Arm swing responsiveness to dopaminergic medication in Parkinson's disease depends on task complexity.
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ABSTRACT:
SUBMITTER: Warmerdam E
PROVIDER: S-EPMC8492858 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
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Arm swing responsiveness to dopaminergic medication in Parkinson's disease depends on task complexity.
Warmerdam Elke E Romijnders Robbin R Hansen Clint C Elshehabi Morad M Zimmermann Milan M Metzger Florian G FG von Thaler Anna-Katharina AK Berg Daniela D Schmidt Gerhard G Maetzler Walter W
NPJ Parkinson's disease 20211005 1
The evidence of the responsiveness of dopaminergic medication on gait in patients with Parkinson's disease is contradicting. This could be due to differences in complexity of the context gait was in performed. This study analysed the effect of dopaminergic medication on arm swing, an important movement during walking, in different contexts. Forty-five patients with Parkinson's disease were measured when walking at preferred speed, fast speed, and dual-tasking conditions in both OFF and ON medica ...[more]
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Project description:BackgroundGait dysfunction is a common symptom of Parkinson's disease that can cause significant disability and put patients at risk for falls. These symptoms show variable responsiveness to dopaminergic therapy.ObjectiveTo determine whether dopaminergic (rs1076560 DRD2 G > T and rs4680 catechole-o-methyltranspherase (COMT) Val158Met) or brain derived neurotrophic factor (rs6265 BDNF Val66Met) genetic polymorphisms are associated with gait function and medication responsiveness in Parkinson's disease.MethodGait function was evaluated on two days for patients (ON and OFF medication in a counterbalanced fashion) and a single session for controls. Investigators were blinded to genotype during data collection. Associations between genotype and medication responsiveness were analyzed using mixed model ANOVAs. A priori hypotheses were tested using GAITRite® electronic mat spatiotemporal gait parameters including step length, step width, velocity, portion of double and single support per gait cycle, and variability of these measures ON and OFF medication.ResultsWe found that the DRD2 polymorphism, but neither COMT nor BDNF, was consistently associated with gait function and medication responsiveness in the patients. Specifically, Parkinson's disease patients with reduced striatal D2 expression (DRD2 T allele carriers) had worse gait dysfunction and showed greater dopamine responsiveness of gait function compared to patients who were homozygous for the G allele. There was no effect of any of the genetic polymorphisms on gait for controls.Conclusions and relevanceThe findings suggest that genetic subgrouping, in particular for DRD2, may be used to identify Parkinson's disease patient subgroups that are more dopamine responsive for gait function.
| S-EPMC5826846 | biostudies-literature
Project description:ObjectiveA recent study reporting significantly reduced symmetry in arm swing amplitude in early Parkinson's disease (PD), as measured during single strides in a gait laboratory, led to this investigation of arm swing symmetry and coordination over many strides using wearable accelerometers in PD.MethodsForearm accelerations were recorded while eight early PD subjects and eight Controls performed 8-min walking trials. Arm swing asymmetry (ASA), maximal cross-correlation (MXC), and instantaneous relative phase (IRP) of bilateral arm swing were compared between PD and Controls. Correlations between arm swing measurements (ASA and MXC) and Unified PD Rating Scale (UPDRS) scores were estimated.ResultsPD subjects demonstrated significantly higher ASA (p=0.002) and lower MXC (p<0.001) than Controls. The IRP probability distribution for PD was significantly different than Controls (p<0.001), with an angular standard deviation of 67.2° for PD and 50.6° for Controls. Among PD subjects, ASA was significantly correlated with the UPDRS score for the limbs (R(2)=0.58, p=0.049), whereas MXC was significantly correlated with the tremor subscore of the limbs (R(2)=0.64, p=0.031).DiscussionThe study confirms previously reported higher arm swing asymmetry in PD but also shows there is significantly lower MXC and greater IRP variability, suggesting that reduction in bilateral arm coordination may contribute to clinically observed asymmetry in PD. The differential correlation of clinical measures of motor disability with measurements of arm swing during gait is intriguing and deserves further investigation.
