Converging evidence for gamma synchrony deficits in schizophrenia

Roach, Brian J.; Ford, JM; Hoffman, Ralph E.; Mathalon, Daniel H.

doi:10.1016/b978-0-7020-5307-8.00011-9

Cited by 40 publications

(31 citation statements)

References 69 publications

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“…We and others have recently reported decreased early gamma activity in response to auditory stimuli in patients with schizophrenia, as reflected by evoked power (Hall et al, 2011a; Hall et al, 2011b; Leicht et al, 2010b) and phase-locking factor (Hall et al, 2011b; Leicht et al, 2010b; Roach and Mathalon, 2008; Roach, this issue). In auditory oddball paradigms, schizophrenia has been associated with an abnormal reduction of GBRs to target (Haig et al, 2000b; Symond et al, 2005) and non-target (Haig et al, 2000b; Hall et al, 2011b; Roach and Mathalon, 2008) auditory tones, suggesting that the early-evoked GBRs to auditory stimuli are either compromised by a lack of phase consistency across trials, reduced response magnitude, or some combination of the two.…”

Section: Introductionmentioning

confidence: 66%

“…In auditory oddball paradigms, schizophrenia has been associated with an abnormal reduction of GBRs to target (Haig et al, 2000b; Symond et al, 2005) and non-target (Haig et al, 2000b; Hall et al, 2011b; Roach and Mathalon, 2008) auditory tones, suggesting that the early-evoked GBRs to auditory stimuli are either compromised by a lack of phase consistency across trials, reduced response magnitude, or some combination of the two. While gamma oscillation abnormalities are evident in chronic schizophrenia patients (Gallinat et al, 2004; Hall et al, 2011a; Hall et al, 2011b; Kwon et al, 1999; Light et al, 2006; e.g., Roach and Mathalon, 2008; Roach, this issue), in first-episode psychosis (Spencer et al, 2008b; Symond et al, 2005; Williams et al, 2009), and to a lesser degree, in unaffected relatives (Hall et al, 2011b; Hong et al, 2004b; Leicht et al, 2010a), but see (Hall et al, 2011a), it remains unclear whether they are present in individuals at clinical high risk for the development of psychosis.…”

Section: Introductionmentioning

confidence: 99%

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Early auditory gamma-band responses in patients at clinical high risk for schizophrenia

Perez

Roach

Woods

et al. 2013

Supplements to Clinical Neurophysiology

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Background Gamma band oscillations and their synchronization have been implicated in the coordination of activity between distributed neuronal assemblies in the service of sensory registration of stimuli and perceptual binding of their features. Prior electroencephalographic (EEG) studies of chronic schizophrenia patients have documented deficits in the magnitude and/or phase synchrony of stimulus-evoked gamma oscillations, findings that have been linked to neurotransmission abnormalities involving GABA and NMDA-glutamate receptors. However, it remains unclear whether these abnormalities are present at the onset of the illness, or indeed, whether they are present during the prodromal period preceding illness onset. Accordingly, we examined the magnitude and phase-synchrony of the transient gamma band response (GBR) elicited by an auditory stimulus in young patients with schizophrenia and in patients at clinical high risk for psychosis based on their manifestation of putatively prodromal symptoms. Methods EEG was recorded during an auditory oddball target detection task in 3 groups: young schizophrenia patients early in their illness (YSZ; n=19), patients at clinical high risk for psychosis (CHR; n=43), and healthy controls (HC; n=42). Single trial EEG epochs and the average event-related potential time-locked to standard tones from the oddball task were subjected to time-frequency decomposition using Morlet wavelet transformations. The GBR between 50-100 msec following the tone onset was quantified in terms of evoked power, total power, and the phase-locking factor (PLF) reflecting cross-trial phase synchrony. Results GBR evoked power was significantly reduced in YSZ (p<.01) and CHR (p<.05) patients, relative to HC. Similarly, GBR PLF was significantly reduced in YSZ (p<.01) and showed a marginal reduction in CHR patients (p=.057), relative to HC. GBR total power was not reduced in CHR patients (p=.68) and showed only a trend level reduction in YSZ (p=.072). Within the CHR group, there were no significant GBR differences between the patients who converted to a psychotic disorder and those who did not convert to psychosis during a 12-month follow-up period. Conclusion Reductions in the transient auditory GBR, as reflected by evoked power and phase synchrony, are evident in the early stages of schizophrenia and appear to precede psychosis onset. However, the absence of total power GBR abnormalities in CHR patients, with only a trend toward reduction in YSZ patients, suggests that the magnitude of the GBR is intact early in the course of schizophrenia, whereas the phase synchrony of this response is deficient. Given that the GBR failed to distinguish the CHR patients who converted to psychosis from those who did not convert, the role of GBR disruption in the emergence of psychosis warrants further investigation. Asynchronous gamma activity may represent an elemental neurobiological abnormality in schizophrenia that is also evident in patients at high clinical risk for psychosis regardless of their longer-ter...

