Alterations of functional and structural connectivity of freezing of gait in Parkinson’s disease

Abstract

This study assessed the patterns of functional and structural connectivity abnormalities in patients with Parkinson's disease with freezing of gait (PD FOG+) compared with those without freezing (PD FOG-) and healthy controls (HCs). Resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) scans were obtained from 14 PD FOG+, 16 PD FOG- and 16HCs. Between-group difference in pedunculopontine nucleus (PPN) functional connectivity (FC) was performed to assess FC dysfunction. Tract-based spatial statistics (TBSS) was applied to compare white matter (WM) impairment across the whole brain between groups. PD FOG+ patients exhibited abnormal PPN FC, compared with HCs and with PD FOG-, mainly in the corticopontine-cerebellar pathways (in the bilateral cerebellum and in the pons), as well as the visual temporal areas (in the right middle temporal gyrus and in the right inferior temporal gyrus). Moreover, PD FOG+ patients, showed more pronounced WM abnormalities, relative to controls, including the interhemispheric connections of corpus callosum, the cortico-cortical WM tracts of the cingulum, the superior longitudinal fasciculus and inferior fronto-occipital fasciculus, the corticofugal tract (cerebral peduncles, internal capsule, corona radiata), as well as tracts connecting the thalamus (thalamic radiation). This study suggests that FOG in PD is associated with abnormal PPN FC network, mainly affecting the corticopontine-cerebellar pathways as well as visual temporal areas involved in visual processing, and with diffuse WM deficits extending to motor, sensory and cognitive regions. Combining rs-fMRI and DTI method, our study should advance the understanding of neural mechanisms underlying FOG in PD.

Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human

“…In PD this includes degeneration of cholinergic (Rinne et al, 2008; Karachi et al, 2010; Pienaar et al, 2013), GABAergic and glycinergic cells (Pienaar et al, 2013). Neuroimaging indicates that locomotor deficits in PD patients are associated with additional MLR abnormalities (notably in the PPN), including altered connectivity between the MLR, thalamus, and motor cortical regions (Fling et al, 2013, 2014), abnormal microstructure (Vercruysse et al, 2015; Youn et al, 2015; Wang et al, 2016), atrophy of the MLR gray matter (Snijders et al, 2011; Fioravanti et al, 2015) and abnormal metabolic activity following a walking task (Tard et al, 2015). Additionally, anatomopathological studies revealed the presence in the MLR of alpha-synuclein immuno-reactive Lewy Bodies (e.g., Seidel et al, 2015), and mitochondrial abnormalities (Pienaar et al, 2013) in PD.…”

Cholinergic circuit genes in the healthy brain are differentially expressed in regions that exhibit gray matter loss in Parkinson’s disease

“…Clinical symptoms involve impairment of diverse motor and non-motor symptoms that get progressively worse over time. The decline in clinical performance has been associated with changes in morphological properties of structural and functional neuroimaging networks (Lucas-Jiménez et al 2016; Wang et al 2016; de Schipper et al 2017). In turn, studies have investigated the relationship between these imaging networks and genetic variants in PD-related genes to provide new insights into the pathogenesis of PD (van der Vegt et al 2009).…”

The New Freezing of Gait Questionnaire: Unsuitable as an Outcome in Clinical Trials?

“…The fact that NFOG‐Q scores did not differ significantly between time points as such and that no systematic decrease or increase of scores was found across the cohorts suggests that becoming more aware of freezing behavior could go in both directions, that is, more or less positive assessments of FOG. Several studies reported recall bias as a limitation in the previous freezing of gait questionnaire (FOG‐Q) or other clinical scales . As a result, one study even used the second assessment of the FOG‐Q instead of the first to compensate for this issue .…”

“…Several studies reported recall bias as a limitation in the previous freezing of gait questionnaire (FOG-Q) or other clinical scales. [36][37][38] As a result, one study even used the second assessment of the FOG-Q instead of the first to compensate for this issue. 39 To help the accuracy of retrospective assessment of FOG, the NFOG-Q is accompanied by exemplary videos of FOG to serve as a reference before it is completed.…”