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Project description:BackgroundAccurately measuring hypokinetic arm swing during free-living gait in Parkinson's disease (PD) is challenging due to other concurrent arm activities. We developed a method to isolate gait segments without these arm activities.MethodsWrist accelerometer and gyroscope data were collected from 25 individuals with PD and 25 age-matched controls while performing unscripted activities in their home environment. This was done after overnight withdrawal of dopaminergic medication ('pre-medication') and approximately one hour after intake ('post-medication'). Using video annotations as ground truth, we trained and evaluated two classifiers: one for detecting gait and one for detecting gait segments without other arm activities. Based on the filtered gait segments, arm swing was quantified using the median and 95th percentile range of motion (RoM). These arm swing parameters were evaluated in three ways: (1) the agreement between predicted and video-annotated gait segments without other arm activities, (2) the sensitivity to differences between PD and controls, and (3) the sensitivity to the effects of dopaminergic medication.ResultsOn the most affected side, the mean (SD) balanced accuracy for detecting gait without other arm activities was 0.84 (0.10) pre-medication and 0.88 (0.09) post-medication. The agreement between arm swing parameters of predicted and video-annotated gait segments without other arm activities was high irrespective of medication state (intra-class correlation coefficients: median RoM: 0.99; 95th percentile RoM: 0.97). Both the median and 95th percentile RoM were smaller in PD pre-medication compared to controls (median: Δ = - 18 . 80 ∘ , 95% CI [ - 30.63, - 10.60], p < 0.001; 95th percentile: Δ = - 28 . 34 ∘ , 95% CI [ - 38.26, - 18.18], p < 0.001), and smaller in pre- compared to post-medication (median: Δ = - 12 . 31 ∘ , 95% CI [ - 21.35, - 5.59], p < 0.001; 95th percentile: Δ = - 19 . 04 ∘ , 95% CI [ - 28.48, - 11.14], p < 0.001). The differences in RoM between pre- and post-medication were larger after filtering gait for the median (p < 0.01) and 95th percentile RoM (p = 0.01).ConclusionsFiltering out gait segments with other concurrent arm activities is feasible and increases the change in arm swing parameters following dopaminergic medication in free-living conditions. This approach may be used to monitor treatment effect and disease progression in daily life.
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Project description:The neurotransmitter dopamine is crucial for decision-making under uncertainty but its computational role is still a subject of intense debate. To test potential roles, we had patients with Parkinson's disease (PD), who have less internally-generated dopamine, participate in a visual decision-making task in which uncertainty in both prior and current sensory information was varied and where behavior is often predicted by Bayesian statistics. We found that many aspects of uncertainty processing were conserved in PD: they could learn the prior uncertainty and utilize both priors and current sensory information. As predicted by prominent theories, we found that dopaminergic medication influenced the weight given to sensory information. However, as PD patients learn, this bias disappeared. In addition, throughout the experiment the patients exhibited lower sensitivity to current sensory uncertainty. Our results provide empirical evidence for the idea that dopamine levels, which are affected by PD and the drugs used for its treatment, influence the reliance on new information.
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Project description:The arm elevation strategy assists in recovering stability during slips in healthy young and elderly individuals. However, in people with Parkinson's Disease, one of the main motor symptoms affecting the upper limbs is reduced arm swing which intensifies throughout the course of the disease before becoming absent. This holds direct implications for these individuals when encountering slips as the arm elevation strategy is an integral component in the interlimb slip response to restore stability. Arm swing's effect in recovering from slips in people with Parkinson's Disease though remains unexamined. Twenty people with Parkinson's Disease (63.78 ± 8.97 years) walked with restricted and unrestricted arm swing conditions on a dual-belt treadmill where slips were induced on the least and most affected sides. Data were collected on the CAREN Extended System (Motek Medical, Amsterdam, NL). The Margin of Stability, linear and angular trunk velocities, as well as step length, time, and width were calculated. Data were examined during the slipped step and recovery step. The restricted arm swing condition, compared to unrestricted, caused a faster step time during the slipped step. Compared to the most affected leg, the least affected had a wider step width during the slipped step. During the recovery step, the least affected leg had a larger anteroposterior Margin of Stability and longer step time than the most affected. No differences between our arm swing conditions suggests that the normal arm swing in our participants was not more effective at restoring stability after an induced slip compared to when their arm motion was restricted. This may be due to the arm elevation strategy being ineffective in counteracting the slip's backward destabilization in these individuals. Differences between the legs revealed that our participants were asymmetrically impaired in their slip recovery response.
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Project description:Exaggerated basal ganglia beta activity (13-35 Hz) is commonly found in patients with Parkinson's disease and can be suppressed by dopaminergic medication, with the degree of suppression being correlated with the improvement in motor symptoms. Importantly, beta activity is not continuously elevated, but fluctuates to give beta bursts. The percentage number of longer beta bursts in a given interval is positively correlated with clinical impairment in Parkinson's disease patients. Here we determine whether the characteristics of beta bursts are dependent on dopaminergic state. Local field potentials were recorded from the subthalamic nucleus of eight Parkinson's disease patients during temporary lead externalization during surgery for deep brain stimulation. The recordings took place with the patient quietly seated following overnight withdrawal of levodopa and after administration of levodopa. Beta bursts were defined by applying a common amplitude threshold and burst characteristics were compared between the two drug conditions. The amplitude of beta bursts, indicative of the degree of local neural synchronization, progressively increased with burst duration. Treatment with levodopa limited this evolution leading to a relative increase of shorter, lower amplitude bursts. Synchronization, however, was not limited to local neural populations during bursts, but also, when such bursts were cotemporaneous across the hemispheres, was evidenced by bilateral phase synchronization. The probability of beta bursts and the proportion of cotemporaneous bursts were reduced by levodopa. The percentage number of longer beta bursts in a given interval was positively related to motor impairment, while the opposite was true for the percentage number of short duration beta bursts. Importantly, the decrease in burst duration was also correlated with the motor improvement. In conclusion, we demonstrate that long duration beta bursts are associated with an increase in local and interhemispheric synchronization. This may compromise information coding capacity and thereby motor processing. Dopaminergic activity limits this uncontrolled beta synchronization by terminating long duration beta bursts, with positive consequences on network state and motor symptoms.
