Neural mechanisms of mismatch negativity dysfunction in schizophrenia.
Schizophrenia is associated with cognitive deficits that reflect impaired cortical information processing. Mismatch negativity (MMN) indexes pre-attentive information processing dysfunction at the level of primary auditory cortex. This study investigates mechanisms underlying MMN impairments in schizophrenia using event-related potential, event-related spectral decomposition (ERSP) and resting state functional connectivity (rsfcMRI) approaches. For this study, MMN data to frequency, intensity and duration-deviants were analyzed from 69 schizophrenia patients and 38 healthy controls. rsfcMRI was obtained from a subsample of 38 patients and 23 controls. As expected, schizophrenia patients showed highly significant, large effect size (P=0.0004, d=1.0) deficits in MMN generation across deviant types. In ERSP analyses, responses to deviants occurred primarily the theta (4-7 Hz) frequency range consistent with distributed corticocortical processing, whereas responses to standards occurred primarily in alpha (8-12 Hz) range consistent with known frequencies of thalamocortical activation. Independent deficits in schizophrenia were observed in both the theta response to deviants (P=0.021) and the alpha-response to standards (P=0.003). At the single-trial level, differential patterns of response were observed for frequency vs duration/intensity deviants, along with At the network level, MMN deficits engaged canonical somatomotor, ventral attention and default networks, with a differential pattern of engagement across deviant types (P<0.0001). Findings indicate that deficits in thalamocortical, as well as corticocortical, connectivity contribute to auditory dysfunction in schizophrenia. In addition, differences in ERSP and rsfcMRI profiles across deviant types suggest potential differential engagement of underlying generator mechanisms.
Division of Experimental Therapeutics, Department of Psychiatry, Columbia University, New York, NY, USA.|Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
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M
Lee
Division of Experimental Therapeutics, Department of Psychiatry, Columbia University, New York, NY, USA.|Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
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Sehatpour
Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
M J
MJ
Hoptman
Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
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P
Lakatos
Division of Experimental Therapeutics, Department of Psychiatry, Columbia University, New York, NY, USA.|Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
E C
EC
Dias
Division of Experimental Therapeutics, Department of Psychiatry, Columbia University, New York, NY, USA.|Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
J T
JT
Kantrowitz
Division of Experimental Therapeutics, Department of Psychiatry, Columbia University, New York, NY, USA.|Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
A M
AM
Martinez
Division of Experimental Therapeutics, Department of Psychiatry, Columbia University, New York, NY, USA.|Schizophrenia Research Division, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
D C
DC
Javitt
D000161:Acoustic Stimulation / Q000379:methods; D000328:Adult; D001288:Attention / Q000502:physiology; D001303:Auditory Cortex / Q000378:metabolism / Q000503:physiopathology; D001307:Auditory Perception / Q000502:physiology; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000150:complications / Q000503:physiopathology; D004569:Electroencephalography / Q000379:methods*; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D012559:Schizophrenia / Q000150:complications / Q000503:physiopathology*