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

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.

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Disorganized resting‐state functional connectivity between the dorsal attention network and intrinsic networks in Parkinson's disease with freezing of gait

European Journal of Neuroscience ◽

10.1111/ejn.15439 ◽

2021 ◽

Author(s):

Qian Yu ◽

Qun Li ◽

Weidong Fang ◽

Yuchan Wang ◽

Yingcheng Zhu ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Resting State ◽

Freezing Of Gait ◽

Resting State Functional Connectivity ◽

Attention Network ◽

Dorsal Attention Network

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Changes in Resting-State Functional Connectivity Related to Freezing of Gait in Parkinson's Disease

Neuroscience ◽

10.1016/j.neuroscience.2019.08.042 ◽

2019 ◽

Vol 418 ◽

pp. 311-317 ◽

Cited By ~ 2

Author(s):

Alexandra Potvin-Desrochers ◽

Trina Mitchell ◽

Thomas Gisiger ◽

Caroline Paquette

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Resting State ◽

Freezing Of Gait ◽

Resting State Functional Connectivity

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Motor Symptom Lateralization Influences Cortico-Striatal Functional Connectivity in Parkinson's Disease

Frontiers in Neurology ◽

10.3389/fneur.2021.619631 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wen Su ◽

Kai Li ◽

Chun-Mei Li ◽

Xin-Xin Ma ◽

Hong Zhao ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Orbitofrontal Cortex ◽

Resting State ◽

Right Hemisphere ◽

Motor Symptom ◽

Control Group ◽

Significant Difference ◽

The Right

Objective: The striatum is unevenly impaired bilaterally in Parkinson's disease (PD). Because the striatum plays a key role in cortico-striatal circuits, we assume that lateralization affects cortico-striatal functional connectivity in PD. The present study sought to evaluate the effect of lateralization on various cortico-striatal circuits through resting-state functional magnetic resonance imaging (fMRI).Methods: Thirty left-onset Parkinson's disease (LPD) patients, 27 right-onset Parkinson's disease (RPD) patients, and 32 normal controls with satisfactory data were recruited. Their demographic, clinical, and neuropsychological information was collected. Resting-state fMRI was performed, and functional connectivity changes of seven subdivisions of the striatum were explored in the two PD groups. In addition, the associations between altered functional connectivity and various clinical and neuropsychological characteristics were analyzed by Pearson's or Spearman's correlation.Results: Directly comparing the LPD and RPD patients demonstrated that the LPD patients had lower FC between the left dorsal rostral putamen and the left orbitofrontal cortex than the RPD patients. In addition, the LPD patients showed aberrant functional connectivity involving several striatal subdivisions in the right hemisphere. The right dorsal caudate, ventral rostral putamen, and superior ventral striatum had decreased functional connectivity with the cerebellum and parietal and occipital lobes relative to the normal control group. The comparison between RPD patients and the controls did not obtain significant difference in functional connectivity. The functional connectivity between the left dorsal rostral putamen and the left orbitofrontal cortex was associated with contralateral motor symptom severity in PD patients.Conclusions: Our findings provide new insights into the distinct characteristics of cortico-striatal circuits in LPD and RPD patients. Lateralization of motor symptoms is associated with lateralized striatal functional connectivity.

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Neurofeedback-guided kinesthetic motor imagery training in Parkinson's disease: Randomized trial

10.1101/2022.01.05.22268816 ◽

2022 ◽

Author(s):

Sule Tinaz ◽

Serageldin Kamel ◽

Sai S Aravala ◽

Mohamed Elfil ◽

Ahmed Bayoumi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Motor Function ◽

