Impairments in frontal cortical γ synchrony and cognitive control in schizophrenia
Abstract
A critical component of cognitive impairments in schizophrenia can be characterized as a disturbance in cognitive control, or the ability to guide and adjust cognitive processes and behavior flexibly in accordance with one's intentions and goals. Cognitive control impairments in schizophrenia are consistently linked to specific disturbances in prefrontal cortical functioning, but the underlying neurophysiologic mechanisms are not yet well characterized. Synchronous γ-band oscillations have been associated with a wide range of perceptual and cognitive processes, raising the possibility that they may also help entrain prefrontal cortical circuits in the service of cognitive control processes. In the present study, we measured induced γ-band activity during a task that reliably engages cognitive control processes in association with prefrontal cortical activations in imaging studies. We found that higher cognitive control demands were associated with increases in induced γ-band activity in the prefrontal areas of healthy subjects but that control-related modulation of prefrontal γ-band activity was absent in schizophrenia subjects. Disturbances in γ-band activity in patients correlated with illness symptoms, and γ-band activity correlated positively with performance in control subjects but not in schizophrenia patients. Our findings may provide a link between previously reported postmortem abnormalities in thalamofrontocortical circuitry and alterations in prefrontal activity observed in functional neuroimaging studies. They also suggest that deficits in frontal cortical γ-band synchrony may contribute to the cognitive control impairments in schizophrenia.
Acknowledgments
We thank Joseph M. Orr for help with graphics and data processing. This work was supported by National Institute of Mental Health Grant MH64190 and a Translational Clinical Scientist Award from the Burroughs–Wellcome Foundation (to C.S.C.) and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award (to R.Y.C.).
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© 2006 by The National Academy of Sciences of the USA.
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Received: June 27, 2006
Published online: December 26, 2006
Published in issue: December 26, 2006
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Acknowledgments
We thank Joseph M. Orr for help with graphics and data processing. This work was supported by National Institute of Mental Health Grant MH64190 and a Translational Clinical Scientist Award from the Burroughs–Wellcome Foundation (to C.S.C.) and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award (to R.Y.C.).
Notes
This article contains supporting information online at www.pnas.org/cgi/content/full/0609440103/DC1.
¶
“Synchrony” can refer to “phase synchrony” that describes consistent phase relationships with respect to a stimulus or response. In this context, however, we refer to the fact that for increases in induced γ band power, clustered, similarly oriented groups of neurons must fire at the same time with respect to each other on any given trial. These requirements are true for any detectable scalp EEG signal, as with regular event-related potentials, but in this case, the synchronous activations modulate in an oscillatory manner.
‖
This central frequency is close to that of line noise (60 Hz). Although a 60-Hz notch filter was used, imperfect filtering could lead to spurious results. As an extra check, for the significant electrodes for the γ band analysis, data were reanalyzed by using a lower sub-band of γ (38–48 Hz, central frequency of 43 Hz). The frontal electrodes retained significance, which is perhaps not surprising given that most of the condition and group related differences were seen in the lower range of γ (see Fig. 3).
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The authors declare no conflict of interest.
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Impairments in frontal cortical γ synchrony and cognitive control in schizophrenia, Proc. Natl. Acad. Sci. U.S.A.
103 (52) 19878-19883,
https://doi.org/10.1073/pnas.0609440103
(2006).
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