Re-examining episodic amnesia with patient and fMRI studies

Jenny RabinNeuropsychology Rounds

September 9, 2013

What is Amnesia?

Impaired Abilities

• Episodic memory (EM)

Spared Abilities

• General intelligence

• Semantic memory

• Procedural memory

• Working memory

• Attention

Amnesia

Amnesia• 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)

EM and Future Thinking

Remembering Future Thinking

• Both abilities supported by a common core network

Addis et al., 2007, Neuropsychologia

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

eventsAddis et al., 2007, Neuropsychologia

Are there other abilities impaired in amnesia?

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

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)

EM and ToM• There is evidence supporting the idea that ToM may rely

– 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)

EM, Future Thinking, and ToM EM Future Thinking ToM

Addis et al., 2007 Saxe & Kanwisher, 2003

Buckner & Carroll, 2007

EM, Future Thinking, and ToM

Schacter, Addis & Buckner, 2008, Nat. Neurosci.

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?

Outline

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?

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

Patient H.C.• 20-year old woman

• Hypoxia one week after birth

• 30 - 50% 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

Patient H.C. cont.

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)

Mind in the Eyes Test

Hateful Jealous

Arrogant Panicked

Mind in the Eyes Test

Hateful Jealous

Arrogant Panicked

Faux Pas TaskJill 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?

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

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

Outline

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

Study 2: Details

Participants:

• 18 healthy, middle aged adults (9 males; 9 females)

• Mean age = 57.2 years; SD = 8.0 years;

Family Photos Paradigm

Rabin et al., 2010, JOCN

EM ToM

Participant Unfamiliar people

EM ToM

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.

Button Press

20 sec

Button Press

Elaboration PhaseConstruction Phase

20 sec

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

0 1 2 3 4 5 6

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

0 1 2 3 4 5 6

Common Areas of Activation

Differences in Activation

• All regions activated were engaged to a greater extent during EM vs. ToM

Construction Phase

• 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)

Elaboration Phase

• 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)

Elaboration Phase

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

Outline

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

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?

Study 3

• Participants:

– 18 healthy females (mean age = 19.44; SD = 1.24)

Methods Unknown others (ToM)Personal event; EM

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

MethodsPersonally known others (pToM) Unknown others (ToM)Personal event; EM

Participant Participant’s brother Unfamiliar people

Rabin & Rosenbaum, 2012, NeuroImage

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

Within Scanner Rating ScalesEM

pToM and ToM EM, pToM, ToM

• Postscan interview: Describe events

Rate the vividness of your memory/imagined event

1 2 3 4 Not vivid VIvid

Was your imagined event different from a memory?

1 2 3 4 Similar Different

Remember / Know / Don’t Know

Within Scanner Rating ScalesEM

pToM and ToM EM, pToM, ToM

• Postscan interview: Describe events

Rate the vividness of your memory/imagined event

1 2 3 4 Not vivid VIvid

Was your imagined event different from a memory?

1 2 3 4 Similar Different

Remember / Know / Don’t Know

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 generationMcIntosh et al., 2004

Results: Common network

Series1

-100-80-60-40-20

020406080

EM pToM ToM Num

Pattern 1: EM and pToM vs. ToM

2 – 4 s

10 – 12 s

Pattern 2: EM vs. pToM

2 – 4 s

10 – 12 s

pToM vs. ToM

2 – 4 s

10 – 12 s

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

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

Study 4

• Participants:

– Patient H.C. – A group of demographically matched controls

MethodsPersonally known others (pToM) Unknown others (ToM)Personal event; EM

Participant Participant’s brother Unfamiliar people

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

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

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

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

Autobiographical InterviewLevine et al. 2002

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

Descriptive vs. Elaborative Details

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)

pToM ToM EM0

HCControls

Mean number of elaborative details per event

Mean proportion of elaborative : total internal details

pToM ToM EM0

HC Controls

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

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

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

General Conclusions

Common Core Network

Schacter, Addis & Buckner, 2008, Nat. Neurosci.

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

Future Directions

• Scanning H.C. with fMRI on the EM, pToM, and ToM paradigm

Future Directions

• Scanning H.C. with fMRI on the EM, pToM, and ToM paradigm

EM pToM ToM

Acknowledgements

• Shayna Rosenbaum

• Nicole Carson

• Cognitive Neuroscience Lab at York University

Thank you

Questions?

Mean number of elaborative details per event

* p < .08, p < .05

The mean proportion of elaborative-to-total-number of internal detail

* p < .01, p < .001

Re-examining episodic amnesia with patient and fMRI studies

Documents

Transcript of Re-examining episodic amnesia with patient and fMRI studies

Amnesia (1)

Episodic Assignments

Referat Amnesia

Event-related fMRI (er-fMRI)

Amnesia Shin

Human intracranial high-frequency activity maps episodic ...memory.psych.upenn.edu/files/pubs/BurkEtal14.pdf · (SM) paradigm, functional magnetic resonance imaging (fMRI) studies

Amnesia - pruebat.org

Episodic future thinking and episodic counterfactual ...

Amnesia Ikki

severe anterograde amnesia temporally graded retrograde amnesia Long-term Memory.

Functional Anatomic Study of Episodic Retrieval Using fMRIweb.mit.edu/wagner/www/papers/BUC_NI98.pdf · Functional–Anatomic Study of Episodic Retrieval Using fMRI I. Retrieval Effort

AMNESIA HIPOCAMPICA.pptx

Aggleton, John P. & Malcolm W. Brown (June 1999). Episodic Memory, Amnesia, And the Hippocampal-Anterior Thalamic Axis. Behavioral and Brain Sciences 22(3), 425-444.

Amnesia (Psp)

Dissociative Amnesia

Episodic Memory (memory for episodes; also called autobiographical memory) Encoding Retrieval Encoding x Retrieval interactions Amnesia/Implicit memory.

RED AMNESIA

Amnesia Lobulo Temporal

Impact of Sex and Menopausal Status on Episodic Memory ...in addition to functional and structural magnetic resonance and diffu-sion tensor imaging (fMRI, structural MRI, Diffusion

Inductive Amnesia