1. Memory and Amnesia Nathan Spreng Cognitive Neuroscience: PSY393 August 2, 2005

2. Amnesia at the movies

3. Remember Sammy Jankis?

4. Memory Lecture Summary Memory –Process and Definitions –Systems Medial Temporal Lobe & Classic Amnesia –Encoding & Retrieval –Case studies Frontal Lobes –Working Memory & DLPFC –Working with Memory –Case study Autobiographical Memory

5. Memory is... A group of mechanisms or processes by which experience shapes us, changing our brain and behaviour The product of learning

6. Memory involves... Acquisition Retention Ability to retrieve –information –personal experiences –procedures (skills and habits).

7. Memory enables... Adaptation to the environment Improvement of our interactions with the outside world Intergenerational transfer of knowledge

8. Short and Long Term Memory Memory can be divided into –Time (seconds to minutes to years) –Contents (7 plus minus 2) –Systems by type of information

9. Memory processes 1. Registration 2. Encoding 3. Consolidation 4. Storage 5. Retrieval 6. Re-encoding Sensory perception in sensory brain areas Initial processing (association with previous information) - Trace Deeper processing: Engram formation Stable representation in central nervous system Reproduction of previously stored information: Recollection Re-encoding through retrieval; initial trace (engram) changes

10. Memory Systems

11. Implicit Memory: Memory without awareness –Skills, priming, etc (spared in amnesia) Explicit Memory/Declarative Memory –Memory accompanied by an awareness of recollection. May be “declared” or verbally reported

12. Amnesia Definition: “An abnormal mental state in which memory and learning are effected out of all proportion to other cognitive functions in an otherwise alert and responsive patient” Kopelman (2002) Memory can be compromised in isolation from other cognitive abilities Amnesia is selective, effecting certain capacities, showing that there are many systems of memory

13. Temporal Extent of Amnesia Anterograde amnesia –Deficit in new learning –Inability to form new memories AFTER time of injury Retrograde amnesia –impairment of memory of information PRIOR to onset of amnesia –temporal gradient, effecting recent > remote

14. Temporal Extent of Amnesia Ribot’s Law (1882): “The progression of the destruction of memory follows a logical order. It begins with the most recent recollections, being rarely repeated, and having no permanent associations” Greater compromise of recent memory over remote

15. Temporal Extent of Amnesia

16. The case of H.M. HM - surgery for intractable epilepsy. Resection of hippocampus, parahippocampal gyrus, amygdala & uncus. HM could not form new memories (anterograde amnesia). Retrograde amnesia (11 years) Right: HM vs. 66-yr old Control (Corkin et al., 1997) Anterior Posterior

17. Etiology of Amnesia Korsakoff’s syndrome (Jimmy) Herpes encephalitis (Clive) Severe hypoxia Vascular disorders Head Injury (K.C.) Dementia (J.S.) Transient global amnesia (fugue state)

18. Amnesia Inability to form new long term memories Assessed with –Free recall (no info) –Cued recall (starting with “c”) –Recognition (target and lures used) Savings in relearning (also impaired in amnesia)

19. Memory Systems ImpairedSpared

20. Implicit Memory “Memory without awareness” Spared in classical amnesia Priming – Primary Sensory Cortex Procedural Memory - Striate

21. Implicit Memory Gollin Incomplete Pictures task Repetition Priming Bias to previous exposure

22. Implicit Memory Eye movements to assess implicit memory Top: Initial exposure, eye movements over 3 items Bottom: 2nd exposure, eye movements over where one item would be

23. Implicit Memory Procedural Memory Improvement in performance without recollection of the material Spared in amnesia Mirror Reading Task

24. Declarative Memory Semantic Memory: “Knowing” –Knowledge of words and their meanings, objects, concepts and facts. Episodic Memory: “Remembering” –Re-experiencing of an event that occurred in the past including time and place of original encoding episode…mental time travel.

25. The case of K.C. TBI Bilateral hippocampus & frontal lobe damage Severe RA and AA No episodic memory Intact semantic memory K.C. normal

27. Memory Circuit (Mayes, 2000)

28. Main memory structures & connections MTL Diencephalon

29. Mamillary bodies Hippocampal formation 3. Parahippocampal cortex 2. Entorhinal cortex 1. Perirhinal cortex Structures of the Medial Temporal Lobe Subiculum CA1 CA2 CA3 Dentate gyrus 1-3 = Parahippocampus

30. Medial Temporal Lobe Hippocampus as Convergence zone Memories are not stored within the hippocampus Hippocampus acts as an “indexor” and lays trace of memories. Memories are stored in sensory cortex Hippocampus has access to all sensory information Relational Memory

31. Medial Temporal Lobe Morris Water Maze Hippocampal lesions Deficits in learning and remembering spatial relations

32. Medial Temporal Lobe Hippocampal Lesions: Material specific memory disorder Unilateral –Left: verbal impairment –Right: nonverbal impairment Bilateral - Global impairment fMRI Hippocampus: Material dependent activity at encoding Verbal - Left Nonverbal - Right

33. Medial Temporal Lobe Hippocampal activity predicts successful recall –During encoding –During retrieval (Nyberg, et al., 1996) “Subsequent Memory Effect”

34. Medial Temporal Lobe While memories are young, they depend upon an intact hippocampus Are old episodic memories independent hippocampus once consolidated?

