Reduced Early Auditory Evoked Gamma-Band Response in Patients with Schizophrenia

BACKGROUND There is growing evidence for abnormalities of certain gamma-aminobutyric acid (GABA)-ergic interneurons and their interaction with glutamatergic pyramidal cells in schizophrenia. These interneurons are critically involved in generating neural activity in the gamma-band (30-100 Hz) of the electroencephalogram. One example of such gamma oscillations is the early auditory evoked gamma-band response (GBR). Although auditory processing is obviously disturbed in schizophrenia, there is no direct evidence providing a reduced early auditory evoked GBR so far. We addressed two questions: 1) Is the early auditory evoked GBR decreased regarding power and phase-locking in schizophrenic patients?; and 2) Is this possible decrease a result of reduced activity in the auditory cortex and/or the anterior cingulate cortex (ACC), which were identified as sources of the GBR previously? METHODS We investigated the early auditory evoked GBR and its sources in the ACC and the auditory cortex in 90 medicated patients with schizophrenia and in age-, gender-, and education-matched healthy control subjects with an auditory reaction task. RESULTS Patients with schizophrenia showed a significant reduction of power and phase-locking of the early auditory evoked GBR. This effect was due to a reduced activity in the auditory cortex and the ACC/medial frontal gyrus region (low-resolution brain electromagnetic tomography analysis). CONCLUSIONS Generally, these findings are in line with earlier reports on the impaired ability of schizophrenic patients in generating gamma activity. In addition, this is the first study to demonstrate disturbance of gamma activity in auditory processing as assessed by the early auditory GBR power.

[1]  Christoph Mulert,et al.  The relationship between reaction time, error rate and anterior cingulate cortex activity. , 2003, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

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

[3]  D. Senkowski,et al.  Effects of task difficulty on evoked gamma activity and ERPs in a visual discrimination task , 2002, Clinical Neurophysiology.

[4]  K. Reinikainen,et al.  Selective attention enhances the auditory 40-Hz transient response in humans , 1993, Nature.

[5]  Carol A. Tamminga,et al.  Subanesthetic Doses of Ketamine Stimulate Psychosis in Schizophrenia , 1995, Neuropsychopharmacology.

[6]  Robert Schmitt,et al.  Integration of fMRI and simultaneous EEG: towards a comprehensive understanding of localization and time-course of brain activity in target detection , 2004, NeuroImage.

[7]  D. Javitt,et al.  Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia , 2008, Trends in Neurosciences.

[8]  O. Bertrand,et al.  Attention modulates gamma-band oscillations differently in the human lateral occipital cortex and fusiform gyrus. , 2005, Cerebral cortex.

[9]  Gregor Leicht,et al.  Auditory cortex and anterior cingulate cortex sources of the early evoked gamma-band response: Relationship to task difficulty and mental effort , 2007, Neuropsychologia.

[10]  M. Leboyer,et al.  Conscious and subliminal conflicts in normal subjects and patients with schizophrenia: The role of the anterior cingulate , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. Pandya,et al.  Efferent connections of the cingulate gyrus in the rhesus monkey , 1981, Experimental Brain Research.

[12]  D. Senkowski,et al.  Reduced oscillatory gamma-band responses in unmedicated schizophrenic patients indicate impaired frontal network processing , 2004, Clinical Neurophysiology.

[13]  I D Wilkinson,et al.  Neural activity in speech-sensitive auditory cortex during silence. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[14]  P. Teale,et al.  Alterations in tonotopy and auditory cerebral asymmetry in schizophrenia , 2002, Biological Psychiatry.

[15]  Ole Paulsen,et al.  Hippocampal gamma‐frequency oscillations: from interneurones to pyramidal cells, and back , 2005, The Journal of physiology.

[16]  Matthias M. Müller,et al.  Suppression of the auditory middle-latency response and evoked gamma-band response in a paired-click paradigm , 2001, Experimental Brain Research.

[17]  A Malanda,et al.  Gamma band responses to target and non-target auditory stimuli in humans , 2004, Neuroscience Letters.

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

[19]  Gavin P. Reynolds,et al.  A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia , 2002, Schizophrenia Research.

[20]  Karl J. Friston,et al.  Schizophrenia: a disconnection syndrome? , 1995, Clinical neuroscience.

