Learning, memory & amnesiaLearning, memory & amnesia

Chapter 11Chapter 11

The case of H.M.The case of H.M. Intractable epilepsyIntractable epilepsy

one generalized convulsion each weekone generalized convulsion each weekSeveral partial convulsions each daySeveral partial convulsions each day

1953 surgery: Bilateral medial temporal 1953 surgery: Bilateral medial temporal lobectomylobectomy temporal poletemporal poleamygdalaamygdalaentorhinal cortexentorhinal cortexhippocampushippocampus

Corkin et al. (1997)Corkin et al. (1997)

Corkin et al. (1997)Corkin et al. (1997)

Effects of Bilateral Medial Temporal Effects of Bilateral Medial Temporal LobectomyLobectomy

Convulsions were dramatically reducedConvulsions were dramatically reduced IQ increased from 104 to 118IQ increased from 104 to 118Short-term memory (STM) intactShort-term memory (STM) intactTemporally-graded retrograde amnesiaTemporally-graded retrograde amnesiaSevere anterograde amnesiaSevere anterograde amnesia

AmnesiaAmnesiaRetrograde Retrograde (backward-acting) – unable to (backward-acting) – unable to

remember the pastremember the pastAnterograde Anterograde (forward-acting) – unable to (forward-acting) – unable to

form new memoriesform new memoriesWhile H.M. was unable to form most types While H.M. was unable to form most types

of new long-term memories, his STM was of new long-term memories, his STM was intact intact

Mirror-drawing taskMirror-drawing taskH.M.’s performance H.M.’s performance

improved over 3 improved over 3 days (10 trials/day) days (10 trials/day) despite the fact despite the fact that he could not that he could not consciously consciously remember the task remember the task on days 2 and 3.on days 2 and 3.

Rotary-Pursuit TestRotary-Pursuit TestH.M.’s performance H.M.’s performance

improved over 9 improved over 9 daily practice daily practice sessions; again, sessions; again, with no recognition with no recognition of the experienceof the experience

Explicit vs Implicit MemoriesExplicit vs Implicit Memories Explicit memoriesExplicit memories – conscious memories – conscious memories Implicit memoriesImplicit memories – unconscious memories – unconscious memories

Repetition priming tests were developed to assess Repetition priming tests were developed to assess implicit memory performance; implicit memory performance;

Incomplete pictures testIncomplete pictures test

Implications of H.M.’s amnesiaImplications of H.M.’s amnesiaMedial temporal lobes are involved in Medial temporal lobes are involved in

memory formation.memory formation.STM and LTM are dissociable – H.M. is STM and LTM are dissociable – H.M. is

unable to consolidate certain kinds of unable to consolidate certain kinds of explicit memory.explicit memory.

the fact that he could form some memories the fact that he could form some memories suggests that there are multiple memory suggests that there are multiple memory systems in the brain.systems in the brain.

Medial Temporal Lobe AmnesiaMedial Temporal Lobe Amnesia Not all patients with this form of amnesia are Not all patients with this form of amnesia are

unable form new explicit long-term memories, as unable form new explicit long-term memories, as was the case with H.M.was the case with H.M.

Two kinds of explicit memory:Two kinds of explicit memory:Semantic memorySemantic memory (general information) may (general information) may

function normally while function normally while episodic memoryepisodic memory (events (events that one has experienced) does not – they are that one has experienced) does not – they are able to learn facts, but do not remember doing able to learn facts, but do not remember doing so (the episode when it occurred)so (the episode when it occurred)

Vargha-Khadem et al., (1997)Vargha-Khadem et al., (1997)Studied three children that had bilateral Studied three children that had bilateral

temporal lobe damage early in life.temporal lobe damage early in life.Like H.M., the children could not form Like H.M., the children could not form

episodic memory, however they did episodic memory, however they did acquire reasonable levels of factual acquire reasonable levels of factual knowledge and language ability in knowledge and language ability in mainstream school.mainstream school.

Effects of Cerebral Ischemia on the Effects of Cerebral Ischemia on the Hippocampus and MemoryHippocampus and Memory

R.B. suffered damage to just one part of R.B. suffered damage to just one part of the hippocampus (CA1 pyramidal cell the hippocampus (CA1 pyramidal cell layer) and developed amnesialayer) and developed amnesia

R.B.’s case suggests that hippocampal R.B.’s case suggests that hippocampal damage alone can produce amnesiadamage alone can produce amnesia

H.M.’s damage and amnesia was more H.M.’s damage and amnesia was more severe than R.B.’ssevere than R.B.’s

Object-Recognition MemoryObject-Recognition Memory Early animal models of amnesia involved implicit Early animal models of amnesia involved implicit

memory and assumed the hippocampus was memory and assumed the hippocampus was keykey

