Serial model. Amnesia. Amnesia. Neurobiology of Learning and Memory. Prof. Stephan Anagnostaras. Lecture 3: HM, the medial temporal lobe, and amnesia

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1 Neurobiology of Learning and Memory Serial model Memory terminology based on information processing models e.g., Serial Model Prof. Stephan Anagnostaras Lecture 3: HM, the medial temporal lobe, and amnesia Can test these models in brain damaged subjects Amnesia Amnesia Amnesia Partial or total loss of memory, usually resulting from shock, psychological disturbance, brain injury, or illness. Organic caused by shock, brain injury, illness hypoxic episode, herpes encephalitis epilepsy, brain injury, Alzheimer s disease Amnesia can be global or material-specific Global any kind of information is affected Material-specific certain kinds of material (e.g., faces) Amnesia can be anterograde or retrograde Psychogenic caused by psychological trauma dissociative disorders psychogenic fugue multiple personality disorder Anterograde amnesia inability to learn anything new since the time of the trauma (usually organic) Retrograde amnesia loss of memory for events prior to the time of the trauma (psychogenic or organic) HM HM s lesion: bilateral medial temporal lobe removal Most famous case reported by Scoville & Milner (1957) Scoville did the surgeries for psychosis but didn t work, so tried it for epilepsy on about 30 patients. Patients studied by Brenda Milner HM: bilateral medial temporal lobe lesion for status epilepticus in

2 HM = no hippocampus, amygdala, overlying (rhinal) cortex HM = no hippocampus, amygdala, overlying (rhinal) cortex normal hpc HM = no hpc, no rhinal ctx HM s amnesic syndrome Retrograde vs. anterograde amnesia normal memory for remote events (childhood, etc) Severe deficit (global anterograde amnesia) show word or face, ask later, doesn t know reads newspapers repeatedly doesn t remember own physician see on formal tests or everyday life word lists faces and objects recall or recognition for HM, retrograde amnesia is approx. 2 yrs Retrograde and anterograde amnesia can occur together or separately (HM has both) HM also has this Only mild retrograde amnesia loss of memories that are a up to 2-3 years old at the time of the lesion, but childhood memories in tact known as a time-limited or temporally-graded retrograde amnesia Medial temporal lobe amnesia: what s special? Remote versus Recent Memory: HM, Loss of Recent memory Deficit very specific for Long-Term Memory (LTM) not dementia IQ normal and unchanged perceptual skills excellent social skills and personality intact Short-Term Memory (STM = 3 min, 7±2 items) good (e.g., digit span) forgetting curve for STM normal Memory scale more than 3 std dev from controls! 2

3 Rey-Osterrieth Figure Rey-Osterrieth Figure Famous Faces test of explicit memory and retrograde amnesia NF = non-famous (control) Retrograde amnesia often shows a gradient: memory for older events (1950 s) is better than memory for newer events (1980 s) Amnesics worse than controls Damage to hpc = Memory that was still in hpc buffer got lost before it could be consolidated into permanent memory elsewhere in the brain Spared learning HM could improve on task but didn t recognize task each day Learns some things normally: visual motor pursuit priming mirror drawing task normal eyeblink classical conditioning (e.g., puff of air/tone on eye but not fear) but doesn t ever remember doing task before (source amnesia) These tasks do not necessarily share anything in common. Fig

4 HM improved in performance despite not remembering the test Fig Repetition Priming: Testing Implicit Memory (Graf et al., 1984) First the list: ABSENT INCOME FILLY DISCUSS CHEESE ELEMENT Then complete the word: ABS INC FIL DIS CHE ELE Amnesics don t remember word list well But they still can complete the fragment with the previously seen word free recall cued recall: complete word stem with specific word from study list abs?? word stem completion: complete word stem with first word that comes to mind dis?? same cue in cued recall & word-stem completion but only cued recall requires conscious access to past Mirror Reading Some spatial memory Explicit versus Implicit Memory Memory impacted by the lesion termed explicit (or declarative) memory - must be stated verbally and requires conscious recollection (note: doesn t work for animals) -includes semantic (facts, knowledge) and episodic (events, memory) memory Not disrupted: implicit memory (procedural or nondeclarative) - learning is demonstrated through performance and may not be available to verbal recollection (e.g., tying your shoelaces) Note that implicit memory is a junk term that includes several different forms of memory, including most forms of classical conditioning Neuroanatomy The hippocampus is the critical structure for explicit memory Patient RB: damage only to CA1 Disruption of hippocampal-circuitry can give a similar deficit (dorsomedial thamalus) The greater the disruption to surrounding cortex the more severe the amnesia Anterograde and retrograde amnesia usually correlated (HM is an exception) 4

5 More selective brain damage can produce explicit memory problems (amnesia), also RB s brain Korsakoff s amnesia: damage to MD thalamus (diencephalon area of brain) Pt R.B.: damage to CA1 area of hpc (very selective) Zola-Morgan, Squire, & Amaral, 1986 medial diencephalic amnesia (Korsakoff s and Pt N.A.) Normal Herpes encephalitis Alzheimer s disease: plaques & tangles in memory areas Herpes Simplex Encephalitis Reed & Squire (1998) severe and more general memory loss (explicit + verbal implicit, e.g., priming) affects entorhinal ctx (1), then hpc (2), frontal (3), parietal (3) lobes Other forms of amnesia Multiple memory systems in the brain Unilateral hippocampal damage results in material-specific deficits left = words, names, etc. right = faces, objects, etc. Explicit memory Medial temporal lobe; diencephalon Implicit memory Classical conditioning Priming (neocortex) Korsakoff s psychosis results in similar amnesia plus confabulation Facts (semantic) Events (episodic) Procedural memory: skills & habits (basal ganglia) Skeletal musculature (cerebellum) Emotional Responses (amygdala) Frontal lobes STM, working memory, temporal order, confabulation Eyeblink conditioning in rabbit Electroconvulsive Therapy (ECT,ECS) 5

6 HM normal on this? Explicit or Implicit learning? Classical (Pavlovian) conditioning and memory There are many different forms of classical conditioning and the responsible brain structure depends on the form Examples: a) Pavlovian fear conditioning: Tone --> Shock Then: Tone --> freeze (CS) (US) (CS) (CR) Depends on the amygdala + the hippocampus with trace procedure + the hippocampus if the CS is a context b) Eyeblink conditioning Tone --> puff of air to eye Then: Tone --> eyeblink (CS) (US) (CS) (CR) Depends on cerebellum + hippocampus with trace procedure Declarative knowledge of task always depends on hippocampus 6