Unveiling distinct representations of P3a in schizophrenia through two-stimulus and three-stimulus auditory oddball paradigms.

Background: P3a event-related potential (ERP) is considered a potential biomarker for schizophrenia (SZ), can be elicited through both passive two-stimulus and active three-stimulus auditory oddball paradigms. While both types of P3a reflect involuntary attention shifts, the nuanced understanding of what P3a represents in different contexts is important and rarely studied. This study aims to examine correlations between P3a ERPs elicited from different paradigms and associations of each P3a with cognitive function, clinical symptoms, and antipsychotic medication.

Methods: Our sample included 178 SZ patients and 127 healthy controls (HC). Data on two-stimulus paradigm, three-stimulus oddball paradigm, Chinese version of MATRICS Consensus Cognitive Battery (MCCB), symptom severity, and medication use were collected.

Results: In both paradigms, SZ group's P3a amplitude was significantly reduced compared to HC's (both p < 0.05). P3a evoked by the two-stimulus paradigm and the three-stimulus paradigm were not correlated (r = -0.06, p = 0.661). Three-stimulus paradigm-P3a was significantly correlated with attention/vigilance (r = 0.27, p = 0.017) in SZ, and with working memory (r = 0.39, p = 0.001) and overall MCCB score (r = 0.25, p = 0.042) in HC. Additionally, the two-stimulus paradigm-P3a correlated with olanzapine equivalent antipsychotic dose (r = -0.26, p = 0.022).

Conclusions: Our findings offer new insights into the role of P3a in clinical research. P3a ERPs from different paradigms may represent functionally distinct components. The context in which the P3a is elicited should be taken into account when discussing its functional or neurocognitive significance.