Cognitive Impairments in Schizophrenia as Assessed Through Activation and Connectivity Measures of Magnetoencephalography (MEG) Data

The cognitive dysfunction present in patients with schizophrenia is thought to be driven in part by disorganized connections between higher-order cortical fields. Although studies utilizing electroencephalography (EEG), PET and fMRI have contributed significantly to our understanding of these mechanisms, magnetoencephalography (MEG) possesses great potential to answer long-standing questions linking brain interactions to cognitive operations in the disorder. Many experimental paradigms employed in EEG and fMRI are readily extendible to MEG and have expanded our understanding of the neurophysiological architecture present in schizophrenia. Source reconstruction techniques, such as adaptive spatial filtering, take advantage of the spatial localization abilities of MEG, allowing us to evaluate which specific structures contribute to atypical cognition in schizophrenia. Finally, both bivariate and multivariate functional connectivity metrics of MEG data are useful for understanding how these interactions in the brain are impaired in schizophrenia, and how cognitive and clinical outcomes are affected as a result. We also present here data from our own laboratory that illustrates how some of these novel functional connectivity measures, specifically imaginary coherence (IC), are quite powerful in relating disconnectivity in the brain to characteristic behavioral findings in the disorder.

[1]  Ruben C Gur,et al.  Sensory contributions to impaired emotion processing in schizophrenia. , 2009, Schizophrenia bulletin.

[2]  Manzar Ashtari,et al.  Reduced frontal white matter integrity in Early-Onset schizophrenia: a preliminary study , 2004, Biological Psychiatry.

[3]  Y. Wada,et al.  Interhemispheric EEG Coherence in Never-Medicated Patients with Paranoid Schizophrenia: Analysis at Rest and during Photic Stimulation , 1998, Clinical EEG.

[4]  G. A. Miller,et al.  Electromagnetic brain activity evoked by affective stimuli in schizophrenia. , 2006, Psychophysiology.

[5]  Timothy Edward John Behrens,et al.  New approaches for exploring anatomical and functional connectivity in the human brain , 2004, Biological Psychiatry.

[6]  Andreas A. Ioannides,et al.  Real-time neural activity and connectivity in healthy individuals and schizophrenia patients , 2004, NeuroImage.

[7]  Matthias M. Müller,et al.  MEG gamma band activity in schizophrenia patients and healthy subjects in a mental arithmetic task and at rest , 2000, Clinical Neurophysiology.

[8]  E. Halgren,et al.  Spatiotemporal mapping of brain activity by integration of multiple imaging modalities , 2001, Current Opinion in Neurobiology.

[9]  G Comi,et al.  EEG coherence in pathological conditions. , 1999, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[10]  J. Ford,et al.  Reduced communication between frontal and temporal lobes during talking in schizophrenia , 2002, Biological Psychiatry.

[11]  Y. Hirano,et al.  Abnormal Neural Oscillatory Activity to Speech Sounds in Schizophrenia: A Magnetoencephalography Study , 2008, The Journal of Neuroscience.

[12]  G. A. Miller,et al.  Spontaneous brain magnetic activity in schizophrenia patients treated with aripiprazole. , 1998, Psychopharmacology bulletin.

[13]  Robert T. Knight,et al.  Five-dimensional neuroimaging: Localization of the time–frequency dynamics of cortical activity , 2008, NeuroImage.

[14]  J.C. Mosher,et al.  Multiple dipole modeling and localization from spatio-temporal MEG data , 1992, IEEE Transactions on Biomedical Engineering.

[15]  A. Schnitzler,et al.  Dynamic imaging of coherent sources: Studying neural interactions in the human brain. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Ford,et al.  Widespread cortical dysfunction in schizophrenia: the FBIRN imaging consortium. , 2009, Schizophrenia bulletin.

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

[18]  John J. Foxe,et al.  Sensory Contributions to Impaired Prosodic Processing in Schizophrenia , 2005, Biological Psychiatry.

[19]  Michael Eichler,et al.  Abstract Journal of Neuroscience Methods xxx (2005) xxx–xxx Testing for directed influences among neural signals using partial directed coherence , 2005 .

[20]  Bhaskar D. Rao,et al.  Sparse signal reconstruction from limited data using FOCUSS: a re-weighted minimum norm algorithm , 1997, IEEE Trans. Signal Process..

