Medial Temporal Lobe (MTL) Amnesia: Past, Present, and Future

Transcription

1 Medial Temporal Lobe (MTL) Amnesia: Past, Present, and Future Mieke Verfaellie, Ph.D. VA Boston Healthcare System and Boston University School of Medicine

2 MTL Amnesia: An Uncommon Disorder Striking clinical presenta>on MTL pathology: common to various neurological and psychiatric disorders! MTL amnesia as model system for understanding effects of MTL pathology Study of MTL amnesia: elucidates the role of the MTL in cogni>on

3 Early Neuropsychological Studies of Amnesia Henry Molaison (HM) Corkin et al., J. Neurosci, 1997

4 The Scope of Global Amnesia HM s clinical presenta>on Retrograde amnesia 1953 surgery Anterograde amnesia Unable to acquire new memories of events or facts - - all materials - - all modali>es High average intelligence Intact short term memory Good memory of distant past

5 Procedural memory Milner, 1962 Priming Milner et al., Neuropsychologia 1968

6 Mul>ple Memory Systems Squire and Zola, PNAS, 1996

7 Rosenbaum et al., Ann. NY Acad Sci, 2014

8 Func>onal specializa>on within the MTL Neuropsychologia, 1996 They also point to a dis>nct subgroup of amnesias associated with selec>ve damage in the hippocampus or its diencephalic targets, in which there is a rela>ve sparing of recogni>on under certain test condi>ons.

9 Recollec>on and familiarity as dissociable processes I enter a friend s room and see on the wall a pain>ng. At first, I have the strange, wondering consciousness, surely I have seen that before, but when or how does not become clear. There only clings to the picture a sort of penumbra of familiarity, when suddenly I exclaim: I have it, it is a copy of part of one of the Fra Angelicos in the Floren>ne Academy I recollect it there! The Principles of Psychology, William James Recollec>on = reac>va>on of contextual elements Familiarity = undifferen>ated trace strength

10 Neural basis of recollec>on and familiarity 31 % " 88% " Verfaellie, Neuropsychology, 1994 Aggleton et al., Neuropsychologia 2005 Bowles et al., PNAS, 2007

11 Recollec>on and familiarity as dissociable processes Recollec>on = reac>va>on of contextual elements Familiarity = undifferen>ated trace strength Recall Associa>ve Recogni>on Context memory Yes/no recogni>on Forced choice recogni>on

12 Associa>ve vs Item Recogni>on in MTL amnesia Study Rope- Apple Candle- Grape Pencil- Water Cashew- Radio Test (old/new?) Candle- Grape (O) Pencil- Radio (R) Rope (O) Skirt (N) P(Hits) - P(False Alarms) control patient Item Associative Giovanello et al., CABN, 2003 Associa>ve memory = Old pair vs Recombined pair Item memory = Old item vs New item

13 Associa>ve Recogni>on in MTL amnesia: Rela>onal binding vs. Uni>za>on Study Test (old/new?) Rope- Apple Candle- Grape Pencil- Water Cashew- Radio Candle- Grape (O) Pencil- Radio (R)! Linked elements retain separate iden>>es d' % " control patient 58% " Study Black- Mail Jail- Bird Land- Scape Test (old/new?) Black- Bird (R) Land- Scape (O) Unrelated Compound Giovanello et al., Neuropsychologia, 2006! Elements become part of uni>zed whole

14 Rela>onal Binding vs. Uni>za>on Hippocampus mediates rela>onal binding (unrelated pairs) Perirhinal cortex mediates uni>za>on (compounds) Ford et al., Neuropsychologia, 2010

15 Mapping of recollec>on and familiarity with dis>nct types of binding processes: recollec>on = rela>onal binding! hippocampus familiarity = uni>zed representa>ons! perirhinal cortex Does the MTL also mediate binding processes in STM? rela>onal vs uni>zed representa>ons?

