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      Resting-state gamma-band power alterations in schizophrenia reveal E/I-balance abnormalities across illness-stages

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          Abstract

          We examined alterations in E/I-balance in schizophrenia (ScZ) through measurements of resting-state gamma-band activity in participants meeting clinical high-risk (CHR) criteria (n = 88), 21 first episode (FEP) patients and 34 chronic ScZ-patients. Furthermore, MRS-data were obtained in CHR-participants and matched controls. Magnetoencephalographic (MEG) resting-state activity was examined at source level and MEG-data were correlated with neuropsychological scores and clinical symptoms. CHR-participants were characterized by increased 64–90 Hz power. In contrast, FEP- and ScZ-patients showed aberrant spectral power at both low- and high gamma-band frequencies. MRS-data showed a shift in E/I-balance toward increased excitation in CHR-participants, which correlated with increased occipital gamma-band power. Finally, neuropsychological deficits and clinical symptoms in FEP and ScZ-patients were correlated with reduced gamma band-activity, while elevated psychotic symptoms in the CHR group showed the opposite relationship. The current study suggests that resting-state gamma-band power and altered Glx/GABA ratio indicate changes in E/I-balance parameters across illness stages in ScZ.

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          Most cited references42

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          The positive and negative syndrome scale (PANSS) for schizophrenia.

          The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
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            Neocortical excitation/inhibition balance in information processing and social dysfunction.

            Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.
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              Abnormal neural oscillations and synchrony in schizophrenia.

              Converging evidence from electrophysiological, physiological and anatomical studies suggests that abnormalities in the synchronized oscillatory activity of neurons may have a central role in the pathophysiology of schizophrenia. Neural oscillations are a fundamental mechanism for the establishment of precise temporal relationships between neuronal responses that are in turn relevant for memory, perception and consciousness. In patients with schizophrenia, the synchronization of beta- and gamma-band activity is abnormal, suggesting a crucial role for dysfunctional oscillations in the generation of the cognitive deficits and other symptoms of the disorder. Dysfunctional oscillations may arise owing to anomalies in the brain's rhythm-generating networks of GABA (gamma-aminobutyric acid) interneurons and in cortico-cortical connections.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                27 September 2018
                2018
                : 7
                : e37799
                Affiliations
                [1 ]deptInstitute of Neuroscience and Psychology University of Glasgow GlasgowUnited Kingdom
                [2 ]Institute for Biomagnetism and Biosignalanalysis, University of Muenster MuensterGermany
                [3 ]deptMEG-Unit Goethe University Frankfurt am MainGermany
                [4 ]deptMental Health and Wellbeing Institute of Health and Wellbeing, University of Glasgow GlasgowUnited Kingdom
                [5 ]deptDepartment of Psychiatry University of Edinburgh EdinburghUnited Kingdom
                [6 ]deptDepartment of Clinical Psychology University Edinburgh EdinburghUnited Kingdom
                [7 ]University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern BernSwitzerland
                [8 ]deptDepartment of Psychiatry and Psychotherapy Medical Faculty, Heinrich-Heine-University DüsseldorfGermany
                [9 ]deptKavli Institute for Systems Neuroscience and Centre for Neural Computation Norwegian University of Science and Technology TrondheimNorway
                [10 ]deptDepartment of Psychosomatics and Psychotherapeutic Medicine Central Institute of Mental health, Medical Faculty Mannheim, Heidelberg University MannheimGermany
                [11 ]deptBrain and Mind Centre University of Sydney SydneyAustralia
                [12 ]deptDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health Medical Faculty Mannheim, Heidelberg University MannheimGermany
                [13 ]deptDepartment of Neurophysiology Max Planck Institute for Brain Research Frankfurt am MainGermany
                [14 ]Ernst Strüngmann Institute for Neuroscience and the Max Planck Society Frankfurt am MainGermany
                [15 ]Frankfurt Institute for Advanced Studies Frankfurt am MainGermany
                University of California, Berkeley United States
                University of California, Berkeley United States
                University of California, Berkeley United States
                Author information
                http://orcid.org/0000-0003-3177-5346
                http://orcid.org/0000-0001-8010-5862
                https://orcid.org/0000-0002-2444-5675
                http://orcid.org/0000-0002-4683-2596
                http://orcid.org/0000-0001-6498-1846
                https://orcid.org/0000-0002-8163-195X
                http://orcid.org/0000-0002-8299-2319
                http://orcid.org/0000-0002-0892-2224
                Article
                37799
                10.7554/eLife.37799
                6160226
                30260771
                c8d38c89-1c27-4392-a74a-967fceffe4f9
                © 2018, Grent-'t-Jong et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 23 April 2018
                : 30 August 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000265, Medical Research Council;
                Award ID: MR/L011689/1
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Neuroscience
                Custom metadata
                Resting-state MEG-activity and MRS-GABA/Glx measurements reveal that there is a significant shift in excitability during the course of schizophrenia, involving hyperexcitability during the onset and a reduction at chronic stages.

                Life sciences
                schizophrenia,e/i-balance,gamma-band activity,human
                Life sciences
                schizophrenia, e/i-balance, gamma-band activity, human

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