Increased Resting-State Gamma-Band Connectivity in First-Episode Schizophrenia.

BACKGROUND Schizophrenia has long been suggested to represent a disorder with prominent neural dysconnectivity. Gamma-band oscillations are highly relevant in this context, due both to their proposed involvement in neuronal synchronization and to their association with neurotransmitter systems relevant for schizophrenia. Several task-related studies have confirmed reduced power and synchronization of gamma-band oscillations in schizophrenia, but it has been suggested that these findings might not apply to the resting state. The present study aimed to investigate resting-state gamma-band connectivity in patients with schizophrenia. METHODS Sixty-four channel resting-state electroencephalography (eyes closed) was recorded in 22 patients with first-episode schizophrenia and 22 healthy controls matched for age and gender. Orthogonalized power envelope correlation was used as a measure of connectivity across 80 cortical regions at 40 Hz. Mean connectivity at each region was compared across groups using the nonparametric randomization approach. Additionally, the network-based statistic was applied to identify affected networks in patients. RESULTS Patients displayed increased mean functional gamma-band connectivity compared to controls in the left rolandic operculum. Network-based analyses indicated increased connectivity in patients within a strongly lateralized network consisting mainly of left inferior frontal/orbitofrontal, lateral and medial temporal, and inferior parietal areas. Within this network, gamma-band connectivity was higher in patients with low positive and disorganization symptom levels. CONCLUSIONS The present study provides a link between resting-state gamma-band connectivity and the core symptoms of schizophrenia. The observed findings are different than those reported by task-related studies, suggesting that resting-state studies might reveal new aspects in the pathophysiology of schizophrenia.

[1]  Wolf Singer,et al.  Deficits in high- (>60 Hz) gamma-band oscillations during visual processing in schizophrenia , 2013, Front. Hum. Neurosci..

[2]  M. Bellani,et al.  Structural imaging techniques in schizophrenia , 2012, Acta psychiatrica Scandinavica.

[3]  K. Deisseroth,et al.  Parvalbumin neurons and gamma rhythms enhance cortical circuit performance , 2009, Nature.

[4]  Wei Deng,et al.  Short-term effects of antipsychotic treatment on cerebral function in drug-naive first-episode schizophrenia revealed by "resting state" functional magnetic resonance imaging. , 2010, Archives of general psychiatry.

[5]  Takefumi Ueno,et al.  Reduced high and low frequency gamma synchronization in patients with chronic schizophrenia , 2011, Schizophrenia Research.

[6]  Otto W. Witte,et al.  Thalamocortical connectivity during resting state in schizophrenia , 2014, European Archives of Psychiatry and Clinical Neuroscience.

[7]  W. Singer,et al.  Cortical Oscillatory Activity Is Critical for Working Memory as Revealed by Deficits in Early-Onset Schizophrenia , 2009, The Journal of Neuroscience.

[8]  Mark W. Woolrich,et al.  Inferring task-related networks using independent component analysis in magnetoencephalography , 2012, NeuroImage.

[9]  Jordan P. Hamm,et al.  Abnormalities of Neuronal Oscillations and Temporal Integration to Low- and High-Frequency Auditory Stimulation in Schizophrenia , 2011, Biological Psychiatry.

[10]  平野 昭吾 Abnormal neural oscillatory activity to speech sounds in schizophrenia : a magnetoencephalography study , 2009 .

[11]  L Elliot Hong,et al.  Sensory gating endophenotype based on its neural oscillatory pattern and heritability estimate. , 2008, Archives of general psychiatry.

[12]  A. Engel,et al.  Neuronal Synchronization along the Dorsal Visual Pathway Reflects the Focus of Spatial Attention , 2008, Neuron.

[13]  Matthew J. Brookes,et al.  The relationship between MEG and fMRI , 2014, NeuroImage.

[14]  R. McCarley,et al.  Left auditory cortex gamma synchronization and auditory hallucination symptoms in schizophrenia , 2009, BMC Neuroscience.

[15]  R. McCarley,et al.  Neural synchrony indexes disordered perception and cognition in schizophrenia. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[16]  T. Hergueta,et al.  The mini international neuropsychiatric interview , 1998, European Psychiatry.

[17]  K. Hugdahl,et al.  Left Temporal Lobe Structural and Functional Abnormality Underlying Auditory Hallucinations in Schizophrenia , 2008, Front. Neurosci..

