Cortical source estimates of gamma band amplitude and phase are different in schizophrenia

Reductions in gamma band phase synchrony and evoked power have been reported in schizophrenic subjects in response to auditory stimuli. These results have been observed in the EEG at one or two electrode sites. We wished to extend these results using magnetic field data to estimate the responses at the neural generators themselves in each hemisphere. Whole head magnetoencephalographic (MEG) recordings were used to estimate the phase and amplitude behavior of sources in primary auditory cortex in both hemispheres of schizophrenic and comparison subjects. Both ipsi- and contralateral cases were evaluated using a driving (40 Hz modulated 1 kHz carrier) and a non-driving (1 kHz tone) stimulus. We used source space projection (SSP) to collapse the magnetic field data into estimates of the time course of source strengths in individual trials. Complex wavelet based time-frequency decomposition was used to compute inter-trial phase locking factor (PLF), and mean evoked and induced amplitude for each cortical generator. Schizophrenic subjects showed reduced SSP PLF and evoked source strength for contralateral generators responding to the driving stimulus in both hemispheres. For the pure tone stimulus, only the left hemisphere PLF's in the transient window were reduced. In contrast, subjects with schizophrenia exhibited higher induced 40 Hz power to both stimulus types, consistent with the reduced PLF findings. The method of SSP combined with wavelet based complex demodulation produces a significant improvement in signal-to-noise ratio, and directly estimates the activity of the cortical generators responsible for gamma band auditory MEG evoked fields. Schizophrenic subjects exhibit significant impairment of generation and phase locking of this activity in auditory cortex, suggesting an impairment of GABA-ergic inhibitory interneuronal modulation of pyramidal cell activity.

[1]  Samuel J. Williamson,et al.  Magnetic Fields of the Cerebral Cortex , 1980 .

[2]  A. Bacci,et al.  Enhancement of Spike-Timing Precision by Autaptic Transmission in Neocortical Inhibitory Interneurons , 2006, Neuron.

[3]  Risto J. Ilmoniemi,et al.  New Method for the Study of Spontaneous Brain Activity. , 1988 .

[4]  Stephen E. Robinson Theory and Properties of Lead Field Synthesis Analysis , 1989 .

[5]  C Pantev,et al.  A high-precision magnetoencephalographic study of human auditory steady-state responses to amplitude-modulated tones. , 2000, The Journal of the Acoustical Society of America.

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

[7]  Edward O. Mann,et al.  Role of GABAergic inhibition in hippocampal network oscillations , 2007, Trends in Neurosciences.

[8]  K. Nuechterlein,et al.  Symptom dimensions in recent-onset schizophrenia and mania: a principal components analysis of the 24-item Brief Psychiatric Rating Scale , 2000, Psychiatry Research.

[9]  J. Pernier,et al.  Stimulus Specificity of Phase-Locked and Non-Phase-Locked 40 Hz Visual Responses in Human , 1996, The Journal of Neuroscience.

[10]  C D Tesche,et al.  Signal-space projections of MEG data characterize both distributed and well-localized neuronal sources. , 1995, Electroencephalography and clinical neurophysiology.

[11]  Hannah Monyer,et al.  Differential involvement of oriens/pyramidale interneurones in hippocampal network oscillations in vitro , 2005, The Journal of physiology.

[12]  O. Paulsen,et al.  Spike Timing of Distinct Types of GABAergic Interneuron during Hippocampal Gamma Oscillations In Vitro , 2004, The Journal of Neuroscience.

[13]  Peter J. Siekmeier,et al.  Modeling GABA alterations in schizophrenia: a link between impaired inhibition and altered gamma and beta range auditory entrainment. , 2008, Journal of neurophysiology.

[14]  M. Annett Left, right, hand and brain : the right shift theory , 1985 .

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

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

[17]  Y. Okada,et al.  Contributions of principal neocortical neurons to magnetoencephalography and electroencephalography signals , 2006, The Journal of physiology.

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

[19]  J. Pierri,et al.  Alterations in chandelier neuron axon terminals in the prefrontal cortex of schizophrenic subjects. , 1999, The American journal of psychiatry.

[20]  Leanne M Williams,et al.  "Gamma (40 Hz) phase synchronicity" and symptom dimensions in schizophrenia , 2003, Cognitive neuropsychiatry.

[21]  P. Teale,et al.  Reduced laterality of the source locations for generators of the auditory steady-state field in schizophrenia , 2003, Biological Psychiatry.

[22]  R. Traub,et al.  Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation , 1995, Nature.

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

[24]  W. Freeman The physiology of perception. , 1991, Scientific American.

[25]  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.

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

[27]  R. Llinás,et al.  The neuronal basis for consciousness. , 1998, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[28]  P. Teale,et al.  Development of the 40Hz steady state auditory evoked magnetic field from ages 5 to 52 , 2006, Clinical Neurophysiology.

[29]  Olaf Sporns,et al.  EEG synchronization to modulated auditory tones in schizophrenia, schizoaffective disorder, and schizotypal personality disorder. , 2003, The American journal of psychiatry.

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

[31]  Wei Zhang,et al.  Reduced Dendritic Spine Density in Auditory Cortex of Subjects with Schizophrenia , 2009, Neuropsychopharmacology.

[32]  R. McCarley,et al.  Cognitive dysfunction in schizophrenia: unifying basic research and clinical aspects , 1999, European Archives of Psychiatry and Clinical Neuroscience.

[33]  T. Elbert,et al.  Specific tonotopic organizations of different areas of the human auditory cortex revealed by simultaneous magnetic and electric recordings. , 1995, Electroencephalography and clinical neurophysiology.

[34]  T. Wassink,et al.  Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms , 1999, Biological Psychiatry.

[35]  Xiao-Jing Wang,et al.  What determines the frequency of fast network oscillations with irregular neural discharges? I. Synaptic dynamics and excitation-inhibition balance. , 2003, Journal of neurophysiology.

[36]  C Pantev,et al.  Right hemispheric laterality of human 40 Hz auditory steady-state responses. , 2005, Cerebral cortex.

[37]  Robert A. Sweet,et al.  Anatomical Evidence of Impaired Feedforward Auditory Processing in Schizophrenia , 2007, Biological Psychiatry.

[38]  W Singer,et al.  Role of the temporal domain for response selection and perceptual binding. , 1997, Cerebral cortex.

[39]  A. Sampson,et al.  Regional specificity of chandelier neuron axon terminal alterations in schizophrenia , 2006, Neuroscience.