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

Abstract

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.

Risk of Parkinson disease in stroke patients: A nationwide cohort study in South Korea

“…Motor reserve in PD may compensate for the dopaminergic degeneration in PD, and parkinsonian symptoms can present when motor reserve fails to compensate for the dopaminergic degeneration in PD patients. Motor reserve in PD is associated with various brain structures, including the basal ganglia and extrabasal ganglia structures, and brain structural lesions from stroke can damage the motor reserve in PD [40–42]. In our study, PD was more common in stroke patients; thus, our results support the connection between PD and stroke.…”

“…Motor reserve in PD is associated with various brain structures, including the basal ganglia and extrabasal ganglia structures, and brain structural lesions from stroke can damage TA B L E 2 Hazard ratios and 95% confidence intervals for incidence of Parkinson's disease among stroke survivors compared to the matched control group. the motor reserve in PD [40][41][42]. In our study, PD was more common in stroke patients; thus, our results support the connection between PD and stroke.…”

Defining the concept of reserve in the motor domain: a systematic review

“…Review articles underwent a full-text reading to search for possible eligible papers. Among the remaining 21 studies, 12 focused on MR ( Palmer et al, 2009 ; Sunwoo et al, 2017 ; Dalecki et al, 2019 ; Olsson et al, 2020 ; Chung et al, 2020a , b , 2021 , 2022 ; Kim et al, 2022 ; Oh et al, 2022 ; Siciliano et al, 2022 ; Youn et al, 2023 ), five studies focused on BR ( Jouvent et al, 2016 ; Sumowski et al, 2016 ; Schirmer et al, 2019 ; Wang et al, 2022 ; Sastre-Garriga et al, 2023 ), one study investigated CER ( Sadeghihassanabadi et al, 2022 ), one study explored MUR ( Habets et al, 2021 ), and two studies were conducted on compensatory processes ( van Nuenen et al, 2012 ; Greenbaum et al, 2013 ) ( Table 1 ). The search for NIBS and reserve restituted 51 items.…”

“…On the contrary, MR relies not only on structural properties but also on functional processes. Albeit the concept has not been fully addressed yet, the MR has been preliminary defined as an active process explaining the discrepancy between the severity of symptoms exhibited by patients with Parkinson’s disease (PD) and their levels of brain degeneration ( Youn et al, 2023 ). The ability to perform without functional impairment until the damage reaches a critical threshold and the observation that the amount of motor deficits may differ among patients with similar levels of dopamine depletion has been conceptualized as the MR ( Youn et al, 2023 ).…”

“…Albeit the concept has not been fully addressed yet, the MR has been preliminary defined as an active process explaining the discrepancy between the severity of symptoms exhibited by patients with Parkinson’s disease (PD) and their levels of brain degeneration ( Youn et al, 2023 ). The ability to perform without functional impairment until the damage reaches a critical threshold and the observation that the amount of motor deficits may differ among patients with similar levels of dopamine depletion has been conceptualized as the MR ( Youn et al, 2023 ). Indeed, in some PD patients, motor symptoms appear only once 50 to 60% of dopaminergic neurons have been lost, thus suggesting that compensatory processes may take place allowing patients to reach rather normal performances in the face of the disease burden.…”