Cho RY, Konecky RO, Carter CS. Impairments in frontal cortical gamma synchrony and cognitive control in schizophrenia. Proc Natl Acad Sci USA 103: 19878-19883

Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/2007; 103(52):19878-83. DOI: 10.1073/pnas.0609440103
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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 gamma-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 gamma-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 gamma-band activity in the prefrontal areas of healthy subjects but that control-related modulation of prefrontal gamma-band activity was absent in schizophrenia subjects. Disturbances in gamma-band activity in patients correlated with illness symptoms, and gamma-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 gamma-band synchrony may contribute to the cognitive control impairments in schizophrenia.

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    • "In the last decade clinical research on oscillatory brain dynamics reported altered neuronal oscillations in neuropsychiatric disorders (Basar, 2013; Basar and Guntekin, 2008; Herrmann and Demiralp, 2005; Uhlhaas and Singer, 2010), suggesting that reduced gamma oscillations could be common to bipolar disorder (BPD), major depressive disorder (MDD) and schizophrenia (SCZ) (Maharajh et al., 2007; O'Donnell et al., 2004b). Frontal cortical gamma activity (30–50 HZ), as indexed through electroencephalography (EEG), is reduced in patients with SCZ (Uhlhaas et al., 2008), in response to odd-ball paradigm (Gallinat et al., 2004; Haig et al., 2000; Symond et al., 2005) or cognitive control task (Cho et al., 2006). EEG power and phase synchronization in beta/gamma frequencies bands after to 40 Hz auditory stimulation are also reduced (Kwon et al., 1999; Light et al., 2006). "
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    ABSTRACT: Recent studies have demonstrated that cortical brain areas tend to oscillate at a specific natural frequency when directly perturbed by transcranial magnetic stimulation (TMS). Fast electroencephalographic (EEG) oscillations, which typically originate from frontal regions, have been reported to be markedly reduced in schizophrenia. Here we employed TMS/EEG to assess the natural frequency of the premotor area in a sample of 48 age-matched participants (12 each in major depression disorder (MDD)), bipolar disorder (BPD), schizophrenia (SCZ) and healthy controls. Event related spectral perturbations (ERSP) were obtained for each study participant using wavelet decomposition. TMS resulted in a significant activation of the beta/gamma band response (21-50Hz) to frontal cortical perturbation in healthy control subjects. By contrast, the main frequencies of frontal EEG responses to TMS were significantly reduced in patients with BPD, MDD and SCZ (11-27Hz) relative to healthy subjects. Patients with bipolar disorder, major depression and schizophrenia showed a significantly lower natural frequency of frontal cortico-thalamocortical circuits compared to healthy controls. These results suggest a common neurobiological mechanism of corticothalamic impairment. The most likely candidates include dysfunction of GABAergic circuits. Further studies are needed to consider other biological markers, gene variants, and their interaction with clinical variables. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 06/2015; 184:111-115. DOI:10.1016/j.jad.2015.05.043 · 3.38 Impact Factor
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    • "Patients with schizophrenia show deficits across all sensory modalities which can impact upstream cortical processing with consequences in higher order cognitive operations (Javitt, 2009; Arguello and Gogos, 2010). Moreover, the deficits in cognitive control exhibited by subjects with schizophrenia are correlated with deficits in gamma oscillation production (Cho et al., 2006; Lesh et al., 2011). "
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    Reviews in the neurosciences 01/2015; 26(3). DOI:10.1515/revneuro-2014-0085 · 3.33 Impact Factor
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    • "Many studies involving neuropsychiatric disorders have focused on abnormalities in gamma oscillations because of its association with higher order cognitive processes including sensory processing, attention, working memory, and executive functioning, all domains in which patients with schizophrenia are impaired (Uhlhaas et al., 2008). For example, patients with schizophrenia have impairments in gamma oscillatory activity in response to 40 Hz auditory stimulation (Light et al., 2006), during perception of gestalt objects (Spencer et al., 2003) and during working memory performance (Cho et al., 2006; Barr et al., 2010). Disrupted gamma oscillatory activity has also been demonstrated in schizophrenia using TMS and EEG (Ferrarelli et al., 2008; Farzan et al., 2010a; Frantseva et al., 2014). "
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    ABSTRACT: Abnormal gamma-aminobutyric acid inhibitory neurotransmission is a key pathophysiological mechanism underlying schizophrenia. Transcranial magnetic stimulation can be combined with electroencephalography to index long-interval cortical inhibition, a measure of GABAergic receptor-mediated inhibitory neurotransmission from the frontal and motor cortex. In previous studies we have reported that schizophrenia is associated with inhibitory deficits in the dorsolateral prefrontal cortex compared to healthy subjects and patients with bipolar disorder. The main objective of the current study was to replicate and extend these initial findings by evaluating long-interval cortical inhibition from the dorsolateral prefrontal cortex in patients with schizophrenia compared to patients with obsessive-compulsive disorder. A total of 111 participants were assessed: 38 patients with schizophrenia (average age: 35.71 years, 25 males, 13 females), 27 patients with obsessive-compulsive disorder (average age: 36.15 years, 11 males, 16 females) and 46 healthy subjects (average age: 33.63 years, 23 females, 23 males). Long-interval cortical inhibition was measured from the dorsolateral prefrontal cortex and motor cortex through combined transcranial magnetic stimulation and electroencephalography. In the dorsolateral prefrontal cortex, long-interval cortical inhibition was significantly reduced in patients with schizophrenia compared to healthy subjects (P = 0.004) and not significantly different between patients with obsessive-compulsive disorder and healthy subjects (P = 0.5445). Long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex were also significantly greater in patients with schizophrenia compared to patients with obsessive-compulsive disorder (P = 0.0465). There were no significant differences in long-interval cortical inhibition across all three groups in the motor cortex. These results demonstrate that long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex are specific to patients with schizophrenia and are not a generalized deficit that is shared by disorders of severe psychopathology. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:
    Brain 12/2014; 138(2). DOI:10.1093/brain/awu360 · 9.20 Impact Factor
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