Disrupted Brain Network Hubs in Subtype-Specific Parkinson's Disease.

BACKGROUND/AIMS: The topological organization of brain functional networks is impaired in Parkinson's disease (PD). However, the altered patterns of functional network hubs in different subtypes of PD are not completely understood. METHODS: 3T resting-state functional MRI and voxel-based graph-theory analysis were employed to systematically investigate the intrinsic functional connectivity patterns of whole-brain networks. We enrolled 31 patients with PD (12 tremor dominant [TD] and 19 with postural instability/gait difficulty [PIGD]) and 22 matched healthy controls. Whole-brain voxel-wise functional networks were constructed by measuring the temporal correlations of each pair of brain voxels. Functional connectivity strength was calculated to explore the brain network hubs. RESULTS: We found that both the TD and PIGD subtypes had comprehensive disrupted regions. These mainly involved the basal ganglia, cerebellum, superior temporal gyrus, pre- and postcentral gyri, inferior frontal gyrus, middle temporal gyrus, lingual gyrus, insula, and parahippocampal gyrus. Furthermore, the PIGD subgroup had more disrupted hubs in the cerebellum than the TD subgroup. These disruptions of hub connectivity were not correlated with the HY stage or disease duration. CONCLUSION: Our results emphasize the subtype-specific PD-related degeneration of brain hubs, providing novel insights into the pathophysiological mechanisms of connectivity dysfunction in different PD subgroups.

Hyper- and hypo-connectivity in sensorimotor network of drug-naïve patients with cervical dystonia.

BACKGROUND: Cervical dystonia (CD) is the most common form of focal dystonia with involuntary movements and postures of the head. The pathogenesis and neural mechanisms underlying CD have not been fully elucidated. METHODS: Twenty-seven newly drug-naïve patients with CD and 21 healthy controls (HCs) were recruited with clinical assessment and resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Severity of CD was measured by Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui scores. Whole-brain voxel-wise intrinsic connectivity (IC) and seed-based functional connectivity (FC) analyses were performed for detection of changes in the CD group relative to HCs, controlling for age, gender, and global time series correlation, followed by correlation analyses of IC, seed-based FC and clinically relevant features, respectively. RESULTS: In comparison with HCs, CD patients showed significantly increased IC measurement in the anterior part of the left supramarginal gyrus and extended to the inferior left postcentral gyrus (AL-SMG/IL-PCG). With this cluster as a seed, decreased FC was found in the right precentral and postcentral gyrus. Moreover, the regional IC value in the AL-SMG/IL-PCG was significantly positively correlated with TWSTRS-1 (severity) score, and significantly negatively correlated with the associated seed-based FC strength. CONCLUSIONS: Our results showed signs of both hyper- and hypo-connectivity in bilateral regions of the sensorimotor network related to CD. The imbalance of functional connectivity (both hyper- and hypo-) may hint both overloading and disrupted somatosensory or sensorimotor integration dysfunction within the sensorimotor network underlying the pathophysiology of CD, thus providing a network target for future therapies.

Nitrated alpha-synuclein in minor salivary gland biopsies in Parkinson's disease.

Alpha-synuclein (α-SYN) is found in peripheral autonomic neuronal network apart from brain in Parkinson's disease (PD). Nitrated α-SYN is an undesirable modification associated with oxidative and nitrative damage and has been found extensively in brain, gastrointestinal(GI) tract and blood cells in PD. We aim to investigate the presence of nitrated α-SYN in minor salivary gland biopsy in PD. Patients with PD and age-matched controls underwent minor salivary gland biopsy. Motor impairment was assessed by Hoehn-Yahr (H-Y) stage and Unified Parkinson's Disease Rating Scale (UPDRS) Part III in off-state. 11C-methyl-N-2b-carbomethoxy-3b-(4-fluorophenyl) tropane (11C-CFT) DAT-PET scan was performed in all subjects. Immunohistochemical staining for nitrated α-SYN was performed in the minor salivary gland tissues. The minor salivary gland tissues of 8 PD cases and 7 controls with early stage (H-Y stage 1-2) were detected. All PD patients showed asymmetrical and reduction of 11C-CFT uptake in the caudate, anterior and posterior putamen, while all control subjects showed normal DAT-PET scan. Positive nitrated α-SYN immunostaining was observed in all PD patients (8/8,100%) but not in control subjects (0/7). The results were consistent well with that of DAT-PET. These nitrated alpha-synuclein positive structures were mainly located in the periacinar stroma in PD patients. Our result suggests that nitrated α-SYN exists in the early stage and is probably a promising biomarker for PD. Minor salivary gland is an ideal site for α-SYN nitration detection. Despite of the small number of subjects, attention should be given to α-SYN nitration in PD and more investigations on nitrated α-SYN in different sites and large sample using should be explored in future.

Effective network of deep brain stimulation of subthalamic nucleus with bimodal positron emission tomography/functional magnetic resonance imaging in Parkinson's disease.

AIMS: Deep brain stimulation of the subthalamic nucleus (STN-DBS) has become an effective treatment strategy for patients with Parkinson's disease. However, the biological mechanism underlying DBS treatment remains poorly understood. METHOD: In this study, we investigated how STN-DBS modulated the brain network using a bimodal positron emission tomography (PET)/functional magnetic resonance imaging (fMRI) dataset. We first performed an activation likelihood estimation meta-analysis of 13 PET/SPECT studies concerning STN-DBS effects on resting-state brain activity in Parkinson's disease. Additionally, using a functional connectivity analysis in resting-state fMRI, we investigated whether these STN-DBS-affected regions were functionally connected to constitute an effective network. RESULTS: The results revealed that STN-DBS reduced brain activity in the right thalamus, bilateral caudal supplementary area, and the left primary motor cortex, and it increased brain activity in the left thalamus during rest. Second, these STN-DBS-affected areas were functionally connected within an STN-DBS effective network. CONCLUSION: Deep brain stimulation of the subthalamic nucleus (STN-DBS) may deactivate the motor cortex as a remote and network effect, affecting the target and the neighboring subcortical areas. These areas may constitute an effective network of STN-DBS modulation. Our results shed light on the mechanisms of STN-DBS treatment from a network perspective and highlight the potential therapeutic benefits of targeted network modulation.