[21]  T. Woo,et al.  Density of glutamic acid decarboxylase 67 messenger RNA-containing neurons that express the N-methyl-D-aspartate receptor subunit NR2A in the anterior cingulate cortex in schizophrenia and bipolar disorder. , 2004, Archives of general psychiatry.

[22]  S. Potkin,et al.  Effects of temporal variability on p50 and the gating ratio in schizophrenia: a frequency domain adaptive filter single-trial analysis. , 2000, Archives of general psychiatry.

[23]  F. Benes,et al.  Emerging principles of altered neural circuitry in schizophrenia , 2000, Brain Research Reviews.

[24]  A. Engel,et al.  Cognitive functions of gamma-band activity: memory match and utilization , 2004, Trends in Cognitive Sciences.

[25]  R. S. Jones,et al.  Basket-like interneurones in layer II of the entorhinal cortex exhibit a powerful NMDA-mediated synaptic excitation , 1993, Neuroscience Letters.

[26]  E. Gordon,et al.  Synchronous Gamma activity: a review and contribution to an integrative neuroscience model of schizophrenia , 2003, Brain Research Reviews.

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

[28]  D. Rujescu,et al.  Alterations of hippocampal and prefrontal GABAergic interneurons in an animal model of psychosis induced by NMDA receptor antagonism , 2007, Schizophrenia Research.

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

[30]  Karl J. Friston,et al.  Abnormal Cingulate Modulation of Fronto-Temporal Connectivity in Schizophrenia , 1999, NeuroImage.

[31]  C. Herrmann,et al.  Gamma responses and ERPs in a visual classification task , 1999, Clinical Neurophysiology.

[32]  Robert W. McCarley,et al.  A Pharmacological Model for Psychosis Based on N-methyl-D-aspartate Receptor Hypofunction: Molecular, Cellular, Functional and Behavioral Abnormalities , 2006, Biological Psychiatry.

[33]  D. Javitt,et al.  Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia. , 2000, Archives of general psychiatry.

[34]  L. Elliot Hong,et al.  Evoked gamma band synchronization and the liability for schizophrenia , 2004, Schizophrenia Research.

[35]  R. Coppola,et al.  Functional and effective frontotemporal connectivity and genetic risk for schizophrenia , 2003, Biological Psychiatry.

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

[37]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[38]  Bita Moghaddam,et al.  NMDA receptor hypofunction produces concomitant firing rate potentiation and burst activity reduction in the prefrontal cortex. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[39]  K. D. Singh,et al.  Magnetic field tomography of coherent thalamocortical 40-Hz oscillations in humans. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[40]  N. Makris,et al.  Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging. , 1999, Archives of general psychiatry.

[41]  P. Kalus,et al.  Altered distribution of parvalbumin-immunoreactive local circuit neurons in the anterior cingulate cortex of schizophrenic patients , 1997, Psychiatry Research: Neuroimaging.

[42]  Stefan Debener,et al.  Size matters: effects of stimulus size, duration and eccentricity on the visual gamma-band response , 2004, Clinical Neurophysiology.

[43]  Miles A Whittington,et al.  Interneuron Diversity series: Inhibitory interneurons and network oscillations in vitro , 2003, Trends in Neurosciences.

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

[45]  Fiona E. N. LeBeau,et al.  Region-Specific Reduction in Entorhinal Gamma Oscillations and Parvalbumin-Immunoreactive Neurons in Animal Models of Psychiatric Illness , 2006, The Journal of Neuroscience.

[46]  W. Singer,et al.  The role of oscillations and synchrony in cortical networks and their putative relevance for the pathophysiology of schizophrenia. , 2008, Schizophrenia bulletin.

[47]  Shirley Hansen,et al.  γ-AMINOBUTYRIC-ACID DEFICIENCY IN BRAIN OF SCHIZOPHRENIC PATIENTS , 1979, The Lancet.

[48]  Gregor Leicht,et al.  Prediction of treatment response in major depression: integration of concepts. , 2007, Journal of affective disorders.

[49]  B. Moghaddam,et al.  Positive Allosteric Modulation of Metabotropic Glutamate 5 (mGlu5) Receptors Reverses N-Methyl-D-Aspartate Antagonist-Induced Alteration of Neuronal Firing in Prefrontal Cortex , 2007, Biological Psychiatry.

[50]  J. Coyle,et al.  The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia , 2004, Psychopharmacology.

