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      Test-retest reliability of time-frequency measures of auditory steady-state responses in patients with schizophrenia and healthy controls

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          Abstract

          Background

          Auditory steady-state response (ASSR) paradigms have consistently demonstrated gamma band abnormalities in schizophrenia at a 40-Hz driving frequency with both electroencephalography (EEG) and magnetoencephalography (MEG). Various time-frequency measures have been used to assess the 40-Hz ASSR, including evoked power, single trial total power, phase-locking factor (PLF), and phase-locking angle (PLA). While both EEG and MEG studies have shown power and PLF ASSR measures to exhibit excellent test-retest reliability in healthy adults, the reliability of these measures in patients with schizophrenia has not been determined.

          Methods

          ASSRs were obtained by recording EEG data during presentation of repeated 20-Hz, 30-Hz and 40-Hz auditory click trains from nine schizophrenia patients (SZ) and nine healthy controls (HC) tested on two occasions. Similar ASSR data were collected from a separate group of 30 HC on two to three test occasions. A subset of these HC subjects had EEG recordings during two tasks, passively listening and actively attending to click train stimuli. Evoked power, total power, PLF, and PLA were calculated following Morlet wavelet time-frequency decomposition of EEG data and test-retest generalizability (G) coefficients were calculated for each ASSR condition, time-frequency measure, and subject group.

          Results

          G-coefficients ranged from good to excellent (> 0.6) for most 40-Hz time-frequency measures and participant groups, whereas 20-Hz G-coefficients were much more variable. Importantly, test-retest reliability was excellent for the various 40-Hz ASSR measures in SZ, similar to reliabilities in HC. Active attention to click train stimuli modestly reduced G-coefficients in HC relative to the passive listening condition.

          Discussion

          The excellent test-retest reliability of 40-Hz ASSR measures replicates previous EEG and MEG studies. PLA, a relatively new time-frequency measure, was shown for the first time to have excellent reliability, comparable to power and PLF measures. Excellent reliability of 40 Hz ASSR measures in SZ supports their use in clinical trials and longitudinal observational studies.

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          Most cited references35

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          Developing criteria for establishing interrater reliability of specific items: applications to assessment of adaptive behavior.

          A set of criteria based upon biostatistical considerations for determining the interrater reliability of specific adaptive behavior items in a given setting was presented. The advantages and limitations of extant statistical assessment procedures were discussed. Also, a set of guidelines for differentiating type of adaptive behavior that are statistically reliable from those that are reliable in a clinical or practical sense was delineated. Data sets were presented throughout in order to illustrate the advantages of recommended statistical procedures over other available ones.
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            A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior

            Synchronous recruitment of fast-spiking (FS) parvalbumin (PV) interneurons generates gamma oscillations, rhythms that emerge during performance of cognitive tasks. Administration of N-methyl-D-aspartate (NMDA) receptor antagonists alters gamma rhythms, and can induce cognitive as well as psychosis-like symptoms in humans. The disruption of NMDA receptor (NMDAR) signaling specifically in FS PV interneurons is therefore hypothesized to give rise to neural network dysfunction that could underlie these symptoms. To address the connection between NMDAR activity, FS PV interneurons, gamma oscillations and behavior, we generated mice lacking NMDAR neurotransmission only in PV cells (PV-Cre/NR1f/f mice). Here, we show that mutant mice exhibit enhanced baseline cortical gamma rhythms, impaired gamma rhythm induction after optogenetic drive of PV interneurons and reduced sensitivity to the effects of NMDAR antagonists on gamma oscillations and stereotypies. Mutant mice show largely normal behaviors except for selective cognitive impairments, including deficits in habituation, working memory and associative learning. Our results provide evidence for the critical role of NMDAR in PV interneurons for expression of normal gamma rhythms and specific cognitive behaviors.
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              GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia.

              Synchronization of neuronal activity in the neocortex may underlie the coordination of neural representations and thus is critical for optimal cognitive function. Because cognitive deficits are the major determinant of functional outcome in schizophrenia, identifying their neural basis is important for the development of new therapeutic interventions. Here we review the data suggesting that phasic synaptic inhibition mediated by specific subtypes of cortical gamma-aminobutyric acid (GABA) neurons is essential for the production of synchronized network oscillations. We also discuss evidence indicating that GABA neurotransmission is altered in schizophrenia and propose mechanisms by which such alterations can decrease the strength of inhibitory connections in a cell-type-specific manner. We suggest that some alterations observed in the neocortex of schizophrenia subjects may be compensatory responses that partially restore inhibitory synaptic efficacy. The findings of altered neural synchrony and impaired cognitive function in schizophrenia suggest that such compensatory responses are insufficient and that interventions aimed at augmenting the efficacy of GABA neurotransmission might be of therapeutic value.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                05 June 2019
                2019
                05 June 2019
                : 23
                : 101878
                Affiliations
                [a ]Psychiatry Service, San Francisco VA, San Francisco, CA, USA
                [b ]Psychiatry Service, VA Connecticut Healthcare System, West Haven, CT, USA
                [c ]Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA
                [d ]Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
                [e ]Department of Psychiatry, UCSF, San Francisco, CA, USA
                Author notes
                [* ]Corresponding author at: San Francisco VA Healthcare System, Psychiatry Service (116D), 4150 Clement Street, San Francisco, CA 94121, USA. daniel.mathalon@ 123456ucsf.edu
                Article
                S2213-1582(19)30228-1 101878
                10.1016/j.nicl.2019.101878
                6587022
                31228795
                6da8f1b5-c5e6-4f39-8c63-4a7dfdc26b09
                © 2019 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 11 February 2019
                : 18 April 2019
                : 25 May 2019
                Categories
                Regular Article

                auditory steady-state response (assr),gamma,electroencephalography (eeg),schizophrenia,reliability,generalizability,oscillations,power,phase angle

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