Background: Mismatch negativity (MMN) and P3a are event-related potential measures of early auditory information processing that are increasingly used as translational biomarkers in the development of treatments for neuropsychiatric disorders. These responses are reduced in schizophrenia patients over the frontocentral scalp electrodes and are associated with important domains of cognitive and psychosocial functioning. While MMN and P3a responses are generated by a dynamic network of cortical sources distributed across the temporal and frontal brain regions, it is not clear how these sources independently contribute to MMN and P3a at the primary frontocentral scalp electrode or to abnormalities observed in schizophrenia. This study aimed to determine the independent source contributions and characterize the magnitude of impairment in source-level MMN and P3a responses in schizophrenia patients.
Methods: A novel method was applied to back-project the contributions of 11 independent cortical source components to Fz, the primary scalp sensor that is used in clinical studies, in n = 589 schizophrenia patients and n = 449 healthy comparison subjects.
Results: The groups showed comparable individual source contributions underlying both MMN and P3a responses at Fz. Source-level responses revealed an increasing magnitude of impairment in schizophrenia patients from the temporal to more frontal sources.
Conclusions: Schizophrenia patients have a normal architecture of source contributions that are accompanied by widespread abnormalities in source resolved mismatch and P3a responses, with more prominent deficits detected from the frontal sources. Quantification of source contributions and source-level responses accelerates clarification of the neural networks underlying MMN reduction at Fz in schizophrenia patients.
Keywords: Independent component analysis; Mismatch negativity; P3a; Schizophrenia; Source-level analysis; Translational biomarker.
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