Daniel L. Schacter Harvard University

1. Episodic Simulation of Future Events and the Medial Temporal Lobe Daniel L. Schacter Harvard University Banbury Center, April 13, 2009

2. Amnesic Patient KC: No Past, No Future Tulving, Canadian Psychology (1985)

3. Commonalities between Past and Future Events * Amnesic patients: Difficulties imagining personal futures/novel scenes (Tulving, 1985; Klein, Loftus, & Kihlstrom, 2002; Hassabis et al., 2007) * Depressed patients/older adlts: Reduction in episodic specificity of past events and future events significantly correlated (Williams et al., 1996; Addis, Wong, & Schacter, 2008) * Cognitive studies: Manipulations/individual differences similarly influence past and future events (D’Argembeau & van der Linden, 2004; 2006; Spreng & Levine, 2006) • Neuroimaging: Similar areas active when remembering past and imagining future (Addis, Wong, & Schacter, 2007; Hassabis et al., 2007; Okuda et al., 2003; Szpunar, Watson, & McDermott, 2007) Reviewed by Schacter, Addis, & Buckner, Nature Reviews Neuroscience (2007); Year in Cognitive Neuroscience, Annals of the NY Academy of Sciences (2008)

4. Core Network of Regions Involved in Remembering the Past, Imagining the Future, & Related Forms of Mental Simulation Schacter, Addis, & Buckner, Nature Reviews Neuroscience (2007)

5. Constructive Episodic Simulation Hypothesis (Schacter & Addis, 2007, Nature; Phil.Trans. Royal Society B) • Episodic memory involves constructive processes: *Details are stored as fragments in cortical regions; during retrieval they are reactivated by these cortices and reintegrated by hippocampus into a coherent event. • The constructive nature of episodic memory makes it well-suited to building simulations of possible future events: *Enables one to extract details from past events *Enables the flexible recombination of details from past events into coherent future scenarios – which likely relies heavily on relational processing capacities supported by the hippocampal region. • Though well-suited to simulating future events, constructive nature of episodic memory has a cost: *Miscombination of details can result in memory errors such as false recognition.

6. Past & Future: A Neuroimaging Approach • We used event-related fMRI to examine the neural substrates of past and future event construction and elaboration; focus on everyday autobiographical events • Instructions (14 young adult participants): • Cued to recall past event or imagine future event • Future events should be novel and plausible • Three time periods for both past and future: last/next week, last/next year, last/next 5-20 yrs. Subjects describe events in post-scan interview Addis, Wong, & Schacter (Neuropsychologia, 2007)

7. Past and Future: Common Neural Substrates? RATINGS CONSTRUCTION ELABORATION CUE 0 2 RT 20 35 time • 3 scales, shown consecutively each for 5 s • Event cue screen presented for 20 s • Button press made when event in mind – signifies end of construction & beginning of elaboration • 24 past and 24 future event task trials Detail 1 2 3 4 5 FUTURE event Next year DRESS task PAST event Last 5-20 yrs CAR Emotion 1 2 3 4 5 OR time-period cue Perspective field/observer

8. Past and Future: Control Tasks RATINGS CONSTRUCTION ELABORATION CUE 0 2 RT 20 35 time • 3 scales, shown consecutively each for 5 s • Event cue screen presented for 20 s • Button press made when event in mind – signifies end of construction & beginning of elaboration • 24 semantic and 24 visuospatial task trials Detail 1 2 3 4 5 WORDS-sentence 2 related words CABLE OBJECTS- triangle bigger / smaller LEAF task Relatedness 1 2 3 4 5 OR items to generate cue Difficulty easy / difficult

9. FUSIFORM & R. MIDDLE OCCIPITAL L. HIPPOCAMPUS Cue processing / object recognition Initial retrieval past events future events control tasks Past and Future Events: Common Neural Substrates? CONSTRUCTION ELABORATION CUE OVERLAP:

10. past events future events control tasks Construction: Neural differentiation CONSTRUCTION ELABORATION CUE future > past R. HIPPOCAMPUS R. FRONTAL POLE (BA 10) Novelty encoding? Recombining details to form specific episodes ? Novelty / Recombining details

11. L. FRONTAL POLE L. HIPPOCAMPUS Self referential processing Reintegrate/recombine event details L. TEMPORAL POLE MEDIAL PARIETAL / PARAHIPPOCAMPUS Conceptual details Imagery / context past events future events control tasks Past and Future Events: Common Neural Substrates? CONSTRUCTION ELABORATION CUE OVERLAP:

12. Past and Future Detail Background Are hippocampal responses to detail similar for past and future events? Constructive Episodic Simulation Hypothesis: • Past events: reintegration of relevant event details • Future events: recombination of various details into novel event

13. Past and Future Detail Method RATE DETAIL CONSTRUCTION ELABORATION CUE 0 2 20 25 RT time RATE DETAIL 1 2 3 4 5 RECALL PAST Last 5-20 yrs CAR RATE DETAIL 1 2 3 4 5 IMAGINE FUTURE Next year DRESS • Past & future detail did not differ on average • Parametric modulation: what regions vary with amount of detail?

