Balance In Parkinson's Disease Research Articles

Unraveling the stride: exploring the influence of neurogenic orthostatic hypotension on gait and balance in Parkinson's disease.

Neurogenic orthostatic hypotension (nOH) and gait impairment are frequent sources of disability in Parkinson's disease (PD). However, the impact of nOH on balance and gait features remains unclear. This cross-sectional study aimed to assess the influence of nOH on postural and gait parameters in a cohort of patients with PD by means of wearable inertial sensors. Gait and balance were assessed using Opal inertial sensors. nOH was defined as sustained systolic blood pressure (BP) drop ≥ 20mmHg or diastolic BP drop ≥ 10mmHg within 3min of standing, with a ΔHR/ΔSBP ratio ≤ 0.5bpm/mmHg. Analysis of covariance was performed to evaluate differences in gait/balance features between patients with and without nOH, adjusting for age, cognitive status, and motor disability. Moreover, we performed the same analysis considering the presence of hemodynamically relevant nOH (orthostatic mean BP ≤ 75mmHg). A total of 82 patients were enrolled, 26 with nOH (31.7%), of which 13 presented with hemodynamically relevant nOH. After correcting for confounders, nOH was independently associated with lower gait speed (p = 0.027), shorter stride length (p = 0.033), longer time for postural transitions (p = 0.004), and increased postural sway (p = 0.019). These differences were even more pronounced in patients with hemodynamically relevant nOH. Higher postural sway was associated with a 7.9-fold higher odds of falls (p = 0.040). Our study presents an objective demonstration of the independent negative impact of nOH on gait and balance in PD, emphasizing the need for careful detection and management of nOH to mitigate gait and balance disturbances in PD.

Evolution characteristics of dynamic balance disorder over the course of PD and relationship with dopamine depletion.

This study aimed to assess the evolution of dynamic balance impairment during the course of Parkinson's disease (PD) and to clarify the contribution of striatal dopaminergic innervation to poor dynamic balance. In our study, 89 patients with PD (divided into 2 groups according to the H-Y stage) and 39 controls were included. Kinematic data were recorded by a portable inertial measurement unit system. Dopaminergic loss in the striatal subregion was verified through the 11C-CFT PET examination. The severity of white matter hyperintensities (WMHs) was assessed by the Scheltens scale. The correlation between dynamic kinematic parameters and dopamine transporter availability was analyzed by multivariate regression analysis. Patients with early PD presented with imbalance featured by smaller three-dimensional trunk ROM with reduced trunk coronal angular velocity during walking and with reduced trunk sagittal angular velocity during the stand-to-sit task (all p < 0.05). These abnormalities were not more severe at a later stage. The ROM in the coronal and transverse planes during walking correlated with caudate DAT uptake (β = 0.832, p = 0.006, Q = 0.030, and β = 0.890, p = 0.003, Q = 0.030) after controlling for age, gender, and WMHs. As the disease progressed, the trunk sagittal and transverse angular velocities during walking and trunk sagittal angular velocity when turning and sitting-to-standing were slower, which was accompanied by reduced gait velocity gradually (all p < 0.05). These parameters related to disease progression have no association with striatal DAT uptake (all p > 0.05). The dynamic balance in PD was impaired from the early stages, and the characteristics of the impairment changed differently as the disease progressed. Dopaminergic denervation has a lower contribution to dynamic balance disorders throughout PD.

