Neural Basis of CognitionNeural Basis of Cognition

Lecture 5Learning and MemoryLearning and Memory

The Famous Patient, H.M.The Famous Patient, H.M.

• Severe epilepsy can be debilitating and even lead p p y gto death. In extreme cases, surgery is used to treat epilepsy

• In 1953 a patient called H M (to preserve• 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 amygdalaparahippocampal gyrus, and amygdala

– Damaged/Atrophied: the remainder of his hippocampus, entorhinal cortex, some of his anterolateral temporal cortexanterolateral temporal cortex

H.M.H.M.

• What happened?at appe ed?– 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 

h llthe operation, allowing extensive postoperative analysis.

– Today’s imaging techniques did not exist; the fact thatToday 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.H.M.

• What abilities have been destroyed?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 minutesminutes

– Learning of new information– He would misidentify current pictures of himselfHe would misidentify current pictures of himself as pictures of his father

– He had no idea of his fame

H.M.H.M.

• What abilities were not destroyed?What abilities were not destroyed?– Linguistic ability, recall of memories formed before the operation ability to reason ‐ almost allthe 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)g y ( )

H.M.H.M.

• The extensive study of H M taught us muchThe extensive study of H.M. taught us much about what we now know about learning and memory in humansmemory in humans.

• He passed away in 2008, still unaware of his famefame.

MemoryMemory

• What is memory?What is memory?– Memory is the storing of information related to day‐to‐day experiences for later retrievalday to day experiences for later retrieval.

• Are there different types of memory?Yes– Yes.

• Is memory stored in a single part of the brain?– No.

How can amnesia occur?How can amnesia occur?

• Damage to the medial temporal lobeDamage to the medial temporal lobe– Herpes simplex encephalitis, blockage of blood supply hypoxic ischemia trauma Alzheimer’ssupply, hypoxic ischemia, trauma, Alzheimer s disease

• Damage to the midline diencephalic regionDamage to the midline diencephalic region– Korsakoff’s diease (due to chronic alcohol abuse), blockage of blood supply, third ventricle tumorsblockage of blood supply, third ventricle tumors

Is amnesia always permanent?Is amnesia always permanent?

• NoNo.– Closed head injury (such as in a motorcycle accident) can cause amnesia that almostaccident) can cause amnesia that almost completely disappears

– Electroconvulsive therapy (memory recovers overElectroconvulsive therapy (memory recovers over weeks to months)

– Seizures can temporarily induce amnesia that p yheals completely.

Memory impairmentMemory 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 eventI l d h d i j t d i t d b k l th– 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’su t gto s

– Temporal gradient (Ribot’s Law): generally, more recent memories are more severely affected, e.g. identifying Ronal Reagan

– “Flat” Gradients have been observed

AmnesiaAmnesia

• Modality general, including in H.M.’s caseModality general, including in H.M.s case• Therefore, amnesia is a deficit in memory functions rather than perceptual, linguistic, orfunctions rather than perceptual, linguistic, or other cognitive processes

• Unilateral hippocampal damage CAN beUnilateral hippocampal damage CAN be modality‐specific– Left hemisphere damage can lead to selective p gimpairment for verbal material, right hemisphere damage for nonverbal material

Working MemoryWorking Memory

• Digit span task: repeating back, in order, aDigit span task: repeating back, in order, a string of digits– H.M.: Normal performance (7 +/‐ 2 digits)p ( / g )

• Extended digit span task: once a patient’s digit span is known, the same string is iteratively p , g ylengthened by one digit until a limit is reached– Normal performance: 20+ digits– H.M.’s performance: no longer than the digit span task

Retained abilitiesRetained abilities

• Skill learningSkill learning– H.M. did exhibit some forms of learning, though he was unaware of having done sohe was unaware of having done so

– Mirror tracing task: tracing the outline of a figure by looking at it in a mirrorby 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 abilitiesRetained abilities

• These are motor skills that are repeated overThese are motor skills that are repeated over and over; are amnesiacs learning the specific instance of those tasks (such as drawing ainstance of those tasks (such as drawing a particular figure) or the skill in general?

