Dataset Information

Aberrant Advanced Cognitive and Attention-Related Brain Networks in Parkinson's Disease with Freezing of Gait.

ABSTRACT: Background:Freezing of gait (FOG) is a disabling gait disorder influencing patients with Parkinson's disease (PD). Accumulating evidence suggests that FOG is related to the functional alterations within brain networks. We investigated the changes in brain resting-state functional connectivity (FC) in patients with PD with FOG (FOG+) and without FOG (FOG-). Methods:Resting-state functional magnetic resonance imaging (RS-fMRI) data were collected from 55 PD patients (25 FOG+ and 30 FOG-) and 26 matched healthy controls (HC). Differences in intranetwork connectivity between FOG+, FOG-, and HC individuals were explored using independent component analysis (ICA). Results:Seven resting-state networks (RSNs) with abnormalities, including motor, executive, and cognitive-related networks, were found in PD patients compared to HC. Compared to FOG- patients, FOG+ patients had increased FC in advanced cognitive and attention-related networks. In addition, the FC values of the auditory network and default mode network were positively correlated with the Gait and Falls Questionnaire (GFQ) and Freezing of Gait Questionnaire (FOGQ) scores in FOG+ patients. Conclusions:Our findings suggest that the neural basis of PD is associated with impairments of multiple functional networks. Notably, alterations of advanced cognitive and attention-related networks rather than motor networks may be related to the mechanism of FOG.

SUBMITTER: Li Y

PROVIDER: S-EPMC7568140 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Aberrant Advanced Cognitive and Attention-Related Brain Networks in Parkinson's Disease with Freezing of Gait.

Li Yuting Y Ruan Xiuhang X Li E E Zhang Guoqin G Liu Yanjun Y Du Yuchen Y Wang Zhaoxiu Z Yu Shaode S Yang Ruimeng R Li Mengyan M Wei Xinhua X

Neural plasticity 20201008

<h4>Background</h4>Freezing of gait (FOG) is a disabling gait disorder influencing patients with Parkinson's disease (PD). Accumulating evidence suggests that FOG is related to the functional alterations within brain networks. We investigated the changes in brain resting-state functional connectivity (FC) in patients with PD with FOG (FOG+) and without FOG (FOG-).<h4>Methods</h4>Resting-state functional magnetic resonance imaging (RS-fMRI) data were collected from 55 PD patients (25 FOG+ and 30 ...[more]

PMID: 33101404

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Project description:Freezing of gait is a common and debilitating symptom in Parkinson's disease. Although high-frequency subthalamic deep brain stimulation is an effective treatment for Parkinson's disease, post-operative freezing of gait severity has been reported to alleviate, deteriorate or remain constant. We conducted this study to explore the optimal stimulation sites and related connectivity networks for high-frequency subthalamic deep brain stimulation treating freezing of gait in Parkinson's disease. A total of 76 Parkinson's disease patients with freezing of gait who underwent bilateral high-frequency subthalamic stimulation were retrospectively included. The volumes of tissue activated were estimated based on individual electrode reconstruction. The optimal and sour stimulation sites were calculated at coordinate/voxel/mapping level and mapped to anatomical space based on patient-specific images and stimulation settings. The structural and functional predictive connectivity networks for the change of the post-operative Freezing of Gait-Questionnaire were also identified based on normative connectomes derived from the Parkinson's Progression Marker Initiative database. Leave-one-out cross-validation model validated the above results, and the model remained significant after including covariates. The dorsolateral two-thirds of the subthalamic nucleus was identified as the optimal stimulation site, while the ventrocentral portion of the right subthalamic nucleus and internal capsule surrounding the left central subthalamic nucleus were considered as the sour stimulation sites. Modulation of the fibre tracts connecting to the supplementary motor area, pre-supplementary motor area and pedunculopontine nucleus accounted for the alleviation of freezing of gait, whereas tracts connecting to medial and ventrolateral prefrontal cortices contributed to the deterioration of freezing of gait. The optimal/sour stimulation sites and structural/functional predictive connectivity networks for high-frequency subthalamic deep brain stimulation treating freezing of gait are identified and validated through sizable Parkinson's disease patients in this study. With the growing understanding of stimulation sites and related networks, individualized deep brain stimulation treatment with directional leads will become an optimal choice for Parkinson's disease patients with freezing of gait in the future.