Spinal cord stimulation for freezing of gait in Parkinson's disease and progressive supranuclear palsy: a case series

Background: Freezing of gait (FOG) in Parkinson's disease (PD) and progressive supranuclear palsy (PSP) exert a significant adverse impact on the patients quality of life, the degree of their disability, and the risk of falls. A specific characteristic of FOG is a poor response to medical treatment. According to the data of open-label clinical trials and clinical case series published in the last decade, spinal cord stimulation (SCS) can be considered as one of the methods to improve this type of movement disorders.&#x0D; Materials and methods: We present a clinical series of patients with PD and PSP, who underwent implantation of a chronic epidural SCS system at the mid-thoracic level to correct FOG. The efficacy of surgical treatment was assessed at 2 and 5 months with the following scales and questionnaires: part III Unified Parkinson's Disease Rating Scale of Movement Disorder Society (MDS-UPDRS), Freezing of Gait Questionnaire (FOG-Q), Activity-Specific Balance Confidence Scale (ABC), Parkinson's Disease Quality of Life Questionnaire-8 (PDQ-8), Time up and Go Test (TUG), 10 Meter Walk Test. The patients were asked to report possible adverse reactions after the procedure.&#x0D; Results: The results of a 5-month follow-up were obtained from 4 patients (2 with PD and 2 with PSP). There were no adverse events associated with SCS. Оnly one patient with PD experienced a decrease in the severity of motor symptoms according to the MDS-UPDRS part III scale. An increase in the speed of 10 meters' walking distance and TUG test performance was observed in 3 patients. All patients reported an improvement in the quality of life (according to the PDQ-8 questionnaire) and confidence in maintaining balance (according to the ABC questionnaire) by month 2 after surgery. However, at month 5, a negative trend was noted again.&#x0D; Conclusion: The SCS method was safe in all 4 clinical cases described. There was a positive effect of SCS on the improvement of FOG and postural balance in PD and PSP. However, the duration of the therapeutic effect may vary.

The effect of galvanic vestibular stimulation on postural balance in Parkinson's disease: A systematic review and meta-analysis

People with Parkinson's disease (PD) develop postural imbalance and falls. Galvanic Vestibular Stimulation (GVS) may potentially improve postural balance in humans and hence reduce falls in PD. This systematic review and meta-analysis investigate the effects of GVS on postural balance in PD.Six separate databases and research registers were searched for cross-over design trials that evaluated the effects of GVS on postural balance in PD. We used standardized mean difference (Hedges' g) as a measure of effect size in all studies.We screened 223 studies, evaluated 14, of which five qualified for the meta-analysis. Among n = 40 patients in five studies (range n = 5 to 13), using a fixed effects model we found an effect size estimate of g = 0.43 (p < 0.001, 95% CI [0.29,0.57]). However, the test for residual heterogeneity was significant (p < 0.001), thus we used a random effects model and found a pooled effect size estimate of 0.62 (p > 0.05, 95% CI [− 0.17, 1.41], I2 = 96.21%). Egger's test was not significant and thus trim and funnel plot indicated no bias. To reduce heterogeneity, we performed sensitivity analysis and by removing one outlier study (n = 7 patients), we found an effect size estimate of 0.16 (p < 0.05, 95% CI [0.01, 0.31], I2 = 0%).Our meta-analysis found GVS has a favourable effect on postural balance in PD patients, but due to limited literature and inconsistent methodologies, this favourable effect must be interpreted with caution.

Dual-Task Treadmill Training for the Prevention of Falls in Parkinson's Disease: Rationale and Study Design.

Various factors, such as fear of falling, postural instability, and altered executive function, contribute to the high risk of falling in Parkinson's disease (PD). Dual-task training is an established method to reduce this risk. Motor-perceptual task combinations typically require a patient to walk while simultaneously engaging in a perceptual task. Motor-executive dual-tasking (DT) combines locomotion with executive function tasks. One augmented reality treadmill training (AR-TT) study revealed promising results of a perceptual dual-task training with a markedly reduced frequency of falls especially in patients with PD. We here propose to compare the effects of two types of concurrent tasks, perceptual and executive, on high-intensity TT). Patients will be trained with TT alone, in combination with an augmented reality perceptual DT (AR-TT) or with an executive DT (Random Number Generation; RNG-TT). The results are expected to inform research on therapeutic strategies for the training of balance in PD.

