampal amnesics
than comparisons while patients with right hippocampal damage perform more similarly
to comparisons participants but not patients with bilateral hippocampal damage.
During the pronoun window, comparison of left hippocampal patients to healthy
comparisons revealed a significant group by gender by order of mention interaction (t=2.60, p<.014), but showed no group main effect (t = -0.46, p = 1.0) or group interactions
compared to the bilateral hippocampal amnesic patients (order of mention by group, t =
1.88, p = 0.061; gender by group, t = -1.44, p = 0.366; and order or mention by gender by
group, t = 1.71, p = 0.459) indicating that their performance was fairly similar to amnesic
performance.
108
In contrast, during the pronoun window, comparison of right hippocampal
patients to healthy comparisons revealed no group or group interactions (ps > 0.228)
while comparison to the bilateral hippocampal amnesic patients revealed a significant
group by order of mention interaction (t = -3.43, p = 0.026), where patients with right
hippocampal damage had a larger target preference than the bilateral hippocampal
patients.
6.4.2. Narrative construction analysis for patients with
unilateral hippocampal damage
6.4.2.1. Autobiographical memory interview and consistency analysis of multiple tellings
in patients with unilateral hippocampal damage
Analysis of the multiple tellings of personal stories comparing individuals with
either left or right hippocampal damage revealed no significant group or group by time
interactions. The only tests to reach statistical significance were effects of time on
internal details, F(3,12) = 16.54, p < 0.001, total details, F(3,12) = 9.83, p = 0.030, and
percentage of added details, F(3,12) = 4.45, p = 0.050. Follow-up contrasts revealed the
first telling had more internal details than the third (p = 0.020) and the final telling (p =
0.021), the first telling had more total details than the second (p = 0.016) and no
significant pairwise comparisons for the added details.
The left and right hippocampal patients were then compared to the bilateral
hippocampal patients and their healthy comparisons. Significant effects of group were
found for internal details, F(3,15) = 5.33, p = 0.011 (see Figure 10), total details, F(3,15)
= 4.92, p = 0.014, words, F(3,15) = 4.72, p = 0.016, repeated details, F(3,15) = 9.07, p <
109
0.001, and added details, F(3,15) = 15.28, p < 0.001 (see Figure 11). Follow-up contrasts
revealed that hippocampal amnesic participants performed significantly worse than
healthy comparisons across these measures (ps < 0.05). Additionally, hippocampal
amnesic participants performed significantly worse than left and right hippocampal
patients on repeated and added details, (ps < 0.05). Patients with left or right hippocampal
damage did not differ significantly from healthy comparison participants.
6.5.2.2. War of the Ghosts analysis for patients with unilateral hippocampal damage
In the analysis of the multiple tellings of the “War of the Ghosts” stories there
were no significant group or group by time interactions for the comparison of right and
left unilateral hippocampal patients. The only test that was significantly different was the
within subjects effect of time on accuracy, F(3,12) = 4.08, p = 0.033, although follow-up
tests did not reveal any significant contrasts.
The left and right hippocampal patients were then compared to the hippocampal
amnesics and their healthy comparisons. A 4X4 repeated measures ANOVA (group – left
hippocampus, right hippocampus, bilateral hippocampus and healthy comparison; time –
1, 2, 3, and 4) on accuracy revealed both an effect of time, F(3,45) = 4.60, p = 0.026 and
group, F(3,15) = 13.60, p < 0.001. Follow-up contrasts revealed that the bilateral
hippocampal amnesics performed significantly worse than healthy comparisons (p <
0.001) and patients with right hippocampal damage (p = 0.007) but not left hippocampal
damage (p = 0.095). Additionally, the first telling was more accurate than the final retelling (p = 0.003). There were also significant effects of group on repeated, F(3,15) =
11.85, p < 0.001, changed, F(3,15) = 3.99, p = 0.028 and added details, F(3,15) = 7.54, p
110
= 0.003. Follow-up contrasts revealed that bilateral hippocampal amnesics had less
repeated details than healthy comparisons (p < 0.001), and right hippocampal patients, (p
= 0.021), less changed details than healthy comparisons, (p = 0.024), and less added
details than healthy comparisons, (p = 0.004), and left hippocampal patients, (p = 0.004).