Project description:Objective: This study aimed to explore alterations in the topological properties of the functional brain network in primary Parkinson's disease (PD) patients with freezing of gait (PD-FOG). Methods: Resting-state functional magnetic resonance imaging (Rs-fMRI) data were obtained in 23 PD-FOG patients, 33 PD patients without FOG (PD-nFOG), and 24 healthy control (HC) participants. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 90 brain regions, and topological properties were analyzed by using graph theory approaches. The network-based statistics (NBS) method was used to determine the suprathreshold connected edges (P < 0.05; threshold T = 2.725), and statistical significance was estimated by using the non-parametric permutation method (5,000 permutations). Statistically significant topological properties were further evaluated for their relationship with clinical neurological scales. Results: The topological properties of the functional brain network in PD-FOG and PD-nFOG showed no abnormalities at the global level. However, compared with HCs, PD-FOG patients showed decreased nodal local efficiency in several brain regions, including the bilateral striatum, frontoparietal areas, visual cortex, and bilateral superior temporal gyrus, increased nodal local efficiency in the left gyrus rectus. When compared with PD-nFOG patients and HCs, PD-FOG showed increased betweenness centrality in the left hippocampus. Moreover, compared to HCs, both PD-FOG and PD-nFOG patients displayed reduced network connections by using the NBS method, mainly involving the sensorimotor cortex (SM), visual network (VN), default mode network (DMN), auditory network (AN), dorsal attention network (DAN), subcortical regions, and limbic network (LIM). The local node efficiency of the right temporal pole: superior temporal gyrus in PD-FOG patients was positively correlated with the Freezing of Gait Questionnaire (FOGQ) scores. Conclusions: This study demonstrates the disrupted regional topological organization in PD-FOG patients, especially associated with damage to the subcortical regions and multiple cortical regions. Our results provide insights into the dysfunctional mechanisms of the relevant networks and indicate potential neuroimaging biomarkers of PD-FOG.

Project description:BackgroundFreezing of gait (FOG) is a common disabling motor disturbance in Parkinson's disease (PD). Our study aimed to probe the topological organizations of structural and functional brain networks and their coupling in FOG.MethodsIn this cross-sectional retrospective study, a total of 30 PD patients with FOG (PD-FOG), 40 patients without FOG, and 25 healthy controls (HCs) underwent clinical assessments and magnetic resonance imaging (MRI) scanning. Large-scale structural and functional brain networks were constructed. Subsequently, global and nodal graph theoretical properties and functional-structural coupling were investigated. Finally, correlations between the altered brain topological properties and freezing severity were analyzed in PD-FOG.ResultsFor structural networks, at the global level, PD-FOG exhibited increased normalized characteristic path length (P=0.040, Bonferroni-corrected) and decreased global efficiency (P=0.005, Bonferroni-corrected) compared with controls, and showed reduced global (P=0.001, Bonferroni-corrected) and local (P=0.032, Bonferroni-corrected) efficiency relative to patients without FOG. At the nodal level, nodal efficiency of structural networks was reduced in PD-FOG compared with PD patients without FOG, located in the left supplementary motor area (SMA), gyrus rectus, and middle cingulate cortex (MCC) (all P<0.05, Bonferroni-corrected). Notably, altered global and nodal properties of structural networks were significantly correlated with Freezing of Gait Questionnaire scores [all P<0.05, false discovery rate (FDR)-corrected]. However, only an increase in local efficiency (P=0.003, Bonferroni-corrected) of functional networks was identified in PD-FOG compared with those without FOG. No significant structural-functional coupling was detected among the 3 groups.ConclusionsThis study demonstrates the extensively impaired structural and relatively reserved functional network topological organizations in PD-FOG. Our results also provide evidence that the pathogenesis of PD-FOG is primarily attributable to network vulnerability established by crucial structural damage, especially in the left SMA, gyrus rectus, and MCC.