[18]  Yong He,et al.  Differentiating Patterns of Amygdala-Frontal Functional Connectivity in Schizophrenia and Bipolar Disorder , 2013, Schizophrenia bulletin.

[19]  Yul-Wan Sung,et al.  Functional magnetic resonance imaging , 2004, Scholarpedia.

[20]  S. Kapur,et al.  Trajectories of response to treatment with atypical antipsychotic medication in patients with schizophrenia pooled from 6 double-blind, randomized clinical trials , 2011, Schizophrenia Research.

[21]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[22]  P. Uhlhaas Dysconnectivity, large-scale networks and neuronal dynamics in schizophrenia , 2013, Current Opinion in Neurobiology.

[23]  S. Paradiso,et al.  "Cognitive dysmetria" as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? , 1998, Schizophrenia bulletin.

[24]  D. Hubl,et al.  Hallucinations, Thought Disorders, and the Language Domain in Schizophrenia , 2008, Clinical EEG and neuroscience.

[25]  R. McCarley,et al.  Long-range synchrony of γ oscillations and auditory hallucination symptoms in schizophrenia. , 2011, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[26]  Vince D. Calhoun,et al.  Is Aberrant Functional Connectivity A Psychosis Endophenotype? A Resting State Functional Magnetic Resonance Imaging Study , 2013, Biological Psychiatry.

[27]  Angus W. MacDonald,et al.  The functional neuroanatomy of symptom dimensions in schizophrenia: A qualitative and quantitative review of a persistent question , 2010, Neuroscience & Biobehavioral Reviews.

[28]  Wolf Singer,et al.  Neuronal Synchrony: A Versatile Code for the Definition of Relations? , 1999, Neuron.

[29]  K. Spencer The Functional Consequences of Cortical Circuit Abnormalities on Gamma Oscillations in Schizophrenia: Insights from Computational Modeling , 2009, Front. Hum. Neurosci..

[30]  E. Bramon,et al.  The early auditory gamma-band response is heritable and a putative endophenotype of schizophrenia. , 2011, Schizophrenia bulletin.

[31]  Rolando J. Biscay-Lirio,et al.  Assessing interactions in the brain with exact low-resolution electromagnetic tomography , 2011, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[32]  J. Edgar,et al.  Gamma synchrony: Towards a translational biomarker for the treatment-resistant symptoms of schizophrenia , 2012, Neuropharmacology.

[33]  Majnu John,et al.  Resting-state fMRI connectivity impairment in schizophrenia and bipolar disorder. , 2014, Schizophrenia bulletin.

[34]  Cameron S Carter,et al.  Gamma Oscillatory Power is Impaired During Cognitive Control Independent of Medication Status in First-Episode Schizophrenia , 2010, Neuropsychopharmacology.

[35]  Manuel Carreiras,et al.  Long-range neural synchronization supports fast and efficient reading: EEG correlates of processing expected words in sentences , 2013, NeuroImage.

[36]  R. McCarley,et al.  γ-Band Auditory Steady-State Responses Are Impaired in First Episode Psychosis , 2008, Biological Psychiatry.

[37]  Robert W. McCarley,et al.  γ-Band Auditory Steady-State Responses Are Impaired in First Episode Psychosis , 2008, Biological Psychiatry.

[38]  M. Cunningham,et al.  Do cortical gamma oscillations promote or suppress perception? An under-asked question with an over-assumed answer , 2013, Front. Hum. Neurosci..

[39]  Renaud Jardri,et al.  Cortical activations during auditory verbal hallucinations in schizophrenia: a coordinate-based meta-analysis. , 2011, The American journal of psychiatry.

[40]  Kevin M. Spencer,et al.  Baseline gamma power during auditory steady-state stimulation in schizophrenia , 2012, Front. Hum. Neurosci..

[41]  G. Tononi,et al.  Reduced evoked gamma oscillations in the frontal cortex in schizophrenia patients: a TMS/EEG study. , 2008, American Journal of Psychiatry.

[42]  M. Hallett,et al.  Identifying true brain interaction from EEG data using the imaginary part of coherency , 2004, Clinical Neurophysiology.

[43]  D. Rujescu,et al.  Reduced early auditory – evoked gamma band response in patients with schizophrenia , 2009 .

[44]  C. Carter,et al.  Impairments in frontal cortical γ synchrony and cognitive control in schizophrenia , 2006, Proceedings of the National Academy of Sciences.