Benefits of Virtual Reality Balance Training for Patients With Parkinson Disease: Systematic Review, Meta-analysis, and Meta-Regression of a Randomized Controlled Trial.

BackgroundVirtual reality (VR) balance training is increasingly being pursued in biomedical research, specifically with respect to investigating balance ability with VR. However, existing systematic reviews have found inconsistent conclusions about the efficacy of VR in improving balance in Parkinson disease (PD) patients.ObjectiveThe goal of the research was to evaluate the impact of VR balance training on the balance ability of patients with PD.MethodsAll major databases, including Web of Science, PubMed, Scopus, China National Knowledge Infrastructure, and Wanfang, were searched to identify all relevant studies published in English or Chinese since September 15, 2010. Two researchers independently conducted document retrieval, study selection, data extraction, and methodological quality evaluation.ResultsA total of 16 randomized controlled trials were analyzed (n=583 patients with PD), with the methodological quality evaluation score ranging from 5 to 8 points. A random effects model was selected to combine effect sizes. Meta-analysis showed that the balance ability of PD was significantly improved after VR training compared with the control group (standardized mean difference [SMD] 2.127, 95% CI 1.202 to 3.052, P<.001, I2=95.1, df=15). It is worth noting that the intervention platform may be the main reason for heterogeneity. Meta regression analysis showed that no training program could predict the impact of VR training (P=.57 to .94) on PD balance ability. Subgroup result showed that a single training time of 0 to 20 minutes (SMD 6.446), 4 to 6 times per week (SMD 4.067), training for 3 to 5 weeks (SMD 62.478), training course reached more than 30 times (SMD 4.405), and 201 to 300 minutes per week (SMD 4.059) maybe have more benefit.ConclusionsA systematic review and meta-analysis confirmed that VR balance training is a highly effective means to improve balance performance with large effects in PD. In addition, we preliminarily extracted dose-effect relationships for training volume, informing clinicians and practitioners to design effective VR balance training for balance ability. Further research is needed to reveal optimal dose-response relationships following VR balance training.

Action Observation and Motor Imagery Improve Dual Task in Parkinson's Disease: A Clinical/fMRI Study

ABSTRACTBackgroundAction observation training and motor imagery may improve motor learning in Parkinson's disease (PD).ObjectivesThe objectives of this study were to assess mobility and balance (performing motor and dual tasks) and brain functional reorganization following 6 weeks of action observation training and motor imagery associated with dual‐task gait/balance exercises in PD patients with postural instability and gait disorders relative to dual‐task training alone.MethodsTwenty‐five PD–postural instability and gait disorder patients were randomized into 2 groups: the DUAL‐TASK+AOT‐MI group performed a 6‐week gait/balance training consisting of action observation training–motor imagery combined with practicing the observed‐imagined exercises; the DUAL‐TASK group performed the same exercises combined with watching landscape videos. Exercises were increasingly difficult to include the dual task. At baseline and at 6 weeks, patients underwent: mobility, gait, and balance evaluations (also repeated 2 months after training), cognitive assessment, and functional MRI, including motor and dual tasks.ResultsDual‐task gait/balance training enhanced mobility, during both single‐ and dual‐task conditions, and executive functions in PD–postural instability and gait disorders, with a long‐lasting effect at 14 weeks. When exercises were preceded by action observation training–motor imagery, PD–postural instability and gait disorders showed greater improvement of balance and gait velocity both with and without the dual task, particularly during the turning phase. After training, the DUAL‐TASK+AOT‐MI group showed reduced recruitment of frontal areas and increased activity of cerebellum during functional‐MRI motor and dual task, correlating with balance/turning velocity and executive improvements, respectively. The DUAL‐TASK group showed reduced activity of supplementary motor area and increased recruitment of temporo‐parietal areas during the dual task and decreased cerebellar activity during the motor task correlating with faster turning velocity. Functional MRI results were not corrected for multiple comparisons and should be interpreted carefully.ConclusionsAdding action observation training–motor imagery to dual‐task gait/balance training promotes specific functional reorganization of brain areas involved in motor control and executive‐attentive abilities and more long‐lasting effects on dual‐task mobility and balance in PD–postural instability and gait disorders. © 2021 International Parkinson and Movement Disorder Society

