Neural Basis of Cognition

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, parahippocampalgyrus, 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’sdiease (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 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 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

Neural Basis of Cognition