6.5. Discussion
The left hemisphere has been implicated in many language processes (see Chapter
2) and the right hemisphere often associated with the processing of visuospatial
information (Giovagnoli, Casazza & Avanzini, 1995; Gleibner, Helmstaedter, & Elger,
1998), but an open question is whether the deficits in language observed after bilateral
damage to the hippocampus would be differentially expressed after unilateral
hippocampal damage. Here I investigated the contribution of unilateral hippocampal
damage to referential processing and narrative construction. While the results do not
conclusively suggest differential contributions of the left over right to language measures
presented in this dissertation, there is a trend in these data that suggests greater
contributions of left hippocampus to language than to right. This trend warrants further
investigation.
While patients with left hippocampal damage displayed decreased performance in
the pronoun resolution eyetracking task, they did not perform nearly as impaired as the
patients with bilateral hippocampal damage. This is somewhat surprising given the lack
of differences in neuropsychological scores in memory and language between the patients
with unilateral left and right hippocampal damage, but it may also indicate that language,
in particular reference may be a highly sensitive marker for declarative memory
processing deficits (Kurczek & Duff, 2011, Kurczek et al., 2013). It may also indicate
that eye movement experiments are also a more sensitive measure in uncovering memory
111
performance as others have suggested (Hannula, Baym, Warren, & Cohen, 2012).
Beyond the sensitivity of the task and method, the use of linear mixed model regression
may also be more sensitive in detecting small differences in performance as both the
within subject and within trial variability is accounted for. In tasks and patient groups
where performance may be highly variable, this method of analysis may be more
powerful in uncovering subtle differences in performance.
In the narrative tasks, there were no significant differences in group performance
between the unilateral hippocampal patient groups, but there appeared to be a trend
towards worse performance for left over right in narrative construction. This trend could
become a significant difference with better controlled groups in terms of lesion type and
age of seizure onset. This trend does match the predicted outcome of greater impairments
in the left versus right hemisphere for language performance. However, this investigation
is unable to answer whether this (potential) decrease in performance is due to differential
processing capacities of the hippocampus or differential distribution of material specific
processing between the hemispheres. Perhaps rather than the left hippocampus
contributing more of the functional processing capacities than the right, the loss of
afferent and efferent connections to the lateral left temporal lobes impairs performance
within linguistic tasks. Perhaps by varying the linguistic and spatial demands within the
same task we could tease out the relative processing contributions of the left or right
hippocampus.
The comparison of the temporal lobe patients to bilateral hippocampal amnesics
and healthy comparison participants revealed performance of patients with unilateral
hippocampal damage closer to healthy performance than amnesic performance.
Additionally there did not appear to be any gradient of performance from healthy to right
damage to left damage to bilateral hippocampal damage. Perhaps the same issues from
the left versus right comparison are at play in this analysis. It may also indicate the
pervasiveness hippocampal processing capacities in the face of damage. Though left and
112
right hippocampal damage may respectively affect verbal and spatial memories, the types
of processes that referential processing and narrative construction are attempting to
measure, generating and binding representations, may be more resistant to hippocampal
damage. This comparison and lack of statistical differences may indicate a lack of
differential lateral contributions of the hippocampus to the fundamental processing
capacities.
In terms of hippocampal contributions to language and neuroanatomical
interactions, the results from this study may indicate that rather than the hippocampus
being a fundamental aspect of the neuroanatomic language system, the hippocampus may
just be a an early and pervasive contributor to cognition. The comparison of the unilateral
hippocampal patients to bilateral hippocampal patients and healthy comparisons revealed
that the unilateral patients performed more similarly to healthy comparisons. This
indicates that functioning of the hippocampus is fairly robust to damage, especially when
patients do not show neuropsychological deficits in declarative memory performance.
The slight differences in performance when comparing left and right hippocampal
patients may indicate hemisphere processing differences rather than lateralized
hippocampal functioning. The loss of afferent and efferent connections with in a
hemisphere may explain the decrease in performance for patients with left hippocampal
damage, where damage to the left hippocampus impairs the ability of the hippocampal
complex to access neocortical sites of linguistic materials stored in more lateral left
temporal lobe cortices.
