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Re-examining episodic amnesia with patient and fMRI studies Jenny Rabin Neuropsychology Rounds September 9, 2013.

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Presentation on theme: "Re-examining episodic amnesia with patient and fMRI studies Jenny Rabin Neuropsychology Rounds September 9, 2013."— Presentation transcript:

1 Re-examining episodic amnesia with patient and fMRI studies Jenny Rabin Neuropsychology Rounds September 9, 2013

2 What is Amnesia? Impaired Abilities Episodic memory (EM) Spared Abilities General intelligence Semantic memory Procedural memory Working memory Attention

3 Amnesia

4 For a long time it was thought that amnesia results in an isolated deficit in EM However, there is growing evidence that other abilities may be impaired in amnesia E.g., Future thinking –Early support came from conversations Endel Tulving had with K.C. (Tulving, 1985) –Systematically replicated in other amnesic cases (Andelman et al., 2010; Kwan et al, 2010; Race et al., 2011)

5 EM and Future Thinking Remembering Future Thinking Both abilities supported by a common core network Addis et al., 2007, Neuropsychologia

6 EM and Future Thinking Remembering Future Thinking Both abilities supported by a common core network EM and the hippocampus contribute to imagining the future –draw on details from past experiences to imagine future events Addis et al., 2007, Neuropsychologia

7 Are there other abilities impaired in amnesia?

8 Theory of Mind (ToM) The ability to infer other people’s thoughts, feelings, beliefs, desires, and intentions (Premack & Woodruff, 1978) Recognize that other people can have different mental states from our own Use ToM automatically and effortlessly

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11 Theory of Mind (ToM) How do we do infer others’ mental states? We rely on our own past experiences to simulate another person’s mental state (Buckner & Carroll, 2007; Gallagher & Frith, 2003; Spreng & Mar, 2012)

12 EM and ToM There is evidence supporting the idea that ToM may rely on EM –Both abilities emerge around the same time during development (Perner & Ruffman, 1995) –Impaired together in several patient populations (Corcorran & Frith, 2003; Dimaggio et al., 2012) –Supported by a common set of brain regions that includes the hippocampus (Buckner & Carroll, 2007)

13 EM, Future Thinking, and ToM EM Future Thinking ToM Addis et al., 2007 Saxe & Kanwisher, 2003 Buckner & Carroll, 2007

14 EM, Future Thinking, and ToM Schacter, Addis & Buckner, 2008, Nat. Neurosci.

15 Outline Study 1: Is ToM impaired in amnesia? Study 2: What are the unique neural correlates of EM and ToM? Study 3 and 4: Are there certain conditions under which ToM depends on EM?

16 Outline Study 1: Is ToM impaired in amnesia? Study 2: What are the unique neural correlates of EM and ToM? Study 3 and 4: Are there certain conditions under which ToM depends on EM?

17 Study 1 Evidence that a core network of regions supports EM, future thinking, and ToM (Buckner & Carroll, Spreng et al., 2009) Draw on past experiences to imagine the future and to simulate other people’s mental states Amnesic people have difficulty imagining the future (Andelman et al., 2010; Kwan et al, 2010; Race et al., 2011) Do amnesic people also have difficulty with ToM?

18 Study 1 Participants: –H.C., an individual with amnesia –A group of demographically matched controls Rabin et al., 2012, Neuropsychologia, see also Rosenbaum et al., 2007, Science

19 Patient H.C. 20-year old woman Hypoxia one week after birth % bilateral hippocampal volume loss (Olsen et al., 2013) Therefore, she never developed normal episodic memory (Rosenbaum et al., 2011) Graduated from a mainstream high school and completed one year of technical college

20 Patient H.C. cont.

21 ToM Tests Tested H.C. and controls on a battery of ToM tests Same ToM tests that have been shown to activate the core network of regions involved in EM (Buckner & Carroll, 2007; Spreng et al., 2009) ToM tests that are sensitive to ToM impairment in a variety of patient groups (Gregory et al., 2002; Stone et al., 1998; Stone et al., 2003; Stuss et al., 2001) Rabin et al., 2012, Neuropsychologia, see also Rosenbaum et al., 2007, Science

22 Mind in the Eyes Test Hateful Jealous Arrogant Panicked Rabin et al., 2012, Neuropsychologia, see also Rosenbaum et al., 2007, Science

23 Mind in the Eyes Test Hateful Jealous Arrogant Panicked Rabin et al., 2012, Neuropsychologia, see also Rosenbaum et al., 2007, Science

24 Faux Pas Task Jill had just moved into a new apartment. Jill went shopping and bought some new curtains for her bedroom. When she finished decorating the apartment, her best friend, Lisa, comes over. Jill gives her a tour of the apartment and asks, "How do you like my bedroom?" "Those curtains are horrible," Lisa replies. "I hope you're going to get some new ones!" Did anyone say something they shouldn't have said or something awkward? If yes, ask: Who said something they shouldn't have said or something awkward? Why shouldn't he/she have said it or why was it awkward? Why did they say it?

