Differential Relationships of Mismatch Negativity and Visual P1 Deficits to Premorbid Characteristics and Functional Outcome in Schizophrenia

BACKGROUND Mismatch negativity (MMN) and visual P1 are established event-related potential (ERP) markers of impaired auditory and visual sensory function in schizophrenia. Differential relationships of these measures with premorbid and present function and with clinical course have been noted previously in independent cohorts, but measures have not yet been compared within the same patient group. METHODS Twenty-six schizophrenia patients and 19 control subjects participated in a simultaneous visual and auditory ERPs experiment. Attended visual ERPs were obtained to low- and high-spatial frequency stimuli. Simultaneously, MMN was obtained to unattended pitch, duration, and intensity deviant stimuli. Premorbid function, symptom, and global outcome measures were obtained as correlational measures. RESULTS Patients showed substantial P1 reductions to low- but not high-spatial frequency stimuli, unrelated to visual acuity. Patients also exhibited reduced MMN to all deviant types. No significant correlations were observed between visual ERPs and premorbid or global outcome measures or illness duration. In contrast, MMN amplitude correlated significantly and independently with premorbid educational achievement, cognitive symptoms, global function, and illness duration. The MMN to duration versus other deviants was differentially reduced in individuals with poor premorbid function. CONCLUSIONS Visual and auditory ERP measures are differentially related to the pathophysiology of schizophrenia. Visual deficits correlate poorly with functional measures and illness duration and serve primarily as trait vulnerability markers. The MMN deficits are independently related to premorbid function and illness duration, suggesting independent neurodevelopmental and neurodegenerative contributions. The lack of correlation between auditory and visual ERPs in schizophrenia suggests contributions from divergent underlying neurophysiological processes.

[1]  N. Revheim,et al.  The independent living scales as a measure of functional outcome for schizophrenia. , 2004, Psychiatric services.

[2]  D. Javitt,et al.  Neurophysiological biomarkers for drug development in schizophrenia , 2008, Nature Reviews Drug Discovery.

[3]  John J. Foxe,et al.  Early visual processing deficits in schizophrenia: impaired P1 generation revealed by high-density electrical mapping , 2001, Neuroreport.

[4]  R. McCarley,et al.  Progressive and interrelated functional and structural evidence of post-onset brain reduction in schizophrenia. , 2007, Archives of general psychiatry.

[5]  D. Javitt,et al.  Altered volume and hemispheric asymmetry of the superficial cortical layers in the schizophrenia planum temporale , 2009, The European journal of neuroscience.

[6]  A. Baddeley,et al.  Memory dysfunction in schizophrenia , 1990, Schizophrenia Research.

[7]  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.

[8]  Michael F. Green,et al.  Evaluation of functionally meaningful measures for clinical trials of cognition enhancement in schizophrenia. , 2011, The American journal of psychiatry.

[9]  R. Näätänen.  The Mismatch Negativity: A Powerful Tool for Cognitive Neuroscience , 1995, Ear and hearing.

[10]  Martha E Shenton,et al.  Mismatch negativity in chronic schizophrenia and first-episode schizophrenia. , 2002, Archives of general psychiatry.

[11]  Marta Kutas,et al.  Cognitive, neurophysiological, and functional correlates of proverb interpretation abnormalities in schizophrenia , 2007, Journal of the International Neuropsychological Society.

[12]  John J. Foxe,et al.  The neural circuitry of pre-attentive auditory change-detection: an fMRI study of pitch and duration mismatch negativity generators. , 2005, Cerebral cortex.

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

[14]  Elvira Bramon,et al.  Mismatch negativity in schizophrenia: a family study , 2004, Schizophrenia Research.

[15]  D. Javitt.  When doors of perception close: bottom-up models of disrupted cognition in schizophrenia. , 2009, Annual review of clinical psychology.

[16]  D. Braff,et al.  Mismatch negativity deficits are associated with poor functioning in schizophrenia patients. , 2005, Archives of general psychiatry.

[17]  Daniel C. Javitt,et al.  Impairments in generation of early-stage transient visual evoked potentials to magno- and parvocellular-selective stimuli in schizophrenia , 2005, Clinical Neurophysiology.

[18]  D. Javitt,et al.  Impairment of early cortical processing in schizophrenia: An event-related potential confirmation study , 1993, Biological Psychiatry.

[19]  H. Holcomb,et al.  Tone discrimination performance in schizophrenic patients and normal volunteers: impact of stimulus presentation levels and frequency differences , 1995, Psychiatry Research.

[20]  John J. Foxe,et al.  Are Auditory-Evoked Frequency and Duration Mismatch Negativity Deficits Endophenotypic for Schizophrenia? High-Density Electrical Mapping in Clinically Unaffected First-Degree Relatives and First-Episode and Chronic Schizophrenia , 2008, Biological Psychiatry.

[21]  F. Jessen,et al.  Amplitude reduction of the mismatch negativity in first-degree relatives of patients with schizophrenia , 2001, Neuroscience Letters.

[22]  J. Lieberman,et al.  Electrophysiological Indices of Automatic and Controlled Auditory Information Processing in First-Episode, Recent-Onset and Chronic Schizophrenia , 2006, Biological Psychiatry.