Motor Imagery ◽

Resting State ◽

Visual Imagery ◽

Body Awareness ◽

Yahr Stage ◽

The Right

Background: Parkinson's disease (PD) causes difficulty with maintaining the speed, size, and vigor of movements, especially when they are internally generated. We previously proposed that the insula is important in motivating intentional movement via its connections with the dorsomedial frontal cortex (dmFC). We demonstrated that subjects with PD can increase the right insula-dmFC functional connectivity using fMRI-based neurofeedback (NF) combined with kinesthetic motor imagery (MI). The current study is a randomized clinical trial testing whether NF-guided kinesthetic MI training can improve motor performance and increase task-based and resting-state right insula-dmFC functional connectivity in subjects with PD. Methods: We assigned nondemented subjects with mild PD (Hoehn & Yahr stage ≤ 3) to the experimental kinesthetic MI with NF (MI-NF, n=22) and active control visual imagery (VI, n=22) groups. Only the MI-NF group received NF-guided MI training (10-12 runs). The NF signal was based on the right insula-dmFC functional connectivity strength. All subjects also practiced their respective imagery tasks at home daily for 4 weeks. Post-training changes in 1) task-based and resting-state right insula-dmFC functional connectivity were the imaging outcomes, and 2) MDS-UPDRS motor exam and motor function scores were the clinical outcomes. Results: The MI-NF group did not show significant NF regulation and was not significantly different from the VI group in any of the imaging or clinical outcome measures. The MI-NF group reported subjective improvement in kinesthetic body awareness. There was significant and comparable improvement only in motor function scores in both groups. This improvement correlated with NF regulation of the right insula-dmFC functional connectivity only in the MI-NF group. Both groups showed specific training effects in whole-brain functional connectivity with distinct neural circuits supporting kinesthetic motor and visual imagery (exploratory outcome). Conclusions: The functional connectivity-based NF regulation was unsuccessful in our cohort with mild PD. However, kinesthetic MI practice by itself or in combination with other imagery techniques is a promising tool in motor rehabilitation in PD.

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Resting state functional connectivity in levodopa non responsive Parkinson's disease patients with freezing of gait

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2020.06.057 ◽

2020 ◽

Vol 79 ◽

pp. e8

Author(s):

K. Sreenivasan ◽

X. Zhuang ◽

J. Longhurst ◽

Z. Yang ◽

D. Cordes ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Functional Connectivity ◽

Resting State ◽

Freezing Of Gait ◽

Resting State Functional Connectivity

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Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease

npj Parkinson s Disease ◽

10.1038/s41531-021-00163-0 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Nicholas D’Cruz ◽

Griet Vervoort ◽

Sima Chalavi ◽

Bauke W. Dijkstra ◽

Moran Gilat ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Resting State ◽

Freezing Of Gait ◽

Study Entry ◽

Resting State Functional Connectivity ◽

Behavioral Correlates ◽

Local Volume ◽

Linear Evolution ◽

Risk Of Falls

AbstractThe onset of freezing of gait (FOG) in Parkinson’s disease (PD) is a critical milestone, marked by a higher risk of falls and reduced quality of life. FOG is associated with alterations in subcortical neural circuits, yet no study has assessed whether subcortical morphology can predict the onset of clinical FOG. In this prospective multimodal neuroimaging cohort study, we performed vertex-based analysis of grey matter morphology in fifty-seven individuals with PD at study entry and two years later. We also explored the behavioral correlates and resting-state functional connectivity related to these local volume differences. At study entry, we found that freezers (N = 12) and persons who developed FOG during the course of the study (converters) (N = 9) showed local inflations in bilateral thalamus in contrast to persons who did not (non-converters) (N = 36). Longitudinally, converters (N = 7) also showed local inflation in the left thalamus, as compared to non-converters (N = 36). A model including sex, daily levodopa equivalent dose, and local thalamic inflation predicted conversion with good accuracy (AUC: 0.87, sensitivity: 88.9%, specificity: 77.8%). Exploratory analyses showed that local thalamic inflations were associated with larger medial thalamic sub-nuclei volumes and better cognitive performance. Resting-state analyses further revealed that converters had stronger thalamo-cortical coupling with limbic and cognitive regions pre-conversion, with a marked reduction in coupling over the two years. Finally, validation using the PPMI cohort suggested FOG-specific non-linear evolution of thalamic local volume. These findings provide markers of, and deeper insights into conversion to FOG, which may foster earlier intervention and better mobility for persons with PD.

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