25 Study 1: Results & Discussion H.C. performed at the same level as controls on all ToM tests Suggests that EM is not necessary for ToM, at least as measured by standard tests H.C. may be relying on her intact semantic knowledge to perform these tasks Rabin et al., 2012, Neuropsychologia, see also Rosenbaum et al., 2007, Science

26 Study 1: Results & Discussion cont. Activation of a particular region during a task does not necessarily indicate that the region is necessary for that task Activation of the hippocampus during ToM, does not necessarily mean that the hippocampus is necessary for ToM

27 Outline Study 1: Is ToM impaired in amnesia? Study 2: What are the unique neural correlates of EM and ToM? Study 3 and 4: Are there certain conditions under which ToM depends on EM?

28 Study 2 Evidence of a shared brain network underlying EM and ToM based on independent fMRI studies (Buckner & Carroll, 2007; Spreng et al., 2009) Objective: To investigate EM and ToM in the same study using the same participants –Goal 1: Replicate the common pattern of activity observed across studies –Goal 2: Are there differences in activation? Naturalistic paradigm using closely matched conditions

29 Study 2: Details Participants: 18 healthy, middle aged adults (9 males; 9 females) Mean age = 57.2 years; SD = 8.0 years;

30 Family Photos Paradigm Rabin et al., 2010, JOCN

31 Family Photos Paradigm Rabin et al., 2010, JOCN EM ToM Participant Unfamiliar people

32 Family Photos Paradigm Rabin et al., 2010, JOCN EM ToM Participant Unfamiliar people

33 Family Photos Paradigm Rabin et al., 2010, JOCN EM ToM Participant Unfamiliar people Recall each event in as much detail as possible and focus on what you were thinking and feeling at the time. Create a novel event and focus on what one person in the photo was thinking and feeling at the time.

34 Task Button Press 20 sec Rabin et al., 2010, JOCN

35 Task Button Press Elaboration Phase Construction Phase 20 sec Rabin et al., 2010, JOCN

36 Post Scan Interview Viewed the same photos they saw in the scanner Rate the vividness of each EM and ToM event they generated in the scanner vague vivid Rabin et al., 2010, JOCN

37 Post Scan Interview Viewed the same photos they saw in the scanner Rate the vividness of each EM and ToM event they generated in the scanner vague vivid Rabin et al., 2010, JOCN

38 Common Areas of Activation EM ToM Rabin et al., 2010, JOCN EM ToM Base

39 Common Areas of Activation EM ToM Rabin et al., 2010, JOCN EM ToM Base

40 Common Areas of Activation EM ToM Rabin et al., 2010, JOCN EM ToM Base

41 Common Areas of Activation EM ToM Rabin et al., 2010, JOCN EM ToM Base

42 Differences in Activation All regions activated were engaged to a greater extent during EM vs. ToM Construction Phase Rabin et al., 2010, JOCN

43 Differences in Activation Midline regions showed greater activity during EM –Self-related processes (Craik et al., 2002) –Realness of events (Summerfield et al., 2009) Lateral regions showed greater activity during ToM –Involved in semantic memory (Martin & Chao, 2001) Rabin et al., 2010, JOCN EM ToM Elaboration Phase

44 Differences in Activation Midline regions showed greater activity during EM –Self-related processes (Craik et al., 2002) –Realness of events (Summerfield et al., 2009) Lateral regions showed greater activity during ToM –Involved in semantic memory (Martin & Chao, 2001) Rabin et al., 2010, JOCN EM ToM Elaboration Phase

45 Differences in Activation Midline regions showed greater activity during EM –Self-related processes (Craik et al., 2002) –Realness of events (Summerfield et al., 2009) Lateral regions showed greater activity during ToM –Involved in semantic memory (Martin & Chao, 2001) Rabin et al., 2010, JOCN EM ToM Elaboration Phase

46 Differences in Activation Midline regions showed greater activity during EM –Self-related processes (Craik et al., 2002) –Realness of events (Summerfield et al., 2009) Lateral regions showed greater activity during ToM –Involved in semantic memory (Martin & Chao, 2001) Rabin et al., 2010, JOCN EM ToM Elaboration Phase

