Sensory gating and source analysis of the auditory P50 in low and high suppressors

Impairments in sensory gating in schizophrenia have been reflected by diminished suppression of the scalp-recorded middle latency auditory P50 event-related potential (MLAERP) elicited by the second (S(2)) of a pair (S(1)-S(2)) of clicks. As understanding the functional neural substrates of aberrant gating would have important implications for schizophrenia, this study examined the location and time-course of the neural generators of the P50 MLAERP and its gating on subgroups of healthy volunteers exhibiting low (n=12) and high (n=12) P50 suppression. Suppressor differences were observed with S(1) P50 (high>low) and S(2) P50 (high<low) amplitudes, and current source density analysis with standardized Low Resolution Electromagnetic Tomography (sLORETA) evidenced an S(1) P50-related activation of limbic, temporal and parietal regions in the high but not the low suppressors. Distributed source localization of the Gating Difference Wave (GDW), obtained by subtracting the S(2) P50 response from the S(1) P50 response, also revealed a later and sustained frontal activation to characterize high suppressors. These findings suggest that impaired gating of the kind evident in schizophrenia may involve the deficient functioning of multiple interconnected and temporally overlapping activated brain regions.

[1]  Brett A. Clementz,et al.  Multichannel electroencephalographic assessment of auditory evoked response suppression in schizophrenia , 2001, Experimental Brain Research.

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

[3]  Gregor Leicht,et al.  Evidence for a close relationship between conscious effort and anterior cingulate cortex activity. , 2005, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[4]  T Landis,et al.  Non-invasive epileptic focus localization using EEG-triggered functional MRI and electromagnetic tomography. , 1998, Electroencephalography and clinical neurophysiology.

[5]  E. Bramon,et al.  Meta-analysis of the P300 and P50 waveforms in schizophrenia , 2004, Schizophrenia Research.

[6]  R. Freedman,et al.  The activity of hippocampal interneurons and pyramidal cells during the response of the hippocampus to repeated auditory stimuli , 1995, Neuroscience.

[7]  Robert Freedman,et al.  Developmental and genetic influences on the p50 sensory gating phenotype , 1996, Biological Psychiatry.

[8]  R. Näätänen,et al.  The mismatch negativity (MMN) in basic research of central auditory processing: A review , 2007, Clinical Neurophysiology.

[9]  N. Boutros,et al.  A Parametric Study of the N40 Auditory Evoked Response in Rats , 1997, Biological Psychiatry.

[10]  S. Enna.  Neuropsychopharmacology Reviews: The Next Generation of Progress , 2008, Neuropsychopharmacology.

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

[12]  Oleg Korzyukov,et al.  Generators of the intracranial P50 response in auditory sensory gating , 2007, NeuroImage.

[13]  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.

[14]  N. Boutros,et al.  Early and late auditory sensory gating: Moderating influences from schizotypal personality, tobacco smoking status, and acute smoking , 2007, Psychiatry Research.

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

[16]  K. K. Tan,et al.  The spatial location of EEG electrodes: locating the best-fitting sphere relative to cortical anatomy. , 1993, Electroencephalography and clinical neurophysiology.

[17]  Babak A. Ardekani,et al.  Early detection of schizophrenia by diffusion weighted imaging , 2006, Psychiatry Research: Neuroimaging.

[18]  Thomas E. Nichols,et al.  Anterior cingulate gyrus dysfunction and selective attention deficits in schizophrenia: [15O]H2O PET study during single-trial Stroop task performance. , 1997, The American journal of psychiatry.

[19]  R. Murray,et al.  Mapping auditory hallucinations in schizophrenia using functional magnetic resonance imaging. , 2000, Archives of general psychiatry.

[20]  L Kruglyak,et al.  Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[21]  R. Heinrichs,et al.  Meta-analysis and the science of schizophrenia: variant evidence or evidence of variants? , 2004, Neuroscience & Biobehavioral Reviews.

[22]  B. Connors,et al.  Intrinsic oscillations of neocortex generated by layer 5 pyramidal neurons. , 1991, Science.

[23]  R. Patterson,et al.  Frontal processing and auditory perception , 2000, Neuroreport.

[24]  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.

[25]  R. Näätänen.  Processing negativity: an evoked-potential reflection of selective attention. , 1982, Psychological bulletin.