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Section: Introductionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Early auditory gamma-band responses in patients at clinical high risk for schizophrenia

Perez

Roach

Woods

et al. 2013

Supplements to Clinical Neurophysiology

View full text Add to dashboard Cite

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“…To date, there have been over a dozen reports on 40 Hz ASSR in schizophrenia patients (reviewed in O'Donnell et al, 2013;Roach et al, 2013). In a majority of these, a deficit in PLF and/or evoked response has been found relative to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

40 Hz Auditory Steady-State Response Is a Pharmacodynamic Biomarker for Cortical NMDA Receptors

Sivarao

Chen

Senapati

et al. 2016

Neuropsychopharmacol

108

106

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Schizophrenia patients exhibit dysfunctional gamma oscillations in response to simple auditory stimuli or more complex cognitive tasks, a phenomenon explained by reduced NMDA transmission within inhibitory/excitatory cortical networks. Indeed, a simple steady-state auditory click stimulation paradigm at gamma frequency (~40 Hz) has been reproducibly shown to reduce entrainment as measured by electroencephalography (EEG) in patients. However, some investigators have reported increased phase locking factor (PLF) and power in response to 40 Hz auditory stimulus in patients. Interestingly, preclinical literature also reflects this contradiction. We investigated whether a graded deficiency in NMDA transmission can account for such disparate findings by administering subanesthetic ketamine (1-30 mg/kg, i.v.) or vehicle to conscious rats (n = 12) and testing their EEG entrainment to 40 Hz click stimuli at various time points (~7-62 min after treatment). In separate cohorts, we examined in vivo NMDA channel occupancy and tissue exposure to contextualize ketamine effects. We report a robust inverse relationship between PLF and NMDA occupancy 7 min after dosing. Moreover, ketamine could produce inhibition or disinhibition of the 40 Hz response in a temporally dynamic manner. These results provide for the first time empirical data to understand how cortical NMDA transmission deficit may lead to opposite modulation of the auditory steady-state response (ASSR). Importantly, our findings posit that 40 Hz ASSR is a pharmacodynamic biomarker for cortical NMDA function that is also robustly translatable. Besides schizophrenia, such a functional biomarker may be of value to neuropsychiatric disorders like bipolar and autism spectrum where 40 Hz ASSR deficits have been documented.

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“…These impaired interactions between brain regions support the notion of a disconnectivity syndrome in schizophrenia, which suggests dysfunctional coordination or synchronization of neuronal oscillations in large-scale networks (Uhlhaas 2013). Alterations of neuronal synchrony parameters of these brain regions have also been demonstrated to be implicated in the pathophysiological processes of the disorder (Uhlhaas et al 2008;Roach et al 2013;Skåtun et al 2016). …”

Section: Introductionmentioning

confidence: 53%

Differences of temporal dynamics and signal complexity of gamma band oscillations in first-episode psychosis during a working memory task

et al. 2017

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Gamma band oscillations participate in the temporal binding needed to synchronize cortical networks, involved in early sensory and short term memory processes. In earlier studies, alterations of these neurophysiological parameters have been found in psychotic disorders. To date no study has explored the temporal dynamics and signal complexity of gamma band oscillations in first episode psychosis (FEP). To address this issue, gamma band analysis was performed in 15 FEP patients and 18 healthy controls who successfully performed an adapted 2-back working memory task. Multiple linear and logistic regression models were computed to explore the relationship between the cognitive status and gamma oscillation changes over time. Based on regression model results, phase diagrams were constructed and their complexity was estimated using fractal dimension, a mathematical tool that describes shapes as numeric values. When adjusted for gamma values at time lags -3 to -4 ms and -15 to -16 ms, FEP patients displayed significantly higher time-dependent changes than controls, independently of the nature of the task. The present results are consistent with a discoordination of the activity of cortical generators engaged by the stimulus apparition in FEP patients, leading to a global binding deficit. In addition, fractal analysis showing higher complexity of gamma signal, confirmed this deficit. Our results provide evidence for recruitment of supplementary cortical generators as compensating mechanisms and yield further understanding for the pathophysiology cognitive impairments in FEP.

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Converging evidence for gamma synchrony deficits in schizophrenia

Cited by 40 publications

References 69 publications

Early auditory gamma-band responses in patients at clinical high risk for schizophrenia

Early auditory gamma-band responses in patients at clinical high risk for schizophrenia

40 Hz Auditory Steady-State Response Is a Pharmacodynamic Biomarker for Cortical NMDA Receptors

Differences of temporal dynamics and signal complexity of gamma band oscillations in first-episode psychosis during a working memory task

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