Thus, perhaps the deficits previously observed in bilateral hippocampal damage
on language tasks are not a matter of the hippocampus playing a role in language, but
rather that certain aspects of language place a disproportionate amount of demand on the
processing capacities of the hippocampus. This principle would apply across other
domains of cognition that have been revealed to receive hippocampal contributions like
decision making and social interaction. Rather than the hippocampus being recruited for
113
language, decision making and social interaction, the hippocampus may make early and
continuous contributions of fundamental processing capacities that receive greater and
lesser demands depending on the context. Within language, the hippocampus is thus
making contributions to classic perisylvian neocortical circuits through ongoing
interaction with higher cortical structures in the frontal and temporal cortices.
One issue in the patient group was the variable demographics. A surprising
finding was the lack of differences in memory and language performance on
neuropsychological tests between the two patient groups with unilateral hippocampal
damage. Perhaps a left patient group with deficits in verbal memory would show more
dramatic effects within these language measures. The patients were also mixed in their
etiology. One patient (1580) developed damage after herpes simplex encephalitis.
Perhaps having not lived with seizures for some length of his life made him stand out
differently from the other patients. The patients were also variable in their onset of
seizures, which could be an important variable if this investigation continues to enroll
more participants. As discussed earlier, childhood onset of seizures can potentially drive
language development in the brain in different ways than typically developing adults.
Some suggested that epileptic activity (Janszky, Jokeit, Heinemann, Schulz, Woermann,
& Ebner, 2003; Janszky, Mertens, Janszky, Ebner, & Woermann, 2006) or hippocampal
sclerosis may actually drive shifts in language lateralization (Brazdil, Chlebus, Mikl,
Pazourkova, Krupa, & Rektor, 2005; Brazdil, Zakopcan, Kuba, Fanfrdlova, & Rektor,
2003; Cousin, Baciu, Pichat, Kahane, & Le Bas, 2008). With larger groups it will be
important to separate adult from childhood on-set cases of seizures in order to compare
individuals with more similar language development trajectories.
114
Table 6. Demographic characteristics of patients with unilateral hippocampal damage.
Patient
Sex Hand
Age
Etiology
Chron
Sx Onset
Ed
2246
F
Un
70
Resection
17
0
20
3166
M
R
41
Resection
10
3
16
3509
M
R
51
Resection
6
42
14
Left TL
54.0
N/A
11.0
15.0
16.7
Summary
± 14.7
± 5.6
± 23.4
± 3.1
1580
M
R
43
HSE
23
20
16
2962
M
Un
58
Resection
12
8
14
3386
F
R
37
Resection
8
17
18
Right
46.0
N/A
14.3
15.0
16.0
Summary
± 10.8
± 7.8
± 6.2
± 2.0
Difference
t(4) = 0.76,
p = 0.491
t(4) = 0.60, t(2.28) = 0.0, t(4) = 0.32,
p = 0.582
p = 0.999
p = 0.768
Note. Left TL = Left temporal lobectomy participants; F = Female; M = Male; Right TL
= Right temporal lobectomy participants; Hand = Handedness; Un = Unhanded; R =
Right; Resection = Temporal lobectomy resection; HSE = Herpes Simplex Encephalitis;
Chron = Chronicity, time since brain damage; Sx Onset = Age at diagnoses of seizure
disorder; Ed = Years of education
101.7
± 7.6
103
105.0
± 2.0
115
109.0
107
117
109.3
Left TL
Summary ± 11.3
104
3509
1580
2962
3386
Right TL
Summary ± 6.8
105
107
105
93
96
3166
107
VERB
FSIQ
116
WAIS-
WAIS-III
2246
Patient
± 9.1
114.7
123
116
105
± 6.1
110.3
117
105
109
PERF
WAIS-
Intelligence
± 9.9
111.0
118
104
N/A
± 2.0
93.0
95
93
91
GMI
WMS-III
± 3.2
9.7
11
6
12
± 0.6
7.7
7
8
8
Recall
AVLT
Memory
± 0.0
44.0
44
44
N/A
± 3.0
41.0
41
38
44
Test
Token
Table 7. Neuropsychological characteristics of patients with unilateral hippocampal damage.
