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Dopamine replacement therapy (DRT) represents the standard treatment for Parkinson's disease (PD), however, instant and long‐term medication influence on patients' brain function have not been delineated. Here, a total of 97 drug‐naïve patients, 43 patients under long‐term DRT, and 94 normal control (NC) were, retrospectively, enrolled. Resting‐state functional magnetic resonance imaging data and motor symptom assessments were conducted before and after levodopa challenge test. Whole‐brain functional connectivity (FC) matrices were constructed. Network‐based statistics were performed to assess FC difference between drug‐naïve patients and NC, and these significant FCs were defined as disease‐related connectomes, which were used for further statistical analyses. Patients showed better motor performances after both long‐term DRT and levodopa challenge test. Two disease‐related connectomes were observed with distinct patterns. The FC of the increased connectome, which mainly consisted of the motor, visual, subcortical, and cerebellum networks, was higher in drug‐naïve patients than that in NC and was normalized after long‐term DRT (p‐value <.050). The decreased connectome was mainly composed of the motor, medial frontal, and salience networks and showed significantly lower FC in all patients than NC (p‐value <.050). The global FC of both increased and decreased connectome was significantly enhanced after levodopa challenge test (q‐value <0.050, false discovery rate‐corrected). The global FC of increased connectome in ON‐state was negatively associated with levodopa equivalency dose (r = −.496, q‐value = 0.007). Higher global FC of the decreased connectome was related to better motor performances (r = −.310, q‐value = 0.022). Our findings provided insights into brain functional alterations under dopaminergic medication and its benefit on motor symptoms.

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ObjectiveTo determine whether white matter hyperintensity (WMH) volumes in specific regions are associated with Parkinson's disease (PD) compared to non‐PD controls, and to assess their impact on motor signs through cross‐sectional and longitudinal analyses.MethodsA total of 50 PD participants and 47 age‐ and gender‐matched controls were enrolled. All PD participants were followed up for at least 2 years. To detect regions of greater WMH in the PD, the WMH volume of each region was compared with the corresponding region in the control group. Linear regression and linear mixed effects models were respectively used for cross‐sectional and longitudinal analyses of the impact of increases in WMH volume on motor signs.ResultsThe PD group had greater WMH volume in the occipital region compared with the control group. Cross‐sectional analyses only detected a significant correlation between occipital WMH volume and motor function in PD. Occipital WMH volume positively correlated with the severity of tremor, and gait and posture impairments, in the PD group. During the follow‐up period, the participants' motor signs progressed and the WMH volumes remained stable, no longitudinal association was detected between them. The baseline occipital WMH volume cannot predict the progression of signs after adjustment for baseline disease duration and the presence of vascular risk factors.InterpretationPD participants in this study were characterized by greater WMH at the occipital region, and greater occipital WMH volume had cross‐sectional associations with worse motor signs, while its longitudinal impact on motor signs progression was limited.

AimsThe purpose of this study was to clarify the dentato‐rubro‐thalamic (DRT) pathway in action tremor in comparison to normal controls (NC) and disease controls (i.e., rest tremor) by using multi‐modality magnetic resonance imaging (MRI).MethodsThis study included 40 essential tremor (ET) patients, 57 Parkinson's disease (PD) patients (29 with rest tremor, 28 without rest tremor), and 41 NC. We used multi‐modality MRI to comprehensively assess major nuclei and fiber tracts of the DRT pathway, which included decussating DRT tract (d‐DRTT) and non‐decussating DRT tract (nd‐DRTT), and compared the differences in DRT pathway components between action and rest tremor.ResultsBilateral dentate nucleus (DN) in the ET group had excessive iron deposition compared with the NC group. Compared with the NC group, significantly decreased mean diffusivity and radial diffusivity were observed in the left nd‐DRTT in the ET group, which were negatively correlated with tremor severity. No significant difference in each component of the DRT pathway was observed between the PD subgroup or the PD and NC.ConclusionAberrant changes in the DRT pathway may be specific to action tremor and were indicating that action tremor may be related to pathological overactivation of the DRT pathway.