Neural Basis of Cognition
Lecture 5
Learning and Memory
The Famous Patient, H.M.
• Severe epilepsy can be debilitating and even lead
to death. In extreme cases, surgery is used to
treat epilepsy
• In 1953, a patient called H.M. (to preserve
anonymity) with severe epilepsy was treated
surgically via removal of portions of his left and
right medial temporal lobes
– Removed: two thirds of his hippocampus,
parahippocampal gyrus, and amygdala
– Damaged/Atrophied: the remainder of his
hippocampus, entorhinal cortex, some of his
anterolateral temporal cortex
H.M.
• What happened?
– His epilepsy was successful brought under control.
– He developed severe memory deficits - amnesia.
• Why is his case so famous?
– His memory abilities were extensively studied prior to
the operation, allowing extensive postoperative
analysis.
– Today’s imaging techniques did not exist; the fact that
damage was done during surgery meant that it was
known exactly what parts of his brain were damaged.
H.M.
• What abilities have been destroyed?
– Creation of new short term memories – he cannot
recall recent weather, the current date, where he
currently lives, or even a conversation with
someone if there is an interruption that lasts a few
minutes
– Learning of new information
– He would misidentify current pictures of himself
as pictures of his father
– He had no idea of his fame
H.M.
• What abilities were not destroyed?
– Linguistic ability, recall of memories formed before
the operation, ability to reason - almost all
abilities he had before the operation aside from
those listed on the previous slide
– Learning of new skills
– Working memory (until distracted)
H.M.
• The extensive study of H.M. taught us much
about what we now know about learning and
memory in humans.
• He passed away in 2008, still unaware of his
fame.
Memory
• What is memory?
– Memory is the storing of information related to
day-to-day experiences for later retrieval.
• Are there different types of memory?
– Yes.
• Is memory stored in a single part of the brain?
– No.
How can amnesia occur?
• Damage to the medial temporal lobe
– Herpes simplex encephalitis, blockage of blood
supply, hypoxic ischemia, trauma, Alzheimer’s
disease
• Damage to the midline diencephalic region
– Korsakoff’s diease (due to chronic alcohol abuse),
blockage of blood supply, third ventricle tumors
Is amnesia always permanent?
• No.
– Closed head injury (such as in a motorcycle
accident) can cause amnesia that almost
completely disappears
– Electroconvulsive therapy (memory recovers over
weeks to months)
– Seizures can temporarily induce amnesia that
heals completely.
Memory impairment
• Anterograde amnesia: Impairment in forming new memories.
– Almost always associated with some retrograde amnesia.
• Retrograde amnesia: Impairment in memory for information
acquired prior to amnesia-inducing event
– In closed head injury, retrograde amnesia extends back less than a
week before the injury in 80% of patients, but can extend to years.
– H.M.’s retrograde amnesia extended 11 years; unclear how much of
this was due to the seizure disorder, which began 11 years before
surgery, and how much was due to the surgery
– Retrograde amnesia that extends back decades is often seen in
progressive disorders such as Korsakoff’s, Alzheimer’s, Parkinson’s, or
Huntington’s
– Temporal gradient (Ribot’s Law): generally, more recent memories are
more severely affected, e.g. identifying Ronal Reagan
– “Flat” Gradients have been observed
Amnesia
• Modality general, including in H.M.’s case
• Therefore, amnesia is a deficit in memory
functions rather than perceptual, linguistic, or
other cognitive processes
• Unilateral hippocampal damage CAN be
modality-specific
– Left hemisphere damage can lead to selective
impairment for verbal material, right hemisphere
damage for nonverbal material
Working Memory
• Digit span task: repeating back, in order, a
string of digits
– H.M.: Normal performance (7 +/- 2 digits)
• Extended digit span task: once a patient’s digit
span is known, the same string is iteratively
lengthened by one digit until a limit is reached
– Normal performance: 20+ digits
– H.M.’s performance: no longer than the digit span
task
Retained abilities
• Skill learning
– H.M. did exhibit some forms of learning, though
he was unaware of having done so
– Mirror tracing task: tracing the outline of a figure
by looking at it in a mirror
• Across sessions, H.M. began to perform this task more
accurately and more quickly
– Rotary pursuit: tracking a circularly moving target
• With practice, amnesiacs become more adept
Retained abilities
• These are motor skills that are repeated over
and over; are amnesiacs learning the specific
instance of those tasks (such as drawing a
particular figure) or the skill in general?