± 2.3
54.3
57
53
53
± 4.0
54.0
58
50
54
BNT
± 1.2
41.3
40
42
42
± 17.6
41.0
49
28
61
COWA
Language
115
p = 0.502
p = 0.967
p = 0.530
t(4) = 0.69,
p = 0.228
p = 0.394
t(1.05) = 2.54, t(2.13) = 1.06,
p = 0.272
t(4) = 1.34,
p = 0.907
p = 0.977
t(4) = 0.13, t(2.02) = 0.03,
Note. Left TL = Left temporal lobectomy participants; Right TL = Right temporal lobectomy participants; WAIS-III = Wechsler
Adult Intelligence Scale; FSIQ = Full Scale Intelligence Quotient; VERB = Verbal subtest composite score; PERF = Performance
subtest composite score; WMS-III GMI = Wechsler Memory Scale-III; GMI = General Memory Index; AVLT Recall = Recall trial of
the Auditory Verbal Learning Test; CFT = Complex Figure test – Recall Score; BNT = Boston Naming Test; COWA = Controlled
Oral Word Association Test
t(4) = 0.74,
t(4) = 0.04,
Table 7. Continued.
116
117
Percent 'yes' response
Figure 8. Off-line performance for unilateral hippocampal patients.
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
d1
d2
s1
s2
Condition
Left
Right
Note. S = Same; D = Different; 1 = First mentioned character; 2 = Second mentioned
character.
118
Figure 9. Time course of fixation preference data for unilateral hippocampal patients.
Note. A) Unilateral left patients B) Unilateral right patients; S = Same; D = Different; 1 =
First mentioned character; 2 = Second mentioned character. Vertical lines denote time
windows.
119
Number of Internal Dtails
Figure 10. Internal details across multiple tellings for unilateral hippocampal patients.
18
16
14
12
10
8
6
4
2
0
Left
Right
1
2
3
Time
4
120
Figure 11. Consistency data for unilateral hippocampal patients in the multiple telling.
Note: A = Percentage of repeated details; B = Percentage of added details.
121
CHAPTER 7: CONCLUSIONS
The goal of this dissertation was to investigate the role of the hippocampal
declarative memory system’s role in language. This thesis brings together the study of
two quintessential human capacities, memory and language, by examining the role of the
hippocampal declarative memory system (HDMS) in language processing and use. Aim
#1 examined the effects of bilateral damage to the hippocampus on referential processing
and the potential for recovering performance. Although we were able to demonstrate a
recovery in the use of order of mention information, we were unable to further bias looks
to the target character in our repeated mention condition. This slight impairment in
performance was limited to patients with hippocampal damage and not patients with
brain damage to the frontal lobes.
This work, as attempted in Aim #1 has potential clinical and rehabilitative
implications. By understanding the contributions of neural systems to deficits in language
processing and use, we may be able to develop strategies that place demand on other
neural systems. While many efforts in language rehabilitation have attempted to use
procedural memory methods to alleviate language impairments, recent work is beginning
to demonstrate the contribution of the hippocampus to procedural memory tasks (Foerde
et al., 2013). The emerging picture of the hippocampus as a ubiquitous player across
domains of cognition and time periods means that individuals with damage to the
hippocampus or hippocampal dysfunction may make rehabilitative efforts difficult.
Further, repetition as a rehabilitative device when used without context or purpose
may serve a poor rehabilitative tool. Individuals with amnesia received no benefit from
repetition, while healthy comparisons and individuals with damage outside the
122
hippocampus received only marginal benefit in their performance. Clinicians working
with individuals with memory impairments should realize that how repetition is
leveraged matters (Verfaellie et al., 2008) and that social and real-world consequences of
the rehabilitative practice will have significant consequences. As Hengst and colleagues
(2010) cautioned, the aim of rehabilitation takes place within real-world contexts which
need to be realized in the rehabilitative setting.
