Deficits in high- (>60 Hz) gamma-band oscillations during visual processing in schizophrenia

Current theories of the pathophysiology of schizophrenia have focused on abnormal temporal coordination of neural activity. Oscillations in the gamma-band range (>25 Hz) are of particular interest as they establish synchronization with great precision in local cortical networks. However, the contribution of high gamma (>60 Hz) oscillations toward the pathophysiology is less established. To address this issue, we recorded magnetoencephalographic (MEG) data from 16 medicated patients with chronic schizophrenia and 16 controls during the perception of Mooney faces. MEG data were analysed in the 25–150 Hz frequency range. Patients showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces while responses to inverted stimuli were intact. Impaired processing of Mooney faces in schizophrenia patients was accompanied by a pronounced reduction in spectral power between 60–120 Hz (effect size: d = 1.26) which was correlated with disorganized symptoms (r = −0.72). Our findings demonstrate that deficits in high gamma-band oscillations as measured by MEG are a sensitive marker for aberrant cortical functioning in schizophrenia, suggesting an important aspect of the pathophysiology of the disorder.

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

[2]  Philip D. Harvey,et al.  The Brief Assessment of Cognition in Schizophrenia: reliability, sensitivity, and comparison with a standard neurocognitive battery , 2004, Schizophrenia Research.

[3]  W. A. Phillips,et al.  Perceptual grouping in disorganized schizophrenia , 2006, Psychiatry Research.

[4]  Karl J. Friston,et al.  Dysconnection in Schizophrenia: From Abnormal Synaptic Plasticity to Failures of Self-monitoring , 2009, Schizophrenia bulletin.

[5]  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.

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

[7]  MARTI J. ANDERSONa,et al.  PERMUTATION TESTS FOR MULTIFACTORIAL ANALYSIS OF VARIANCE , 2008 .

[8]  F. Benes,et al.  Differential distribution of tyrosine hydroxylase fibers on small and large neurons in layer II of anterior cingulate cortex of schizophrenic brain , 1997, Synapse.

[9]  W. Singer,et al.  Synchronization of Neural Activity across Cortical Areas Correlates with Conscious Perception , 2007, The Journal of Neuroscience.

[10]  Arnaud Delorme,et al.  EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis , 2004, Journal of Neuroscience Methods.

[11]  Catherine Tallon-Baudry,et al.  Unconscious Learning versus Visual Perception: Dissociable Roles for Gamma Oscillations Revealed in MEG , 2009, Journal of Cognitive Neuroscience.

[12]  D. Rosielle,et al.  Psychiatry , 1905, NeuroImage.

[13]  Marti J. Anderson,et al.  Permutation tests for multi-factorial analysis of variance , 2003 .

[14]  P. Fries,et al.  Gamma-Band Synchronization in the Macaque Hippocampus and Memory Formation , 2009, The Journal of Neuroscience.

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

[16]  W. Singer,et al.  Neural Synchrony in Cortical Networks: History, Concept and Current Status , 2009, Front. Integr. Neurosci..

[17]  Marcia A. Bockbrader,et al.  Steady state visual evoked potential abnormalities in schizophrenia , 2005, Clinical Neurophysiology.

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

[19]  J. Lindenmayer,et al.  Psychopathology of Schizophrenia: initial validation of a 5-factor model. , 1995, Psychopathology.

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

[21]  D. Javitt,et al.  Early-stage visual processing deficits in schizophrenia , 2005, Current opinion in psychiatry.

[22]  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.

[23]  J. Jefferys,et al.  High‐frequency gamma oscillations coexist with low‐frequency gamma oscillations in the rat visual cortex in vitro , 2010, The European journal of neuroscience.

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

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

[26]  W. A. Phillips,et al.  Where the rubber meets the road: The importance of implementation , 2003, Behavioral and Brain Sciences.

[27]  P. Goldman-Rakic,et al.  Abnormally high neuronal density in the schizophrenic cortex. A morphometric analysis of prefrontal area 9 and occipital area 17. , 1995, Archives of general psychiatry.

[28]  W. Singer,et al.  Neuroelectromagnetic Correlates of Perceptual Closure Processes , 2010, The Journal of Neuroscience.

[29]  Karim Jerbi,et al.  Simultaneous MEG and intracranial EEG recordings during attentive reading , 2009, NeuroImage.

[30]  W. Singer,et al.  HIGH-FREQUENCY GAMMA-BAND OSCILLATIONS DURING PERCEPTUAL ORGANISATION IN CHRONIC AND FIRST-EPISODE SCHIZOPHRENIA PATIENTS , 2010, Schizophrenia Research.

[31]  P. Uhlhaas,et al.  Perceptual organization in schizophrenia spectrum disorders: empirical research and theoretical implications. , 2005, Psychological bulletin.

