Objective: The aim of this study was to examine whether connectivity between the supplementary motor area and primary motor cortex (SMA-M1) is implicated in Parkinson’s disease (PD) resting tremor ON and OFF levodopa medication.

Background: Resting tremor is the most common presenting motor symptom in PD but is not associated with the typical progressive degeneration of dopaminergic neurons in the basal ganglia. Other brain regions must underpin tremor production in PD. SMA is one of the main output targets of the basal ganglia-thalamo-cortical circuit. In turn, the SMA has direct, facilitatory connections with M1, which is vital for the execution of voluntary movement.

Method: We used a cutting-edge dual-site transcranial magnetic stimulation protocol to characterise facilitatory and/or inhibitory connectivity between SMA-M1 both ON and OFF levodopa medication in tremor-dominant PD. Resting tremor was measured using electromyography and accelerometry recorded from the tremor-dominant hand.

Results: We are the first study to show that stimulating SMA had an inhibitory influence on M1 excitability OFF levodopa medication, which was normalised ON levodopa medication. The normalisation of SMA-M1 connectivity in the ON state might be mediated by an increase in dopamine levels in the basal ganglia, which reduces nett inhibition of the motor thalamic nuclei and increases excitation of the cerebral cortex, including SMA. In addition, individuals with the weakest SMA-M1 connectivity ON medication showed the most severe tremor, suggesting that SMA-M1 connectivity might play an important role in resting tremor.

Conclusion: Together, these findings suggest a role of SMA-M1 connectivity in PD resting tremor and offer a neurophysiological basis for the development of interventions to improve PD resting tremor. This is critical given that there is currently no effective treatment for PD tremor.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cortico-cortical-connectivity-is-normalised-by-levodopa-in-tremor-dominant-parkinsons-disease/