In Aim #2, each participant with bilateral hippocampal damage told two types of
stories (semantic – “War of the Ghosts” and episodic) multiple times. The performance of
the amnesic participants on the “War of the Ghosts” story illustrated the core feature of
amnesia where they were extremely impaired in their ability to learn new declarative
information. In the performance of telling their own remote declarative memories healthy
comparisons were fairly consistent in telling of their stories while participants with
amnesia were much more variable in their tellings. This lability of the tellings from time
to time may indicate the core processing capacities of the hippocampus, generating and
binding representations that are affected by activation of representations in the present
moment. Where healthy comparisons were able to recover previous tellings, amnesics
were unable or impaired in their ability to recover previous episodes and thus were more
susceptible to recently activated representations causing their stories to be drastically
different.
Particularly relevant to the deficits in amnesic’s performance are the social
implications. Previously it has been demonstrated that the hippocampus critically
contributes to the use of various interactional discourse resources including reported
speech (Duff et al., 2007) and verbal play (Duff et al., 2009). Here, I demonstrate that
123
how patients with bilateral hippocampal damage tell stories across multiple social
interactions is different than healthy comparisons. This and other work demonstrating the
importance of the hippocampal memory system in social interaction (Davidson, Drouin,
Kwan, Moscovitch, & Rosenbaum, 2012) may implicate the critical contribution of
hippocampal dysfunction in disorders of social interaction. Perhaps rather than focusing
on frontal lobe dysfunction in disorders of diffuse brain damage (e.g., Alzheimer’s
Disease, Schizophrenia, Autism), we should look to hippocampal dysfunction and
contributions.
Finally, Aim #3 explored the effects of unilateral hippocampal damage on
language processing and use. While the first experiment investigating referential
processing in an eyetracking experiment demonstrated slight impairments for patients
with unilateral left hippocampal damage, the second experiment in narrative construction
did not reveal any differences in performance between patients with left or right
hippocampal damage. The comparison of the patients with unilateral hippocampal
damage to patients with bilateral hippocampal damage and healthy comparisons revealed
performance much closer to that of the healthy comparisons.
The left hemisphere has been implicated in processing verbal material (Mungas,
Ehlers, Walton, & McClutchen, 1985; Ojeman & Dodrill, 1985; Rausch & Babb, 1993;
Sass, Spencer, Kim, Westerveld, Novelly, & Lencz, 1990), while the right hemisphere is
implicated in processing non-verbal material (Abrahams, Pickering, Polkey, & Morris,
1997; Barr, Chelune, Hermann, Loring, Perrine, Strauss, Trenerry, et al., 1997;
Giovagnoli, et al., 1995; Jones-Gotman, 1986; Smith & Milner, 1981; Taylor, 1969;
Feigenbaum, Polkey & Morris, 1996), and it was hypothesized that left hippocampal
124
damage would lead to greater impairments in language processing. The mixed findings in
this investigation could be attributed to variability in the patient groups or differences in
the task demands on the hippocampal declarative memory system. However, while the
differences in the performance on the narrative task were not significantly different, there
was a trend towards impaired performance by patients with left damage. The
comparisons in performance of patients with left and right hippocampal damage may
speak to the question of whether the hippocampus posses a differential distribution of
processing capacities or is part of a hemisphere more adept at processing one material or
another (i.e., left for verbal and right for spatial).
The performance of patients with unilateral hippocampal damage being closer to
healthy comparisons suggests that the hippocampus has similar processing capacities
distributed across left and right hippocampus. The slight differences in performance
within the patients with unilateral damage suggest that the differences in performance are
due to the interactions within the hemisphere that the damaged hippocampus is placed,
where patients with left hippocampal damage have small impairments in language
measures because of deficits accessing neocortically stored linguistic material. To speak
to this question further, future investigations may attempt to vary verbal versus spatial
processing demands with in the same task and either use neuropsychological or
functional imaging methodology to investigate either impaired left performance or
activation of the left hippocampus for verbal materials.
