Neural Indicator of Altered Mismatch Detection Predicts Atypical Cognitive-Perceptual Experiences in Psychotic Psychopathology

Background: Atypical auditory processing (AAP) in psychotic psychopathology is evident in early (N1), mid-latency (P2/N2/mismatch negativity), and late (P3) neural responses. The influence of attention on AAP, and how temporal stages of AAP are associated with phenomenology of psychotic psychopathology are not well understood. Methods: We used a directed attention oddball task to characterize stages of AAP in psychosis and to examine the influence of selective attention. Ninety patients with schizophrenia (SCZ), 53 patients with bipolar disorder (BP), 90 healthy controls and 72 first-degree relatives of SCZ (SREL) were studied. We used principal components analysis to decompose average-reference 64-channel subject-level ERPs. Results: Altered attentional modulation was evident in SCZ at early (N1 factor) and late (P3 factor) stages of AAP, but not at mid-latency P2 factor. Irrespective of condition, N1 and P3 were reduced in SCZ, which predicted greater psychopathology and schizotypal personality traits. Diminished mid-latency mismatch detection (P2 factor) was evident in SCZ, BP, and SREL and was associated with greater positive symptoms of psychosis as well as self-reported atypical cognitive-perceptual experiences. Conclusions: Attentional modulation of early N1, and later P3 neural responses was atypical in patients, but the degree of attentional modulation did not relate to symptom severity or schizotypal traits. Our findings suggest the link between mid-latency mismatch detection and atypical cognitive/perceptual experiences is not driven by attentional deficits alone and point to the promise of mid-latency mismatch detection as a candidate endophenotype and intervention target.