14. More anterior HC activity correlates with future detail • Flexible recombination of details from past events? Cf. Preston et al. (2004) Past and Future Detail Addis and Schacter (2008, Hippocampus) Posterior HC activity correlates with past AND future detail: • Retrieval of details from past events?

15. Hippocampal Response to Recombined Details Preston et al. (2004): Recombined details engage anterior hippocampus

16. Constructive Episodic Simulation: Two Conceptual Issues 1. Comparison has focused on remembering the past vs. imagining the future, but past/future confounded with remembering/imagining: Are observed patterns specific to imagining future events or associated with more general imagination/simulation? According to constructive episodic simulation hypothesis, critical process of recombining event details should occur regardless of whether individuals imagine an event as occurring in the future, present, or past.

17. Constructive Episodic Simulation: Two Conceptual Issues 2. Constructive episodic simulation hypothesis emphasizes recombining of details across events, but it is possible that subjects simply remember entire events and recast them in the future. In previous studies, future simulations could be based on recasting, recombining, or some combination of the two. Are main effects still observed when individuals are required to recombine elements of different episodes?

18. MEMORY POOL IMAGINE PAST IMAGINE FUTURE Fall outside library PERSON: Katie LOCATION: Widener OBJECT: Hat Graduation Day PERSON: Mom LOCATION: Harvard Yard OBJECT: Gown Meeting Cathy PERSON: Cathy LOCATION: Filipes OBJECT: Fajita Imagine PAST event: Mom: Graduation Day Filipes: Meeting Cathy Gown: Graduation Day Imagine FUTURE event: Katie: Fall outside library Harvard Yard: Graduation Day Fajita: Meeting Cathy RECALL TASK CONTROL TASK RECALL memories: Cathy: Meeting Cathy Widener: Fall outside library Hat: Fall outside library CREATE SENTENCE Start with smallest: Cat: Include cat in sentence Bulb: Include bulb in sentence Tree: Include tree in sentence fMRI Paradigm: Experimental Recombination of Details

19. fMRI Paradigm: RATE DETAIL CONSTRUCTION ELABORATION CUE 0 2 24 25 RT time Imagine PAST event : Mom: Graduation Day Filipes: Meeting Cathy Gown: Graduation Day RATE DETAIL 1 2 3 4 5 Button press when event is in mind Imagine FUTURE event : Katie: Fall outside library Harvard Yard: Graduation Fajita: Meeting Cathy RATE DETAIL 1 2 3 4 5 Recall MEMORIES: Cathy: Meeting Cathy Widener: Fall outside library Hat: Fall outside library RATE DETAIL 1 2 3 4 5

20. Experimental Recombination Task Common Core Network Future-Imagine, Past-Imagine & Past-Recall > Control Task Lateral temporal lobe Bilateral hippocampus Lateral parietal lobe Retrosplenial / precuneus Cuneus Retrosplenial / precuneus Medial prefrontal / frontal poles Addis, Pan, Vu, Laiser, & Schacter (in press, Neuropsychologia)

21. Experimental Recombination Task Imagining Subsystem? Future-Imagine and Past-Imagine > Control Task Lateral temporal lobe Bilateral hippocampus Retrosplenial / precuneus Medial prefrontal / frontal poles Lateral parietal lobe Retrosplenial / precuneus

22. Experimental Recombination Task Remembering Subsystem? Past-Recall > Past-Imagine, Future-Imagine & Control Task Cuneus Middle/inferior occipital gyrus

23. Conclusions (see Schacter & Addis, 2009, Phil. Trans. Roy. Soc.) • Constructive nature of the episodic memory system: during retrieval, various elements of past experiences are reintegrated and recombined, allowing us to draw on the past to imagine the future. • Imaging data support the constructive episodic simulation hypothesis - and the possibility that simulation of future events is a primary function of a constructive episodic memory. • The hippocampus plays an important role in recombining and encoding details from past episodes into simulations of the future. Converging evidence from work on prospective coding/preplay of event sequences.

24. Acknowledgements Memory Lab, Harvard Collaborators Brendan Gaesser Donna Addis Kathy GerlachRandy Buckner Adrian Gilmore Theresa ChengYoko Okado Elizabeth Chua Ling Pan Noa Laiser Jessica Payne Ling Pan Nathan Spreng Alana Wong Dale Stevens Gagan Wig Supported by NIMH & NIA