Article “Gamma Synchrony ” in First-Episode Schizophrenia: A Disorder of Temporal Connectivity?

The Brain Dynamics Centre, Westmead Hospital, Westmead, N.S.W., 2145 Australia.
American Journal of Psychiatry (Impact Factor: 12.3). 04/2005; 162(3):459-65. DOI: 10.1176/appi.ajp.162.3.459
Source: PubMed


There has been a convergence of models describing schizophrenia as a disconnection syndrome, with a focus on the temporal connectivity of neural activity. Synchronous gamma-band (40-Hz) activity has been implicated as a candidate mechanism for the binding of distributed neural activity. To the authors' knowledge, this is the first study to investigate "gamma synchrony" in first-episode schizophrenia.
Forty medicated first-episode schizophrenia patients and 40 age- and sex-matched healthy comparison subjects participated in a conventional auditory oddball paradigm. Gamma synchrony, time-locked to target stimuli, was extracted from an ongoing EEG. The magnitude and latency of both early (gamma 1: -150 msec to 150 msec poststimulus) and late (gamma 2: 200 to 550 msec poststimulus) synchrony were analyzed with multiple analysis of variance.
First-episode schizophrenia patients showed a decreased magnitude and delayed latency for global gamma 1 synchrony in relation to healthy comparison subjects. By contrast, there were no group differences in gamma 2 synchrony.
These findings suggest that first-episode schizophrenia patients have a global decrease and delay of temporal connectivity of neural activity in early sensory response to task-relevant stimuli. This is consistent with cognitive evidence of perceptual integration deficits in this disorder and raises the possibility that a breakdown in the early synchrony of distributed neural networks is a marker for the onset of 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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    • "The effect of antipsychotics to modulate γ oscillations may confound much of the literature examining these neural rhythms which has been generated in clinical populations. Although some studies have compared drug-free and medicated patients (Gallinat et al., 2004), or examined first episode patients to eliminate the effects of medication (Symond et al., 2005), the vast majority do not control for drug effects. This therefore remains an understudied area with important clinical implications. "
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    ABSTRACT: Noncompetitive N-methyl-d-aspartate receptor (NMDAr) antagonists can elicit many of the symptoms observed in schizophrenia in healthy humans, and induce a behavioural phenotype in animals relevant to psychosis. These compounds also elevate the power and synchrony of gamma (γ) frequency (30-80 Hz) neural oscillations. Acute doses of antipsychotic medications have been shown to reduce ongoing γ power and to inhibit NMDAr antagonist-mediated psychosis-like behaviour in rodents. This study aimed to investigate how a chronic antipsychotic dosing regimen affects ongoing cortical γ oscillations, and the electrophysiological and behavioural responses induced by the NMDAr antagonist ketamine. Male Wistar rats were chronically treated with haloperidol (0.25 mg/kg/d), clozapine (5 mg/kg/d), LY379268 (0.3 mg/kg/d) or vehicle for 28 d, delivered by subcutaneous (s.c.) osmotic pumps. Weekly electrocorticogram (ECoG) recordings were acquired. On day 26, ketamine (5 mg/kg, s.c.) was administered, and ECoG and locomotor activity were simultaneously measured. These results were compared with data generated previously following acute treatment with these antipsychotics. Sustained and significant decreases in ongoing γ power were observed during chronic administration of haloperidol (64%) or clozapine (43%), but not of LY379268 (2% increase), compared with vehicle. Acute ketamine injection concurrently increased γ power and locomotor activity in vehicle-treated rats, and these effects were attenuated in rats chronically treated with all three antipsychotics. The ability of haloperidol or clozapine to inhibit ketamine-induced elevation in γ power was not observed following acute administration of these drugs. These results indicate that modulation of γ power may be a useful biomarker of chronic antipsychotic efficacy.
    The International Journal of Neuropsychopharmacology 06/2014; 17(11):1-10. DOI:10.1017/S1461145714000959 · 4.01 Impact Factor
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    • "A number of neurological and psychiatric disorders are also characterized by interrupted or decreased gamma-band activity (Garcia-Rill et al. 2014). Aberrant gamma-band activity and coherence during cognitive tasks or attentional load have been reported in schizophrenic and bipolar disorder patients (Flynn et al. 2008; Ozerdem et al. 2011; Spencer et al. 2003; Symond et al. 2005; Uhlhaas and Singer 2010). "
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