Download Anterograde amnesia

Chapter 14
Relational Learning and Amnesia
Human Anterograde Amnesia
• Anterograde amnesia - difficulty in learning new information, due to
head injury or certain degenerative brain diseases; pure form is rare
• Retrograde amnesia – inability to remember events that occurred
prior to brain damage
• Korsakoff’s syndrome – permanent anterograde amnesia caused by
brain damage resulting from chronic alcoholism or malnutrition (due
to thiamine deficiency); also have confabulations (reporting of
memories that did not occur, without the intention to deceive)
• Anterograde amnesia can be caused by damage to temporal lobes
– e.g. patient H.M. – bilateral removal of medial temporal lobe to alleviate
epilepsy; resulted in severe anterograde amnesia
Human Anterograde Amnesia
•
Basic description
–
Results from study with H.M.
1.
2.
3.
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These results are too simple; anterograde amnesia is actually much
more complex
Learning consists of at least 2 stages:
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•
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The hippocampus is not the location of long-term memory (LTM); nor is it
necessary for the retrieval of LTM
The hippocampus is not the location for short-term memory (STM)
The hippocampus is involved in converting STM into LTM
STM – immediate memory for events, which may or may not be
consolidated into LTM; can only hold a limited amount of info
LTM – relatively stable memory of events that occurred in the more distant
past, as opposed to STM; no limit on amount of info
Consolidation – the process by which STM are converted into LTM
Simple model of memory process
• Sensory info enters STM
• Rehearsal keeps that info in STM
• Eventually, info will move into LTM via consolidation
Human Anterograde Amnesia
• Spared learning abilities
– Still capable of:
• Perceptual learning
– e.g. recognize broken drawings; also faces and
melodies
• Stimulus-response learning
– Can acquire a classical conditioned eyeblink
response
• Motor learning
– Mirror drawing task – subjects required to trace
the outline of a figure while looking at the figure
in a mirror
Human Anterograde Amnesia
• Declarative and nondeclarative memories
– Although patients can learn other tasks, they cannot recall ever learning
them
– Learning and memory involve different processes
– 2 major categories of memories
• Declarative memories – memory that can be verbally expressed, such as
memory for events, facts, or specific stimuli; this is impaired with
anterograde amnesia
• Nondeclarative memories – memory whose formation does not depend on
the hippocampal formation; a collective term for perceptual, stimulusresponse, and motor memory; not affected by anterograde amnesia; these
control behavior; cannot always be described in words
Human Anterograde Amnesia
• Failure of relational learning
– Verbal learning is disrupted in anterograde amnesia
• e.g. H.M. did not learn any new words after his surgery (biodegradable =
“two grades”)
– Episodic memories – most complex form of declarative memory;
memory of a collection of perceptions of events organized in time and
identified by a particular context
• e.g. explain what you did this morning after waking up
– The hippocampal formation enables us to learn the relationship b/t the
stimuli that were present at the time of an event (i.e. context) and then
events themselves
Human Anterograde Amnesia
• Anatomy of anterograde amnesia
– Damage to the hippocampus or to regions that supply its inputs and
receive its outputs causes anterograde amnesia
– The most important input to the hippocampal formation is the entorhinal
cortex, which receives inputs from the limbic cortex either directly or via
the perirhinal cortex or the parahippocampal cortex
– How does the hippocampus form new declarative memories?
• Hippocampus receives info about what is going on from sensory and motor
assc. cortex and from some subcortical regions
• It processes this info and then modifies the memories being consolidated by
efferent connections back to these regions
• Experiences that lead to declarative memories activate the hippocampal
formation
– Patient R.B., suffered brain damage that lead to anterograde amnesia;
after autopsy, found that field CA1 of the hippocampal formation was
completely destroyed
Limbic cortex
Human Anterograde Amnesia
• Anatomy of anterograde amnesia
– Damage to other subcortical regions that connect with the hippocampus
can cause memory impairments
• Limbic cortex of the medial temporal lobe
– Semantic memories – a memory of facts and general info; different from episodic
memory
– Destruction of hippocampus alone disrupts episodic memory only; must have
damage to limbic cortex of medial temporal lobe to also impair semantic memory
(and thus all declarative memory)
• Fornix and mammillary bodies
– Patients with Korsakoff’s syndrome suffer degeneration of the mammillary bodies
– Most of the efferent axons of the fornix terminate in the mammillary bodies
– Damage to any part of the neural circuit that includes the hippocampus, fornix,
mammillary bodies and anterior thalamus cause memory impairments
Human Anterograde Amnesia
• Role of the medial temporal lobe in spatial memory
– Individuals with anterograde amnesia are unable to consolidate info
about the location of rooms, corridors, buildings, roads, and other
important items in their env’t
– Bilateral medial temporal lobe lesions produce the most profound
impairment on spatial memory, but enough damage to only the R
