Lateralization of auditory sensory gating and neuropsychological dysfunction in schizophrenia.

OBJECTIVE Sensory gating assessed via EEG in a paired-click paradigm has often served as a neurophysiological metric of attentional function in schizophrenia. However, the standard EEG measure of sensory gating using the P50 component at electrode Cz does not foster differential assessment of left and right hemisphere contributions. Magnetoencephalography (MEG) is complementary to EEG, and its analogous M50 component may be better suited for localization and analysis of such lateralized cortical generators. The authors hypothesized that 1) auditory gating would be evident in M50 sources in superior temporal gyrus, demonstrating ratios similar to P50; 2) M50 would resemble P50 in distinguishing gating in comparison subjects and patients with schizophrenia, but M50 would show lateralization of the gating deficit; and 3) P50 and M50 sensory gating ratios would predict neuropsychological measures in patients and comparison subjects, with the MEG identification of left and right hemisphere sources allowing for the evaluation of lateralization in brain-behavior relationships. METHOD Event-related EEG and MEG recordings were simultaneously obtained from 20 patients with schizophrenia and 15 comparison subjects. P50 amplitudes, M50 dipole source strengths, and P50 and M50 gating ratios were compared and assessed with respect to scores on neuropsychological performance measures. RESULTS M50 dipoles localizing to superior temporal gyrus demonstrated gating similar to that of P50. As expected, patients demonstrated less P50 gating than did comparison subjects. Left (but not right) hemisphere M50 gating 1) correlated with EEG gating, 2) differentiated patients and comparison subjects, and 3) correlated with neuropsychological measures of sustained attention and working memory. CONCLUSIONS Converging evidence from EEG, MEG, and neuropsychological measures points to left hemisphere dysfunction as strongly related to the well-established sensory gating deficit in schizophrenia.

[1]  D. Wechsler.  Manual for the Wechsler Adult Intelligence Scale. , 1955 .

[2]  R Coppola,et al.  Isolating low frequency activity EEG spectrum analysis. , 1979, Electroencephalography and clinical neurophysiology.

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

[4]  R Freedman,et al.  Neurophysiological evidence for a defect in inhibitory pathways in schizophrenia: comparison of medicated and drug-free patients. , 1983, Biological psychiatry.

[5]  J. Alpert,et al.  Neurophysiological studies of sensory gating in mania: comparison with schizophrenia. , 1983, Biological psychiatry.

[6]  R. Reitan,et al.  3/The Halstead-Reitan Neuropsychological Test Battery and Aging , 1986 .

[7]  R Freedman,et al.  Neurobiological studies of sensory gating in schizophrenia. , 1987, Schizophrenia bulletin.

[8]  F. H. Lopes da Silva,et al.  On the magnetic field distribution generated by a dipolar current source situated in a realistically shaped compartment model of the head. , 1987, Electroencephalography and clinical neurophysiology.

[9]  J. Sarvas.  Basic mathematical and electromagnetic concepts of the biomagnetic inverse problem. , 1987, Physics in medicine and biology.

[10]  J. Mäkelä,et al.  Cortical origin of middle-latency auditory evoked responses in man , 1987, Neuroscience Letters.

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

[12]  Robert Freedman,et al.  Sensory gating in schizophrenics and normal controls: Effects of changing stimulation interval , 1989, Biological Psychiatry.

[13]  M. Hämäläinen,et al.  Realistic conductivity geometry model of the human head for interpretation of neuromagnetic data , 1989, IEEE Transactions on Biomedical Engineering.

[14]  G. Gerhardt,et al.  Sensory physiology and catecholamines in schizophrenia and mania , 1990, Psychiatry Research.

[15]  O. Selnes.  A Compendium of Neuropsychological Tests , 1991, Neurology.

[16]  R. Gur,et al.  Neuropsychological function in schizophrenia. Selective impairment in memory and learning. , 1991, Archives of general psychiatry.

[17]  Ruben C. Gur,et al.  Midlatency auditory evoked responses in schizophrenia , 1991, Biological Psychiatry.

[18]  G Zouridakis,et al.  Replication and Extension of P50 Findings in Schizophrenia , 1991, Clinical EEG.

[19]  T R Bashore,et al.  Attentional influence on the P50 component of the auditory event-related brain potential. , 1992, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[20]  D L Braff,et al.  Sensory gating deficits in schizophrenia: new results. , 1992, The American journal of psychiatry.

[21]  Xiao-Li Meng,et al.  Comparing correlated correlation coefficients , 1992 .

[22]  Robert Freedman,et al.  Neurophysiological and neuropsychological evidence for attentional dysfunction in schizophrenia , 1993, Schizophrenia Research.

[23]  L. Adler,et al.  Transient impairment in P50 auditory sensory gating induced by a cold-pressor test , 1993, Biological Psychiatry.

[24]  George Fein,et al.  The reliability of P50 suppression as measured by the conditioning/testing ratio is vastly improved by dipole modeling , 1993, Biological Psychiatry.

[25]  D. Braff.  Information processing and attention dysfunctions in schizophrenia. , 1993, Schizophrenia bulletin.

[26]  A. S. Ferguson,et al.  A complete linear discretization for calculating the magnetic field using the boundary element method , 1994, IEEE Transactions on Biomedical Engineering.

[27]  K. Sax,et al.  Sustained attention and positive formal thought disorder in schizophrenia , 1994, Schizophrenia Research.

[28]  J. Mäkelä,et al.  Whole-head mapping of middle-latency auditory evoked magnetic fields. , 1994, Electroencephalography and clinical neurophysiology.

[29]  J. Neale,et al.  The neuropsychological signature of schizophrenia: generalized or differential deficit? , 1994, The American journal of psychiatry.

