Cholinergic system correlates of postural control changes in Parkinson’s disease freezers

Brain, Journal Year: 2023, Volume and Issue: 146(8), P. 3243 - 3257

Published: April 22, 2023

Abstract Postural instability and freezing of gait are the most debilitating dopamine-refractory motor impairments in advanced stages Parkinson’s disease because increased risk falls poorer quality life. Recent findings suggest an inability to efficaciously utilize vestibular information during static posturography among people with who exhibit gait, associated changes cholinergic system integrity as assessed by vesicular acetylcholine transporter PET. There is a lack adequate understanding how postural control varies function available sensory patients gait. The goal this cross-sectional study was examine cerebral that associate inter-sensory processing features dynamic computerized acetylcholinesterase Seventy-five participants disease, 16 whom exhibited underwent on NeuroCom© Equitest organization test platform, striatal dopamine, PET scanning. Findings demonstrated have greater difficulty maintaining balance absence reliable proprioceptive cues compared those without [β = 0.28 (0.021, 0.54), P 0.034], effect independent severity 0.16 (0.062, 0.26), < 0.01] age 0.092 (−0.005, 0.19), 0.062]. Exploratory voxel-based analysis revealed association between right hemispheric network related visual-vestibular integration self-motion perception. High anti-cholinergic burden predicted impairment manner dependent cortical 0.34 (0.065, 0.61), 0.01]. Our advance perspective might play role supporting after nigro-striatal dopaminergic losses disease. Failure cortex-dependent may impair detection cues. Better plays process augur novel treatments therapeutic interventions ameliorate symptoms

Language: Английский

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Executive Control of Walking in People With Parkinson’s Disease With Freezing of Gait

Neurorehabilitation and neural repair, Journal Year: 2020, Volume and Issue: 34(12), P. 1138 - 1149

Published: Nov. 6, 2020

Background Walking abnormalities in people with Parkinson’s disease (PD) are characterized by a shift locomotor control from healthy automaticity to compensatory prefrontal executive control. Indirect measures of walking (eg, step-to-step variability and dual-task cost) suggest that freezing gait (FoG) may be associated reduced walking. However, the influence FoG status on actual cortex (PFC) activity during remains unclear. Objective To investigate PD. Methods Forty-seven PD were distributed into 2 groups based status, which was assessed New Freezing Gait Questionnaire: PD−FoG (n = 23; UPDRS-III 35) PD+FoG 24; 43.1). Participants walked over 9-m straight path (with 180° turn at each end) for 80 seconds. Two conditions tested off medication: single- (ie, concomitant cognitive task). A portable functional near-infrared spectroscopy system recorded PFC while (including turns). Wearable inertial sensors used calculate spatiotemporal parameters. Results had greater activation both single than ( P .031). There no differences between PD+FoG. Both decreased speed .029) stride length < .001) compared single-task Conclusions These findings have walking, even absence episodes. seems more sensitive identifying reduction

Language: Английский

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

NeuroImage Clinical, Journal Year: 2022, Volume and Issue: 35, P. 103123 - 103123

Published: Jan. 1, 2022

Freezing of gait (FoG) is a paroxysmal and sporadic impairment that severely affects PD patients' quality life. This review summarizes current neuroimaging investigations characterize the neural underpinnings FoG in PD. The presents discusses latest advances across multiple methodological domains shed light on structural correlates, connectivity changes, activation patterns associated with different pathophysiological models Resting-state fMRI studies mainly report cortico-striatal decoupling disruptions along dorsal stream visuomotor processing, thus supporting 'interference' 'perceptual dysfunction' FoG. Task-based MRI employing virtual reality motor imagery paradigms reveal disruption functional between cortical subcortical regions an increased recruitment parieto-occipital regions, corroborating main findings fNIRS actual primarily frontal areas during gait, 'executive model Finally, we discuss how identifying substrates may open new avenues to develop efficient treatment strategies.

Language: Английский

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A meta-analysis identifies factors predicting the future development of freezing of gait in Parkinson’s disease

npj Parkinson s Disease, Journal Year: 2023, Volume and Issue: 9(1)

Published: Dec. 4, 2023

Abstract Freezing of gait (FOG) is a debilitating problem that common among many, but not all, people with Parkinson’s disease (PD). Numerous attempts have been made at treating FOG to reduce its negative impact on fall risk, functional independence, and health-related quality life. However, optimal treatment remains elusive. Observational studies recently investigated factors differ patients PD who later develop FOG, compared those do not. With prediction prevention in mind, we conducted systematic review meta-analysis publications through 31.12.2022 identify risk factors. Studies were included if they used cohort design, without baseline, data possible predictors measured incident was assessed follow-up. 1068 original papers identified, 38 met a-priori criteria, 35 the ( n = 8973; mean follow-up: 4.1 ± 2.7 years). Factors significantly associated included: higher age onset PD, greater severity motor symptoms, depression, anxiety, poorer cognitive status, use levodopa COMT inhibitors. Most results robust four subgroup analyses. These findings indicate changes incidence can be detected subset sometimes as long 12 years before manifests, supporting possibility predicting incidence. Intriguingly, some these may modifiable, suggesting steps taken lower possibly even prevent future development FOG.