This dissertation is grounded in the idea that the processing capacities of the
HDMS that contributes to the formation of new memories, and maintains representations
on-line to be used in service of complex behavior, are the same processes for using and
125
processing language (Duff & Brown-Schmidt, 2012). This dissertation is the latest in a
long line of evidence in support of this proposal from work demonstrating that patients
with hippocampal damage and declarative memory impairment have deficits in a variety
of linguistic and discursive abilities (e.g., Duff et al., 2006; Duff et al., 2007; Duff et al.,
2008; Duff et al., 2009; Duff et al., 2011; MacKay, Stewart & Burke, 1998). Two areas
that this dissertation furthers are referential processing and narrative construction. This
work provides further evidence for the contribution of the hippocampus to referential
processing while also suggesting that rehabilitation of performance will require more
than repetition to provide more salience to the target. Particularly important within the
referential processing is that the deficit is occurring on such a brief timescale. This work
thus extends the evidence of the contribution of the hippocampus to language and its
contribution to on-line processing.
This dissertation also extends the contribution of the hippocampus to narrative
construction. Previous work (Duff & Kurczek, 2013) had implicated the critical
contribution of the hippocampus to generating and combining representations necessary
for telling narratives. This work extends that contribution to how narratives are told over
time and has profound implications of the impact of hippocampal damage on both
language and social interaction processing.
By defining and characterizing the cognitive and neural systems that support
language we gain a better understanding of disorders of language. Although the HDMS
has previously received little consideration as a key neural/cognitive system for language
use and processing (outside of lexical acquisition/consolidation), mounting evidence
points to its critical contribution to the language network that now extends beyond the
126
traditional structures of the left perisylvian areas to include the hippocampus and
declarative memory (Duff & Brown-Schmidt, 2012). As evidence mounts to support the
role of the hippocampus in the generation and use of on-line representations created
during ongoing information processing to support behavioral performance positions the
hippocampus (Kurczek et al., 2013; Rubin, Brown-Schmidt, Duff, Tranel, & Cohen,
2011) in support of other cognitive abilities beyond its traditional role in memory (e.g.,
perception; Warren, Duff, Tranel & Cohen, 2010; 2011 and creativity; Duff, Kurczek,
Rubin, Tranel & Cohen 2013). We now begin to see how promiscuous the hippocampus
is in its contribution to cognition. We are beginning to see the mark of the hippocampus
across all areas of cognition, both early and continuously. Continued research with
complementary methods should look into the time-course of interaction between the
hippocampus and other neural structures in the coordination of higher cognitive abilities.
Early evidence appears to suggest that the processing capacities of the hippocampus are
called upon and used by many (most) other neural structures in the formation and
establishment of complex human behavior. Amnesia is derived from the Greek word,
ἀµνησία, meaning “without memory,” but what are the implications of the use of this
word, when the loss of memory is just one of a host of other impaired cognitive
functions?
127
APPENDIX: THE WAR OF THE GHOSTS
One night two young men from Egulac went down to the river to hunt seals, and
while they were there it became foggy and calm. Then they heard war-cries, and they
thought: "Maybe this is a war party". They escaped to the shore, and hid behind a log.
Now canoes came up, and they heard the noise of paddles, and saw one canoe coming up
to them. There were five men in the canoe, and they said: "What do you think? We wish
to take you along. We are going up the river to make war on the people".
One of the young men said: "I have no arrows".
"Arrows are in the canoe", they said.
"I will not go along. I might be killed. My relatives do not know where I have gone.
But you", he said, turning to the other, "may go with them."
So one of the young men went, but the other returned home. And the warriors
went on up the river to a town on the other side of Kalama. The people came down to the
water, and they began to fight, and many were killed. But presently the young man heard
one of the warriors say: "Quick, let us go home: that Indian has been hit".
Now he thought: "Oh, they are ghosts". He did not feel sick, but they said he had
been shot. So the canoes went back to Egulac, and the young man went ashore to his
house, and made a fire. And he told everybody and said: " Behold I accompanied the
ghosts, and we went to fight. Many of our fellows were killed, and many of those who
attacked us were killed. They said I was hit, and I did not feel sick".
He told it all, and then he became quiet. When the sun rose he fell down.
Something black came out of his mouth. His face became contorted. The people jumped
up and cried. He was dead.
128
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