[51]  S Makeig,et al.  Human auditory evoked gamma-band magnetic fields. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[52]  D. Lehmann,et al.  Low resolution electromagnetic tomography: a new method for localizing electrical activity in the brain. , 1994, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[53]  R. Kikinis,et al.  Planum temporale and Heschl gyrus volume reduction in schizophrenia: a magnetic resonance imaging study of first-episode patients. , 2000, Archives of general psychiatry.

[54]  R. Kikinis,et al.  Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study. , 2002, The American journal of psychiatry.

[55]  Benjamin W. H. Lim,et al.  Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars , 2007, Proceedings of the National Academy of Sciences.

[56]  E. Basar,et al.  Gamma, alpha, delta, and theta oscillations govern cognitive processes. , 2001, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[57]  Christoph Mulert,et al.  Sound level dependence of the primary auditory cortex: Simultaneous measurement with 61-channel EEG and fMRI , 2005, NeuroImage.

[58]  P. Schlattmann,et al.  Reduced Event-Related Current Density in the Anterior Cingulate Cortex in Schizophrenia , 2001, NeuroImage.

[59]  Christian Seifert,et al.  Single-trial coupling of EEG and fMRI reveals the involvement of early anterior cingulate cortex activation in effortful decision making , 2008, NeuroImage.

[60]  Fiona E. N. LeBeau,et al.  Recruitment of Parvalbumin-Positive Interneurons Determines Hippocampal Function and Associated Behavior , 2007, Neuron.

[61]  B. Clementz,et al.  The gamma band response may account for poor P50 suppression in schizophrenia , 1997, Neuroreport.

[62]  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.

[63]  Hannu Tiitinen,et al.  Suppression of transient 40-Hz auditory response by haloperidol suggests modulation of human selective attention by dopamine D2 receptors , 2000, Neuroscience Letters.

[64]  J. Ragland,et al.  Alterations of fronto-temporal connectivity during word encoding in schizophrenia , 2007, Psychiatry Research: Neuroimaging.

[65]  D. Lewis,et al.  Cortical inhibitory neurons and schizophrenia , 2005, Nature Reviews Neuroscience.

[66]  Hans-Jürgen Möller,et al.  A functional single nucleotide polymorphism (V158M) in the COMT gene is associated with aggressive personality traits , 2003, Biological Psychiatry.

[67]  C. Schroeder,et al.  Role of cortical N-methyl-D-aspartate receptors in auditory sensory memory and mismatch negativity generation: implications for schizophrenia. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

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

[69]  O. Paulsen,et al.  Cholinergic induction of network oscillations at 40 Hz in the hippocampus in vitro , 1998, Nature.

[70]  D. Mathalon,et al.  Event-related EEG time-frequency analysis: an overview of measures and an analysis of early gamma band phase locking in schizophrenia. , 2008, Schizophrenia bulletin.

[71]  J. Rice,et al.  Comparison of direct interview and family history diagnoses of alcohol dependence. , 1995, Alcoholism, clinical and experimental research.

[72]  D. Barth,et al.  Thalamic modulation of high-frequency oscillating potentials in auditory cortex , 1996, Nature.

[73]  B. Moghaddam,et al.  NMDA Receptor Hypofunction Produces Opposite Effects on Prefrontal Cortex Interneurons and Pyramidal Neurons , 2007, The Journal of Neuroscience.

[74]  R. Kikinis,et al.  Subgenual cingulate cortex volume in first-episode psychosis. , 1999, The American journal of psychiatry.

[75]  S. Mosolov,et al.  Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial , 2007, Nature Medicine.

[76]  E. Gordon,et al.  Increased absolute magnitude of gamma synchrony in first-episode psychosis , 2008, Schizophrenia Research.

[77]  T. Crow,et al.  Auditory cortex asymmetry, altered minicolumn spacing and absence of ageing effects in schizophrenia. , 2008, Brain : a journal of neurology.

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

[79]  M. Hasselmo,et al.  NMDA-dependent modulation of CA1 local circuit inhibition , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[80]  Daniel Senkowski,et al.  Frontal and Temporal Dysfunction of Auditory Stimulus Processing in Schizophrenia , 2002, NeuroImage.

[81]  R. Näätänen,et al.  The transient 40-Hz response, mismatch negativity, and attentional processes in humans , 1997, Progress in Neuro-psychopharmacology and Biological Psychiatry.

[82]  N. Swerdlow,et al.  Gamma Band Oscillations Reveal Neural Network Cortical Coherence Dysfunction in Schizophrenia Patients , 2006, Biological Psychiatry.