Limited Effect of Dopaminergic Medication on Straight Walking and Turning in Early-to-Moderate Parkinson’s Disease during Single and Dual Tasking

Elshehabi, Morad; Maier, Katrin S.; Hasmann, Sandra E.; Nussbaum, Susanne; Herbst, Heinz; Heger, Tanja; Berg, Daniela; Hobert, Markus A.; Maetzler, Walter

doi:10.3389/fnagi.2016.00004

Cited by 21 publications

(15 citation statements)

References 55 publications

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“…In accordance with the findings in this study, previous behavioural research has shown that the administration of dopaminergic replacement therapy often improves step time variability in Parkinson's disease patients (Hausdorff, et al, 2003a;Lord et al, 2011;Rochester et al, 2011;Bryant et al, 2016). Furthermore, impairments in dual-task walking are also often improved by optimal dopaminergic replacement therapy (Camicioli et al, 1998;Lord et al, 2011;Elshehabi et al, 2016).…”

Section: Approximate Position Figuresupporting

confidence: 91%

Dopamine depletion impairs gait automaticity by altering cortico-striatal and cerebellar processing in Parkinson's disease

et al. 2017

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Impairments in motor automaticity cause patients with Parkinson's disease to rely on attentional resources during gait, resulting in greater motor variability and a higher risk of falls. Although dopaminergic circuitry is known to play an important role in motor automaticity, little evidence exists on the neural mechanisms underlying the breakdown of locomotor automaticity in Parkinson's disease. This impedes clinical management and is in great part due to mobility restrictions that accompany the neuroimaging of gait. This study therefore utilized a virtual reality gait paradigm in conjunction with functional MRI to investigate the role of dopaminergic medication on lower limb motor automaticity in 23 patients with Parkinson's disease that were measured both on and off dopaminergic medication. Participants either operated foot pedals to navigate a corridor ('walk' condition) or watched the screen while a researcher operated the paradigm from outside the scanner ('watch' condition), a setting that controlled for the non-motor aspects of the task. Step time variability during walk was used as a surrogate measure for motor automaticity (where higher variability equates to reduced automaticity), and patients demonstrated a predicted increase in step time variability during the dopaminergic "off" state. During the "off" state, subjects showed an increased blood oxygen level-dependent response in the bilateral orbitofrontal cortices (walk>watch). To estimate step time variability, a parametric modulator was designed that allowed for the examination of brain regions associated with periods of decreased automaticity. This analysis showed that patients on dopaminergic medication recruited the cerebellum during periods of increasing variability, whereas patients off medication instead relied upon cortical regions implicated in cognitive control. Finally, a task-based functional connectivity analysis was conducted to examine the manner in which dopamine modulates large-scale network interactions during gait. A main effect of medication was found for functional connectivity within an attentional motor network and a significant condition by medication interaction for functional connectivity was found within the striatum. Furthermore, functional connectivity within the striatum correlated strongly with increasing step time variability during walk in the off state (r=0.616, p=0.002), but not in the on state (r=-0.233, p=0.284). Post-hoc analyses revealed that functional connectivity in the dopamine depleted state within an orbitofrontal-striatal limbic circuit was correlated with worse step time variability (r=0.653, p<0.001). Overall, this study demonstrates that dopamine ameliorates gait automaticity in Parkinson's disease by altering striatal, limbic and cerebellar processing, thereby informing future therapeutic avenues for gait and falls prevention.

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Section: Approximate Position Figuresupporting

confidence: 91%

Dopamine depletion impairs gait automaticity by altering cortico-striatal and cerebellar processing in Parkinson's disease

et al. 2017

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“…Patients in the lab-based assessment were measured during their medication ON phase, i.e., during the study participant’s perception of having a good “on” phase after regular intake of medication ( Elshehabi et al, 2016 ).…”

Section: Methodsmentioning

confidence: 99%

Effect of Fear of Falling on Turning Performance in Parkinson’s Disease in the Lab and at Home

Haertner

Elshehabi

Zaunbrecher

et al. 2018

Front. Aging Neurosci.

