Abnormalities in the prefrontal cortex (PFC)-related network play an important role in the pathophysiology of major depressive disorder (MDD). Accumulating evidence indicated that fronto-striatal dysconnectivity is critical to MDD pathogenesis. Whether non-invasive brain stimulation, including 10-Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS), may change cortico-striatal functional connectivity (FC) in MDD patients is unclear. Whether the change of cortico-striatal FC is associated with the antidepressant effects is also unknown. In total, 68 adult MDD subjects were randomly assigned to one of three groups: iTBS, 10-Hz rTMS, or sham group. Functional connectivity was analyzed using MRI and seed-based methods. Seeds included left and right dorsal caudate (DC), dorsal rostral putamen (DRP), and ventral rostral putamen (VRP). The results revealed that significant group-by-time interactions in FC were found in all the striatal seeds. Post-hoc analyses revealed significant increases in FC of the left DRP and VRP for both iTBS and rTMS treatments, particularly with the right frontal pole. Greater FC changes of the fronto-striatal networks correlated with the antidepressant effects. The effects of rTMS and iTBS on FCs of the intra-striatal network, default mode network, and other cortico-striatal networks were distinct. In conclusion, the first study demonstrated that iTBS and rTMS had common but unique effects on the cortico-striatal and intra-striatal networks. These results suggest that both treatments regulate brain reward systems and might be used to treat various striatum-related neuropsychiatric illnesses.
© 2025. The Author(s), under exclusive licence to Springer Nature Limited.