[45]  Douglas W. Jones,et al.  Prefrontal broadband noise, working memory, and genetic risk for schizophrenia. , 2004, The American journal of psychiatry.

[46]  Thomas Dierks,et al.  Frontal areas contribute to reduced global coordination of resting-state gamma activities in drug-naïve patients with schizophrenia , 2011, Schizophrenia Research.

[47]  W. Singer,et al.  Dynamic predictions: Oscillations and synchrony in top–down processing , 2001, Nature Reviews Neuroscience.

[48]  C. Carter,et al.  Impairments in frontal cortical gamma synchrony and cognitive control in schizophrenia. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[49]  Christoph Mulert,et al.  EEG-vigilance differences between patients with borderline personality disorder, patients with obsessive-compulsive disorder and healthy controls , 2008, European Archives of Psychiatry and Clinical Neuroscience.

[50]  Jeff H. Duyn,et al.  Large-scale spontaneous fluctuations and correlations in brain electrical activity observed with magnetoencephalography , 2010, NeuroImage.

[51]  Michael W. Cole,et al.  Amygdala connectivity differs among chronic, early course, and individuals at risk for developing schizophrenia. , 2014, Schizophrenia bulletin.

[52]  M. Corbetta,et al.  Large-scale cortical correlation structure of spontaneous oscillatory activity , 2012, Nature Neuroscience.

[53]  Mark van der Gaag,et al.  The five-factor model of the Positive and Negative Syndrome Scale II: A ten-fold cross-validation of a revised model , 2006, Schizophrenia Research.

[54]  C. Westin,et al.  Corpus Callosum Abnormalities and Their Association with Psychotic Symptoms in Patients with Schizophrenia , 2010, Biological Psychiatry.

[55]  P. Jonas,et al.  Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks , 2007, Nature Reviews Neuroscience.

[56]  Robert W. McCarley,et al.  Sensory-Evoked Gamma Oscillations in Chronic Schizophrenia , 2008, Biological Psychiatry.

[57]  W. Singer,et al.  Abnormal neural oscillations and synchrony in schizophrenia , 2010, Nature Reviews Neuroscience.

[58]  A. Mechelli,et al.  Dysconnectivity in schizophrenia: Where are we now? , 2011, Neuroscience & Biobehavioral Reviews.

[59]  S. Nagarajan,et al.  Clinical Symptoms and Alpha Band Resting-State Functional Connectivity Imaging in Patients With Schizophrenia: Implications for Novel Approaches to Treatment , 2011, Biological Psychiatry.

[60]  Krish D. Singh,et al.  Visual gamma oscillations: The effects of stimulus type, visual field coverage and stimulus motion on MEG and EEG recordings , 2013, NeuroImage.

[61]  S. Woods,et al.  Chlorpromazine equivalent doses for the newer atypical antipsychotics. , 2003, The Journal of clinical psychiatry.

[62]  Erick Jorge Canales-Rodríguez,et al.  Association of formal thought disorder in schizophrenia with structural brain abnormalities in language-related cortical regions , 2013, Schizophrenia Research.

[63]  Marcel Bastiaansen,et al.  Integration or Predictability? A Further Specification of the Functional Role of Gamma Oscillations in Language Comprehension , 2012, Front. Psychology.

[64]  Edward T. Bullmore,et al.  Schizophrenia, neuroimaging and connectomics , 2012, NeuroImage.

[65]  J. Ford,et al.  Out-of-Synch and Out-of-Sorts: Dysfunction of Motor-Sensory Communication in Schizophrenia , 2008, Biological Psychiatry.

[66]  Adriano B. L. Tort,et al.  Hippocampal theta rhythm and its coupling with gamma oscillations require fast inhibition onto parvalbumin-positive interneurons , 2009, Proceedings of the National Academy of Sciences.

[67]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[68]  Judith M Ford,et al.  Corollary discharge dysfunction in schizophrenia: can it explain auditory hallucinations? , 2005, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[69]  Tung-Ping Su,et al.  Resting-state fMRI mapping of cerebellar functional dysconnections involving multiple large-scale networks in patients with schizophrenia , 2013, Schizophrenia Research.

[70]  A. Engel,et al.  Intrinsic Coupling Modes: Multiscale Interactions in Ongoing Brain Activity , 2013, Neuron.

