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

Abstract

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 networkbased 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.

Brain network topology and future development of freezing of gait in Parkinson’s disease: a longitudinal study

“…Furthermore, mainly focusing on attentional networks, Maidan and colleagues have reported lower global efficiency of the dorsal attentional network in patients with FOG compared to patients without FOG [21]. However, in one recent study using the same method, the global topology of the PD with FOG has not changed significantly [22]. Our present results show that the global topological properties of whole-brain functional networks may remain relatively intact in patients with PD prior to the development of FOG symptoms.…”

“…Actually, in addition to motor function impairment, patients with FOG also exhibited more severe cognitive dysfunction, particularly in the executive function [11,36,37]. Interestingly, combining with graph theoretical analyses and diffusion tensor imaging (DTI) to investigate the structural organization of the white matter connectome, PD patients who have experienced FOG exhibited lower participation coefficients in frontal and parietal cortical regions and subcortical regions [20], whereas increased nodal centralities of these regions in functional brain networks [22,23]. Similarly, another study of functional brain networks also found remarkably increased nodal centralities in the MFG in patients with FOG, and increased values were significantly correlated with the severity of FOG [24].…”

“…Fourth, a widely accepted hypothesis proposed by Lewis et al that suggests FOG occurs as a result of a dysfunctional convergence and overload of normally segregated motor, cognitive, and limbic circuits in the basal ganglia [47]. Using graph theoretical techniques, several previous crosssectional fMRI studies involving patients who have experienced FOG have reported inconsistent results concerning altered regional topology in the basal ganglia [22][23][24]. In our longitudinal follow-up study, the nodal centralities in the basal ganglia have not changed between PD-FOGt and PD-FOGn.…”

“…In addition, nodal centralities indicate the importance of the nodes within the network [18]. To date, several studies have investigated structural and functional brain networks using graph theory in patients who have experienced FOG, which revealed disrupted topological properties in different levels [20][21][22][23][24]. However, very little research has focused on patients with PD who will develop FOG from the whole-brain network perspective.…”

Mechanisms of Motor Symptom Improvement by Long-Term Tai Chi Training in Parkinson's Disease Patients

“…The visual cue lessens the vestibular noise and improves personal balance in environment [26]. PD patients with freezing of gait displayed reduced network connections in VN [27,28]. Thus, improved VN function might explain for the better performance of BBS in PD after Tai Chi training.…”