Effects of medication and dual tasking on postural sway in Parkinson’s disease: A pilot case study

ABSTRACT Parkinson's disease (PD) is a common neurological disorder, which causes instability in standing balance. The risk factors for falls in PD include disease severity, medication state (On/Off state), and dual tasking. The aim of this study was to assess the effects of dopaminergic medication and dual tasking on standing balance in PD by evaluating not only the center of pressure but also muscle cocontraction. Two patients with PD were included in this pilot case study. Relational trends were found among physical symptoms, COP, and muscle cocontraction. Evaluations of COP and cocontraction may be useful in making decisions for rehabilitation prescription.

Abnormal center of mass feedback responses during balance: A potential biomarker of falls in Parkinson's disease.

Although Parkinson disease (PD) causes profound balance impairments, we know very little about how PD impacts the sensorimotor networks we rely on for automatically maintaining balance control. In young healthy people and animals, muscles are activated in a precise temporal and spatial organization when the center of body mass (CoM) is unexpectedly moved that is largely automatic and determined by feedback of CoM motion. Here, we show that PD alters the sensitivity of the sensorimotor feedback transformation. Importantly, sensorimotor feedback transformations for balance in PD remain temporally precise, but become spatially diffuse by recruiting additional muscle activity in antagonist muscles during balance responses. The abnormal antagonist muscle activity remains precisely time-locked to sensorimotor feedback signals encoding undesirable motion of the body in space. Further, among people with PD, the sensitivity of abnormal antagonist muscle activity to CoM motion varies directly with the number of recent falls. Our work shows that in people with PD, sensorimotor feedback transformations for balance are intact but disinhibited in antagonist muscles, likely contributing to balance deficits and falls.

Anti-Parkinson's evaluation of Brassica juncea leaf extract and underlying mechanism of its phytochemicals.

Background: Parkinson's disease (PD) is associated with progressive neuronal damage and dysfunction. Oxidative stress helps to regulate neurodegenerative and neuronal dysfunction. Natural compounds could attenuate oxidative stress in a variety of neurological disorders. B. juncea is a rich source of antioxidants. The present study aimed to evaluate the therapeutic potential of B. juncea leaves for the treatment of PD by applying behavioral, in vivo and in silico studies. For in vivo studies rats were divided into six groups (n = 6). Group-I served as normal control (vehicle control). Group-II was disease control (haloperidol 1 mg/kg). Group-III was kept as a standard group (L-Dopa 100 mg/kg + carbidopa 25 mg/kg). Groups (IV-VI) were the treatment groups, receiving extract at 200-, 400- and 600 mg/kg doses respectively, for 21 days orally. Results: In vivo study results showed that the extract was found to improve muscles strength, motor coordination, and balance in PD. These behavioral outcomes were consistent with the recovery of endogenous antioxidant defence in biochemical analysis which was further corroborated with histopathological ameliorations. Dopamine levels increased and monoamine oxidase B (MAO-B) levels decreased dose-dependently in the brain during the study. Herein, we performed molecular docking analysis of the proposed extracted phytochemicals has explained that four putative phytochemicals (sinapic acid, rutin, ferulic acid, and caffeic acid) have presented very good results in terms of protein-ligand binding interactions as well as absorption, distribution, metabolism, excretion & toxicity (ADMET) profile estimations. Conclusion: The undertaken study concluded the anti-Parkinson activity of B. juncea and further suggests developments on its isolated compounds in PD therapeutics.

Changes of Peripheral Nerve Function and Vitamin B12 Level in People With Parkinson's Disease.