[21]  E. Halgren,et al.  Dynamic Statistical Parametric Mapping Combining fMRI and MEG for High-Resolution Imaging of Cortical Activity , 2000, Neuron.

[22]  Mingxiong Huang,et al.  Distinct M50 and M100 auditory gating deficits in schizophrenia. , 2005, Psychophysiology.

[23]  Neil D. Woodward,et al.  Abnormal prefrontal cortical activity and connectivity during response selection in first episode psychosis, chronic schizophrenia, and unaffected siblings of individuals with schizophrenia , 2009, Schizophrenia Research.

[24]  Julia P. Owen,et al.  Robust Bayesian estimation of the location, orientation, and time course of multiple correlated neural sources using MEG , 2010, NeuroImage.

[25]  W. Freeman,et al.  Combining fMRI with EEG and MEG in order to relate patterns of brain activity to cognition. , 2009, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[26]  Karl J. Friston Functional and effective connectivity in neuroimaging: A synthesis , 1994 .

[27]  E. Merrin,et al.  Negative symptoms and EEG alpha activity in schizophrenic patients , 1992, Schizophrenia Research.

[28]  F. Babiloni,et al.  Comparison of different multivariate methods for the estimation of cortical connectivity: simulations and applications to EEG data , 2005, 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference.

[29]  David Poeppel,et al.  Reconstructing spatio-temporal activities of neural sources using an MEG vector beamformer technique , 2001, IEEE Transactions on Biomedical Engineering.

[30]  Simona Temereanca,et al.  A non-invasive method to relate the timing of neural activity to white matter microstructural integrity , 2008, NeuroImage.

[31]  R Freedman,et al.  Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. , 1982, Biological psychiatry.

[32]  P. Nunez,et al.  EEG and MEG coherence: Measures of functional connectivity at distinct spatial scales of neocortical dynamics , 2007, Journal of Neuroscience Methods.

[33]  M. Greicius Resting-state functional connectivity in neuropsychiatric disorders , 2008, Current opinion in neurology.

[34]  Paolo Maria Rossini,et al.  Choice of multivariate autoregressive model order affecting real network functional connectivity estimate , 2009, Clinical Neurophysiology.

[35]  G. Barnes,et al.  Assessing interactions of linear and nonlinear neuronal sources using MEG beamformers: a proof of concept , 2005, Clinical Neurophysiology.

[36]  G. A. Miller,et al.  Predicting EEG responses using MEG sources in superior temporal gyrus reveals source asynchrony in patients with schizophrenia , 2003, Clinical Neurophysiology.

[37]  R. Näätänen,et al.  The mismatch negativity (MMN): towards the optimal paradigm , 2004, Clinical Neurophysiology.

[38]  E. Somersalo,et al.  Visualization of Magnetoencephalographic Data Using Minimum Current Estimates , 1999, NeuroImage.

[39]  R Schoonhoven,et al.  A whole head MEG study of the amplitude-modulation-following response: phase coherence, group delay and dipole source analysis , 2003, Clinical Neurophysiology.

[40]  Matthew J. Brookes,et al.  Relating BOLD fMRI and neural oscillations through convolution and optimal linear weighting , 2010, NeuroImage.

[41]  M Reite,et al.  Source location of a 50 msec latency auditory evoked field component. , 1988, Electroencephalography and clinical neurophysiology.

[42]  J. Gruzelier,et al.  Topographical EEG differences between schizophrenic patients and controls during neuropsychological functional activation. , 1990, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[43]  M. Berger,et al.  Mapping functional connectivity in patients with brain lesions , 2008, Annals of neurology.

[44]  R D Pascual-Marqui,et al.  Standardized low-resolution brain electromagnetic tomography (sLORETA): technical details. , 2002, Methods and findings in experimental and clinical pharmacology.

[45]  Gregory A. Miller,et al.  M50 sensory gating predicts negative symptoms in schizophrenia , 2005, Schizophrenia Research.

[46]  F. Pulvermüller,et al.  Language outside the focus of attention: The mismatch negativity as a tool for studying higher cognitive processes , 2006, Progress in Neurobiology.

