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


METHODS
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.
Whitford
T J
TJ
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, 1249 Boylston Street, Boston, MA 02215, USA. whitford@bwh.harvard.edu
Mathalon
D H
DH
Shenton
M E
ME
Roach
B J
BJ
Bammer
R
R
Adcock
R A
RA
Bouix
S
S
Kubicki
M
M
De Siebenthal
J
J
Rausch
A C
AC
Schneiderman
J S
JS
Ford
J M
JM
D000328:Adult; D000368:Aged; D001303:Auditory Cortex / Q000503:physiopathology; D016022:Case-Control Studies; D056324:Diffusion Tensor Imaging; D004569:Electroencephalography; D056228:Feedback, Sensory; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology; D006212:Hallucinations / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009433:Neural Inhibition; D009434:Neural Pathways; D012559:Schizophrenia / Q000503:physiopathology*; D013067:Speech Perception