Background and Purpose: Peripheral nerve function plays an important role in balance control. Impairment of peripheral sensory information appears in people with Parkinson's disease (PD). Furthermore, there is a link between peripheral nerve disorders and vitamin B12 level. Here, we studied whether there were deficits of peripheral nerve function and vitamin B12 level, which may lead to decreased postural stability in PD.Methods: Fifty PD and 50 age-matched healthy subjects were enrolled in the study. This study evaluated folic acid and vitamin B12 levels in serum. Postural balance was studied according to the clinical Tinetti scale. Some comprehensive physiological assessments of peripheral nerve functions, including peripheral sensation, the perception of temperature, pain, and touch sensations, were also undertaken in this study.Results: Compared with the control group, vitamin B12 and folic acid were decreased in PD (P < 0.05). Furthermore, the PD group exhibited declines in peripheral nerve functions, including touch, temperature, pain, and nerve conduction velocity (P < 0.05). Statistical tests identified a significant association between decreased peripheral nerve function and poor balance according to the Tinetti scale (P < 0.05). Low vitamin B12 levels were also associated with deficits of peripheral nerve function, cumulative levodopa dose, and poor balance in PD (P < 0.05).Conclusions: Data suggested that peripheral nerve function was impaired in people with PD. Deficits of sensory input and low vitamin B12 level may contribute to balance deficits in PD.

Responsiveness of Objective vs. Clinical Balance Domain Outcomes for Exercise Intervention in Parkinson's Disease.

Background: Balance deficits in people with Parkinson's disease (PD) are often not helped by pharmacological or surgical treatment. Although balance exercise intervention has been shown to improve clinical measures of balance, the efficacy of exercise on different, objective balance domains is still unknown.Objective: To compare the sensitivity to change in objective and clinical measures of several different domains of balance and gait following an Agility Boot Camp with Cognitive Challenges (ABC-C) intervention.Methods: In this cross-over, randomized design, 86 individuals with PD participated in 6-week (3×/week) ABC-C exercise classes and 6-week education classes, consisting of 3–6 individuals. Blinded examiners tested people in their practical off state. Objective outcome measures from wearable sensors quantified four domains of balance: sway in standing balance, anticipatory postural adjustments (APAs) during step initiation, postural responses to the push-and-release test, and a 2-min natural speed walk with and without a cognitive task. Clinical outcome measures included the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, the Mini Balance Evaluation Systems Test (Mini-BESTest), the Activities of Balance Confidence (ABC), and the Parkinson's Disease Questionnaire (PDQ-39). The standardized response means (SRM) of the differences between before and after each intervention compared responsiveness of outcomes to intervention. A linear mixed model compared effects of exercise with the active control—education intervention.Results: The most responsive outcome measures to exercise intervention with an SRM > 0.5 were objective measures of gait and APAs, specifically arm range of motion, gait speed during a dual-task walk, trunk coronal range of motion, foot strike angle, and first-step length at step initiation. The most responsive clinical outcome measure was the patient-reported PDQ-39 activities daily living subscore, but all clinical measures had SRMs <0.5.Conclusions: The objective measures were more sensitive to change after exercise intervention compared to the clinical measures. Spatiotemporal parameters of gait, including gait speed with a dual task, and APAs were the most sensitive objective measures, and perceived functional independence was the most sensitive clinical measure to change after the ABC-C exercise intervention. Future exercise intervention to improve gait and balance in PD should include objective outcome measures.

