Abstract
Positive symptoms are a prominent feature of schizophrenia. Despite antipsychotic treatment, ~30% of patients develop refractory positive symptoms (RPSs). Current research fails to elucidate the potential neurophysiological mechanisms underlying RPSs, thereby hindering the development of additional treatments. This study, which included 37 patients with RPSs and 40 with non-refractory positive symptoms (NRPSs), aimed to explore their underlying neural mechanisms. Outcome measures were relative power spectrum density and interregional synchronization across frequency bands and theta-gamma phase-amplitude coupling (θ-γ PAC). The single-frequency analysis indicated that RPSs exhibited elevated theta power and reduced lateralization in the left temporal lobe and temporo-parietal junction, along with enhanced functional connectivity in the left frontocentral region. The cross-frequency analysis revealed that RPSs exhibited slightly higher θ-γ coupling at the left temporo-parietal junction compared to NRPSs. Correlation analysis revealed significant associations among theta power, the lateralization index, functional connectivity, and the severity of positive symptoms. The aberrant activation of the theta rhythm in the left temporo-parietal region may lead to increased functional asymmetry in the brain, impeding interregional and inter-frequency information transmission and thus significantly impairing the normal processing of auditory information. These findings offer potential insights into the neurophysiological basis of positive symptoms in schizophrenia and may inform future clinical interventions.