[71]  Wolf Singer,et al.  High-frequency oscillations and the neurobiology of schizophrenia , 2013, Dialogues in clinical neuroscience.

[72]  P. Fries A mechanism for cognitive dynamics: neuronal communication through neuronal coherence , 2005, Trends in Cognitive Sciences.

[73]  G. Buzsáki,et al.  A neural coding scheme formed by the combined function of gamma and theta oscillations. , 2008, Schizophrenia bulletin.

[74]  D. Rujescu,et al.  Alterations of the early auditory evoked gamma-band response in first-degree relatives of patients with schizophrenia: hints to a new intermediate phenotype. , 2011, Journal of psychiatric research.

[75]  W. Singer,et al.  Dysfunctional Long-Range Coordination of Neural Activity during Gestalt Perception in Schizophrenia , 2006, The Journal of Neuroscience.

[76]  Richard Coppola,et al.  Magnetoencephalographic gamma power reduction in patients with schizophrenia during resting condition , 2009, Human brain mapping.

[77]  Edward T. Bullmore,et al.  Network-based statistic: Identifying differences in brain networks , 2010, NeuroImage.

[78]  J. Schoffelen,et al.  Neuronal Coherence as a Mechanism of Effective Corticospinal Interaction , 2005, Science.

[79]  E. Gordon,et al.  "Gamma synchrony" in first-episode schizophrenia: a disorder of temporal connectivity? , 2005, The American journal of psychiatry.

[80]  Viviana Betti,et al.  Synchronous with Your Feelings: Sensorimotor γ Band and Empathy for Pain , 2009, The Journal of Neuroscience.

[81]  B. Maher,et al.  Delusional thinking and perceptual disorder. , 1974, Journal of individual psychology.

[82]  Mark W. Woolrich,et al.  Measuring temporal, spectral and spatial changes in electrophysiological brain network connectivity , 2014, NeuroImage.

[83]  Viviana Betti,et al.  Natural Scenes Viewing Alters the Dynamics of Functional Connectivity in the Human Brain , 2013, Neuron.

[84]  Richard Coppola,et al.  Graph theoretical analysis of resting magnetoencephalographic functional connectivity networks , 2013, Front. Comput. Neurosci..

[85]  S. Sponheim,et al.  Genetic and disorder-specific aspects of resting state EEG abnormalities in schizophrenia. , 2009, Schizophrenia bulletin.

[86]  Dewen Hu,et al.  Convergent and Divergent Functional Connectivity Patterns in Schizophrenia and Depression , 2013, PloS one.

[87]  Colleen A Brenner,et al.  Resting state EEG power and coherence abnormalities in bipolar disorder and schizophrenia. , 2013, Journal of psychiatric research.

[88]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[89]  Vaughan J. Carr,et al.  Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia , 2012, Neuroscience & Biobehavioral Reviews.

[90]  Matthew J. Brookes,et al.  Measuring functional connectivity using MEG: Methodology and comparison with fcMRI , 2011, NeuroImage.

[91]  R. Coppola,et al.  An association between reduced interhemispheric EEG coherence in the temporal lobe and genetic risk for schizophrenia , 2001, Schizophrenia Research.

[92]  Karl J. Friston Schizophrenia and the disconnection hypothesis , 1999, Acta psychiatrica Scandinavica. Supplementum.

[93]  Darren Price,et al.  Investigating the electrophysiological basis of resting state networks using magnetoencephalography , 2011, Proceedings of the National Academy of Sciences.

[94]  Luc H. Arnal,et al.  Cortical oscillations and sensory predictions , 2012, Trends in Cognitive Sciences.

[95]  Hamid Reza Mohseni,et al.  Exploring mechanisms of spontaneous functional connectivity in MEG: How delayed network interactions lead to structured amplitude envelopes of band-pass filtered oscillations , 2014, NeuroImage.

[96]  John Suckling,et al.  Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain , 1999, IEEE Transactions on Medical Imaging.

[97]  M. Corbetta,et al.  Temporal dynamics of spontaneous MEG activity in brain networks , 2010, Proceedings of the National Academy of Sciences.

[98]  Wolf Singer,et al.  Evidence for dysregulated high-frequency oscillations during sensory processing in medication-naïve, first episode schizophrenia , 2013, Schizophrenia Research.

[99]  R. McCarley,et al.  Abnormal Neural Synchrony in Schizophrenia , 2003, The Journal of Neuroscience.