| ObjectiveAs one of the most common neurodegenerative diseases, Parkinson's disease (PD) is characterized by some typical movement symptoms, such as resting tremor, bradykinesia and rigidity. However, present studies have completely discarded the traditional perspective that PD is simply a movement disorder. It is now well known that PD can also impair sensory and cognitive systems, leading to a series of complicated clinical symptoms, among which the tactile deficits is a significant part. Previous neuroelectrophysiological and neuroimaging research showed that such deficits came from abnormal processing and integration of tactile information in brain level. Further, some altered brain activations were also found under tactile perception or discrimination in parkinsonian patients. In spite of these findings, some questions still remained. For instance, early diagnosis and treatment were very important for PD. Since all the former studies focused on the patients at an advanced or late stage, whether the brain abnormalities could equally be found at an early stage was unknown. Moreover, most of the past studies were simply based on the activation level, but what roles the altered regions played and how these regions were interacted and reorganized in the network level was also scarcely known. Still further, whether these functional changed regions had a structural foundation, or whether the patients with early PD had changes in brain structure was still in confusion. This study aims to give a direct and explicit answer to the questions above. Materials and Methods21 patients with early PD (Hoehn & Yahr stage 1-2) and 22 age-, gender-matched normal controls participated in the study. All the subjects gave their written informed consent. The patients were asked to pause for their drug medications for at least 12 hours before the MR scan, and were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) and the Mini-Mental State Examination (MMSE) while off their medications. Data acquisition involved three steps. Firstly, conventional structural images (T1WI & T2WI) were performed by each subject, and any dormant neural diseases were excluded according to these images. Secondly, functional images (BOLD) were acquired with block designs, where tactile stimulations and non-task states occurred by turns. Lastly, high-resolution 3-D structural images were performed. We used neuroimaging software SPM for the data analysis, which contained two parts:the functional data analysis and the structural data analysis. For the functional analysis, the subject-specific, within group and between group activation maps were obtained using general linear model and random effect model respectively. Then all the abnormally activated regions in PD group were taken as regions of interest (ROIs). We abstracted the BOLD signal change in each ROI in each patient, and a correlation analysis was performed between the signal changes and the UPDRS scores. We also adopted a functional connectivity analysis method based on graph theory to investigate how the ROIs were interacted in the network. All the ROIs were referred to as the "nodes" and the connections among them were considered as the "links" in the network. We calculated the total connectivity degree (Γ) of each node as well as connection strength (z) of each link and used two-sample t-test to compare the differences inΓand z values between the two groups. For those ROIs with significantΓchange in group comparison, we investigated the relationships betweenΓand the UPDRS scores with Pearson's correlation analysis. An automatic structural analysis method called "voxel-based morphometry (VBM)" was implemented for the structural image processing. It started with space normalization and image segmentation, then two-sample t-test was performed to compared the changes of grey matter volumes in PD group.Results There were several regions showing hypoactive activation under the tactile perception in PD, including bilateral primary somatosensory cortex (S1), ipsilateral supplementary motor area (SMA), ipsilateral premotor cortex (PMC) and ipsilateral paracentral lobule (PaCL). Conversely, many more regions were hyperactive:bilateral dorsal lateral prefrontal cortex (DLPFC), bilateral anterior cerebellum (ACb), bilateral posterior cerebellum (PCb), bilateral parahippocampal gyrus (PaHG), contralateral inferior frontal gyrus (IFG), contralateral middle frontal gyrus (MFG), contralateral caudate necleus (CN) and contralateral lentiform nucleus (LN). Among these, the BOLD signal change in SMA was negatively correlated to UPDRS scores (r=-0.48, p<0.05). Further, there was a significant decline of functional connectivity degree in SMA in patients (p=0.032), which also presented a negative correlation with UPDRS score (r=-0.57, p<0.01). In terms of connection strength, z value decreased only in 1 link, which was between right SMA and right PMC (p=0.000), but increased in 4 links: between left IFG and left DLPFC (p=0.003), between left DLPFC and right ACb (p=0.004), between left IFG and left CN (p-0.001), between right ACb and left LN (p=0.002). The structural analysis showed there were two regions with decreased grey matter volumes in PD, which were right inferior temporal gyrus (IFG) and left ACb.ConclusionThis study demonstrated that early PD was not only associated with altered activation but also altered functional connectivity in the brain under tactile perception, and these changed regions included sensory and motor cortex, prefrontal cortex, striatum and cerebellum. SMA was the most impaired area, as it showed both a decreased activity and a reduced functional connectivity degree, both of which were closely related to disease severity. Furthermore, this study also suggested a potential compensatory mechanism in PD's tactile function, which may reflect in the increased connection strengths in striato-prefrontal and cerebello-prefrontal loops. Finally, the structural study illustrated that the grey matter volumes in temporal lobe and cerebellum were decreased in early parkinsonian patients. |
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