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Visual and Auditory Event-Related Potential (ERP) Correlates of

Psychophysiology Laboratory. 43 rd Annual Meeting of the Society for Psychophysiological Research (SPR), October 29 – November 2, 2003, Chicago, IL, USA. Visual and Auditory Event-Related Potential (ERP) Correlates of Continuous Word Recognition Memory (RM) in Schizophrenia.

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Visual and Auditory Event-Related Potential (ERP) Correlates of

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  1. Psychophysiology Laboratory 43rd Annual Meeting of the Society for Psychophysiological Research (SPR), October 29 – November 2, 2003,Chicago, IL, USA Visual and Auditory Event-Related Potential (ERP) Correlates of Continuous Word Recognition Memory (RM) in Schizophrenia Jürgen Kayser, Gerard E. Bruder, Craig E. Tenke, Roberto Gil, Jack M. Gorman Department of Biopsychology New York State Psychiatric Institute Columbia University College of Physicians and Surgeons

  2. N1 N2 • Auditory ERP abnormalities in schizophrenia • early and late ERP components: • N1, N2, MMN, P3, CNV, PINV • auditory N2 and P3 reductions in schizophrenia due to medial temporal lobe (MTL) abnormalities • (e.g., McCarley et al., 1991, 1993) P3(00) MTL structures are crucial for recognition memory and may be linked to impairments in verbal learning and memory in schizophrenia (e.g., Saykin et al., 1994; Gur et al., 1994). StimOn • Both structural and functional temporal lobe abnormalities in schizophrenia • neocortical: superior temporal gyrus (e.g., Barta et al., 1990) • subcortical: hippocampus (e.g., Bogerts et al., 1990) • affect primarily the left side (e.g., Barta et al., 1990; Falkai et al., 1995; Salisbury et al., 1998) • left-sided, language-related deficit in the supratemporal plane (e.g., Crow, 1990) • affect both hemispheres (e.g., Weinberger et al., 1991; Pfefferbaum et al., 1989) Ford et al., 1999. Biol Psychiatry, 46:94-101. If left temporal lobe dysfunction involves MTL structures, then schizophrenic patients should show abnormal word recognition memory and its electrophysiological correlates. Background

  3. N1 N2 Old/New Effect Typical ERP finding during explicit memory-retrieval tasks (i.e., judging items as being old or new) N2 P3 P600 Friedman, 2000. Biol. Psychol., 54:175-206. Visual Continuous Word Recognition Memory Kayser et al., 1999. Int. J. Psychophysiol., 34: 249-265. Background (cont.) • begins at 200 – 400 ms • lasts 300 – 500 ms • mostly posterior • words, pictures, faces, etc. • overlaps at least two distinct ERP components: N400 / N2 and P600 / P3b • scalp distribution differs from N2 and P3 topographies _ +

  4. Cognitive ERP deficits in schizophrenia during recognition memory may be more robust with spoken than read words  dysfunction affects primarily auditory modality Behavioral and neurological evidence suggests that visual and auditory short-term memory processes are distinct and involve separate neural pathways • ERPs reflect time course and anatomy of these separate processing streams of • perceptual • linguistic processes • mnemonic Price 2000. J. Anat., 197:335-359. What is the significance of the processing modality? Background (cont.) and should be particularly suited to separate modality-specific recognition memory deficits in schizophrenia Objective: Compare visual and auditory ERP old/new effects in schizophrenia

  5. Visual Auditory … … … habit rock rock fraction Exposure [ms] 400 411 (229 – 718) new item paper filler item (never-repeated) V-A-A-V or A-V-V-A lags: 8 items 24 items shock 4 blocks check check old item 456 trials total time 228 items/modality 92 filler 68 new/old pairs forced choice button press newold Continuous Word Recognition Memory Task SOA 2,000 ms

  6. Demographic Data Healthy Adults (n = 34) Schizophrenic Patients (n = 18) • no history of any psychopathology or neurology disorder • NYSPI inpatients DSM-IV Criteria Medication Status schizophrenia, undifferentiated (n=5) schizophrenia, paranoid (n=6) schizophrenia, disorganized (n=1) schizophrenoform (n=1) psychosis NOS (n=1) schizoaffective Disorder, bipolar (n=3) schizoaffective Disorder, depressive (n=1) Risperidone (n=4) Clozapine (n=3) Olanzapine (n=2) Fluphenazine (n=1) unmedicated > 14 days (n=8) Gender (male/female) 17 / 17 15 / 3 Age (years) 28.4 ± 5.7 (21 – 42 yrs) 27.7 ± 7.6 (18 – 44 yrs) Education (years) 16.7 ± 2.5 12.5 ± 2.3 p < .001 Handedness (EHI) (Oldfield, 1971) 82.1 ± 18.0 79.3 ± 32.1 Total BPRS 31.4 ± 8.2 (range 18 – 48) PANSS general 26.8 ± 7.7 (range 16 – 38) PANSS positive 13.8 ± 5.2 (range 7 – 23) PANSS negative 12.8 ± 5.8 (range 7 – 27)

