1. Memory • Chris Rorden • Anterograde Amnesia • Short vs Long Term Memory • Episodic vs Procedural Memory • Confabulation • www.mricro.com

2. HM • Severe epilepsy, treated with surgery to bilaterally remove medial temporal lobes. • Operation 9/1953, 27 years old • Tested 4/1955, age 29 • Reported date as 3/1953, age of 27 • No memories since operation • IQ better than pre-op (112) • Fewer seizures • Profound failure to create new memories • Can’t find new home (after 10 mos.) • Can’t remember new people, names, tasks

3. HM • Deficits • Complete loss of episodic memory • Events/People since operation • Location of new home • Rey figure: copy but not recalled • Semantic memory • Language essentially frozen in 50’s (Gabrieli et al. 1988) • Exceptions: ayatollah, rock ‘n roll

4. HM – severe anterograde amnesia • Anterograde amnesia – since lesion • Suggests encoding deficit • Retrograde amnesia – prior to lesion retrograde anterograde Memory 1/9/1953 1945 1950 1955

5. HM working memory • Intact working memory • Normal digit span (remembering numbers) • Wickelgren (1968) showed rate of forgetting within normal range • Unless interrupted (constant rehearsal)

6. HM procedural memory • Intact procedural memory • Can learn new motor tasks • Mirror tracing task (Milner 1962, 1965) • Pursuit rotor tracing (Corkin, 1968) • Implicitly familiar w testing equipment • Anterograde amnesics can learn new piano pieces (Starr & Phillips, 1970)

7. HM implicit memory • Perhaps procedural tasks tap ‘implicit’ memory – HM has deficit of ‘explicit’ memory • Milner et al (1968) showed HM learned Gollin incomplete picture task

8. HM implicit memory • HM has also implicitly learned Tower of Hanoi game (Cohen, 1984). • Can not remember playing, but solves quickly. • Start Position • Goal 2 (2 moves) • Goal 10 (5 moves)

9. Memento – Amnesia in Film Noir • Guy Pierce • Sammy Jenkins

10. HM • Temporally graded retrograde amnesia • Old memories (childhood) OK • Memories immediately before lesion lost • Forgot death of favourite uncle in 1950 • Suggests consolidation takes time Memory 1/9/1953 1945 1950 1955

11. How long does consolidation require? • Testing retrograde amnesia. • HM: photos of celebrities suggest retrograde amnesia spans decades, with more distant memories relatively preserved (Marslen-Wilson & Teuber, 1975) • PZ – Butters & Cermak (1986) • Wrote autobiography • Test personal memories

12. Medial Temporal Lobe Memory • MTL patients • Short term memory intact • Old long term memory intact • Suggests ‘consolidation’ deficit • ‘Encoding’ deficit, retrieval intact • See Warrington & Weiskrantz for alternate view • Unable to create new LTM • LTM formation requires years?

13. Anatomy • Anterograde amnesia follows damage to medial temporal lobe or connected regions. • MTL or diencephalic structures like thalamus and mamillary bodies • E.G. NA had fencing foil in nose • Accident in 1960 • Diencephalic damage • Similar to HM, though less retrograde

14. Anterograde Amnesia Similar deficits with damage anywhere in Papez circuit. Fornix (Squire’s Patient) Mammillary body (Korsakoff Patients) Hippocampal formation - HM

15. Hippocampus (T1 MRI) • Folded shape seen in coronal image. • Here: healthy individual

16. HM’s lesion • Surgeon report describes removal of entire hippocampus (Scoville & Milner, 1957). • Recent MRI (Corkin et al., 1997) study suggests posterior hippocampus is present (though atrophied). Scoville & Milner 1957 Corkin et al. 1997

17. HM’s lesion • Corkin et al. (1997) • bilaterally symmetrical • medial temporal pole • most of the amygdaloid complex • most or all of the entorhinal cortex • anterior half of hippocampal formation (dentate gyrus, hippocampus, and subicular complex)

18. Memory – primacy and recency • People often remember the first few and last few items in long lists • First words: primacy – most rehearsal • Final words: recency – least interference • Clearly easier: you do not have to remember as long • These are thought to reflect different processes % recall 1 2 3 4 5 6 7 8 9 10 Item Number

