Extra-Basal Ganglia Brain Structures Are Related to Motor Reserve in Parkinson’s Disease

Background: The “motor reserve” is an emerging concept based on the discrepancy between the severity of parkinsonism and dopaminergic degeneration; however, the related brain structures have not yet been elucidated. Objective: We investigated brain structures relevant to the motor reserve in Parkinson’s disease (PD) in this study. Methods: Patients with drug-naïve, early PD were enrolled, who then underwent dopamine transporter (DAT) scan and diffusion tensor imaging (DTI). The severity of motor symptoms was evaluated with the Unified Parkinson’s Disease Rating Scale score of bradykinesia and rigidity on the more affected side and dopaminergic degeneration of DAT uptake of the more affected putamen. Individual motor reserve estimate (MRE) was evaluated based on the discrepancy between the severity of motor symptoms and dopaminergic degeneration. Using DTI and the Brainnetome atlas, brain structures correlated with MRE were identified. Results: We enrolled 193 patients with drug-naïve PD (mean disease duration of 15.6±13.2 months), and the MRE successfully predicted the increase of levodopa equivalent dose after two years. In the DTI analysis, fractional anisotropy values of medial, inferior frontal, and temporal lobes, limbic structures, nucleus accumbens, and thalamus were positively correlated with the MRE, while no brain structures were correlated with mean diffusivity. Additionally, degree centrality derived from the structural connectivity of the frontal and temporal lobes and limbic structures was positively correlated with the MRE. Conclusion: Our results show empirical evidence for MR in PD and brain structures relevant to MR, particularly, the extra-basal ganglia system including the limbic and frontal structures.