Alterations in white matter network topology contribute to freezing of gait in Parkinson’s disease

Abstract

Freezing of gait (FOG) is a common symptom in advanced Parkinson's disease (PD). Despite current advances, the neural mechanisms underpinning this disturbance remain poorly understood. To this end, we investigated the structural organisation of the white matter connectome in PD freezers and PD non-freezers. We hypothesized that freezers would show an altered network architecture, which could hinder the effective information processing that characterizes the disorder. Twenty-six freezers and twenty-four well-matched non-freezers were included in this study. Using diffusion tensor imaging, we investigated the modularity and integration of the regional connectome by calculating the module degree z score and the participation coefficient, respectively. Compared to non-freezers, freezers demonstrated lower participation coefficients in the right caudate, thalamus, and hippocampus, as well as within superior frontal and parietal cortical regions. Importantly, several of these nodes were found within the brain's 'rich club'. Furthermore, group differences in module degree z scores within cortical frontal and sensory processing areas were found. Together, our results suggest that changes in the structural network topology contribute to the manifestation of FOG in PD, specifically due to a lack of structural integration between key information processing hubs of the brain.

Diffusion Tensor Imaging in Parkinson's Disease and Parkinsonian Syndrome: A Systematic Review

“…It resolves the adverse effects of crossingfibers, which may influence the accuracy the FA assessment, and thus provide better efficiency in diagnosing early PD (53,211). More recently, there are increasing interests in the use of structural connectome measures to identify abnormal structural connectivity in PD or in PD motor-subtypes through networkbased statistical analysis (57,63,(212)(213)(214)(215)(216)(217). The commonly used indices derived from DTI, together with their biological interpretations and clinical correlations in PD, are summarized in Table 2.…”

Neuroimaging advances in Parkinson's disease with freezing of gait: A systematic review

“…(2016)14 PD-FOG (72±6) 16 PD-nFOG (69±6) 16 HS (69±3)TBSS (whole brain skeleton)FA, and MD within the skeletonLower FA; higher MD in left cingulum, CC, internal capsule, posterior thalamic radiations, corona radiate, external capsule, sagittal stratum and SLF Higher MD in cerebral peduncles, inferior fronto-occipital fasciculusNot performedBharti et al. (2019a)15 PD-FOG (71±7) 16 PD-nFOG (66±11) 16 HS (67±8)TBSS (Seeds on SCP, MCP, and inferior cerebellar peduncle)FA, and MD in the cerebellar pedunclesLower FA and higher MD in SCP, and MCPBetween FA, MD of SCP, MCP and FOG-QHall et al. (2018)26 PD-FOG (64±9)24 PD-nFOG (66.9±5)Graph theory analysisModularityHigher involvement of frontal and parietal brain areas along with right caudate, thalamus, and hippocampusNo correlation resultPietracupa et al.…”

Impaired Topographical Organization of Functional Brain Networks in Parkinson’s Disease Patients With Freezing of Gait

“…Therefore, changes in betweenness centrality in areas related to cognitive performance may affect effective information transmission in the network and may explain the occurrence of FOG. Research by Brown et al found that the participation coefficient of the hippocampus was decreased, indicating that changes in structural topological properties of hippocampal are involved in the pathogenesis of FOG (Hall et al, 2018). However, in the FOG group, the left hippocampus showed a higher betweenness centrality, differences in research content should be considered to explain the differences between the results.…”