[26]  R P Lesser,et al.  Recording of auditory evoked potentials in man using chronic subdural electrodes. , 1984, Brain : a journal of neurology.

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

[28]  Hans J. Eysenck,et al.  Manual of the Eysenck personality questionnaire , 1975 .

[29]  Robert J. Zatorre,et al.  There’s more to auditory cortex than meets the ear , 2007, Hearing Research.

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

[31]  Michael Krause,et al.  Auditory sensory gating in hippocampus and reticular thalamic neurons in anesthetized rats , 2003, Biological Psychiatry.

[32]  Robert Freedman,et al.  Elementary neuronal dysfunctions in schizophrenia , 1991, Schizophrenia Research.

[33]  Dezhong Yao,et al.  A Self-Coherence Enhancement Algorithm and its Application to Enhancing Three-Dimensional Source Estimation from EEGs , 2001, Annals of Biomedical Engineering.

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

[35]  D L Braff,et al.  Human and animal studies of schizophrenia-related gating deficits , 1999, Current psychiatry reports.

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

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

[38]  Nash N. Boutros,et al.  P50 sensory gating ratios in schizophrenics and controls: A review and data analysis , 2008, Psychiatry Research.

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

[40]  H. C. Cromwell,et al.  Sensory Gating: A Translational Effort from Basic to Clinical Science , 2008, Clinical EEG and neuroscience.

[41]  Donald J Woodward,et al.  Multiple single units and population responses during inhibitory gating of hippocampal auditory response in freely-moving rats , 1999, Brain Research.

[42]  Brian F. O'Donnell,et al.  Contributions of subtype and spectral frequency analyses to the study of P50 ERP amplitude and suppression in schizophrenia , 2005, Schizophrenia Research.

[43]  M Scherg,et al.  Is frontal lobe involved in the generation of auditory evoked P50? , 2001, Neuroreport.

[44]  Roberto D. Pascual-Marqui,et al.  Functional imaging with low resolution brain electromagnetic tomography (LORETA) : review, new comparisons, and new validation , 2002 .

[45]  G. Carey,et al.  Codistribution of a sensory gating deficit and schizophrenia in multi-affected families , 1991, Psychiatry Research.

[46]  David A. Smith,et al.  Reliability of P50 auditory event-related potential indices of sensory gating. , 1994, Psychophysiology.

[47]  D. Lehmann,et al.  Functional imaging with low-resolution brain electromagnetic tomography (LORETA): a review. , 2002, Methods and findings in experimental and clinical pharmacology.

[48]  D. Pizzagalli,et al.  Functional but not structural subgenual prefrontal cortex abnormalities in melancholia , 2004 .

[49]  J Mazziotta,et al.  A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM). , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[50]  Toshiaki Onitsuka,et al.  Differential characteristics of the middle latency auditory evoked magnetic responses to interstimulus intervals , 2003, Clinical Neurophysiology.

[51]  Karl J. Friston,et al.  Systematic Regularization of Linear Inverse Solutions of the EEG Source Localization Problem , 2002, NeuroImage.

[52]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[53]  J M Badier,et al.  Evoked potentials recorded from the auditory cortex in man: evaluation and topography of the middle latency components. , 1994, Electroencephalography and clinical neurophysiology.

[54]  R. Llinás.  The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. , 1988, Science.

[55]  E Donchin,et al.  A new method for off-line removal of ocular artifact. , 1983, Electroencephalography and clinical neurophysiology.

[56]  Oleg Korzyukov,et al.  Sensory gating deficits during the mid-latency phase of information processing in medicated schizophrenia patients , 2004, Psychiatry Research.

[57]  M. Geyer,et al.  Multiple site evaluation of P50 suppression among schizophrenia and normal comparison subjects , 1998, Schizophrenia Research.

[58]  R. Freedman,et al.  Medial septal neuron activity in relation to an auditory sensory gating paradigm , 1993, Neuroscience.

[59]  B. Brinkmann,et al.  Localization of the Epileptic Focus by Low-Resolution Electromagnetic Tomography in Patients with a Lesion Demonstrated by MRI , 2004, Brain Topography.

[60]  Ann Summerfelt,et al.  Review of clinical correlates of P50 sensory gating abnormalities in patients with schizophrenia. , 2005, Schizophrenia bulletin.

[61]  M. Cohen,et al.  Coronal topography of the middle latency auditory evoked potentials (MLAEPs) in man. , 1982, Electroencephalography and clinical neurophysiology.

