Opposite effects of one session of 1 Hz rTMS on functional connectivity between pre-supplementary motor area and putamen depending on the dyskinesia state in Parkinson's disease.

Objective: To explore the effects of low-frequency repetitive transcranial magnetic stimulation (LF rTMS) on cortico-striatal-cerebellar resting state functional connectivity in Parkinson's disease (PD), with and without dyskinesias.

Methods: Because there is increasing evidence of an involvement of the pre-supplementary motor area (pre-SMA) in the pathophysiology of levodopa induced dyskinesias, we targeted the right pre-SMA with LF rTMS in 17 PD patients. We explored the effects of one sham-controlled LF rTMS session on resting state functional connectivity of interconnected brain regions by using functional MRI, and how it is modified by levodopa. The clinical effect on motor function and dyskinesias was documented.

Results: As expected, one LF rTMS session did not alleviate dyskinesias. However, real, and not sham LF rTMS significantly increased the functional connectivity with the right putamen in patients with dyskinesias. In patients without dyskinesias, the real LF rTMS session significantly decreased functional connectivity in the right putamen and the cerebellum. We found no effects on functional connectivity after levodopa ingestion.

Conclusion: One session of 1 Hz rTMS has opposing effects on pre-SMA functional connectivity depending on the PD patients' dyskinesia state.

Significance: Patients dyskinesias state determines the way LF rTMS affects functional connectivity in late stage PD.