Cortico-cortical connectivity is normalised by levodopa in tremor-dominant Parkinson’s disease

Abstract

AbstractBackgroundResting tremor, which involves involuntary and rhythmic movements of one or more body parts, is the most common presenting motor symptom in Parkinson’s disease. As Parkinson’s disease tremor is not associated with the severity of dopaminergic cell loss in the basal ganglia, other brain regions might play a role in its pathophysiology. The supplementary motor area is one of the main targets of the basal ganglia-thalamo-cortical circuit. In turn, the supplementary motor area has direct connections with the primary motor cortex, which is important for the execution of voluntary movement.ObjectiveThe aim of this study was to examine whether supplementary motor area— primary motor cortex connectivity and dopaminergic neurotransmission are implicated in Parkinson’s disease resting tremor.MethodsDual-site transcranial magnetic stimulation was used to measure supplementary motor area—primary motor cortex connectivity ON and OFF levodopa medication, and resting tremor was measured using electromyography and accelerometry.ResultsStimulating the supplementary motor area had an inhibitory influence on primary motor cortex excitability OFF levodopa, which was normalised ON levodopa. The normalisation of supplementary motor area—primary motor cortex 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. Supplementary motor area—primary motor cortex connectivity ON medication was inhibitory rather than facilitatory in patients with the strongest resting tremor, suggesting that supplementary motor area—primary motor cortex connectivity might play an important role in resting tremor.DiscussionThe current findings contribute to our understanding of the neural networks involved in Parkinson’s disease and provide a neurophysiological basis for the development of interventions to reduce Parkinson’s disease resting tremor severity.