35. Medial Temporal Lobe fMRI: Robustness of hippocampal activity during retrieval related to vividness of memory, not age (Gilboa, 2003) H.M. possesses some remote memories. –Are they episodic? Depends on measure – lack episodic content, “semanticized” (Steinvorth & Corkin, submitted)

36. Medial Temporal Lobe How does the hippocampus bind information? LTP –Hebb’s Law Connectivity (Rolls, 2000)

37. Same brain regions activated for perception and retrieval Regions –fusiform gyrus (a) –superior temporal gyri (d) Retrieval of pictures and sounds, respectively (2004) Proc. Natl. Acad. Sci. USA 101, 5181

38. MTL & Emotion Emotionality enhances memory performance Mediated by the Basolateral limbic circuit Parahippocampus and perirhinal cortex connect with the amygdala Orbitofrontal cortex involved in processing salience at encoding Emotion enhances attention

39. Main memory structures & connections Mayes, 2000 Amyg- dala Basolateral limbic circuit

40. Want Slides? Please provide email address Video: NoT cue 17-27 minutes Video: Tulving/Milner – Clive cue 6-18 minutes

41. Clive Wearing R-handed Above average IQ Prominent Musician Herpes Simplex Encephalitis Bilateral temporal lobe degeneration L>R Dense Anterograde Amnesia (Wilson & Wearing, 1995)

42. Clive Wearing

43. Frontal Lobes Tennessee Williams: “Life is all memory except for the present moment that flies by so quickly that you can hardly catch it going by” WM: moment LTM: past

44. Working Memory Central Executive: Attentional control of the slave systems: –Visuo-spatial sketchpad –Phonological loop Both derive and feed information to and from LTM WM is a combination of maintenance and manipulation operations and works in close interaction with LTM Baddeley & Wilson, 2002 Video: cue @ 27-33 min

45. Basic WM paradigms Delayed response Delayed alternation Object alternation Go No-Go Reversal Delayed match to sample Delayed non-match to sample –Recurring stimuli (recall most recent presentation) –Trial-unique stimuli (distinguish familiar from novel)

46. Component processes of WM Mnemonic –Register (encode) –Store (maintain) –Rehearse Non-Mnemonic –Control interference (inhibit) –Manipulate –Select (retrieve, prepare) –Respond (motor effector) –Domain-specific sensory systems (spatial, object)

47. Working Memory Delayed Response Task: –Access spatial information –Hold information on on-line during delay period –Initiate motor response Delay tasks sensitive to principal suclus Impaired with lesions Evidence for delay- specific neurons

48. Working Memory Shared working memory circuit in humans –BA9/46 (DLPFC) –Posterior Parietal –Left Hemisphere Delayed response Delayed alternation Object alternation “Guide behavior in the absence of external cues”

49. Functional neuroimaging (D’Esposito et al., 2000; Fletcher & Henson, 2001) DLPFC –Encoding (supraspan) –Maintenance –Manipulation –Scanning VLPFC –Maintenance –Rehearsal –Inhibit, select Anterior PFC (Poles) –More complex manipulation CUE DELAY RESPONSE time encoding manipulationscanning maintenance Inhibition/selection

50. Frontal lobes and working with memory Associative retrieval: conscious recollection that are cue-driven –medial temporal lobes (MTL) Strategic Retrieval: problem solving approach to memory where –the frontal lobes work with memories –delivered through the medial temporal lobes and posterior neocortex Video: cue 35 minutes TRAIN

51. Frontal lobes and working with memory Simons & Spires (2003) Frontal-medial temporal interactions –encoding –retrieval

52. Frontal lobes and working with memory Meta memory judgments Source amnesia –Dissociation between item and contextual information (details of study episode) Judgment of recency (Milner, 1971) –Left-sided lesions affect verbal –Right-sided lesions affect verbal and visual Temporal ordering (Milner, 1971)

53. Frontal lobes and working with memory Confabulation –Defined as an honest lying –Requires retrieval, sequencing, output monitoring –Associative retrieval intact, strategic retrieval impaired –“Source amnesia magnified and extended to include an entire lifetime of experience” (Moscovitch, 1989) Schnider, 2003

54. Patient J.S. Frontotemporal dementia R R RLL (McKinnon, et al., in preparation)

55. The case of JS: Confabulation MK: Can you tell me about Detroit again? JS: We were in this nice restaurant and a guy said I don’t think you guys should go outside. There’s a sniper on the roof outside. He said I think you had better stay in here. I’ve just called the cops. (laughter) He said there’s a sniper on the roof. He said you guys had better stay in here. MK: Then what happened? JS: Well the cops came. The cops got the guy. And they said okay guys you can leave now. That was all the help and we went outside.

56. Autobiographical Memory Memory of, or relating to, the self Involves episodic memory (ie autonoetic awareness) Semantic memory Mental Time Travel

57. Autonoetic consciousness Wheeler, Stuss & Tulving (1996); Tulving (2002) Awareness of the self as a continuous entity across time "Remembrance is like a direct feeling; its object is suffused with warmth and intimacy to which no object of mere conception ever attains." James (1890) "It's essence lies in the subjective feeling that the present experience is of an earlier, similar one, and in the belief that the self doing the experiencing now is the same self that did it originally." Wheeler, Stuss, & Tulving (1997)

58. Ascendancy of personal re-experiencing over childhood amnesia Bruce et al., 2000

59. Mental Time Travel: Past & Future Spreng & Levine (in press)

60. Autobiographical memory

61. a) Anteromedial prefrontal cortex b) Superior medial prefrontal cortex c) Ventrolateral prefrontal cortex d) Temporoparietal junction e) Posterior cingulate/Precuneus f) Thalamus (anterior nucleus) a b c d e f x=-4 y=-56 z= 5 Autobiographical recollection Personal episodic versus personal semantic

62. Kopelman, 2002