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Project description:Dopaminergic medication is widely used to alleviate motor symptoms of Parkinson's disease, but these medications also impact cognition with significant variability across patients. It is hypothesized that dopaminergic medication impacts cognition and working memory in Parkinson's disease by modulating frontoparietal-basal ganglia cognitive control circuits, but little is known about the underlying causal signalling mechanisms and their relation to individual differences in response to dopaminergic medication. Here we use a novel state-space computational model with ultra-fast (490 ms resolution) functional MRI to investigate dynamic causal signalling in frontoparietal-basal ganglia circuits associated with working memory in 44 Parkinson's disease patients ON and OFF dopaminergic medication, as well as matched 36 healthy controls. Our analysis revealed aberrant causal signalling in frontoparietal-basal ganglia circuits in Parkinson's disease patients OFF medication. Importantly, aberrant signalling was normalized by dopaminergic medication and a novel quantitative distance measure predicted individual differences in cognitive change associated with medication in Parkinson's disease patients. These findings were specific to causal signalling measures, as no such effects were detected with conventional non-causal connectivity measures. Our analysis also identified a specific frontoparietal causal signalling pathway from right middle frontal gyrus to right posterior parietal cortex that is impaired in Parkinson's disease. Unlike in healthy controls, the strength of causal interactions in this pathway did not increase with working memory load and the strength of load-dependent causal weights was not related to individual differences in working memory task performance in Parkinson's disease patients OFF medication. However, dopaminergic medication in Parkinson's disease patients reinstated the relation with working memory performance. Our findings provide new insights into aberrant causal brain circuit dynamics during working memory and identify mechanisms by which dopaminergic medication normalizes cognitive control circuits.
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Project description:BackgroundArm swing changes are common even in the early stages of Parkinson's disease (PD). We hypothesized that arm swing changes decrease with age and can be detected using a low-cost, RGB-D depth-sensing camera.ObjectiveThis study aimed to assess the differences in arm swing between PD patients and healthy participants and to investigate the possible effects of aging on these differences.MethodsTwenty-five PD patients (aged 45-87 years) and 25 age-matched, healthy subjects (aged 46-88 years) were included. Clinical variables were evaluated using a descriptive analysis. No spatiotemporal variables were normally distributed; therefore, we used a Mann-Whitney U test to compare the continuous variables between groups and to perform age-stratified analysis. A receiver operating characteristic analysis was generated to evaluate the discrimination activity of arm swing asymmetry (ASA).ResultsThe PD group showed significant reductions in arm swing magnitude (left, p = 0.002; right, p = 0.006) and arm swing speed (left, p = 0.002; right, p = 0.004) and significantly greater ASA (p < 0.001). The age-stratified analysis showed significant differences in ASA in the 40-59-year group (p = 0.001) and bilateral arm swing magnitude in the 60-66-year group. No differences were found in those aged >67 years.ConclusionsThe camera detected differences in ASA, arm swing speed, and arm swing magnitude between PD patients and healthy individuals. Analysis of arm swing variables should be stratified by age, and the validity of the analysis may be questionable in patients aged >67 years.
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Project description:Motivational influence on bradykinesia in Parkinson's disease may be observed in situations of emotional and physical stress, a phenomenon known as paradoxical kinesis. However, little is known about motivational modulation of movement speed beyond these extreme circumstances. In particular, it is not known if motivational factors affect movement speed by improving movement preparation/initiation or execution (or both) and how this effect relates to the patients' medication state. In the present study, we tested if provision of motivational incentive through monetary reward would speed-up movement initiation and/or execution in Parkinson's disease patients and if this effect depended on dopaminergic medication. We studied the effect of monetary incentive on simple reaction time in 11 Parkinson's disease patients both "off" and "on" dopaminergic medication and in 11 healthy participants. The simple reaction time task was performed across unrewarded and rewarded blocks. The initiation time and movement time were quantified separately. Anticipation errors and long responses were also recorded. The prospect of reward improved initiation times in Parkinson's disease patients both "off" and "on" dopaminergic medication, to a similar extent as in healthy participants. However, for "off" medication, this improvement was associated with increased frequency of anticipation errors, which were eliminated by dopamine replacement. Dopamine replacement had an additional, albeit small effect, on reward-related improvement of movement execution. Motivational strategies are helpful in overcoming bradykinesia in Parkinson's disease. Motivational factors may have a greater effect on bradykinesia when patients are "on" medication, as dopamine appears to be required for overcoming speed-accuracy trade-off and for improvement of movement execution. Thus, medication status should be an important consideration in movement rehabilitation programmes for patients with Parkinson's disease.
| S-EPMC4057625 | biostudies-literature