Neural substrates of normal and impaired preattentive sensory discrimination in large cohorts of nonpsychiatric subjects and schizophrenia patients as indexed by MMN and P3a change detection responses

• Published in: NeuroImage (Orlando, Fla.) Vol. 66; pp. 594 - 603
• Main Authors: Takahashi, Hidetoshi, Rissling, Anthony J., Pascual-Marqui, Roberto, Kirihara, Kenji, Pela, Marlena, Sprock, Joyce, Braff, David L., Light, Gregory A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.02.2013; Elsevier; Elsevier Limited
• Subjects: Adult; Adult and adolescent clinical studies; Attention - physiology; Biological and medical sciences; Biomarkers; Brain - physiopathology; Cognition; Cohort Studies; Discrimination; EEG; Electroencephalography; Endophenotype; Evoked Potentials - physiology; Female; Humans; Illnesses; Light; LORETA; Male; Medical sciences; Mental disorders; Middle Aged; Mismatch negativity; MMN; P300; P3a; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - physiopathology; Sensory information processing; Signal Processing, Computer-Assisted; Source localization; Studies; Mismatch negativity; Source localization; EEG; P300; Schizophrenia; Sensory information processing; Cognition; LORETA; Endophenotype; MMN; P3a; Human; Stimulus disparity; Electrophysiology; Electroencephalography; P300 potential; Psychosis; Discrimination; Acoustic stimulus; Auditory evoked potential; Information processing; Localization
• ISSN: 1053-8119; 1095-9572; 1095-9572
• DOI: 10.1016/j.neuroimage.2012.09.074

Schizophrenia (SZ) patients have information processing deficits, spanning from low level sensory processing to higher-order cognitive functions. Mismatch negativity (MMN) and P3a are event-related potential (ERP) components that are automatically elicited in response to unattended changes in ongoing, repetitive stimuli that provide a window into abnormal information processing in SZ. MMN and P3a are among the most robust and consistently identified deficits in SZ, yet the neural substrates of these responses and their associated deficits in SZ are not fully understood. This study examined the neural sources of MMN and P3a components in a large cohort of SZ and nonpsychiatric control subjects (NCS) using Exact Low Resolution Electromagnetic Tomography Analyses (eLORETA) in order to identify the neural sources of MMN and P3a as well as the brain regions associated with deficits commonly observed among SZ patients. 410 SZ and 247 NCS underwent EEG testing using a duration-deviant auditory oddball paradigm (1-kHz tones, 500ms SOA; standard p=0.90, 50-ms duration; deviant tones P=0.10, 100-ms duration) while passively watching a silent video. Voxel-by-voxel within- (MMN vs. P3a) and between-group (SZ vs. NCS) comparisons were performed using eLORETA. SZ had robust deficits in MMN and P3a responses measured at scalp electrodes consistent with other studies. These components mapped onto neural sources broadly distributed across temporal, frontal, and parietal regions. MMN deficits in SZ were associated with reduced activations in discrete medial frontal brain regions, including the anterior–posterior cingulate and medial frontal gyri. These early sensory discriminatory MMN impairments were followed by P3a deficits associated with widespread reductions in the activation of attentional networks (frontal, temporal, parietal regions), reflecting impaired orienting or shifts of attention to the infrequent stimuli. MMN and P3a are dissociable responses associated with broadly distributed patterns of neural activation. MMN deficits among SZ patients appear to be primarily accounted for by reductions in medial prefrontal brain regions that are followed by widespread dysfunction across cortical networks associated with P3a in a manner that is consistent with hierarchical information processing models of cognitive deficits in SZ patients. Impairments in automatic stimulus discrimination may contribute to higher-order cognitive and psychosocial deficits in SZ. ► Large cohort of research participants (410 SZ patients, 247 NCS) ► MMN/P3a networks distributed across temporal, frontal, and parietal regions ► MMN deficits associated with reduced activation of discrete medial frontal regions ► P3a deficits associated with reductions in temporal, frontal, and parietal regions ► Results consistent with hierarchical “cascade” models of SZ deficits