Altered inhibitory interaction among inferior frontal and motor cortex in l-dopa-induced dyskinesias

Background: Levodopa-induced dyskinesias are associated with thalamo-cortical disinhibition and frontal area overactivation. Neuroimaging and transcranial magnetic stimulation studies have highlighted the involvement of the right inferior frontal cortex in levodopa-induced dyskinesias. Methods: Using transcranial magnetic stimulation, we tested connectivity between the inferior frontal and contralateral motor cortex in Parkinson's disease patients with and without levodopa-induced dyskinesias compared with age-matched controls. Furthermore, in dyskinetic patients, connectivity between the inferior frontal and contralateral motor cortex was assessed before and after a single session of continuous theta-burst stimulation applied over the inferior frontal cortex. Results: Dyskinetic patients showed abnormal facilitatory connectivity between the inferior frontal and motor cortex when compared with the nondyskinetic group. Continuous theta-burst stimulation over the inferior frontal cortex eliminated such facilitatory connectivity and decreased the levodopa-induced dyskinesias that was induced by a supramaximal dose of levodopa. Conclusion: In dyskinetic patients, a weaker inhibitory cortico-cortical interaction between the inferior frontal and contralateral motor cortex could be involved in levodopa-induced dyskinesias and restored by continuous theta-burst stimulation over the inferior frontal cortex.