19. Amnesics show no primacy effect • Patients like HM remember last few words (when not interrupted) • Recency effect intact • Primacy effect gone: no encoding benefit % recall 1 2 3 4 5 6 7 8 9 10 Item Number

20. Memory • Are primacy and recency effects different processes • Maybe recency is simply easier • Evidence would come from patients who show an opposite pattern of effects: • Primacy intact • Recency impaired • These patients would provide a ‘double dissociation’

21. Primacy and recency Short term (working) memory Long term memory % recall 1 2 3 4 5 6 7 8 9 10 Item Number

22. Patient KF • Shallice & Warrington (1970) • Primacy effect intact • Recency effect impaired • Complements amnesic patients % recall 1 2 3 4 5 6 7 8 9 10 Item Number

23. Potential Paradox Can information get into long term memory if there is no short term memory? Short term memory Long term memory % recall 1 2 3 4 5 6 7 8 9 10 Item Number

24. Does LTM require STM? • According to Atkinson & Shiffrin (1968) • STM rehearsal leads to LTM • Predicts that LTM will depends on STM • Can not accommodate Shallice and Warrington’s patient Sensory (iconic) Memory Short Term Memory Long Term Memory

25. Shallice & Warrington (1970) • S & W suggest that short term and long term memory independent from each other. • Short term memory not required for long term memory • Very controversial model

26. Baddeley working memory • STM is encoded by system dedicated to input • Verbal info: phonological loop • Visual info: visuo-spatial scratchpad • LTM is more modality independent Phonological Loop Visuo-Spatial Scratch pad Phonological Loop Long Term Memory

27. A: Implicit vs explicit memory • MTL amnesics • Explicit memory: unable to create • Implicit memory: relatively intact • So far: single dissociation • 2 possibilities: • Implicit/Explicit 2 independent systems • Implicit simply easier, relies on residual processing of a single, partially damaged system • Double dissociation would support claim of 2 independent systems

28. B: Gabrieli et al. (1995) • Patient MS • 29 year old, right handed male • Intractable epilepsy: surgery removed right BA 17,18, part of 19. • Hemianopic (blind in left field) • Compared to MTL amnesics and healthy controls.

29. C: Results • Explicit memory task • Shown 24 words, later shown 48 words (24 from 1st phase, 24 new foils): asked to say if words were previously seen. • Amnesics poor. • MS fine.

30. D: Conclusion • Implicit memory: word completion task • Shown/Heard 24 words ‘stick’, later asked to complete 48 stems, 24 could be solved with items from 1st phase (‘sti__’) and 24 unrelated stems (‘sta__’). • Healthy people show priming effect (faster if solution seen previously). This effect is much bigger if words were seen (physical match) rather than heard. • Amensics show normal priming. Shows implicit memory. • MS visual priming is no greater than auditory priming. Therefore, shows no extra benefit for physical match of stem and previously seen word. • Conclusion • Double dissociation • Explicit memory has some distinct processing from implicit memory. • ‘Conceptual’ priming intact in MS, perceptual priming damaged

31. Recollection vs Familiarity Memory • Is implicit memory really preserved in MTL amnesics? • Explicit tasks usually much harder: • ‘Explicit’ Recall: “What was the picture I showed you earlier?” Could have thousands of answers. • ‘Implicit’ Recognition: “Which of these two pictures did I show you” only has two answers, and seeing the correct answer may jog memory. • Is this a meaningful dissociation? (see Simons & Spiers, 2003) • Jon and YR have intact Recognition, but impaired recall • Selective lesions to only hippocampus or fornix • LG and PH have poor Recognition, even poorer recall • Damage to hippocampus and surrounding parahippocampal regions • Both groups show same pattern • Not a double dissociation • Harder task impaired for everyone

32. Recollection vs Familiarity Memory • Yonelinas et al. (2002) compare hypoxic patients (H, focal bilateral damage to hippocampus) to patients with unilateral but extensive damage to the hippocampus and surrounding tissue (H+) and controls (C). • For H group, recall correlated with recognition (below, left) • Interaction between groups • H+ poorer at familiarity (poor implicit) • H poorer at recollection (poor explicit) • Suggests Double dissociation is real

33. Semantic vs. episodic memory • HM has impaired semantic and episodic memory: • Semantic: Language frozen in 1950s (Gabrieli et al.) • Episodic: poor at remembering events. • However, his lesions damage both hippocampus and surrounding temporal lobe. • What about patients with more selective damage?

