Source Memory is not Properly Differentiated from Object Memory in Early Schizophrenia An fmri study using virtual reality

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1 Source Memory is not Properly Differentiated from Object Memory in Early Schizophrenia An fmri study using virtual reality Colin S. Hawco, PhD Lisa Buchy Michael Bodnar, Sarah Izadi, Jennifer Dell Elce, Katrina Messina, Ridha Joober, Ashok Malla & Martin Lepage

2 Memory Encoding Recognition/retrieval Object Information Associative Information Temporal Context Source Information 1. Effective Encoding 2. Correct retrieval Source Memory: Identifying the context in which a stimulus was encountered Requires binding together elements of an event into a memory trace Temporal context Spatial context Typically evaluated at retrieval Often tested with relativity simple, artificial tasks E.g. Identifying the encoding question

3 Source Memory Deficits in Schizophrenia Patients with Schizophrenia have a deficit in source monitoring Particularly for self-generated stimuli More so for patients with hallucinations Keefe et al., Schizophrenia Research 57 (2002) Tendency to attribute internally generated stimuli to an external source

4 Source Memory Deficits in Schizophrenia Altered patens of neural activity during retrieval of self vs. externally generated stimuli Altered functional connectivity when evaluating self vs. other generated words Vinogradov et al., Cerebral Cortex November 2008;18: Wang et al. Schizophrenia Research 125 (2011)

5 fmri of Source Memory in Schizophrenia Ragland et al. Schizophr Res Oct;87(1-3): Encoding session with two tasks - Source memory: identifying the task associated with a word - 13 Patients and 13 controls Patients did not activate the same regions as controls Extra Patient activity not associated with performance Inefficient rather than compensatory activity No significant group differences Green: Controls Red: Schizophrenia

6 Demographic Info 24 patients with schizophrenia spectrum 23 controls Controls Schizophrenia Age 24.4 (3.9) 24.4 (4.1) p = 0.99 Gender (M:F) 19:5 22:4 p = 0.95 Education 13.5 (2.0) 11.4 (1.8) *p < Parental SES 47.3 (17.1) 38.7 (14.0) p = Handedness (L/Amb/R) 18/2/2 23/2/1 Time in Treatment (years) 1.4 ± 1.4 (0.12 to 4.5) Total SAPS 10.6 ± 12.1 (0 to 44) Total SANS 19.4 ± 18.5 (0 to 66) Calgary Depression Scale 1.1 ± 1.99 (0 to 7) Hamilton Anxiety Rating Scale 3.1 ± 4.4 (0 to 21) L= left. R= right. Amb = ambidextrous SAPS = Scale for Assessment of Positive Symptoms SANS = Scale for Assessment of Negative Symptoms Total SANS excludes attention (items 23-25) Clinical scores from assessment closest to scanning date

7 Source Memory in Schizophrenia: An fmri VR Study Virtual Reality Encoding Task Performed outside the MRI prior to scanning 20 Encounters (a person in a place with an object)

8 fmri recognition Task Recognition: Person Place Object Bright Source Memory 20 trials per condition Image presented for 8000 ms, with 1000 to 5000ms ISI

9 Data Recording and Analysis 3T Siemnes Tim Trio MRI TR=2000 ms, TE=30 ms, flip angle=90, 36 slices, 4x4x4mm voxels, 64 x 64 voxel plane, 517 volumes Data analyzed using SPM8 Motion corrected, normalized to MNI space and resampled (2x2x2mm) and smoothed 8 mm Contrasts: Person vs. Object and Place vs. Object (source memory) Second level analysis separately for each group (1 sample t-test) and comparing groups (two-samples t-test) Multiple corrections performed using cluster extent defined by monte-carlo simulation

10 Controls Schizophrenia Controls Schizophrenia Person > object Place > object Person AND place > object Object > person Object > place Object > person AND place

11 Schizophrenia vs. Controls Controls Object > place

12 A closer look A: -50, 23, D: -8, 14, controls schizophrenia person place object 0 controls schizophrenia person place object B: , controls schizophrenia person place object E: 30, 44, controls schizophrenia person place object C: 2, -64, controls schizophrenia person place object F: 56, -2, controls schizophrenia person place object

13 Relationship between source memory and hallucinations SAPS total hallucinations at baseline assessment regressed against source memory contrasts Left V/DLPFC Right mid-temporal gyrus Cerebellum L Regions associated with hallucinations

14

15 Martin Lepage Ashok Malla Lisa Buchy Ridha Joober?? Michael Bodnar

16

17 Controls Schizoprehnia p-value Person 79 (14) 70 (14) p = 0.03 Place 75 (17) 78 (14) p= 0.66 Object 92 (13) 91 (13) p = 0.95

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