[23]  D. Javitt,et al.  Early-stage visual processing deficits in schizophrenia , 2005, Current opinion in psychiatry.

[24]  John J. Foxe,et al.  Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments. , 2007, Brain : a journal of neurology.

[25]  John J. Foxe,et al.  Early Visual Processing Deficits in Dysbindin-Associated Schizophrenia , 2008, Biological Psychiatry.

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

[27]  P. Michie,et al.  Association between reduced duration mismatch negativity (MMN) and raised temporal discrimination thresholds in schizophrenia , 2003, Clinical Neurophysiology.

[28]  N. Cowan,et al.  Auditory sensory ("echoic") memory dysfunction in schizophrenia. , 1995, The American journal of psychiatry.

[29]  Michael Wagner,et al.  Prediction of Psychosis by Mismatch Negativity , 2011, Biological Psychiatry.

[30]  L. Deouell,et al.  Representation of harmonic frequencies in auditory memory: a mismatch negativity study. , 2007, Psychophysiology.

[31]  D. Javitt,et al.  Neurocognitive and symptom correlates of daily problem-solving skills in schizophrenia , 2006, Schizophrenia Research.

[32]  P. Thompson,et al.  Gray matter deficits, mismatch negativity, and outcomes in schizophrenia. , 2011, Schizophrenia bulletin.

[33]  M. Tervaniemi,et al.  Preattentive periodicity detection in auditory patterns as governed by time and intensity information. , 1996, Brain research. Cognitive brain research.

[34]  H. Yabe,et al.  Deviant Matters: Duration, Frequency, and Intensity Deviants Reveal Different Patterns of Mismatch Negativity Reduction in Early and Late Schizophrenia , 2008, Biological Psychiatry.

[35]  C. Schroeder,et al.  Dysfunction of early-stage visual processing in schizophrenia. , 2001, The American journal of psychiatry.

[36]  David A Lewis,et al.  Reduced Pyramidal Cell Somal Volume in Auditory Association Cortex of Subjects with Schizophrenia , 2003, Neuropsychopharmacology.

[37]  D. Javitt,et al.  Diminished responsiveness of ERPs in schizophrenic subjects to changes in auditory stimulation parameters: implications for theories of cortical dysfunction , 1999, Schizophrenia Research.

[38]  I. Tendolkar,et al.  Impaired mismatch negativity generation in prodromal subjects and patients with schizophrenia , 2005, Schizophrenia Research.

[39]  Raquel E. Gur,et al.  Profile of auditory information-processing deficits in schizophrenia , 2009, Psychiatry Research.

[40]  J. Lieberman,et al.  Deficits in auditory and visual context-dependent processing in schizophrenia: defining the pattern. , 2000, Archives of general psychiatry.

[41]  S. Andrews,et al.  Mismatch negativity: An index of a preattentive processing deficit in schizophrenia , 1991, Biological Psychiatry.

[42]  Pejman Sehatpour,et al.  Early visual sensory deficits as endophenotypes for schizophrenia: high-density electrical mapping in clinically unaffected first-degree relatives. , 2006, Archives of general psychiatry.

[43]  Erich Schröger,et al.  Rapid extraction of auditory feature contingencies , 2008, NeuroImage.

[44]  David L. Braff,et al.  Preattentive Sensory Processing as Indexed by the MMN and P3a Brain Responses is Associated with Cognitive and Psychosocial Functioning in Healthy Adults , 2007, Journal of Cognitive Neuroscience.

[45]  John J. Foxe,et al.  Visual white matter integrity in schizophrenia. , 2006, The American journal of psychiatry.

[46]  Daniel C. Javitt,et al.  Reading impairment and visual processing deficits in schizophrenia , 2006, Schizophrenia Research.

[47]  S. Sevy,et al.  Pyramidical model of schizophrenia. , 1990, Schizophrenia bulletin.

[48]  John J. Foxe,et al.  Sensory deficits and distributed hierarchical dysfunction in schizophrenia. , 2010, The American journal of psychiatry.

[49]  P. Michie,et al.  Duration mismatch negativity in biological relatives of patients with schizophrenia spectrum disorders , 2002, Biological Psychiatry.

[50]  David A Lewis,et al.  Primary visual cortex volume and total neuron number are reduced in schizophrenia , 2007, The Journal of comparative neurology.

[51]  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.

[52]  D. Umbricht,et al.  Mismatch negativity in schizophrenia: a meta-analysis , 2005, Schizophrenia Research.

[53]  John J. Foxe,et al.  Impaired visual object processing across an occipital-frontal-hippocampal brain network in schizophrenia: an integrated neuroimaging study. , 2010, Archives of general psychiatry.

[54]  P. Fitzgerald,et al.  Superior temporal gyrus volume change in schizophrenia: A review on Region of Interest volumetric studies , 2009, Brain Research Reviews.

[55]  Michael F. Green,et al.  Mismatch Negativity, Social Cognition, and Functioning in Schizophrenia Patients , 2010, Biological Psychiatry.

[56]  D. Javitt.  Intracortical Mechanisms of Mismatch Negativity Dysfunction in Schizophrenia , 2000, Audiology and Neurotology.