Alterations in Degree Centrality and Functional Connectivity in Parkinson’s Disease Patients With Freezing of Gait: A Resting-State Functional Magnetic Resonance Imaging Study

Abstract

Objective: Freezing of gait (FOG) is a common disabling motor symptom in Parkinson's disease (PD), but the potential pathogenic mechanisms are still unclear. Methods: A total of 22 patients with PD with FOG (PD-FOG), 28 patients with PD without FOG (PD-nFOG), and 33 healthy controls (HCs) were recruited in this study. Degree centrality (DC)-a graph theory-based measurement of global connectivity at the voxel level by measuring the number of instantaneous functional connections between one region and the rest of the brain-can map brain hubs with high sensitivity, specificity, and reproducibility. DC was used to explore alterations in the centrality of PD-FOG correlated with brain node levels. PD-FOG cognitive network dysfunction was further revealed via a seed-based functional connectivity (FC) analysis. In addition, correlation analyses were carried out between clinical symptoms and acquired connectivity measurement. Results: Compared to the PD-nFOG group, the PD-FOG group showed remarkably increased DC values in the right middle frontal gyrus (RMFG). There were no significant differences in other gray matter regions. Importantly, the clinical severity of FOG was related to the mean DC values in the RMFG. This brain region served as a seed in secondary seed-based FC analysis, and we further found FC changes in the right precuneus, right inferior frontal gyrus, right superior frontal gyrus (SFG), and cerebellum. Conclusion: Increased RMFG activity and FC network alterations in the middle frontal cortex with the precuneus, inferior, and SFG, and the cerebellum may have great potential in brain dysfunction in PD with FOG.

Regional Neural Activity Changes in Parkinson’s Disease-Associated Mild Cognitive Impairment and Cognitively Normal Patients

“… 22 , 23 Using degree centrality (DC), freezing of gait (FOG) of PD-CN patients has also been correlated with DMN changes indicating the presence of pathological damage. 24 Evidence from ASL research on cognitively normal patients with PD showed that hypoperfusion in the left SMG was negatively correlated with global cognitive performance, consistent with our result. 3 ReHo presumes that the hemodynamic characteristics of each voxel are synchronized with that of every other within a functional cluster, and this synchronization can be altered or adjusted by different conditions.…”

“… 48 Accordingly, the decreased ReHo in the right PCG may be related to an early stage of PD. 13 Hypoactivation in the right PCG of PD patients has been observed in previous RS-fMRI studies, 13 , 17 , 24 whereas the PD-MCI group showed significantly higher ReHo values in the right PCG when compared with the PD-CN group. Overactivation of the sensorimotor cortex has been reported in PD and MCI patients.…”

“… 8 , 30 Interruption of the dynamic equilibrium between the MFG and the DMN may reduce the ability of the cognitive system to prepare for future task execution in PD-FOG patients. 24 Just like Peter, Boord and colleagues saw reduced resting connectivity to the DMN in the PD-nondemented patients but more activation to the frontoparietal network during increased executive challenge. 31 Taken together, the hyperactivation of the right MFG and hypoactivation of DMN may be a compensatory mechanism for counteracting cognitive decline prior to the appearance of MCI in PD due to executive deficits.…”

“…It is surmised that hypoactivation of the DMN may be due to poor regulation of local neural synchronization indicating PD-related damage. 9 , 24 Thus, we posit that the decreased ReHo in DMN may be related to the cognitive impairment of PD and may play a role in the development of PD-associated cognitive decline.…”

“… 26 PD-CN patients with FOG showed a higher DC value in the right MFG than the NC indicating that PD-FOG has significant cognitive dysfunction involving frontal lobe executive impairment. 24 The right MFG is reported to be involved in decision-making in PD. 28 Increased ReHo in the right MFG may, therefore, compensate for dysfunctional decision-making and loss of executive function, so the PD-CN patients may lack any visible signs on cognitive decline.…”