47 Differences in Activation Midline regions showed greater activity during EM –Self-related processes (Craik et al., 2002) –Realness of events (Summerfield et al., 2009) Lateral regions showed greater activity during ToM –TPJ is a key region involved in ToM (Saxe et al., 2006) –VLPFC and lateral temporal cortex; regions known to support semantic memory (Martin & Chao, 2001) Rabin et al., 2010, JOCN EM ToM Elaboration Phase

48 Differences in Activation Midline regions showed greater activity during EM –Self-related processes (Craik et al., 2002) –Realness of events (Summerfield et al., 2009) Lateral regions showed greater activity during ToM –TPJ is a key region involved in ToM (Saxe et al., 2006) –VLPFC and lateral temporal cortex; regions known to support semantic memory (Martin & Chao, 2001) Rabin et al., 2010, JOCN EM ToM Elaboration Phase

49 Differences in Activation Midline regions showed greater activity during EM –Self-related processes (Craik et al., 2002) –Realness of events (Summerfield et al., 2009) Lateral regions showed greater activity during ToM –TPJ is a key region involved in ToM (Saxe et al., 2006) –VLPFC and lateral temporal cortex; regions known to support semantic memory (Martin & Chao, 2001) Rabin et al., 2010, JOCN EM ToM Elaboration Phase

50 Study 2: Discussion Replicated common network supporting EM and ToM –Healthy people may rely on EM during ToM For the first time showed differences between the two Lateral regions engaged during ToM are the same regions known to support semantic memory –Rely on scripts/schemas about how the average person would respond in a given situation –Amnesic patients may rely on these lateral regions to carry out ToM tasks

51 Outline Study 1: Is ToM impaired in amnesia? Study 2: What are the unique neural correlates of EM and ToM? Study 3 and 4: Are there certain conditions under which ToM depends on EM?

52 Study 3 ToM has been studied using tasks that typically involve fictional characters or unfamiliar others (e.g., Baron-Cohen et al., 2001; Stone et al., 1998; Rabin et al., 2010; Spreng et al., 2010) However, in everyday life we typically infer the mental states of people we know well –We have shared past experiences on which one can draw when imagining the thoughts/feelings of personally known others

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54 Study 3 Objective: To test whether different neural and cognitive mechanisms support mental state inferences of personally familiar vs. unfamiliar others –Do individuals rely on EM to a greater extent for ToM involving personally familiar others? –Do individuals rely on semantic to a greater extent for ToM involving unfamiliar others?

55 Study 3 Participants: –18 healthy females (mean age = 19.44; SD = 1.24)

56 Methods Unknown others (ToM) Personal event; EM Participant Unfamiliar people Recall each event in as much detail as possible and focus on what you were thinking and feeling at the time. Create a novel event and focus on what one person in the photo was thinking and feeling at the time. Do not draw on specific past experiences. Rabin & Rosenbaum, 2012, NeuroImage

57 Methods Personally known others (pToM) Unknown others (ToM) Personal event; EM ParticipantParticipant’s brother Unfamiliar people Recall each event in as much detail as possible and focus on what you were thinking and feeling at the time. Create a novel event and focus on what one person in the photo was thinking and feeling at the time. Do not draw on specific past experiences. Rabin & Rosenbaum, 2012, NeuroImage

58 Hypotheses We expected that familiarity with the target person would modulate the relationship between EM and ToM 1)Greater neural overlap between EM and pToM vs. ToM –Midline regions, including the hippocampus –Draw on past experiences to a greater extent when imagining the mental states of personally known others 2)ToM vs. EM and pToM –Recruit lateral frontal and temporal regions to a greater extent –Script-like knowledge and semantic processing Rabin & Rosenbaum., 2012, NeuroImage

59 Within Scanner Rating Scales EM pToM and ToM EM, pToM, ToM Postscan interview: Describe events Rate the vividness of your memory/imagined event Not vivid VIvid Was your imagined event different from a memory? Similar Different Remember / Know / Don’t Know

60 Within Scanner Rating Scales EM pToM and ToM EM, pToM, ToM Postscan interview: Describe events Rate the vividness of your memory/imagined event Not vivid VIvid Was your imagined event different from a memory? Similar Different Remember / Know / Don’t Know

61 fMRI Analyses Spatiotemporal Partial Least Squares (PLS) A data reduction technique that identifies the strongest effects in the data Data-driven approach (vs. using a priori contrasts) Early vs. Late phase of event generation McIntosh et al., 2004

