Objective: To test the hypothesis that cortical disinhibition in Parkinson’s disease is a dopamine-independent process.

Background: Motor cortex alterations in Parkinson’s disease are classically considered as a pathophysiological or compensatory consequence of dopamine depletion and altered basal ganglia output. In contrast with this view, we recently observed that cortical disinhibition, as measured by short-interval intracortical inhibition (SICI) using transcranial magnetic stimulation (TMS), seems to be independent on the stage of the disease. Even though this result comes from a cross-sectional study and thus is not conclusive, it suggests that cortical disinhibition may be a dopamine-independent process in Parkinson’s disease.

Method: To more rigorously test our hypothesis, here we considered three experimental paradigms. First, we compared SICI between the clinically more affected side (presumably more dopamine depleted) and the clinically less affected side in a relatively large sample of right-handed Parkinson’s disease patients (n=165), all studied OFF medication. Second, in a subset of patients (n=24) we also evaluated SICI after administration of a clinically effective dose of levodopa (100-150% of morning dose). Third, in another subset of patients (n=19, recently diagnosed) we longitudinally repeated the assessment of SICI 2 years after the first visit. All analyses of SICI recordings were carried out automatically and with a rigorous EMG cleaning to avoid potential confounds. Statistical analyses were performed with Bayesian statistics.

Results: First, despite considerable clinical lateralization (and thus presumable lateralization of dopamine depletion) we found a similar amount of cortical disinhibition (i.e. loss of SICI) in both the clinically more affected and less affected side. We obtained similar results when we compared left vs. right hemisphere. Second, an acute, clinically effective dose of levodopa did not improve cortical disinhibition. Third, cortical disinhibition did not worsen after two years of disease evolution in recently diagnosed patients.

Conclusion: Altogether these results indicate that cortical disinhibition is a dopamine-independent alteration, suggesting it may either emerge very early in the disease evolution or even be a risk factor for the development of Parkinson’s disease.

« Back to 2022 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/dopamine-independent-cortical-disinhibition-in-parkinsons-disease/