Impact of low-frequency rTMS on functional connectivity of the dentate nucleus subdomains in schizophrenia patients with auditory verbal hallucination

Despite low-frequency repetitive transcranial magnetic stimulation (rTMS) is effective in treating schizophrenia patients with auditory verbal hallucinations (AVH), the underlying neural mechanisms of the effect still need to be clarified. Using the cerebellar dentate nucleus (DN) subdomain (dorsal and versal DN) as seeds, the present study investigated resting state functional connectivity (FC) alternations of the seeds with the whole brain and their associations with clinical responses in schizophrenia patients with AVH receiving 1 Hz rTMS treatment. The results showed that the rTMS treatment improved the psychiatric symptoms (e.g., AVH and positive symptoms) and certain neurocognitive functions (e.g., visual learning and verbal learning) in the patients. In addition, the patients at baseline showed increased FC between the DN subdomains and temporal lobes (e.g., right superior temporal gyrus and right middle temporal gyrus) and decreased FC between the DN subdomains and the left superior frontal gyrus, right postcentral gyrus, left supramarginal gyrus and regional cerebellum (e.g., lobule 4-5) compared to controls. Furthermore, these abnormal DN subdomain connectivity patterns did not persist and decreased FC of DN subdomains with cerebellum lobule 4-5 were reversed in patients after rTMS treatment. Linear regression analysis showed that the FC difference values of DN subdomains with the temporal lobes, supramarginal gyrus and cerebellum 4-5 between the patients at baseline and posttreatment were associated with clinical improvements (e.g., AVH and verbal learning) after rTMS treatment. The results suggested that rTMS treatment may modulate the neural circuits of the DN subdomains and hint to underlying neural mechanisms for low-frequency rTMS treating schizophrenia with AVH.