62 Results: Common network

63 Pattern 1: EM and pToM vs. ToM 2 – 4 s EM 10 – 12 s

64 Pattern 2: EM vs. pToM EM 2 – 4 s 10 – 12 s

65 pToM vs. ToM 2 – 4 s 10 – 12 s

66 Study 3: Discussion Familiarity with the target person in a ToM task modulates the neural relationship between EM and ToM Multiple routes to ToM –Involve some balance between EM and semantic memory Strategy adopted likely depend on one’s relationship with the target person –Draw on past experiences for personally known others –Draw on semantic memory for unfamiliar others

67 Study 4 Goal: Test whether EM, supported by the hippocampus, is necessary for imagining events from the perspective of personally known others. To address this question, we tested an amnesic person with impaired EM on the family photos test Rabin et al., 2012, Frontiers in Psychology

68 Study 4 Participants: –Patient H.C. –A group of demographically matched controls Rabin et al., 2012, Frontiers in Psychology

69 Methods Personally known others (pToM) Unknown others (ToM) Personal event; EM ParticipantParticipant’s brother Unfamiliar people Recall each event in as much detail as possible and focus on what you were thinking and feeling at the time. Create a novel event and focus on what one person in the photo was thinking and feeling at the time. Do not draw on specific past experiences. Rabin et al., 2012, Frontiers in Psychology

70 Methods H.C. tested on this paradigm twice for reliability purposes Control participants tested only once Excluded H.C.’s EM events from the first testing session –Rehearsed events

71 Postscan Interview Photos with the highest vividness ratings were selected for a semi-structured interview Describe the events as they had been remembered/imagined in the scanner No time limit

72 Narrative Scoring Adapted Autobiographical Interview scoring procedure (Levine et al, 2002) –Internal: event, temporal, perceptual, spatial, thought/emotion –External: semantic facts, details that were irrelevant to the central event, repetitions, metacognitive statement

73 Narrative Scoring Adapted Autobiographical Interview scoring procedure (Levine et al, 2002) –Internal: event, temporal, perceptual, spatial, thought/emotion –External: semantic facts, details that were irrelevant to the central event, repetitions, metacognitive statement

74 Autobiographical Interview Levine et al. 2002

75 Descriptive vs. Elaborative Details Internal details were further divided into descriptive vs. elaborative details –Descriptive detail – details that describe the visual content of the photo –Elaborative detail – details that go beyond what is visually depicted in the photo Rabin et al., 2012, Frontiers in Psychology

76 Descriptive vs. Elaborative Details

77 Analyses Mean number of elaborative details Mean proportion of elaborative details/total internal details –Weight given to elaborative vs. descriptive details Crawford’s t -test (Crawford & Howell, 1998) Rabin et al., 2012, Frontiers in Psychology

78 Mean number of elaborative details per event * * Rabin et al., 2012, Frontiers in Psychology

79 Mean proportion of elaborative : total internal details * * Rabin et al., 2012, Frontiers in Psychology

80 Qualitative Nature of Responses H.C. –“they’re both really excited” –“he looks really happy” Control –“they were probably afraid but they are trying to look cool” –“her mother was pleased that her daughter was having so much fun” Rabin et al., 2012, Frontiers in Psychology

81 Study 4: Discussion H.C. impaired at pToM and EM H.C’s performance on pToM was not at floor Approximately 50% of H.C.’s pToM narratives were comprised of descriptive details –Relied on visual information depicted in the photos –Compensatory strategy? Rabin, Carson et al., 2012, Frontiers in Psychology

82 Study 4: Discussion cont. H.C. impaired at pToM and EM but not ToM –Therefore may need EM for pToM but not ToM These findings are consistent with: –Previous fMRI findings (Rabin & Rosenbaum, 2012) –H.C.’s intact performance on standard ToM tests (Rabin et al., 2012) Need to replicate this finding in other amnesic cases

83 General Conclusions

84 Common Core Network Schacter, Addis & Buckner, 2008, Nat. Neurosci.

85 What is Amnesia? Impaired Abilities Episodic memory (EM) Future Thinking ToM involving personally known others Spared Abilities General intelligence Semantic memory Procedural memory Working memory Attention

86 Future Directions Scanning H.C. with fMRI on the EM, pToM, and ToM paradigm

87 Future Directions Scanning H.C. with fMRI on the EM, pToM, and ToM paradigm EM pToM ToM

88 Acknowledgements Shayna Rosenbaum Nicole Carson Cognitive Neuroscience Lab at York University

89 Thank you

90 Questions?

91 Mean number of elaborative details per event Rabin et al., 2012, Frontiers in Psychology * p <.08, p <.05

92 The mean proportion of elaborative-to- total-number of internal detail Rabin et al., 2012, Frontiers in Psychology * p <.01, p <.001


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