Effect of rTMS on cerebral functional hierarchical structure in schizophrenia.

Abstract

Background: The hierarchical functional structure reflects the process of integrating primary information to form higher-order cognition in the human brain. Schizophrenia, as a severe chronic psychiatric illness, has been demonstrated to exhibit an abnormal cerebral functional hierarchical structure. Although repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex has shown therapeutic efficacy on schizophrenia, the mechanism of rTMS in schizophrenia is still unclear. Thus, this study attempted to reveal the modulation of rTMS on the cerebral functional hierarchy and its potential molecular mechanism in schizophrenia.

Methods: A longitudinal study was performed on 53 patients with schizophrenia (randomly assigned to the rTMS group or drug treatment group). Additionally, 24 age- and gender-matched healthy adults were recruited. Functional gradient analysis was executed to depict the hierarchical organization of schizophrenia. The alteration of the functional gradients at baseline and after 4 weeks of treatment was evaluated in schizophrenia to detect the effect of rTMS on the cerebral hierarchical structure.

Results: We found rTMS alleviated the compression of the fronto-parietal network, the core node of the salience network, and the bilateral middle temporal areas in schizophrenia. Leveraging human brain gene expression data, we identified a spatial correlation between the expression of schizophrenia-related genes and impaired functional gradients, and further revealed a close association of the modulatory effects of rTMS with pathways related to neuroplasticity and neuroimmune processes. Furthermore, the alterations of gradient induced by rTMS were associated with the alleviation of clinical symptoms in schizophrenia, suggesting that the altered hierarchical structure may play an important role in the treatment of schizophrenia.

Conclusions: Our findings indicate that the alteration of cerebral hierarchy induced by rTMS contributes to clinical symptom improvement in schizophrenia and provides new evidence for the efficacy of rTMS in the treatment of schizophrenia.