[62]  S. Arnfred,et al.  Exploration of auditory P50 gating in schizophrenia by way of difference waves , 2006, Behavioral and Brain Functions.

[63]  M. Geyer,et al.  Poor P50 suppression among schizophrenia patients and their first-degree biological relatives. , 1998, The American journal of psychiatry.

[64]  C. Gonsalvez,et al.  Suppression of P50 evoked potential component, schizotypal beliefs and smoking , 2004, Psychiatry Research.

[65]  E Jefferson.  Sensory gating in the human hippocampal and rhinal regions , 2005 .

[66]  J D Watson,et al.  Nonparametric Analysis of Statistic Images from Functional Mapping Experiments , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[67]  C M Michel,et al.  Extracranial localization of intracranial interictal epileptiform activity using LORETA (low resolution electromagnetic tomography). , 1997, Electroencephalography and clinical neurophysiology.

[68]  M. Geyer,et al.  Haloperidol Differentially Modulates Prepulse Inhibition and P50 Suppression in Healthy Humans Stratified for Low and High Gating Levels , 2008, Neuropsychopharmacology.

[69]  R. Freedman,et al.  P50 sensory gating in adolescents from a pacific island isolate with elevated risk for schizophrenia , 2004, Biological Psychiatry.

[70]  Yasuhiro Kawasaki,et al.  Differential contributions of prefrontal and temporolimbic pathology to mechanisms of psychosis. , 2005, Brain : a journal of neurology.

[71]  D L Braff,et al.  Sensory gating deficits assessed by the P50 event-related potential in subjects with schizotypal personality disorder. , 2000, The American journal of psychiatry.

[72]  Deborah A. Vitacco,et al.  Correspondence of event‐related potential tomography and functional magnetic resonance imaging during language processing , 2002, Human brain mapping.

[73]  T. Braver,et al.  Executive Functioning Component Mechanisms and Schizophrenia , 2008, Biological Psychiatry.

[74]  N. Boutros,et al.  P50 sensory gating: impact of high vs. low schizotypal personality and smoking status. , 2006, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[75]  Christina R. Maxwell,et al.  Effects of Nicotine Vary Across Two Auditory Evoked Potentials in the Mouse , 2007, Biological Psychiatry.

[76]  Jürgen Gallinat,et al.  Test-retest reliability of P50, N100 and P200 auditory sensory gating in healthy subjects. , 2008, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

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

[78]  H. Crawford,et al.  Enhancement of auditory sensory gating and stimulus-bound gamma band (40 Hz) oscillations in heavy tobacco smokers , 2002, Neuroscience Letters.

[79]  G. Chatrian,et al.  Responses to clicks from the human brain: some depth electrographic observations. , 1960, Electroencephalography and clinical neurophysiology.

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

[81]  Thomas Grunwald,et al.  Neuronal substrates of sensory gating within the human brain , 2003, Biological Psychiatry.

[82]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[83]  Robert Freedman,et al.  Proof-of-Concept Trial of an α7 Nicotinic Agonist in Schizophrenia , 2006 .

[84]  James Robert Brašić,et al.  Neurodevelopmental hypothesis of schizophrenia: a central sensory disturbance. , 2000, Medical hypotheses.

[85]  Karen A. Moxon,et al.  Inhibitory control of sensory gating in a computer model of the CA3 region of the hippocampus , 2003, Biological Cybernetics.

[86]  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.

[87]  D. Braff,et al.  Sensory gating deficits in schizophrenia: can we parse the effects of medication, nicotine use, and changes in clinical status? , 2003, Clinical Neuroscience Research.

[88]  F. Vollenweider,et al.  Comparison of simultaneously recorded [H215O]‐PET and LORETA during cognitive and pharmacological activation , 2004, Human brain mapping.

[89]  Wei-Xing Shi,et al.  The Auditory Cortex in Schizophrenia , 2007, Biological Psychiatry.

[90]  N. Boutros,et al.  Range of sensory gating values and test-retest reliability in normal subjects. , 2007, Psychophysiology.

[91]  M. Stanford,et al.  Mid-latency evoked potentials in self-reported impulsive aggression. , 2001, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[92]  R. Freedman,et al.  Deficits in sensory gating in schizophrenic patients and their relatives. Evidence obtained with auditory evoked responses. , 1984, Archives of general psychiatry.