[30]  Jeffrey A. Lieberman,et al.  Anterior hippocampal volume reductions predict frontal lobe dysfunction in first episode schizophrenia , 1995, Schizophrenia Research.

[31]  Aetiology of schizophrenia: an evolutionary theory. , 1995 .

[32]  L. Heller,et al.  Evaluation of boundary element methods for the EEG forward problem: effect of linear interpolation , 1995, IEEE Transactions on Biomedical Engineering.

[33]  J. Lewine,et al.  CHAPTER 9 – Magnetoencephalography and Magnetic Source Imaging , 1995 .

[34]  P. Ward,et al.  Replication of a P50 auditory gating deficit in Australian patients with schizophrenia , 1996, Psychiatry Research.

[35]  Source localization of middle latency auditory evoked magnetic fields , 1996 .

[36]  D. Pandya,et al.  Comparison of prefrontal architecture and connections. , 1996, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[37]  Robert Freedman,et al.  Gating of auditory P50 in schizophrenics: Unique effects of clozapine , 1996, Biological Psychiatry.

[38]  G. Fein,et al.  Cocaine abusers have reduced auditory P50 amplitude and suppression compared to both normal controls and alcoholics , 1996, Biological Psychiatry.

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

[40]  Brett A. Clementz,et al.  P50 Suppression among schizophrenia and normal comparison subjects: A methodological analysis , 1997, Biological Psychiatry.

[41]  C. M. Yee,et al.  Effects of attentional and stressor manipulations on the P50 gating response. , 1997, Psychophysiology.

[42]  Steven G Potkin,et al.  Effects of P50 temporal variability on sensory gating in schizophrenia , 1997, Psychiatry Research.

[43]  A. Clair,et al.  Performance on tests sensitive to impaired executive ability in schizophrenia, mania and well controls: acute and subacute phases , 1997, Schizophrenia Research.

[44]  C. Armstrong.  Selective versus sustained attention: A continuous performance test revisited , 1997 .

[45]  B. Rockstroh,et al.  Failure of dominant left‐hemispheric activation to right‐ear stimulation in schizophrenia , 1998, Neuroreport.

[46]  R. Ilmoniemi,et al.  Combined mapping of human auditory EEG and MEG responses. , 1998, Electroencephalography and clinical neurophysiology.

[47]  T. J. Crow,et al.  Anomalies of cerebral asymmetry in schizophrenia interact with gender and age of onset: a post-mortem study , 1998, Schizophrenia Research.

[48]  K H Nuechterlein,et al.  P50 suppression in recent-onset schizophrenia: clinical correlates and risperidone effects. , 1998, Journal of abnormal psychology.

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

[50]  M. Mishkin,et al.  Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex , 1999, Nature Neuroscience.

[51]  B. Clementz,et al.  Hemispheric differences on auditory evoked response suppression in schizophrenia. , 1999, Neuroreport.

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

[53]  George Fein,et al.  Sensory gating in chronic posttraumatic stress disorder: reduced auditory p50 suppression in combat veterans , 1999, Biological Psychiatry.

[54]  R. Knight,et al.  Prefrontal cortex regulates inhibition and excitation in distributed neural networks. , 1999, Acta psychologica.

[55]  Jane S. Paulsen,et al.  Generalized cognitive deficits in schizophrenia: a study of first-episode patients. , 1999, Archives of general psychiatry.

[56]  N. Cohen,et al.  Prefrontal regions play a predominant role in imposing an attentional 'set': evidence from fMRI. , 2000, Brain research. Cognitive brain research.

[57]  Jeffrey A. Lieberman,et al.  Reduced anterior cingulate gyrus volume correlates with executive dysfunction in men with first-episode schizophrenia , 2000, Schizophrenia Research.

[58]  M. Reite,et al.  Impaired auditory gating and P50 nonsuppression following traumatic brain injury. , 2000, The Journal of neuropsychiatry and clinical neurosciences.

[59]  J. Nici,et al.  A Compendium of Neuropsychological Tests, 2nd ed , 2000 .

[60]  J. Lieberman,et al.  Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. , 2000, The American journal of psychiatry.

[61]  T. Onitsuka,et al.  The effect of interstimulus intervals and between-block rests on the auditory evoked potential and magnetic field: is the auditory P50 in humans an overlapping potential? , 2000, Clinical Neurophysiology.

[62]  D L Braff,et al.  Normal P50 suppression in schizophrenia patients treated with atypical antipsychotic medications. , 2000, The American journal of psychiatry.

[63]  J. Barth,et al.  The Halstead-Reitan Neuropsychological Test Battery. , 2000 .

[64]  Arthur F. Kramer,et al.  fMRI Studies of Stroop Tasks Reveal Unique Roles of Anterior and Posterior Brain Systems in Attentional Selection , 2000, Journal of Cognitive Neuroscience.

[65]  R. Kahn,et al.  Language lateralization in schizophrenia, an fMRI study , 2001, Schizophrenia Research.

[66]  B. Wexler,et al.  Verbal working memory impairment in schizophrenia. , 2001, The American journal of psychiatry.

[67]  F. Jessen,et al.  Sensory gating deficit expressed by a disturbed suppression of the P50 event-related potential in patients with Alzheimer's disease. , 2001, The American journal of psychiatry.

[68]  M. Myles-Worsley,et al.  P50 sensory gating in multiplex schizophrenia families from a Pacific island isolate. , 2002, The American journal of psychiatry.

[69]  E. Schröger,et al.  Differential Contribution of Frontal and Temporal Cortices to Auditory Change Detection: fMRI and ERP Results , 2002, NeuroImage.

[70]  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.