Schizophrenia is a syndrome that is typically accompanied by delusions and hallucinations that might be associated with insular pathology. Music intervention, as a complementary therapy, is commonly used to improve psychiatric symptoms in the maintenance stage of schizophrenia. In this study, we employed a longitudinal design to assess the effects of listening to Mozart music on the insular functional connectivity (FC) in patients with schizophrenia. Thirty-six schizophrenia patients were randomly divided into two equal groups as follows: the music intervention (MTSZ) group, which received a 1-month music intervention series combined with antipsychotic drugs, and the no-music intervention (UMTSZ) group, which was treated solely with antipsychotic drugs. Resting-state functional magnetic resonance imaging (fMRI) scans were performed at the following three timepoints: baseline, 1 month after baseline and 6 months after baseline. Nineteen healthy participants were recruited as controls. An FC analysis seeded in the insular subregions and machine learning techniques were used to examine intervention-related changes. After 1 month of listening to Mozart music, the MTSZ showed increased FC in the dorsal anterior insula (dAI) and posterior insular (PI) networks, including the dAI-ACC, PI-pre/postcentral cortices, and PI-ACC connectivity. However, these enhanced FCs had vanished in follow-up visits after 6 months. Additionally, a support vector regression on the FC of the dAI-ACC at baseline yielded a significant prediction of relative symptom remission in response to music intervention. Furthermore, the validation analyses revealed that 1 month of music intervention could facilitate improvement of the insular FC in schizophrenia. Together, these findings revealed that the insular cortex could potentially be an important region in music intervention for patients with schizophrenia, thus improving the patients' psychiatric symptoms through normalizing the salience and sensorimotor networks.
Keywords: functional connectivity; insular cortex; music intervention; resting-state fMRI; schizophrenia; validation analysis.