34. A: Graham et al. 2000 • Graham et al. suggest double dissociation: • Early Alzheimer's patients • ‘Semantic dementia’ patients Alzheimers Patient Hippocampus atrophy Semantic Dementia Temporal lobe atrophy

35. B: Test stimuli • A: Semantic naming task (‘phone’) • Correct answer: ‘phone’. Memory tested 30 minutes later: • B: Episodic memory task (perceptually identical) • Correct answer: ‘I saw a phone earlier’ • C: Episodic memory task (perceptually different) • Correct answer: ‘I saw a phone earlier’.

36. C: Semantic naming • Semantic dementia patients have difficulty naming items. • AD patients are fine at this task.

37. D: Episodic memory • AD patients • poor episodic memory. • SD patients • OK with identical items • Poor with perceptually different (especially if unable to name item in picture naming phase).

38. E: Conclusions • Suggests semantic and episodic memory may be separate. • Hippocampal formation: encoding episodic memories • Temporal lobe: storage of semantic memories. • Additional support from Vargha-Khadem (1997), who reports 4 patients with selective hippocampal damage: all show impaired episodic but intact semantic memory. • Note: all sustained hippocampal damage early in life, so does not necessarily generalize to adult brain.

39. Memory & Prefrontal Cortex (PFC) • PFC damage results in • Disinhibition • Impulsiveness • Disorganization • Memory deficits • Other deficits can hide memory problems • Less ‘pure’ than MTL amnesia • Note: oribtofrontal cortex subdivided: • Ventromedial PFC • Ventrolateral PFC

40. Memory structure (Squire & Knowlton, 1994) • Simplified from page 349 of Gazzaniga book Declarative memory (explicit) Nondeclarative memory (implicit) Events (episodic) Experiences particular to time/place MTL, PFC Facts (semantic) World/word, language knowledge, conceptual priming MTL, PFC Procedural Motor, cognitive skills Basal ganglia, cerebellum Perceptual Perceptual priming Association cortex

41. Interaction of different brain regions • Lesions in animals and functional imaging suggest network of regions work together to encode memory. • Beyond scope of neuropsychology course.

42. Spontaneous confabulation • Confabulation syndrome: • Spontaneously produce confabulations (no need to make things up, no external trigger) • Convinced of accuracy of their confabulations • Acted on confabulations (indication of conviction)

43. Double dissociation • Spontaneous and provoked confabulation dissociate: Schnider et al. (1996), Brain 119, 1365-1375. • Spontaneous confabulation • Generate false memories without prompting • Often whole gist of memory is false • Provoked confabulation, false recognition: • Can be seen in healthy adults • Accidentally report having seen word earlier in list if it is similar to previous word • Errors with small details of overall story

44. Example of spontaneous confabulator • 58-year old woman • Aneurysm of anterior communicating artery. • Reported: needed to go home to feed her baby • Her ‘baby’ was 30 years old

45. Case 2 • 48 year old tax accountant • Traumatic damage to orbitofrontal lobe • Left hospital convinced taxi was waiting to take him to meeting • Consistently thought he had business meeting

46. Reflections • Ideas tend to be internally consistent but inaccurate. • Careful testing shows they are disoriented, confuse date and time. • When confronted, often search for explanations but fail to adapt their ideas • Patient in Berne convinced he was in Bordeaux. • Admitted view from window inconsistent with belief. • Did not change belief.

47. Most confabulations about present • Plausible • Traced to actual events • Usually accurate regarding old memories • Majority eventually stop confabulating despite permanent brain injury

48. Eliciting confabulations • Individual is asked if they saw an image before earlier in run. • Do not report having seen image if you only saw it in a previous run.

49. Eliciting confabulations • Both amnesics and confabulators do poorly at remembering if they have seen an item before. • Amnesics forget previously seen items. • Confabulators report having seen an image from previous set in current set. • Problem with context, not recognition per se.

50. Anatomy of t • Patients who spontaneously confabulate tend to have orbitofrontal damage (aka damage to the ventromedial PFC).