Cortical substrates and functional correlates of auditory deviance processing deficits in schizophrenia.
Although sensory processing abnormalities contribute to widespread cognitive and psychosocial impairments in schizophrenia (SZ) patients, scalp-channel measures of averaged event-related potentials (ERPs) mix contributions from distinct cortical source-area generators, diluting the functional relevance of channel-based ERP measures. SZ patients (n = 42) and non-psychiatric comparison subjects (n = 47) participated in a passive auditory duration oddball paradigm, eliciting a triphasic (Deviant-Standard) tone ERP difference complex, here termed the auditory deviance response (ADR), comprised of a mid-frontal mismatch negativity (MMN), P3a positivity, and re-orienting negativity (RON) peak sequence. To identify its cortical sources and to assess possible relationships between their response contributions and clinical SZ measures, we applied independent component analysis to the continuous 68-channel EEG data and clustered the resulting independent components (ICs) across subjects on spectral, ERP, and topographic similarities. Six IC clusters centered in right superior temporal, right inferior frontal, ventral mid-cingulate, anterior cingulate, medial orbitofrontal, and dorsal mid-cingulate cortex each made triphasic response contributions. Although correlations between measures of SZ clinical, cognitive, and psychosocial functioning and standard (Fz) scalp-channel ADR peak measures were weak or absent, for at least four IC clusters one or more significant correlations emerged. In particular, differences in MMN peak amplitude in the right superior temporal IC cluster accounted for 48% of the variance in SZ-subject performance on tasks necessary for real-world functioning and medial orbitofrontal cluster P3a amplitude accounted for 40%/54% of SZ-subject variance in positive/negative symptoms. Thus, source-resolved auditory deviance response measures including MMN may be highly sensitive to SZ clinical, cognitive, and functional characteristics.
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Anthony J
AJ
Rissling
Swartz Center for Computational Neuroscience, Institute for Neural Computation, University of California San Diego, La Jolla, CA, USA ; Japan Society for the Promotion of Science, Japan.
Makoto
M
Miyakoshi
Department of Psychiatry, University of California Los Angeles, Los Angeles, CA, USA ; Department of Biostatistics, University of California Los Angeles, Los Angeles, CA, USA ; VISN-22 Mental Illness, Research, Education and Clinical Center (MIRECC), Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA.
Catherine A
CA
Sugar
VISN-22 Mental Illness, Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, Los Angeles, CA, USA ; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
David L
DL
Braff
Swartz Center for Computational Neuroscience, Institute for Neural Computation, University of California San Diego, La Jolla, CA, USA.
Scott
S
Makeig
VISN-22 Mental Illness, Research, Education and Clinical Center (MIRECC), VA San Diego Healthcare System, Los Angeles, CA, USA ; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Gregory A
GA
Light
D000161:Acoustic Stimulation; D000328:Adult; D001288:Attention / Q000502:physiology*; D001307:Auditory Perception / Q000502:physiology*; D001921:Brain / Q000503:physiopathology*; D003627:Data Interpretation, Statistical; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000503:physiopathology*
Attention; EEG; Independent component analysis; Mismatch negativity; Schizophrenia