Language: Английский

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Subthalamic and nigral neurons are differentially modulated during parkinsonian gait

Brain, Journal Year: 2023, Volume and Issue: 146(7), P. 2766 - 2779

Published: Feb. 2, 2023

Abstract The parkinsonian gait disorder and freezing of are therapeutically demanding symptoms with considerable impact on quality life. aim this study was to assess the role subthalamic nigral neurons in control using intraoperative microelectrode recordings basal ganglia during a supine stepping task. Twelve male patients (56 ± 7 years) suffering from moderate idiopathic Parkinson’s disease (disease duration 10 3 years, Hoehn Yahr stage 2), undergoing awake neurosurgery for deep brain stimulation, participated study. After s resting, at self-paced speed 35 followed by short intervals response random ‘start’ ‘stop’ cues. Single- multi-unit activity analysed offline relation different aspects task (attentional cues, heel strikes, irregularities) terms firing frequency, pattern oscillatory activity. Subthalamic nucleus substantia nigra responded Of neurons, 24% exhibited movement-related modulation as an increase rate, suggesting predominant motor task, while 8% showed attentional In contrast, responsive changes exclusively associated (15%). revealed gait-related regularization drop beta oscillations performance. During episodes instead, there rise This shows first time specific, task-related single-unit gait-like movements humans differential roles gait. emergence perturbed patterns indicates disrupted information transfer within network, resulting

Language: Английский

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Freezing of Gait in People with Parkinson’s Disease: Nature, Occurrence, and Risk Factors

Journal of Parkinson s Disease, Journal Year: 2020, Volume and Issue: 10(2), P. 631 - 640

Published: Feb. 28, 2020

Freezing of gait (FOG) is a common symptom Parkinson's disease (PD) which can result in falls and fall related injuries, poor quality life reduced functional independence. It heterogeneous phenomenon that difficult to quantify eludes unified pathophysiological framework.

Language: Английский

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

Frontiers in Aging Neuroscience, Journal Year: 2020, Volume and Issue: 12

Published: Oct. 21, 2020

Objective: This study aimed to explore alterations in the topological properties of functional brain network primary Parkinson's disease (PD) patients with freezing gait (PD-FOG). Methods: Resting-state magnetic resonance imaging (Rs-fMRI) data were obtained 23 PD-FOG patients, 33 PD without FOG (PD-nFOG), and 24 healthy control (HC) participants. The whole-brain connectome was constructed by thresholding Pearson correlation matrices 90 regions, analyzed using graph theory approaches. network-based statistics (NBS) method used determine suprathreshold connected edges (P < 0.05; threshold T = 2.725), statistical significance estimated non-parametric permutation (5,000 permutations). Statistically significant further evaluated for their relationship clinical neurological scales. Results: PD-nFOG showed no abnormalities at global level. However, compared HCs, decreased nodal local efficiency several including bilateral striatum, frontoparietal areas, visual cortex, superior temporal gyrus, increased left gyrus rectus. When betweenness centrality hippocampus. Moreover, both displayed reduced connections NBS method, mainly involving sensorimotor cortex (SM), (VN), default mode (DMN), auditory (AN), dorsal attention (DAN), subcortical limbic (LIM). node right pole: positively correlated Freezing Gait Questionnaire (FOGQ) scores. Conclusions: demonstrates disrupted regional organization especially associated damage regions multiple cortical regions. Our results provide insights into dysfunctional mechanisms relevant networks indicate potential neuroimaging biomarkers PD-FOG.

Language: Английский

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Behavioural manifestations and associated non-motor features of freezing of gait: A narrative review and theoretical framework

Neuroscience & Biobehavioral Reviews, Journal Year: 2020, Volume and Issue: 116, P. 350 - 364

Published: June 27, 2020

Language: Английский

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Discussion of Research Priorities for Gait Disorders in Parkinson's Disease

Movement Disorders, Journal Year: 2021, Volume and Issue: 37(2), P. 253 - 263

Published: Dec. 22, 2021

ABSTRACT Gait and balance abnormalities develop commonly in Parkinson's disease are among the motor symptoms most disabling refractory to dopaminergic or other treatments, including deep brain stimulation. Efforts effective therapies challenged by limited understanding of these complex disorders. There is a major need for novel appropriately targeted research expedite progress this area. The Scientific Issues Committee International Parkinson Movement Disorder Society has charged panel experts field consider current knowledge gaps determine routes with highest potential generate groundbreaking data. © 2021

Language: Английский

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

npj Parkinson s Disease, Journal Year: 2021, Volume and Issue: 7(1)

Published: March 2, 2021

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

Language: Английский

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