• Mirror-reading task: mirror images of word
triplets shown
– Amnesiacs show the same improvement in this
task – even with new words – that non-amnesiacs
do, even if the patients cannot recall practicing
Retained abilities
• Repetition priming: performance is enhanced
as a result of previous exposure to an item
– Gollin incomplete pictures task: patients are
shown very degraded and incomplete line
drawings of objects and are asked to name them
• The procedure is repeated with increasingly incomplete
drawings
• Amnesiacs showed improvement on this task
Retained abilities
• Word-stem completion task
– Patient is given a list of words to study
– After a delay, memory is tested in two ways using
three-word stems of these words:
• Patient is asked to recall the word from the study list
that began with the given three-letter stem
– Amnesiacs perform poorly
• Patient is asked to give “the first word that comes to
mind” when given a three-letter stem
– Amnesiacs performed at normal levels
Memory loss patterns
• Explicit memory:
– Conscious recollection of some prior event
• Implicit memory:
– Subconscious recollection of information about some
prior event
– Does not depend on consciously remembering that
event – “memory without awareness”
• Explicit but not implicit memory can be impaired
or destroyed due to hippocampal damage
Eye-movement monitoring
• Amnesiac is shown an image with three points of
interest
– Eye movements indicate he looks at each of the three
points of interest
• After a delay, the amnesiac is shown the same image
with one point of interest removed
– There are about as many eye movements to the nowabsent third point of interest as there are to the other two
points of interest, but if the patient is asked, he will not
remember that there was a third point of interest
• This is a demonstration of implicit versus explicit
memory impairment due to hippocampal damage
Neuroimaging evidence
• PET and fMRI provide converging evidence
that the hippocampal system is associated
with relational memory
• Higher activation when given a task that
requires memory of relations among items
The role of the hippocampal area
• After damage to the hippocampal area,
amnesia can develop
• Therefore, the hippocampal area is vital for
the formation of new memory
• After damage, previously formed memories
can still be recalled
• Therefore, the hippocampus neither stores
memories nor is mandatory for memory recall
Where is memory stored?
• Imaging studies and cell recording studies show
that declarative memory is distributed by
modality, in the regions which initially process
sensory input
– Visual information is stored in the visual system,
auditory information is stored in the auditory system,
and so on
• Similar studies show that procedural memory is
stored in the parts of the brain involved in
carrying out the related action
– For example, motor skills are learned and “stored” in
the motor cortex
Integration of memory systems
• Unclear.
The memory system
• Encoding:
– Memories must be created and stored
• Consolidation:
– Memories may be “strengthened”
• Retrieval:
– Memories must be retrieved for later use
Hippocampus
• Encoding:
– Activation during encoding of faces, words, scenes,
objects; degree of activity is proportional to degree of
memorization
– fMRI studies show that the amount of activity at the
time an item is first seen and encoded predicts how
well that item is remembered later on
– Subsequent memory effect: subsequently
remembered items are associated with greater
activation at encoding time than items not
subsequently remembered
Hippocampus
• Consolidation:
– Unclear mechanism
– Theory: reactivation of already stored memories
during the time after learning plays a crucial role
in consolidation
– There is some evidence tying such reactivation to
activity in the hippocampus during sleep
subsequent to a learning event
Hippocampus
• Retrieval:
– Hippocampal system activation occurs during
retrieval of memory
– The purpose of this activation has not been
determined
Next Lecture
• Other areas involved in encoding,
consolidation, retrieval
• Mechanism of the forming of memories
(learning)
• Computational and theoretical modeling of
learning