Reliability and Validity of Pupillary Response During Dual-Task Balance in Parkinson Disease

ObjectiveTo investigate the reliability and validity of pupillary response during dual-task balance conditions in individuals with Parkinson disease (PD). DesignCross-sectional study. SettingUniversity of Kansas Medical Center Parkinson's Disease and Movement Disorder Center. ParticipantsParticipants (N=68) included individuals with PD (n=33) and healthy controls (n=35). InterventionsNot applicable. Main Outcome MeasuresPupillary response was the main outcome measure that was measured during the following conditions: single-task balance eyes open, single-task balance eyes occluded, dual-task eyes open, and dual-task eyes occluded. After each condition, the National Aeronautics and Space Administration-Task Load Index (NASA-TLX) was administered to assess self-reported cognitive workload. To examine the test-retest reliability of the pupillary response, the conditions were administered twice for each individual within 2 hours. Intraclass correlation coefficients (ICC) were used to analyze the test-retest reliability of pupillary response in each condition for both groups. Pearson’s r correlation was used to assess the convergent validity of pupillary response against the NASA-TLX. ResultsThe test-retest reliability was excellent for both groups in almost all conditions (ICC>0.75). There were no correlations between pupillary response and the NASA-TLX. However, increased mental demand (a subitem of the NASA-TLX) significantly correlated with increased pupillary response in individuals with PD (r=0.38; P=.03). ConclusionsPupillary response showed excellent test-retest reliability and validity during dual-task balance for individuals with PD and healthy controls. Overall, these results suggest that pupillary response represents a stable index of cognitive workload during dual-task balance in individuals with PD.

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

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. Inthe 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 unrealized potential exists for the use of VR to provide personalized assessment and rehabilitation that optimizes motor learning in both the clinic and home environments and adapts to changes in individuals over time. Design of such systems will require collaboration between all stakeholders to maximize useability, engagement, safety and effectiveness.

Controlling the Uncontrollable: Perceptions of Balance in People With Parkinson Disease.

BackgroundExercise improves balance in Parkinson disease (PD), yet the majority of people with the diagnosis are physically inactive. Insights gained from understanding how people with PD (PwPD) make sense of their symptoms and their ability to control them may inform the communication strategies and motivational approaches adopted by physical therapists. To our knowledge, no previous study has qualitatively explored how PwPD perceive the concept of balance and the beliefs they hold concerning their ability to affect balance.ObjectiveThis study aimed to explore the meaning of balance for PwPD and the beliefs they hold regarding their ability to influence their balance in everyday life.DesignThe design was a qualitative study with an inductive approach.MethodsIn-depth interviews were conducted with 18 participants with PD (age range 46–83 years, Hoehn and Yahr range 1–4), and transcripts were analyzed using qualitative content analysis.ResultsFive main themes emerged from the analysis: remaining in control over the body, adapting behavior to deal with uncertainty, directing focus to stay 1 step ahead, resilience as a defense, and exercise beliefs and reservations. Interpretation of the underlying patterns in the main themes yielded the overarching theme of focus and determination to regain control over shifting balance.ConclusionsThe concept of balance was perceived as both bodily equilibrium and mind-body interplay and was described in the context of remaining in control over one’s body and everyday life. Cognitive resources were utilized to direct focus and attention during balance-challenging situations in a process involving internal dialogue. Even participants who did not express beliefs in their ability to affect balance through exercise used psychological resilience to counter the challenges of impaired balance.

Trunk Exercises Improve Balance in Parkinson Disease: A Phase II Randomized Controlled Trial.