[32]  V. Peralta,et al.  Psychopathological dimensions in schizophrenia. , 1995, Schizophrenia bulletin.

[33]  Mooney Cm,et al.  A new closure test. , 1951 .

[34]  W. Singer,et al.  Interhemispheric synchronization of oscillatory neuronal responses in cat visual cortex , 1991, Science.

[35]  Derek K. Jones,et al.  Resting GABA concentration predicts peak gamma frequency and fMRI amplitude in response to visual stimulation in humans , 2009, Proceedings of the National Academy of Sciences.

[36]  P. Uhlhaas,et al.  Perceptual anomalies in schizophrenia: integrating phenomenology and cognitive neuroscience. , 2006, Schizophrenia bulletin.

[37]  W. Singer,et al.  The gamma cycle , 2007, Trends in Neurosciences.

[38]  N. Crone,et al.  High-frequency gamma oscillations and human brain mapping with electrocorticography. , 2006, Progress in brain research.

[39]  Srikantan S. Nagarajan,et al.  High-Frequency Oscillations in Distributed Neural Networks Reveal the Dynamics of Human Decision Making , 2007, Frontiers in human neuroscience.

[40]  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.

[41]  W. Singer,et al.  Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties , 1989, Nature.

[42]  Ulf Ziemann,et al.  Inhibitory circuits and the nature of their interactions in the human motor cortex – a pharmacological TMS study , 2008, The Journal of physiology.

[43]  Werner Lutzenberger,et al.  Human gamma-band activity: a window to cognitive processing. , 2005, Neuroreport.

[44]  N. Andreasen A unitary model of schizophrenia: Bleuler's "fragmented phrene" as schizencephaly. , 1999, Archives of general psychiatry.

[45]  Henning Saß,et al.  Diagnostisches und statistisches Manual psychischer Störungen , 2004 .

[46]  W. Singer,et al.  Modulation of Neuronal Interactions Through Neuronal Synchronization , 2007, Science.

[47]  J. Schoffelen,et al.  Nonparametric statistical testing of coherence differences , 2007, Journal of Neuroscience Methods.

[48]  C. M. Mooney,et al.  A new closure test. , 1951, Canadian journal of psychology.

[49]  Catherine Tallon-Baudry,et al.  The many faces of the gamma band response to complex visual stimuli , 2005, NeuroImage.

[50]  D. Pinault,et al.  N-Methyl d-Aspartate Receptor Antagonists Ketamine and MK-801 Induce Wake-Related Aberrant γ Oscillations in the Rat Neocortex , 2008, Biological Psychiatry.

[51]  F. Benes,et al.  GABAergic Interneurons: Implications for Understanding Schizophrenia and Bipolar Disorder , 2001, Neuropsychopharmacology.

[52]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

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

[54]  J. Grier,et al.  Nonparametric indexes for sensitivity and bias: computing formulas. , 1971, Psychological bulletin.

[55]  D. Umbricht,et al.  Mismatch negativity in schizophrenia: a meta-analysis , 2005, Schizophrenia Research.

[56]  Wolf Singer,et al.  Gamma-Band Activity in Human Prefrontal Cortex Codes for the Number of Relevant Items Maintained in Working Memory , 2012, The Journal of Neuroscience.

[57]  J. Polich,et al.  Meta-analysis of P300 and schizophrenia: patients, paradigms, and practical implications. , 2003, Psychophysiology.

[58]  David A. Lewis,et al.  Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia , 2012, Trends in Neurosciences.

[59]  M. Hasselmo,et al.  Gamma frequency-range abnormalities to auditory stimulation in schizophrenia. , 1999, Archives of general psychiatry.

[60]  Robert Oostenveld,et al.  Localizing human visual gamma-band activity in frequency, time and space , 2006, NeuroImage.

[61]  D. Javitt When doors of perception close: bottom-up models of disrupted cognition in schizophrenia. , 2009, Annual review of clinical psychology.

[62]  Ilona Kovács,et al.  An fMRI examination of visual integration in schizophrenia. , 2009, Journal of integrative neuroscience.

[63]  W. Singer,et al.  Phase Sensitivity of Synaptic Modifications in Oscillating Cells of Rat Visual Cortex , 2004, The Journal of Neuroscience.

[64]  S. Kapur,et al.  Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation. , 2002, Archives of general psychiatry.

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

[66]  Ilona Kovács,et al.  Perceptual organization, the disorganization syndrome, and context processing in chronic schizophrenia , 2000, Schizophrenia Research.

[67]  L. J. Bour,et al.  A meta-analysis of P50 studies in patients with schizophrenia and relatives: Differences in methodology between research groups , 2007, Schizophrenia Research.