• Mirror reading task: mirror images of word• Mirror‐reading task: mirror images of word triplets shown

A i h th i t i thi– Amnesiacs show the same improvement in this task – even with new words – that non‐amnesiacs do even if the patients cannot recall practicingdo, even if the patients cannot recall practicing

Retained abilitiesRetained abilities

• Repetition priming: performance is enhancedRepetition priming: performance is enhanced as a result of previous exposure to an item– Gollin incomplete pictures task: patients are– Gollin incomplete pictures task: patients are shown very degraded and incomplete line drawings of objects and are asked to name themg j

• The procedure is repeated with increasingly incomplete drawings

• Amnesiacs showed improvement on this task

Retained abilitiesRetained abilities

• Word‐stem completion taskWord stem completion task– Patient is given a list of words to studyAfter a delay memory is tested in two ways using– 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 listPatient 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 levelsp

Memory loss patternsMemory loss patterns

• Explicit memory:Explicit memory:– Conscious recollection of some prior event

• Implicit memory:• Implicit memory:– Subconscious recollection of information about some prior eventp

– 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 monitoringEye movement monitoring• Amnesiac is shown an image with three points of interest– Eye movements indicate he looks at each of the three points of interestp

• 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 now‐– There are about as many eye movements to the now‐absent 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 interestp

• This is a demonstration of implicit versus explicit memory impairment due to hippocampal damage

Neuroimaging evidenceNeuroimaging evidence

• PET and fMRI provide converging evidencePET and fMRI provide converging evidence that the hippocampal system is associated with relational memorywith relational memory

• Higher activation when given a task that requires memory of relations among itemsrequires memory of relations among items

The role of the hippocampal areaThe role of the hippocampal area

• After damage to the hippocampal areaAfter damage to the hippocampal area, amnesia can develop

• Therefore the hippocampal area is vital for• Therefore, the hippocampal area is vital for the formation of new memoryAf d i l f d i• 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?Where is memory stored?

• Imaging studies and cell recording studies show g g gthat declarative memory is distributed by modality, in the regions which initially process sensory inputsensory input– Visual information is stored in the visual system, auditory information is stored in the auditory system, and so onand so on

• Similar studies show that procedural memory is stored in the parts of the brain involved in pcarrying out the related action– For example, motor skills are learned and “stored” in the motor cortexthe motor cortex

Integration of memory systemsIntegration of memory systems

• UnclearUnclear.

The memory systemThe memory system

• Encoding:Encoding:– Memories must be created and stored

• Consolidation• Consolidation:– Memories may be “strengthened”

• Retrieval:– Memories must be retrieved for later use

HippocampusHippocampus

• Encoding:cod g:– Activation during encoding of faces, words, scenes, objects; degree of activity is proportional to degree of 

i timemorization– fMRI studies show that the amount of activity at the time an item is first seen and encoded predicts how pwell that item is remembered later on

– Subsequent memory effect: subsequently b d it i t d ith tremembered items are associated with greater 

activation at encoding time than items not subsequently remembered

HippocampusHippocampus

• Consolidation:Consolidation:– Unclear mechanismTheory: reactivation of already stored memories– Theory: reactivation of already stored memories during the time after learning plays a crucial role in consolidationin consolidation

– There is some evidence tying such reactivation to activity in the hippocampus during sleep y pp p g psubsequent to a learning event

HippocampusHippocampus

• Retrieval:Retrieval:– Hippocampal system activation occurs during retrieval of memoryretrieval of memory

– The purpose of this activation has not been determineddetermined

Next LectureNext Lecture

• Other areas involved in encodingOther areas involved in encoding, consolidation, retrieval

• Mechanism of the forming of memories• Mechanism of the forming of memories (learning)C i l d h i l d li f• Computational and theoretical modeling of learning