  7. Condition p < .0001 Modality p < .0001 Behavioral Data Schizophrenic Patients (n = 18) Healthy Adults (n = 34) Group p = .002 Group p = .001 Modality x Condition p < .0001 Group x Condition p = .04 Group p < .0001 Modality x Condition x Group p = .02

  8. ElectroCap (30-channel) Left Mastoid Right Mastoid 10-20 System EEG Montage (Nose Reference) Nose

  9. N2 N1 P2 P3 Nose-referenced ERP Waveforms Healthy Adults (n = 34)

  10. N2 N1 P2 P3 Nose-referenced ERP Waveforms Schizophrenic Patients (n = 18)

  11. N2 N1 P3 P1 Nose-referenced ERP Waveforms Healthy Adults (n = 34)

  12. N1 P3 N2 P1 Nose-referenced ERP Waveforms Schizophrenic Patients (n = 18) ?

  13. Auditory Visual Inverted nose-referenced N1 P3 ‘N1’ P3 ERP Waveforms re-referenced to ‘Linked’ Mastoids (TP9/10) Healthy Adults (n = 26) Schizophrenic Patients (n = 18) Healthy Adults (n = 26) Schizophrenic Patients (n = 18)

  14. Laplacian (CSD) Topographies • Spatial Enhancement (‘deblurring’) technique • Mathematical transformation (simplifications of Poisson's equation) relating current generators to the (negative) second spatial derivative of the field potential at each electrode • Removes volume-conducted activity • Provides a concise, reference-free simplification of a field topography • Indicates neuronal depolarization as a current sink (negativity), repolarization or hyperpolarization as a current source (positivity)

  15. Laplacian (CSD) Topographies Time interval: 0 – 1495 ms Spherical Splines (Perrin et al., 1989) Emotional Content Negative Neutral Negative - Neutral Controls (n=16) Patients (n=30)

  16. Laplacian (CSD) Topographies Time interval: 0 – 1495 ms Spherical Splines (Perrin et al., 1989) Emotional Content Negative Neutral Negative - Neutral Controls (n=16) Patients (n=30)

  17. N1 sink N2 sink P2 source P3 source Reference-free CSD Waveforms Healthy Adults (n = 34) Schizophrenic Patients (n = 18)

  18. N1 sink N2 sink P3 source P1 source Reference-free CSD Waveforms Healthy Adults (n = 34) Schizophrenic Patients (n = 18)

  19. Explained Variance 835 28.0% 1380 25.7% 480 21.6% 205 5.0% 660 3.2% 140 3.0% 290 2.2% 88.7% Explained Variance 675 24.8% 1580 23.0% 1045 18.3% 425 15.1% 215 3.5% 110 1.6% 155 1.0% 87.3% P3 source P3 source Healthy Adults (n = 34) Schizophrenic Patients (n = 18) New Old Old - New New Old Old - New PCA for CSD Component Measurement • covariance matrix • unrestricted factor extraction • unscaled Varimax rotation Kayser & Tenke, 2003. Clin. Neurophysiol., 114(12):2307-2325 110 215 1045 1580 425 155 290 1380 480 675 835 660 140 205

  20. Auditory Visual 110 425 140 290 205 CSD Factor Healthy Adults (n = 34) Schizophrenic Patients (n = 18) Group C3/4 p = .04 Group Fz/Cz p < .05 Hemi x Group P7/8 p = .04 Group Cz p = .05 Group P9/10 p = .03 Topographies of PCA Factor Scores

  21. For both controls and patient, visual/auditory word recognition memory tasks produced • distinct ERP components • discrete topographies reflecting anatomy of visual/auditory pathways • systematic reference changes • reference-free CSD measures dissociate neural generators of ERP old/new effects • The CSD equivalent of the posterior old/new effect was • observed in both modalities: • comparable time course (maximal between 500-700 ms) • modality-specific scalp topography: auditory - more posterior • visual - more anterior • common cognitive process • separable neural generators This applies to both groups, particularly for the auditory modality, despite poorer recognition memory* of schizophrenic patients. However, the lateral, asymmetric parietal sources observed in healthy adults were clearly different from the mid-posterior current source of schizophrenic patients, implicating different neuronal generators of the posterior old/new effect. These group differences in source activity may result from earlier stimulus-processing deficits, as indexed by modality-specific reductions of early ERP negativities (sinks related to N1 and N2) in schizophrenia. Conclusions * Note: Only participants performing above chance were included!

  22. http://psychophysiology.cpmc.columbia.edu New York State Psychiatric Institute Department of Clinical Psychobiology Department of Biopsychology Gerard Bruder Craig Tenke Regan Fong Nathan Gates Charlye Griggs Paul Leite Mia Sage James Sedouruk Jack Gorman Roberto Gil Department of Medical Genetics Charles Brown David Friedman

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