Trunk control is important for maintaining balance; hence, deficient trunk control may contribute to balance problems in people with Parkinson disease (PD). Unfortunately, this deficit is poorly managed with pharmacological therapies, emphasizing the need for alternative therapies for these patients. This randomized controlled trial sought to examine the effects of a 12-week trunk-specific exercise-based intervention on balance in people with PD. Twenty-four people with PD and with a history of falls completed assessments of motor symptom severity, balance confidence, mobility, quality of life, and quiet-standing balance. Participants were then randomized to receive either 12 weeks of exercise or education and reassessed after 12 and 24 weeks. Linear mixed-models analyses showed no significant changes in clinical outcomes following the intervention. However, during quiet standing, sway area on a foam surface without vision was reduced for the exercise group at 12 (-6.9 ± 3.1 cm; 95% confidence interval [CI] = -13.1 to -0.7; P = 0.029; d = 0.66) and 24 weeks (-7.9 ± 3.1 cm; 95% CI = -14.1 to -1.7; P = 0.013; d = 0.76). Furthermore, the exercise group demonstrated reduced sway variability at 12 (-0.2 ± 0.1 cm; 95% CI = -0.4 to 0.0; P = 0.042; d = 0.62) and 24 weeks in the medial-lateral direction (-0.2 ± 0.1 cm; 95% CI = -0.4 to 0.0; P = 0.043; d = 0.62). No changes in quiet standing balance were recorded for the education group. The results of this study suggest that exercise-based interventions targeting trunk strength, endurance, and mobility may be effective for improving quiet-standing balance in people with PD. However, additional research is needed to determine whether these improvements are sufficient to reduce falls risk.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A254).

Galvanic Vestibular Stimulation (GVS) Augments Deficient Pedunculopontine Nucleus (PPN) Connectivity in Mild Parkinson's Disease: fMRI Effects of Different Stimuli.

Falls and balance difficulties remain a major source of morbidity in Parkinson's Disease (PD) and are stubbornly resistant to therapeutic interventions. The mechanisms of gait impairment in PD are incompletely understood but may involve changes in the Pedunculopontine Nucleus (PPN) and its associated connections. We utilized fMRI to explore the modulation of PPN connectivity by Galvanic Vestibular Stimulation (GVS) in healthy controls (n = 12) and PD subjects even without overt evidence of Freezing of Gait (FOG) while on medication (n = 23). We also investigated if the type of GVS stimuli (i.e., sinusoidal or stochastic) differentially affected connectivity. Approximate PPN regions were manually drawn on T1 weighted images and 58 other cortical and subcortical Regions of Interest (ROI) were obtained by automatic segmentation. All analyses were done in the native subject's space without spatial transformation to a common template. We first used Partial Least Squares (PLS) on a subject-by-subject basis to determine ROIs across subjects that covaried significantly with the voxels within the PPN ROI. We then performed functional connectivity analysis on the PPN-ROI connections. In control subjects, GVS did not have a significant effect on PPN connectivity. In PD subjects, baseline overall magnitude of PPN connectivity was negatively correlated with UPDRS scores (p < 0.05). Both noisy and sinusoidal GVS increased the overall magnitude of PPN connectivity (p = 6 × 10−5, 3 × 10−4, respectively) in PD, and increased connectivity with the left inferior parietal region, but had opposite effects on amygdala connectivity. Noisy stimuli selectively decreased connectivity with basal ganglia and cerebellar regions. Our results suggest that GVS can enhance deficient PPN connectivity seen in PD in a stimulus-dependent manner. This may provide a mechanism through which GVS assists balance in PD, and may provide a biomarker to develop individualized stimulus parameters.

Brown adipose tissue activation in a rat model of Parkinson's disease.

Loss of body weight and fat mass is one of the nonmotor symptoms of Parkinson's disease (PD). Weight loss is due primarily to reduced energy intake and increased energy expenditure. Whereas inadequate energy intake in PD patients is caused mainly by appetite loss and impaired gastrointestinal absorption, the underlying mechanisms for increased energy expenditure remain largely unknown. Brown adipose tissue (BAT), a key thermogenic tissue in humans and other mammals, plays an important role in thermoregulation and energy metabolism; however, it has not been tested whether BAT is involved in the negative energy balance in PD. Here, using the 6-hydroxydopamine (6-OHDA) rat model of PD, we found that the activity of sympathetic nerve (SN), the expression of Ucp1 in BAT, and thermogenesis were increased in PD rats. BAT sympathetic denervation blocked sympathetic activity and decreased UCP1 expression in BAT and attenuated the loss of body weight in PD rats. Interestingly, sympathetic denervation of BAT was associated with decreased sympathetic tone and lipolysis in retroperitoneal and epididymal white adipose tissue. Our data suggeste that BAT-mediated thermogenesis may contribute to weight loss in PD.

