Structural And Functional MRI Study On Tremor-Dominant Parkinson’s Disease

Part 1 Distinct macrostructural changes in asymmetric tremor-dominant Parkinson’s disease using voxel-based morphometryObjective The pathological progression of Parkinson’s disease (PD) leads to brain structural changes. However, the morphological volume changes in tremor-dominant PD are still unclear. The aim of present study is to test the hypothesis that grey matter volume (GMV) changes are detectable accompanied by Parkinson’s disease using voxel-based morphometry method; and to explore the possible GMV changes with more-affected hemiparkinsonism.Methods 45 PD and 46 healthy controls (HC) were recruited and examined using 3D T1WI MPRAGE sequence. The brains of the patients with left-sided tremor were flipped right-to-left. Grey matter volume (GMV) differences between PD and HC were compared and evaluated correlation coefficients with clinical variables (i.e. disease duration, tremor score, mUPDRS and daily dosage of levodopa (DDL)).Results Compared with HC, GMV was reduced in PD in limbic, paralimbic, and frontal areas, whereas that was increased in the motor-related areas. (P< 0.05, FWE corrected). After images flipped left-to-right, we found atrophy in areas such as left medial superior frontal gyrus, left parahippocampus, left amygdala, left precuneus, left thalamus, and brainstem, whereas that was increased in the right cerebellum (P< 0.001, uncorrected). The disease duration was negatively correlated with the GMV in the left parahippocampus, whereas positively correlated with that in the right cerebellum (P< 0.05). Moreover, GMV in the left thalamus showed positive trend with the disease duration (P=0.056). GMV in the left medial superior frontal gyrus and right cerebellum were positively correlated with tremor (P<0.05). The mUPDRS was positively related with GMV in the right cerebellum and negatively correlated with that in the left parahippocampus (P< 0.05), respectively. The daily dose of levodopa was negatively associated with GMV in the left thalamus and left parahippocampus (P<0.05).Conclusions Tremor-dominant PD is characteristic of GM changes in the cerebello-thalamic circuit. The thalamic atrophy may suggest the complex combination of pathologic and compensatory long-term levodopa medication.Part 2 Altered activation in cerebellum contralateral to unilateral thalamotomy may mediate tremor suppression in Parkinson’s disease:A short-term regional homogeneity fMRI studyObjective Ventral intermediate nucleus thalamotomy is an effective treatment for Parkinson’s disease tremor. However, its mechanism is still unclear. We used resting-state fMRI to investigate short-term ReHo changes after unilateral thalamotomy in tremor-dominant PD, and to speculate about its possible mechanism on tremor suppression.Methods 26 PD and 31 HC were recruited. Patients were divided into two groups according to right-(rPD) and left-side (1PD) thalamotomy. Tremor was assessed using the 7-item scale from Unified Parkinson’s disease rating scale motor score (mUPDRS). Patients were scanned using resting state fMRI on OFF medication, preoperatively (PDpre) and 7-days postoperatively (PDpost), whereas healthy subjects were scanned once. The regions associated with tremor and altered ReHo due to thalamic ablation were examined.Results The impact of unilateral VIM thalamotomy was characterized in the frontal, parietal, temporal regions, basal ganglia, thalamus, and cerebellum. Compared with PDpre, significantly reduced ReHo was found in the left cerebellum in patients with rPDpost, whereas slightly decreased ReHo in the cerebellum vermis in patients with IPDpost, which was significantly higher than HC. We demonstrated that a positive correlation between the ReHo values in cerebellum (in rPD, peak coordinate [-12,-54,-21], R=0.64, P=0.0025,and peak coordinate [-9,-54,-18], R=0.71, P=0.0025; in 1PD, peak coordinate [3,-45,-15], R=0.71, P=0.004) in the pre-surgical condition, changes of ReHo induced by thalamotomy (in rPD, R =0.63, P=0.021, R=0.6, P=0.009,; in 1PD, R=0.58, P=0.028) and tremor scores contralateral to the surgical side, respectively.Conclusions The specific area that may be associated with PD tremor and altered ReHo due to thalamic ablation is the cerebellum. The neural basis underlying thalamotomy is complex; cerebellum involvement is far beyond cerebello-thalamic tract breakage.Part 3 The ALE Meta-analysis of voxel-based morphometry (VBM) studies on Parkinson’s diseaseObjective Parkinson’s disease (PD) is a common neurodegenerative disease in the elderly. Large numbers of VBM studies on PD have been independently conducted, but the results have been conflicting. Identifying consistent brain structure changes in PD by meta-analysis may aid in the understanding of its pathophysiological mechanism.Methods The voxel-based morphometry (VBM) studies on patients with PD compared with healthy controls (HC) were conducted in the PubMed and Web of Science databases between 1995 and December 2015. The anatomical distribution of the coordinates of grey matter differences was analyzed using the anatomical likelihood estimation (ALE) method.Results 42 studies (1253 PD and 1037 HC) were included. There is coherent brain atrophy in PD, such as the cortex, putamen, and cerebellar culmen. In PD with no non-motor symptoms, the brain atrophy still focused on the cortex, putamen, and cerebellar tonsil.Conclusions Our meta-analysis provides evidence that right putamen and cerebellum are two of PD-specific structural alterations. ALE method is able to quantitatively analyze across studies, providing neuroimaging evidences for PD.