Download Human MTL Lesions: Evidence Against the PM Hypothesis

Perception and the Medial Temporal
Lobe: Evaluating the Current
Evidence
Wendy A. Suzuki
NYU
Outline
• Anatomy of the medial temporal lobe (MTL)
• Medial temporal lobe memory system
(MTLMS) hypothesis
–
Evidence towards MTLMS from humans and
non-human primates
• Perceptual-mnemonic (PM) hypothesis
– Evidence against PM from humans, non-human
primates and rats
Human Medial Temporal Lobe
(MTL)
•
•
•
•
Hippocampus
Entorhinal cortex
Perirhinal cortex
Parahippocampal
cortex
Kandel et al., 2000
Animal MTL Anatomy
Medial Temporal Lobe Memory
System (MTLMS)
• Traditional view:
–
MTL is involved in the ability to learn and retain
declarative memory
–
Declarative memory involves information for
events, facts and relationships (Eichenbaum and Cohen,
2001; Squire and Zola-Morgan, 1991)
–
Procedural learning, perceptual priming, and
emotional memory are spared
Perceptual-Mnemonic Hypothesis
• Novel view:
–
MTL is involved in declarative memory AND
perception (Bussey and Saksida, 2007; Lee et al., 2005; Murray and
Wise, 2004)
–
Specifically, the perirhinal cortex
–
High feature ambiguity (overlapping features)
Perception in the Lateral Temporal
Lobe
Dorsal Stream
(Vision for Action)
Ventral Stream (Vision
for Perception)
Milner and Goodale, 1995
Wendy Suzuki: Argument
I argue that little
or no convincing
evidence exists in
favour of the role of the
MTL in perception
MTLMS: Evidence from Human
Amnesic Patients
• Patient H.M. (Henry
Gustav Molaison)
– Mostly anterograde amnesia,
but also temporally graded
retrograde amnesia
– Bilateral removal of
hippocampus (2/3),
amygdala, parahippocampal
gyrus, perirhinal and
entorhinal cortices
– Declarative memory gone,
perception spared
MTLMS: Evidence from Non-human
Primates
• Induce lesions
–
Large MTL lesions modeled from H.M. (Mishkin, 1978; ZolaMorgan and Squire, 1985)
–
Selective MTL lesions – perirhinal and entorhinal, just
perirhinal (Meunier et al., 1993), or hippocampus (Alvarez et al.,
1995; etc)
• All involved in declarative/relational memory
with online perceptual processing spared
–
Can still process features (colours/shapes)
–
Can differentiate between stimuli
MTLMS: Evidence from Non-human
Primates
• MTL receives inputs
from many high-order
sensory and
association areas
• MTL might be sight
for integration of
perceptual stimuli
(Suzuki and Amaral, 1994)
Delayed Nonmatching-to-Sample
(DNMS) Task
(Mishkin, 1978)
Zola-Morgan et al., 1989
Perirhinal Lesions: No Perceptual
Deficits in Monkeys
• Tested for perceptual generalization (Hampton and
Murray, 2002)
–
Modified stimuli (rotated, enlarged, shrunken,
or masked)
–
Criticism for similarity to Shepard–Metzler
• DNMS task (Buffalo et al., 2000)
–
Two superimposed objects (high overlap)
–
Short delay (0.5s)
Monkey Perirhinal Lesions:
Evidence Against the PM Hypothesis
• Studies claiming MTL involvement in
perception have:
–
Confounded impairment in learning/memory
–
Required working memory in perception tasks
–
Extent of the lesion not identified
Monkey Perirhinal Lesions:
Evidence Against the PM Hypothesis
• Bilateral rhinal ablation
(Eacott et al., 1994)
– Reported perceptual
impairment in 0s delay
and simultaneous
matching conditions
– Large stimulus sets
– Averaged together
– Later reported that some
samples were left out
– When left out, no difference!
Buckely and Gaffan, 1998
Monkey Perirhinal Lesions:
Evidence Against the PM Hypothesis
• Concept of visual
discrimination learning
– Can you test perception in
animals without engaging
memory?