1970’s – monkeys with bilateral medial temporal 1970’s – monkeys with bilateral medial temporal lobectomies showed LTM deficits in the delayed lobectomies showed LTM deficits in the delayed nonmatching-to-sample testnonmatching-to-sample test

Like H.M., performance was normal when Like H.M., performance was normal when memory needed to be held for only a few memory needed to be held for only a few seconds (within the duration of STM)seconds (within the duration of STM)

Delayed nonmatching-to-sample taskpretend you’re the monkey

Sample stimulustouch it and get a yummy treat

10 min delay during which other sample stimuli are presented

Choice phase: pick the image that is new

Another yummy treat

Darn, no food

Testing object-recognition memoryTesting object-recognition memory

Medial temporal lobe (MTL)Medial temporal lobe (MTL)

Delayed non-match to sample resultsDelayed non-match to sample results

The Mumby BoxThe Mumby Box

Object recognition in ratsObject recognition in rats

Comparison Comparison of lesions in of lesions in

monkeys monkeys and ratsand rats

Neuroanatomy of object recognitionNeuroanatomy of object recognitionBilateral removal of the rhinal cortex Bilateral removal of the rhinal cortex

consistently results in object-recognition consistently results in object-recognition deficits.deficits.

Bilateral removal of the hippocampus Bilateral removal of the hippocampus produces moderate deficits or none at all.produces moderate deficits or none at all.

Bilateral removal of the amygdala has no Bilateral removal of the amygdala has no effect on object-recognition.effect on object-recognition.

Is the hippocampus involved in Is the hippocampus involved in object recognition memory?object recognition memory?

The Case of R.B. suggests that the lesions The Case of R.B. suggests that the lesions of the CA1 region of the hippocampus of the CA1 region of the hippocampus (due to ischemia) can produce severe (due to ischemia) can produce severe memory deficitsmemory deficits

Ischemia in animal models also produces Ischemia in animal models also produces deficits in object recognitiondeficits in object recognition

Yet deficits in object recognition are only Yet deficits in object recognition are only moderate to non-existent in other animal moderate to non-existent in other animal lesion modelslesion models

Why?Why?

Mumby et al. (1996)Mumby et al. (1996)Bilateral hippocampectomy actually blocks Bilateral hippocampectomy actually blocks

the damage produced by ischemia!the damage produced by ischemia!Explanation:Explanation: Ischemia causes hippocampal neurons to Ischemia causes hippocampal neurons to

release glutamate, which produces release glutamate, which produces damage outside of the hippocampus damage outside of the hippocampus (particularly in rhinal cortex), although (particularly in rhinal cortex), although standard histological techniques do not standard histological techniques do not show the damage follow-up functional show the damage follow-up functional imaging studies have confirmed the imaging studies have confirmed the dysfunction.dysfunction.

The HippocampusThe HippocampusRhinal cortex plays an important role in Rhinal cortex plays an important role in

object recognition.object recognition.Hippocampus plays a key role in memory Hippocampus plays a key role in memory

for spatial location.for spatial location.Hippocampectomy produces deficits on Hippocampectomy produces deficits on

Morris maze and radial arm maze Morris maze and radial arm maze (Chapter 5)(Chapter 5)

Many hippocampal cells are place cells – Many hippocampal cells are place cells – responding when a subject is in a responding when a subject is in a particular placeparticular place

Theories of Hippocampal FunctionTheories of Hippocampal Function

O’Keefe & Nadel (1978) Cognitive map theory – O’Keefe & Nadel (1978) Cognitive map theory – constructs and stores allocentric maps of the constructs and stores allocentric maps of the worldworld

Rudy & Sutherland (1992) Configural Rudy & Sutherland (1992) Configural association theory – involved in retaining the association theory – involved in retaining the behavioral significance of combinations of behavioral significance of combinations of stimulistimuli

Brown & Aggleton (1999) is involved in Brown & Aggleton (1999) is involved in recognizing the spatial arrangements of objectsrecognizing the spatial arrangements of objects

Synaptic Mechanisms of Learning Synaptic Mechanisms of Learning and Memoryand Memory

What is happening within the brain What is happening within the brain structures involved in memory?structures involved in memory?

Hebb – changes in synaptic efficiency are Hebb – changes in synaptic efficiency are the basis of LTMthe basis of LTM

Long-term potentiation (LTP) – synapses Long-term potentiation (LTP) – synapses are effectively made stronger by repeated are effectively made stronger by repeated stimulationstimulation

Long Term Potentiation (LTP)

C a 2+

N a A P -5

H A -966

M K -801M g 2+

+

K+

M g 2+

G lu tam ate

Zn 2+

G lyc ine

P o lyam ine

P C P

N M D A

D -C yclose rine

Cross-section of the NMDA receptor complex