Hitting the brakes: pathological subthalamic nucleus activity in Parkinson’s disease gait freezing

Georgiades, Matthew J.; Shine, James M.; Gilat, Moran; McMaster, Jacqueline; Owler, Brian; Mahant, Neil; Lewis, Simon J.G.

doi:10.1093/brain/awz325

Cited by 41 publications

(45 citation statements)

References 35 publications

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“…The definition of FOG in this VR paradigm therefore remains arbitrary 21,27 . Still, the degree of FOG tested during the VR task correlated with FOG during actual gait 58 , and a study using electromyography of the legs showed that VR-defined FOG events in eight people with PD were characterized by an increased freezing-ratio 82 resembling the severe trembling of the legs observed during FOG in the clinic 83 . Future studies adopting electromyography or position data of the feet in large samples are needed to fully validate this paradigm.…”

Section: [H2] Brain Imaging Resultsmentioning

confidence: 98%

Virtual reality in research and rehabilitation of gait and balance in Parkinson disease

et al. 2020

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Virtual reality (VR) technology has emerged as a promising tool for studying and rehabilitating gait and balance impairments in people with Parkinson disease (PD) as it allows users to be engaged in an enriched and highly individualized complex environment. This Review examines the rationale and evidence for using VR in the assessment and rehabilitation of people with PD, makes recommendations for future research and discusses the use of VR in the clinic. In the assessment of people with PD, VR has been used to manipulate environments to enhance study of the behavioural and neural underpinnings of gait and balance, improving understanding of the motor-cognitive neural circuitry involved. Despite suggestions that VR can provide rehabilitation that is more effective and less labour intensive than non-VR rehabilitation, little evidence exists to date to support these claims. Nevertheless, much unrealised potential exists for the use of VR to provide personalized assessment and rehabilitation that optimises motor learning both in the clinic and home environments, and adapts to change in individuals over time. Design of such systems will require collaboration between all stakeholders to maximise useability, engagement, safety and effectiveness. [H1] INTRODUCTIONParkinson disease (PD) is a complex, progressive multi-system neurodegenerative disorder associated with motor and non-motor impairments 1 . The hallmark motor symptoms include bradykinesia, rigidity, tremor and postural instability,

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Section: [H2] Brain Imaging Resultsmentioning

confidence: 98%

Virtual reality in research and rehabilitation of gait and balance in Parkinson disease

et al. 2020

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“…Indeed, dynamic balance activities including walking indicate that PD who freeze exhibit more activity of the frontal cortex than those who do not freeze [25]. Further, these increased demands on the cortico-basal ganglia system may place the individual closer to a freezing event, which could be triggered by a cognitive, affective, or motor conflict [26], underpinned by a de-coupling of the cortico-thalamic system [27].…”

Section: Discussionmentioning

confidence: 99%

Relating Parkinson freezing and balance domains: A structural equation modeling approach

Peterson

Liew

Stuart

et al. 2020

Parkinsonism & Related Disorders

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Background: People with PD who exhibit freezing of gait (FOG) also exhibit poor balance compared to those who do not freeze. However, balance is a broad construct that can be subdivided into subdomains that include dynamic balance (gait), anticipatory postural adjustments (APAs) & gait initiation, postural sway in stance, and automatic postural responses (e.g., reactive stepping). Few studies have provided a robust investigation on how each of these domains is impacted by FOG, and no studies have compared balance across groups while rigorously controlling for disease severity.Methods: Structural equation modeling was used to evaluate the relationships between FOG and balance domains constructed as latent variables and controlling for disease severity. Domains included: dynamic balance (gait), APAs, postural sway, and reactive stepping. Models were run relating domains to both the presence and severity of FOG.Results: Latent variables reflecting domains of Gait and APAs, but not postural sway or reactive stepping, were significantly related to the severity of FOG. Models for presence of FOG showed the same results, as Gait and APAs, but not postural sway or reactive stepping, were related to presence of FOG.Conclusion: These results are consistent with hypotheses that balance deficits in people with PD who freeze are most pronounced in gait and anticipatory postural adjustments. Reactive stepping and postural control domains are less effected. These findings suggest that rehabilitative strategies focused on gait and APAs may be most effective for people with PD who freeze.

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“…Owing to the limited evidence, an investigation into neural markers of conversion is warranted for additional predictive purposes and to help explain the elusive mechanisms leading to the onset of FOG 19 . While freezing episodes likely signify transient dysfunctional information processing across the cortico-basal ganglia-thalamo-cortical parallel circuits [20][21][22] , these transient events are challenging to elicit and interpret, and therefore have poor applicability as predictive markers. Compensatory or maladaptive structural alterations of the nodes within these circuits, however, are more persistent and therefore easier to capture as possible predictive markers for FOG in PD.…”

Section: Introductionmentioning

confidence: 99%

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

DʼCruz

Vervoort

Chalavi

et al. 2021

npj Parkinsons Dis.

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The 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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Hitting the brakes: pathological subthalamic nucleus activity in Parkinson’s disease gait freezing

Cited by 41 publications

References 35 publications

Virtual reality in research and rehabilitation of gait and balance in Parkinson disease

Virtual reality in research and rehabilitation of gait and balance in Parkinson disease

Relating Parkinson freezing and balance domains: A structural equation modeling approach

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

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