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Electrophysiological and diffusion tensor imaging evidence of delayed corollary discharges in patients with schizophrenia

Published online by Cambridge University Press:  22 July 2010

T. J. Whitford*
Affiliation:
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Melbourne, Victoria, Australia
D. H. Mathalon
Affiliation:
Brain Imaging and EEG Laboratory, Department of Psychiatry, University of California, San Francisco, CA, USA Psychiatry Services, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA
M. E. Shenton
Affiliation:
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Boston Veterans Affairs Healthcare System, Brockton Division, Harvard Medical School, Brockton, MA, USA
B. J. Roach
Affiliation:
Brain Imaging and EEG Laboratory, Department of Psychiatry, University of California, San Francisco, CA, USA Psychiatry Services, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA
R. Bammer
Affiliation:
Radiological Sciences Laboratory, School of Medicine, Stanford University, CA, USA
R. A. Adcock
Affiliation:
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
S. Bouix
Affiliation:
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
M. Kubicki
Affiliation:
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Boston Veterans Affairs Healthcare System, Brockton Division, Harvard Medical School, Brockton, MA, USA
J. De Siebenthal
Affiliation:
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
A. C. Rausch
Affiliation:
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
J. S. Schneiderman
Affiliation:
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
J. M. Ford
Affiliation:
Brain Imaging and EEG Laboratory, Department of Psychiatry, University of California, San Francisco, CA, USA Psychiatry Services, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA
*
*Address for correspondence: Dr T. J. Whitford, Psychiatry Neuroimaging Laboratory, 1249 Boylston Street, Boston, MA 02215, USA. (Email: whitford@bwh.harvard.edu)

Abstract

Background

Patients with schizophrenia (SZ) characteristically exhibit supranormal levels of cortical activity to self-induced sensory stimuli, ostensibly because of abnormalities in the neural signals (corollary discharges, CDs) normatively involved in suppressing the sensory consequences of self-generated actions. The nature of these abnormalities is unknown. This study investigated whether SZ patients experience CDs that are abnormally delayed in their arrival at the sensory cortex.

Method

Twenty-one patients with SZ and 25 matched control participants underwent electroencephalography (EEG). Participants' level of cortical suppression was calculated as the amplitude of the N1 component evoked by a button press-elicited auditory stimulus, subtracted from the N1 amplitude evoked by the same stimulus presented passively. In the three experimental conditions, the auditory stimulus was delivered 0, 50 or 100 ms subsequent to the button-press. Fifteen SZ patients and 17 healthy controls (HCs) also underwent diffusion tensor imaging (DTI), and the fractional anisotropy (FA) of participants' arcuate fasciculus was used to predict their level of cortical suppression in the three conditions.

Results

While the SZ patients exhibited subnormal N1 suppression to undelayed, self-generated auditory stimuli, these deficits were eliminated by imposing a 50-ms, but not a 100-ms, delay between the button-press and the evoked stimulus. Furthermore, the extent to which the 50-ms delay normalized a patient's level of N1 suppression was linearly related to the FA of their arcuate fasciculus.

Conclusions

These data suggest that SZ patients experience temporally delayed CDs to self-generated auditory stimuli, putatively because of structural damage to the white-matter (WM) fasciculus connecting the sites of discharge initiation and destination.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2010

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