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Background: Parkinson’s disease (PD) is a neurodegenerative movement disorder associated with gait and balance problems and a substantially increased risk of falling. Falls occur often during complex movements, such as turns. Both fear of falling (FOF) and previous falls are relevant risk factors for future falls. Based on recent studies indicating that lab-based and home assessment of similar movements show different results, we hypothesized that FOF and a positive fall history would influence the quantitative turning parameters differently in the laboratory and home.Methods: Fifty-five PD patients (43 underwent a standardized lab assessment; 40 were assessed over a mean of 12 days at home with approximately 10,000 turns per participant; and 28 contributed to both assessments) were classified regarding FOF and previous falls as “vigorous” (no FOF, negative fall history), “anxious” (FOF, negative fall history), “stoic” (no FOF, positive fall history) and “aware” (FOF, positive fall history). During the assessments, each participant wore a sensor on the lower back.Results: In the lab assessment, FOF was associated with a longer turning duration and lowered maximum and middle angular velocities of turns. In the home evaluations, a lack of FOF was associated with lowered maximum and average angular velocities of turns. Positive falls history was not significantly associated with turning parameters, neither in the lab nor in the home.Conclusion: FOF but not a positive fall history influences turning metrics in PD patients in both supervised and unsupervised environments, and this association is different between lab and home assessments. Our findings underline the relevance of comprehensive assessments including home-based data collection strategies for fall risk evaluation.

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“…Comparable to Ref. (19), medication OFF was defined as overnight withdrawal from dopaminergic medication, and medication ON as the study participant’s perception of having a “Good On Phase,” after regular intake of medication. The assessment consisted of daily activity-like procedures, such as walking in the rooms and corridors of the lab environment without restriction, opening and closing doors, climbing stairs, performing transfers such as sit-to-stand, sit-to-walk, stand-to-sit and walk-to-sit, brushing teeth, making coffee, drinking a cup of tea, and ironing (18).…”

Section: Methodsmentioning

confidence: 99%

Algorithm for Turning Detection and Analysis Validated under Home-Like Conditions in Patients with Parkinson’s Disease and Older Adults using a 6 Degree-of-Freedom Inertial Measurement Unit at the Lower Back

et al. 2017

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IntroductionAging and age-associated disorders such as Parkinson’s disease (PD) are often associated with turning difficulties, which can lead to falls and fractures. Valid assessment of turning and turning deficits specifically in non-standardized environments may foster specific treatment and prevention of consequences.MethodsRelative orientation, obtained from 3D-accelerometer and 3D-gyroscope data of a sensor worn at the lower back, was used to develop an algorithm for turning detection and qualitative analysis in PD patients and controls in non-standardized environments. The algorithm was validated with a total of 2,304 turns ≥90° extracted from an independent dataset of 20 PD patients during medication ON- and OFF-conditions and 13 older adults. Video observation by two independent clinical observers served as gold standard.ResultsIn PD patients under medication OFF, the algorithm detected turns with a sensitivity of 0.92, a specificity of 0.89, and an accuracy of 0.92. During medication ON, values were 0.92, 0.78, and 0.83. In older adults, the algorithm reached validation values of 0.94, 0.89, and 0.92. Turning magnitude (difference, 0.06°; SEM, 0.14°) and duration (difference, 0.004 s; SEM, 0.005 s) yielded high correlation values with gold standard. Overall accuracy for direction of turning was 0.995. Intra class correlation of the clinical observers was 0.92.ConclusionThis wearable sensor- and relative orientation-based algorithm yields very high agreement with clinical observation for the detection and evaluation of ≥90° turns under non-standardized conditions in PD patients and older adults. It can be suggested for the assessment of turning in daily life.

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Limited Effect of Dopaminergic Medication on Straight Walking and Turning in Early-to-Moderate Parkinson’s Disease during Single and Dual Tasking

Cited by 21 publications

References 55 publications

Dopamine depletion impairs gait automaticity by altering cortico-striatal and cerebellar processing in Parkinson's disease

Dopamine depletion impairs gait automaticity by altering cortico-striatal and cerebellar processing in Parkinson's disease

Effect of Fear of Falling on Turning Performance in Parkinson’s Disease in the Lab and at Home

Algorithm for Turning Detection and Analysis Validated under Home-Like Conditions in Patients with Parkinson’s Disease and Older Adults using a 6 Degree-of-Freedom Inertial Measurement Unit at the Lower Back

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