Cortico-cortical paired associative stimulation increases SMA-M1 facilitation in tremor-dominant Parkinson’s disease

• Cortico-cortical paired associative stimulation (ccPAS) in tremor-dominant Parkinson’s disease (PD) was investigated. • ccPAS increases supplementary motor area (SMA) facilitation of primary motor cortex activity (M1) in tremor-dominant PD. • A single session of SMA-M1 ccPAS was insufficient in modulating tremor severity. Tremor is a common motor symptom of Parkinson’s disease (PD) that reduces quality of life. Cortico-cortical paired associative stimulation (ccPAS) is a transcranial magnetic stimulation protocol that induces connective associative plasticity between cortical regions. This study investigated the effects of ccPAS over supplementary motor area (SMA) and primary motor cortex (M1) on SMA-M1 facilitation and tremor severity in individuals with tremor-dominant PD. Fourteen individuals with tremor-dominant PD (mean age 66.5 ± 6.3 years; 5 females) received real and sham ccPAS in separate sessions. SMA-M1 activity and tremor severity were measured before and after ccPAS. Participants were tested OFF dopaminergic medication. SMA-M1 facilitation increased significantly after real but not sham ccPAS. There was no significant change in tremor severity after either real or sham ccPAS. Tremor severity was not associated with the change in SMA-M1 activity following ccPAS or with baseline SMA-M1 activity. ccPAS can increase SMA-M1 facilitation in individuals with tremor-dominant PD. A single session of SMA-M1 ccPAS was insufficient in modulating tremor severity. This study provides preliminary evidence of significant increases in SMA-M1 facilitation from ccPAS in tremor-dominant PD OFF dopamine medication. Future research should explore ccPAS effects ON dopamine medication, and the effects of multi-session ccPAS.