More Than Just Static: Dynamic Functional Connectivity Changes of the Thalamic Nuclei to Cortex in Parkinson's Disease With Freezing of Gait

Abstract

Background: The thalamus is not only a key relay node of the thalamocortical circuit but also a hub in the regulation of gait. Previous studies of resting-state functional magnetic resonance imaging (fMRI) have shown static functional connectivity (FC) between the thalamus and the cortex are disrupted in Parkinson's disease (PD) patients with freezing of gait (FOG). However, temporal dynamic FC between the thalamus and the cortex has not yet been characterized in these patients.Methods: Fifty PD patients, including 25 PD patients with FOG (PD-FOG) and 25 PD patients without FOG (PD-NFOG), and 25 healthy controls (HC) underwent resting-state fMRI. Seed-voxel-wise static and dynamic FC were calculated between each thalamic nuclei and other voxels across the brain using the 14 thalamic nuclei in both hemispheres as regions of interest. Associations between altered thalamic FC based on significant inter-group differences and severity of FOG symptoms were also examined in PD-FOG.Results: Both PD-FOG and PD-NFOG showed lower static FC between the right lateral posterior thalamic nuclei and right inferior parietal lobule (IPL) compared with HC. Altered FC dynamics between the thalamic nuclei and several cortical areas were identified in PD-FOG, as shown by temporal dynamic FC analyses. Specifically, relative to PD-NFOG or HC, PD-FOG showed greater fluctuations in FC between the left intralaminar (IL) nuclei and right IPL and between the left medial geniculate and left postcentral gyrus. Furthermore, the dynamics of FC between the left pulvinar anterior nuclei and left inferior frontal gyrus were upregulated in both PD-FOG and PD-NFOG. The dynamics of FC between the right ventral lateral nuclei and left paracentral lobule were elevated in PD-NFOG but were maintained in PD-FOG and HC. The quantitative variability of FC between the left IL nuclei and right IPL was positively correlated with the clinical scales scores in PD-FOG.Conclusions: Dynamic FC between the thalamic nuclei and relevant associative cortical areas involved in sensorimotor integration or cognitive function was disrupted in PD-FOG, which was reflected by greater temporal fluctuations. Abnormal dynamic FC between the left IL nuclei of the thalamus and right IPL was related to the severity of FOG.

Abnormal interhemispheric and intrahemispheric functional connectivity dynamics in drug‐naïve first‐episode schizophrenia patients with auditory verbal hallucinations

“…Moreover, the previous studies found reduced PAS scores of the thalamus and IFG was found in schizophrenia patients and ultra‐high risk for psychosis (F. Zhu et al, 2019 ). However, we found opposite pattern between the whole‐brain and intrahemispheric dFCD variances and sFCD in drug‐naïve FES patients with AVHs or NAVH, which is consistent with the findings in the previous study exploring the neural substrates of other neurological diseases, such as bipolar depression and major depressive disorders (Pang et al, 2020 ), generalized anxiety disorder (Lu et al, 2020 ), and Parkinson's disease (S. Wang, Cai, et al, 2021 ). Higher dFCD may reflect the indicative of flexible communication, but it may also be a sign of unstable interactions (S. Wang, Cai, et al, 2021 ).…”

“…However, we found opposite pattern between the whole‐brain and intrahemispheric dFCD variances and sFCD in drug‐naïve FES patients with AVHs or NAVH, which is consistent with the findings in the previous study exploring the neural substrates of other neurological diseases, such as bipolar depression and major depressive disorders (Pang et al, 2020), generalized anxiety disorder (Lu et al, 2020), and Parkinson's disease (S. Wang, Cai, et al, 2021). Higher dFCD may reflect the indicative of flexible communication, but it may also be a sign of unstable interactions (S. Wang, Cai, et al, 2021). And weaker sFCD may be the result of unstable interactions.…”

“…Higher dFCD may reflect the indicative of flexible communication, but it may also be a sign of unstable interactions (S. Wang, Cai, et al, 2021). And weaker sFCD may be the result of unstable interactions.…”

Acupuncture Regulates Symptoms of Parkinson’s Disease via Brain Neural Activity and Functional Connectivity in Mice

“…Furthermore, several studies suggested that brain connectivity among various brain regions changed in PD patients, which might be related to the pathological changes of various brain regions occurring in PD patients. It was reported that functional connectivity was decreased in the thalamic nuclei and associative cortical areas related to the sensorimotor integration or cognitive function in PD patients with freezing of the gate, and the changes in connectivity was associated with disease severity (Wang et al, 2021 ). In addition, it was also reported that the treatment for PD patients could modify the changed brain connectivity: the subthalamic nucleus-deep brain stimulation showed increased functional connectivity of the supplementary motor cortex, putamen, inferior frontal gyrus, and dorsal frontoparietal network, which was also correlated with changes of UPDRS-III scores (Huang L. C. et al, 2022 ), indicative of the importance of functional connectivity in the treatment of PD.…”

Imaging the neural underpinnings of freezing of gait in Parkinson’s disease

“… Structural DTI Functional Connectivity (FC) ROI seed-based analyses Cross-sectional Diffuse WM deficits in tracts projecting from PPN to motor, sensory & cognitive areas (C/T HC). Lower FC of right PPN with right MTG, ITG, & bilateral CRB (C/T to HC & FoG-) Interference AND/OR Perceptual Dysfunction Wang et al (2021) 25 FoG+ 25 FoG- 25 HC OFF H&Y, LEDD, MMSE, UPDRS-III, new FoG-Q and clockwise vs anti-clockwise turning. Functional connectivity (FC) ROI seed-based analyses Cross-sectional Correlational (indirect with FoG-Q scores) Higher dynamic FC between left thalamic nuclei and right IPL (positively correlated with N -FoGQ) & left PCG (C/T FoG- & HC).…”