– Learning over multiple
trials
– Studies reported spared
‘elemental’ discriminations,
but impaired ‘object’
discrimination (Buckley and Gaffan,
1998; Bussey et al., 2002, 2003)
Buckely and Gaffan, 1998
Oddity Discrimination Task
• Developed in attempt to
tease out perception
from memory
– No difference in perirhinal
lesioned monkeys during
easy and moderate
discrimination (colours,
shapes)
– Problems during complex
object discrimination
– Perhaps implies
impairment in visual
associative learning to
associate multiple face
views as one (Messinger et al.,
2001; etc)
Buckley et al., 2001
Oddity Discrimination Task
• Find the scene outlier
– Only 10 scenes
– Could use long-term
memory to recall the
identities of each scene.
Buckley et al., 2001
Morphing Features
• Different stages of
morphing flowers
– Each one is morphed into
previous one (cumulative)
• “High feature overlap”
– High feature ambiguity must
be held in working memory
(Bussey, 2006)
• Learning over multiple
trials (Bussey et al., 2002)
– Must retain object/spatial
features in working memory
Buckley et al., 2001
Rat Perirhinal Lesions: Evidence
Against the PM Hypothesis
• Bilateral ablation (Bartko et al., 2007)
• Simultaneous oddity discrimination task
–
Impaired discrimination with high feature
ambiguity
–
PROBLEM: large objects used relative to rats
Summary Thus Far: MTLMS
• MTL is involved in only declarative memory
–
No perceptual/procedural deficits
• Studies that support PM hypothesis are
unconvincing
–
Do not adequately isolate perceptual demands
from declarative/relational learning or memory
• Results are inconsistent
Human MTL Lesions
• Major advantages of working with humans:
–
Verbal/written instructions
–
Probe to ensure instructions are followed
–
Follow-up of subject’s opinions
• However, many contradictory outcomes in
the literature exist
Human MTL Lesions: Evidence
in Favour of MTLMS Hypothesis
• Large bilateral MTL/hippocampal lesions (Stark
and Squire, 2000)
• Performed same oddity discrimination task
as Buckley et al., 2001
–
No perceptual impairment
–
Maybe prefrontal inputs associated with rules of
task?
Human MTL Lesions: Evidence
Against the PM Hypothesis
• Lee et al., 2005 found impaired
discrimination in complex face and scene
oddity tasks
–
Larger stimulus sets
–
Simultaneous presentation of target and test
item (faces/VR rooms)
–
Added trial-unique discrimination task
Reasons for Discrepancies
• Different testing procedures in different labs?
Controls performed equally as well in both
studies at all five difficulties and in all three tasks
Reproduced lack of perceptual impairment for
trial-unique discrimination(Squire, personal communication)
• Differences in extent/location of lesion?
Some subjects also had anterior temporal,
anterior insula, fusiform gyri lesions, and even
lateral TE damage
–
TE involved in high-order visual perception
Reasons for Discrepancies (cont)
• Differences in extent/location of lesion (cont)
–
–
–
Lesion loci were estimated by visual inspection
(4/5 rating scale) (Lee et al., 2005)
Single slice through each area (biased?)
Authors mention validation to volumetric analysis
(Galton et al., 2001), but provide no details of validation
• Squire’s group performed detailed volumetric
analysis throughout MTL and LTL
• Recently, MTL has been validated (Barense et al.,
2007), but LTL has not
Reasons for Discrepancies (cont)
• Lee et al. (2005) argue that MTL group
has minimal TE damage since they can
discriminate colours and moderately
complex objects
– TE active during high overlap, not colours
(Buckley et al, 1997)
– TE neurons respond
to faces (Alfred et al., 2005; etc)
– TE neurons may reflect
upstream input into
perirhinal cortex
TE vs Perirhinal Neurons
• TE neurons respond to brightness of cue (Liu
and Richmond, 2000)
• Perirhinal neurons respond to visual-reward
associative information of cue
- Trial schedule independent of cue
TE = perception
Perirhinal = link
between perceptual
information and
memory
Conclusions
• MTLMS hypothesis states MTL is involved in
declarative/relational learning and memory
with little or no contribution to perception
–
60 years old
• Animal models lack ability to differentiate
perception from memory (strategies)
• Human MTL lesions are inconsistent (extent
and location)
Future Directions
• Further pursue findings with rats (Bartko et al., 2007)
–
Define semantics
–
Tease out perceptual and working memory
differences (possible continuum)
–
May be due to axonal connections between MTL
and LTL
–
Add muscimol to perirhinal cortex and record
from TE (in monkeys)
• Look for compensatory activity in humans
–
fMRI or connectivity analysis (fcMRI, DTI, DSI,
Granger causality)
Thank you ;-)