Project description:ObjectiveTo use a multimodal approach to assess brain structural pathways and resting state (RS) functional connectivity abnormalities in patients with Parkinson's disease and freezing of gait (PD-FoG).MethodsT1-weighted, diffusion tensor (DT) MRI and RS functional MRI (fMRI) were obtained from 22 PD-FoG patients and 35 controls on a 3.0 T MR scanner. Patients underwent clinical, motor, and neuropsychological evaluations. Gray matter (GM) volumes and white matter (WM) damage were assessed using voxel based morphometry and tract-based spatial statistics, respectively. The pedunculopontine tract (PPT) was studied using tractography. RS fMRI data were analyzed using a model free approach investigating the main sensorimotor and cognitive brain networks. Multiple regression models were performed to assess the relationships between structural, functional, and clinical/cognitive variables. Analysis of GM and WM structural abnormalities was replicated in an independent sample including 28 PD-FoG patients, 25 PD patients without FoG, and 30 healthy controls who performed MRI scans on a 1.5 T scanner.ResultsCompared with controls, no GM atrophy was found in PD-FoG cases. PD-FoG patients showed WM damage of the PPT, corpus callosum, corticospinal tract, cingulum, superior longitudinal fasciculus, and WM underneath the primary motor, premotor, prefrontal, orbitofrontal, and inferior parietal cortices, bilaterally. In PD-FoG, right PTT damage was associated with a greater disease severity. Analysis on the independent PD sample showed similar findings in PD-FoG patients relative to controls as well as WM damage of the genu and body of the corpus callosum and right parietal WM in PD-FoG relative to PD no-FoG patients. RS fMRI analysis showed that PD-FoG is associated with a decreased functional connectivity of the primary motor cortex and supplementary motor area bilaterally in the sensorimotor network, frontoparietal regions in the default mode network, and occipital cortex in the visual associative network.ConclusionsThis study suggests that FoG in PD can be the result of a poor structural and functional integration between motor and extramotor (cognitive) neural systems.

Project description:Freezing of gait, characterized by involuntary interruptions of walking, is a debilitating motor symptom of Parkinson's disease that restricts people's autonomy. Previous brain imaging studies investigating the mechanisms underlying freezing were restricted to scan people in supine positions and yielded conflicting theories regarding the role of the supplementary motor area and other cortical regions. We used functional near-infrared spectroscopy to investigate cortical haemodynamics related to freezing in freely moving people. We measured functional near-infrared spectroscopy activity over multiple motor-related cortical areas in 23 persons with Parkinson's disease who experienced daily freezing ('freezers') and 22 age-matched controls during freezing-provoking tasks including turning and doorway passing, voluntary stops and actual freezing. Crucially, we corrected the measured signals for confounds of walking. We first compared cortical activity between freezers and controls during freezing-provoking tasks without freezing (i.e. turning and doorway passing) and during stops. Secondly, within the freezers, we compared cortical activity between freezing, stopping and freezing-provoking tasks without freezing. First, we show that turning and doorway passing (without freezing) resemble cortical activity during stopping in both groups involving activation of the supplementary motor area and prefrontal cortex, areas known for their role in inhibiting actions. During these freezing-provoking tasks, the freezers displayed higher activity in the premotor areas than controls. Secondly, we show that, during actual freezing events, activity in the prefrontal cortex was lower than during voluntary stopping. The cortical relation between the freezing-provoking tasks (turning and doorway passing) and stopping may explain their susceptibility to trigger freezing by activating a stopping mechanism. Besides, the stopping-related activity of the supplementary motor area and prefrontal cortex seems to be out of balance in freezers. In this paper, we postulate that freezing results from a paroxysmal imbalance between the supplementary motor area and prefrontal cortex, thereby extending upon the current role of the supplementary motor area in freezing pathophysiology.

Dataset Information

Aberrant Advanced Cognitive and Attention-Related Brain Networks in Parkinson's Disease with Freezing of Gait.

Publications

Aberrant Advanced Cognitive and Attention-Related Brain Networks in Parkinson's Disease with Freezing of Gait.

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