[47]  S. Lawrie,et al.  Structural disconnectivity in schizophrenia: a diffusion tensor magnetic resonance imaging study , 2003, British Journal of Psychiatry.

[48]  Carl-Fredrik Westin,et al.  The Application of DTI to Investigate White Matter Abnormalities in Schizophrenia , 2005, Annals of the New York Academy of Sciences.

[49]  A M McIntosh,et al.  Connecting the brain and new drug targets for schizophrenia. , 2009, Current pharmaceutical design.

[50]  A. Georgopoulos,et al.  Synchronous neural interactions assessed by magnetoencephalography: a functional biomarker for brain disorders , 2007, Journal of neural engineering.

[51]  Jun Soo Kwon,et al.  Pre-Attentive Auditory Processing in Ultra-High-Risk for Schizophrenia with Magnetoencephalography , 2009, Biological Psychiatry.

[52]  F. Boers,et al.  Optimized mismatch negativity paradigm reflects deficits in schizophrenia patients A combined EEG and MEG study , 2008, Biological Psychology.

[53]  D. Javitt Sensory processing in schizophrenia: neither simple nor intact. , 2009, Schizophrenia bulletin.

[54]  B. Rockstroh,et al.  Source distribution of neuromagnetic slow-wave activity in schizophrenic patients—effects of activation , 2003, Schizophrenia Research.

[55]  V. Strelets,et al.  Cortical connectivity in high frequency beta-rhythm in schizophrenics with positive and negative symptoms. , 2002, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[56]  John W. Goethe,et al.  EEG coherence and power in the discrimination of psychiatric disorders and medication effects , 1986, Biological Psychiatry.

[57]  A. Iwanami,et al.  Neuromagnetic correlates of impaired automatic categorical perception of speech sounds in schizophrenia , 2003, Schizophrenia Research.

[58]  D. Weinberger,et al.  Cognitive deficits and the neurobiology of schizophrenia , 1995, Current Opinion in Neurobiology.

[59]  J. Vrba,et al.  Signal processing in magnetoencephalography. , 2001, Methods.

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

[61]  Thomas Elbert,et al.  Emotion Processing in the Visual Brain: A MEG Analysis , 2008, Brain Topography.

[62]  G. A. Miller,et al.  Cross-modal generality of the gating deficit. , 2005, Psychophysiology.

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

[64]  Wolfgang Grodd,et al.  Mismatch negativity responses in schizophrenia: a combined fMRI and whole-head MEG study. , 2004, The American journal of psychiatry.

[65]  C. Kohler,et al.  Facial emotion perception in schizophrenia: a meta-analytic review. , 2010, Schizophrenia bulletin.

[66]  Jong H. Yoon,et al.  Neuroimaging of cognitive disability in schizophrenia: Search for a pathophysiological mechanism , 2007, International review of psychiatry.

[67]  M Huang,et al.  Multi-start downhill simplex method for spatio-temporal source localization in magnetoencephalography. , 1998, Electroencephalography and clinical neurophysiology.

[68]  関原 謙介,et al.  Adaptive Spatial Filters for Electromagnetic Brain Imaging , 2008 .

[69]  C. Stam,et al.  Phase lag index: Assessment of functional connectivity from multi channel EEG and MEG with diminished bias from common sources , 2007, Human brain mapping.

[70]  Ahmed H. Tewfik,et al.  Classification of schizophrenia with spectro-temporo-spatial MEG patterns in working memory , 2009, Clinical Neurophysiology.

[71]  Risto Näätänen,et al.  Central auditory dysfunction in schizophrenia as revealed by the mismatch negativity (MMN) and its magnetic equivalent MMNm: a review. , 2009, The international journal of neuropsychopharmacology.

[72]  K. Linkenkaer-Hansen,et al.  Interhemispheric phase synchrony and amplitude correlation of spontaneous beta oscillations in human subjects: a magnetoencephalographic study , 2001, Neuroreport.

[73]  D. Javitt,et al.  BRAIN IMAGING NEUROREPORT , 2005 .

[74]  G. A. Miller,et al.  Lateralization of auditory sensory gating and neuropsychological dysfunction in schizophrenia. , 2003, The American journal of psychiatry.

[75]  K. Shinosaki,et al.  Information Processing Flow and Neural Activations in the Dorsolateral Prefrontal Cortex in the Stroop Task in Schizophrenic Patients , 2005, Neuropsychobiology.