hemisphere is sufficient
– R hippocampal formation is activated when a person is remembering or
performing a navigational task
– Damage to this area also impairs ability to learn spatial arrangement of
objects
Human Anterograde Amnesia
• Role of the medial temporal lobe in memory retrieval
– The hippocampal formation and its related structures also play a role in
memory retrieval
– Anterograde amnesia is usually accompanied by retrograde amnesia;
brain damage can either cause loss of memories or loss of access to
memories
– However, if damage is only limited to field CA1, patients do not show
additional retrograde amnesia
– Semantic dementia – loss of semantic memories caused by progressive
degeneration of the neocortex of the lateral temporal lobes
• Impairment for meaning of words, and functions of common objects
Human Anterograde Amnesia
• Confabulation
– May be a result of disruption of the normal functions of the prefrontal
cortex
– Frontal lobes may be involved in distinguishing b/t real and imaginary
memories; may do this by helping us to distinguish items with general
familiarity from specific items we have encountered before
Relational learning in lab animals
• Lab animals with hippocampal
formation lesions do not sow
impairment in stimulus-response
learning, but with relational
learning tasks
• Remembering places visited
– Radial maze task – food placed
at end of each arm, rats did not
go down arm that they had
already collected food from;
lesions to hippocampus, fornix, or
entorhinal cortex impaired this
task; animals must remember
which arm they have collected
from that exact day (as opposed
to another testing day)
Relational learning in lab animals
• Spatial perception and learning
– Lab animals with hippocampal
lesions show problems with
navigational tasks just as humans
do
– Morris water maze task – requires
rat to find a particular location in the
water drum, by means of visual cues
external to the apparatus; if rats wit
hippocampal lesions are released
from same position every testing
time, they perform fine (e.g. S-R
learning), but if they are started from
a different place, they cannot
complete the task correctly (e.g.
relational learning)
Relational learning in lab animals
• Spatial perception and learning
– Hippocampal lesions disrupt performance of homing pigeons
– Hippocampal formation of animals that normally store seeds or food in
hidden caches and later retrieve them is larger than that in animals
without this ability
• Role of hippocampal formation in memory consolidation
– Brain activity in the hippocampus is increased in mice learning a spatial
task; however, after 25 days of testing, the activity there decreases,
suggesting that the hippocampus is involved in consolidating spatial
memories for only a limited time
Relational learning in lab animals
• Place cells in the hippocampal formation
– When recording the activity of individual neurons in the hippocampus of
an animals moving around its env’t, some neurons fired at a high rate
only when the rat was in a particular location
– The suggests evidence that different neurons have different spatial
receptive fields (i.e. they responded when the animals were in different
locations) – these neurons were named place cells
– When placed on a circular platform that is rotated slowly within a larger
chamber, rats will ignore local cues and orient themselves to face a cue
card; the place cells however, oriented themselves to the local cues
– When animals encounter new env’ts, they learn the layout and “maps”
become established in their hippocampus; an animal’s location within
each env’t is encoded by the pattern of firing of these neurons
– Place cells are guided by both visual stimuli and internal stimuli (e.g.
proprioceptive feedback)
– Hippocampus receives spatial info via the entorhinal cortex
Relational learning in lab animals
• Role of LTP in relational learning
– When place cells become active when an animal is present in a
particular location, this causes changes in the excitability of neurons in
the hippocampal formation
– Knockout mice for NMDA receptors specific for the field CA1: no
establishment of LTP in field CA1, smaller and less focused spatial
receptive fields, and learn Morris water maze task much slower
– NMDA mediated LTP appears to be required for the consolidation of
spatial receptive fields in field CA1 pyramidal cells but not their shortterm establishment
• Modulation of hippocampal functions
– Hippocampal formation receives input from ACh, NE, DA, and 5-HT
neurons
– They appear to control the information-processing functions of the
hippocampal formation
– 5-HT has suppressive effect on establishment of LTP in hipp. form.
Relational learning in lab animals
• Modulation of hippocampal functions (con’t)
– NE has a facilitator effect, particularly on synapses of terminals of
entorhinal neurons of the dentate gyrus
– DA had excitatory effects on LTP and memory-related functions of the
hippocampal formation
• Synaptic plasticity is induced by simultaneous depolarization of hippocampal
neurons and activation of DA receptors on these neurons
– ACh neurons from medial septum project to hippocampus via fornix;
activity of these neurons is responsible for hippocampal theta rhythms
(medium amplitude, medium frequency waves) that influence the
establishment of LTP in the hippocampus
• If theta activity is disrupted, animals show deficits in learning tasks that are
affected by hippocampal lesions
• Theta behaviors – exploration or investigation
• Nontheta behaviors – alert immobility, drinking, self-directed behaviors