16 Rela>onal Binding in Short Term Memory

17 Rela>onal Binding in Short Term Memory Olson et al., J. Neurosci, 2006

18 Rela>onal Binding in Short Term Memory Manohar, Pertzov and Husain, 2017

19 Short Term Memory for Uni>zed Representa>ons Race et al., JEP: LMC, 2013

20 Equivalent MTL contribu>ons to STM and LTM MTL regions important for the forma>on of visual representa>ons in STM and LTM HPC: rela>ons between object & loca>on; between objects in scene Perirhinal cortex: individual objects Diana et al., TICS, 2007

21 MTL mediated binding processes LTM STM Percep>on?

22 Lee et al., Neuropsychologia, 2005

23 MTL mediated binding processes LTM STM Percep>on

24 MTL Dependence across Domains Not all is equal! Demands on binding Low Medium High None (Percep>on) Short (STM) Long (LTM) Temporal Delay

25 From past to present to future

26 Future Thinking in Amnesia E.T.: Let s try the ques>on again about the future. What will you be doing tomorrow (There is a 15- second pause.) N.N. smiles faintly, then says, I don t know. E.T.: Do you remember the ques>on? N.N.: About what I ll be doing tomorrow? E.T.: Yes. How would you describe your state of mind when you try to think about it? (A 5- second pause.) N.N. Blank, I guess. It s like being in a room with nothing there and having a guy tell you to go find a chair, and there s nothing there. Tulving, Canadian Psychology, 1985

27 Role of the hippocampus in future thinking Neuroimaging evidence: Schacter et al., 2007 Addis et al., 2007 Neuropsychological evidence: Hassabis et al. (2007): construc>on of atemporal scenes impaired

28 Episodic prospec>on in MTL amnesia! Is the impairment in prospec>on related to the impairment in memory?! Is the impairment in prospec>on related to narra>ve construc>on? Memory Recollect personal events from the past (e.g., gradua>on ceremony) Picture Narra,ve Tell a story based on a picture Prospec,on Imagine personal events in the future (e.g., taking a trip) Imagine the picture is a scene taken from a movie and tell a story about what s going on in the scene.

29 Adapted Autobiographical Interview Scoring Procedure (Levine et al., 2002) Segment narraave into disanct details, then categorize details as: EPISODIC: Happenings and individuals present (event, place, >me perceptual, thought/emo>on) SEMANTIC: General knowledge and facts, ongoing events, extended states of being (general seman>c, sem- autobiographical, sem- >me, sem- place) EXTERNAL: Details from incidents external to the main event being described

30 Episodic Details Number of Details Controls MTL pa,ents Controls 0 Remote Past Recent Past Near Future Distant Future Picture Narra>ve # Suggests that a common MTL mechanism is cri>cal for both episodic memory and episodic future thinking Race, Keane & Verfaellie, J. Neurosci, 2011

31 Isola>ng Mental Construc>on in MTL amnesia Context: Jungle Items: >ger, tree, snake Relate items to one another within the imagined context Romero & Moscovitch, Journal of Memory and Language, 2012

32 Demands on Mental Construc>on impact other cogni>ve domains Problem solving (Sheldon, McAndrews & Moscovitch, 2011; Warren, Kurczek & Duff, 2016) Crea>vity (Duff, Kurczek, Rubin, Cohen, & Tranel, 2013) Empathy (Beadle, Tranel, Cohen, & Duff, 2013; Davidson, Drouin, Kwan, et al., 2012)

33 Impact of future thinking on decision making: Intertemporal choice paradigm Would you prefer: $30 now $34 in 6 months! Devalue larger reward to account for its delayed arrival

34 Impact of future thinking on decision making: Intertemporal choice paradigm Imagine how you would spend $34 at a bar in 6 months Would you prefer: $30 now $34 in 6 months! Imagining reward brings it subjec>vely closer in >me

35 Impact of future thinking on decision making: Intertemporal choice paradigm Baseline Imagine how you would spend $34 at a bar in 6 months Would you prefer: $30 now $34 in 6 months Imagine future event

36 Reward Index Controls Baseline Patients Imagine Palombo, Keane & Verfaellie, Hippocampus, 2015

37 Intertemporal choice decisions in amnesia: effect of seman>c prospec>on Baseline If you received $42 in 4 months what items would you buy with that money? Would you prefer: $30 now $42 in 4 months Imagine semanac future

38 Controls Amnesics Reward Index Baseline Semantic Palombo, Keane, Verfaellie, Neuropsychologia, 2016

39 Where have we come since HM? Memory is not unitary Dis>nct processes = dis>nct MTL regions LTM STM - percep>on Mental construc>on across domains

40 MTL Amnesia: Past, Present, and Future Iden>fying commonali>es underlying disparate areas of impairment and/or preserva>on Focus on func>onal networks - - altera>ons within the DFN - - disrupted connec>vity between networks Focal lesion studies with greater anatomical precision - - longitudinal extent of HPC lesion - - specific subfields

41 Thank you! Collaborators Margaret Keane Scor Hayes Ginere Lafleche Kelly Giovanello Daniela Palombo Elizabeth Race Support