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

[77]  Se Robinson,et al.  Functional neuroimaging by Synthetic Aperture Magnetometry (SAM) , 1999 .

[78]  B. Rockstroh,et al.  Source distribution of neuromagnetic slow waves and MEG-delta activity in schizophrenic patients , 2001, Biological Psychiatry.

[79]  Gregory A. Miller,et al.  Impaired secondary somatosensory gating in patients with schizophrenia , 2007, Psychiatry Research.

[80]  George Fein,et al.  EEG coherence in unmedicated schizophrenic patients , 1989, Biological Psychiatry.

[81]  C. Gilbert,et al.  Brain States: Top-Down Influences in Sensory Processing , 2007, Neuron.

[82]  G. V. Simpson,et al.  Timing is everything: neural response dynamics during syllable processing and its relation to higher-order cognition in schizophrenia and healthy comparison subjects. , 2010, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[83]  E E Smith,et al.  Components of verbal working memory: evidence from neuroimaging. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[84]  Hagai Attias,et al.  A probabilistic algorithm integrating source localization and noise suppression for MEG and EEG data , 2006, NeuroImage.

[85]  Miki Uetsuki,et al.  Abnormal association between reduced magnetic mismatch field to speech sounds and smaller left planum temporale volume in schizophrenia , 2004, NeuroImage.

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

[87]  R. Schlösser,et al.  Intensive practice of a cognitive task is associated with enhanced functional integration in schizophrenia , 2009, Psychological Medicine.

[88]  Ryouhei Ishii,et al.  Parallel distributed processing neuroimaging in the Stroop task using spatially filtered magnetoencephalography analysis , 2002, Neuroscience Letters.

[89]  G. Rosoklija,et al.  White matter and cognitive function in schizophrenia. , 2007, The international journal of neuropsychopharmacology.

[90]  R. Salmelin,et al.  Global optimization in the localization of neuromagnetic sources , 1998, IEEE Transactions on Biomedical Engineering.

[91]  Peter Falkai,et al.  Effects of antipsychotics on brain structure , 2006, Current opinion in psychiatry.

[92]  Disordered semantic representation in schizophrenic temporal cortex revealed by neuromagnetic response patterns , 2006, BMC psychiatry.

[93]  Sophie Schwartz,et al.  Role of frontal versus temporal cortex in verbal fluency as revealed by voxel-based lesion symptom mapping , 2006, Journal of the International Neuropsychological Society.

[94]  R. Bluhm,et al.  Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network. , 2007, Schizophrenia bulletin.

[95]  Gareth J. Barker,et al.  Diffusion tensor imaging in schizophrenia , 2008, European Psychiatry.

[96]  J.C. Mosher,et al.  Recursive MUSIC: A framework for EEG and MEG source localization , 1998, IEEE Transactions on Biomedical Engineering.

[97]  M. E. Spencer,et al.  A Study of Dipole Localization Accuracy for MEG and EEG using a Human Skull Phantom , 1998, NeuroImage.

[98]  Peter Rappelsberger,et al.  Low frontal electroencephalographic coherence in neuroleptic-free schizophrenic patients , 1998, Biological Psychiatry.

[99]  W Sperling,et al.  Spontaneous, slow and fast magnetoencephalographic activity in patients with schizophrenia , 2002, Schizophrenia Research.

[100]  O. Blin,et al.  Schizophrenia and frontal cortex: Where does it fail? , 2007, Schizophrenia Research.

[101]  G. V. Simpson,et al.  When top-down meets bottom-up: auditory training enhances verbal memory in schizophrenia. , 2009, Schizophrenia bulletin.

[102]  R. Franciotti,et al.  A Cartesian Time–Frequency Approach to Reveal Brain Interaction Dynamics , 2007, Brain Topography.

[103]  D. Weinberger,et al.  Magnetoencephalography. Applications in psychiatry. , 1989, Archives of general psychiatry.

[104]  E. Moran,et al.  Emotional response deficits in schizophrenia: insights from affective science. , 2008, Schizophrenia bulletin.

[105]  David P. Wipf,et al.  A unified Bayesian framework for MEG/EEG source imaging , 2009, NeuroImage.