Acute and Long-Term Effects of Multidirectional Treadmill Training on Gait and Balance in Parkinson Disease

BackgroundTreadmill training has been shown to be a promising rehabilitation strategy for improving gait and balance in persons with Parkinson disease (PD). Most studies have involved only forward walking as an intervention. The effects of multidirectional treadmill (forward, backward, and left and right sideways) on gait and balance have not been reported. ObjectiveTo investigate the acute and long-term effects of multidirectional treadmill training (MDTT) on gait and balance in persons with PD, and to determine the optimal training duration. DesignSingle group, repeated-measures design. SettingResearch laboratory in a hospital. ParticipantsTen persons with PD (mean age 65.9 ± 7.4 years; average disease duration 3.90 ± 2.18 years). InterventionsMDTT was used. Participants walked forward, backward, and left and right sideways for 5-7 minutes in each direction at their fastest tolerated speed. The training was 3 days per week continuously for 8 weeks. Main Outcome MeasurementsGait speed, cadence, and stride length of forward, backward and sideways walks; time and number of steps to turn 360°; and the timed 5-step test and Timed Up-and-Go (TUG) test were performed after the first session of MDTT and every 2 weeks. Effect size of MDTT on each gait and balance variable was measured every 2 weeks for 8 weeks to determine the optimal training duration. Gait and balance variables after the first session of MDTT were compared to the baseline values (pre-MDTT) to study the acute effect of MDTT. ResultsStride length of forward, backward, and sideways walks improved immediately after 1 session of MDTT (P = .031, .012, and .001, respectively). The number of steps to turn and the timed 5-step test score decreased after the first session (P = .016, and .010, respectively). Six weeks of training was found to yield the largest mean effect size of all gait and balance variables. At 6 weeks of MDTT, gait speed of all walking directions (P = .001-.031), stride length of backward (P < .005) and sideways (P = .001) walks, cadence of sideways walk (P = .036), number of steps to turn (P = .014), and timed 5-step test (P = .033) improved from pre-MDTT measures. ConclusionsMDTT immediately improved gait and balance in persons with PD. Six weeks of MDTT might be the optimal training duration to improve gait and balance in the long term. Level of EvidenceIV

Cueing effects in Parkinson's disease: Benefits and drawbacks

Gait and balance impairments are considered a priority area for research in Parkinson's disease (PD) as these problems are not well-controlled by levodopa. Many studies demonstrated that providing additional sensory information to motor training can improve gait and balance in PD. The extraordinary sensitivity for sensory-motor input can be attributed to the automaticity deficit as a result of basal ganglia dysfunction in PD. Hence, movement guidance by sensory cues, music or augmented feedback has been used to promote a goal-oriented mode of motor control. Cueing is defined as temporal or spatial stimuli, which facilitate repetitive movement usually provided as visual, tactile or auditory rhythmic signals. Several systematic reviews have shown the cueing has an immediate and sustained effect on gait and reduces the severity of freezing of gait. However, not all patients respond well to cueing and this may be why studies showed heterogeneity. Several factors may explain this lack of response, of which cognitive overload and inflexibility and lack of perceptual rhythmicity are the most important. In almost all studies, cueing was delivered in a one-size fit all fashion without being adjusted to walking performance. Therefore, we conducted a study as part of the CuPiD project (FP7 EU-funded) to investigate if intelligent cueing was more effective than a conventional gait-training program. The CuPiD system was developed especially for PD and comprised of sensor-technology embedded in a smartphone, allowing online cueing and feedback when patients’ gait deviated from their reference walk. Forty PD patients participated in a six-week training program in which they walked three times for 30 minutes per week outside their home. Participants were randomly assigned to (i) CuPiD, or (ii) control, who received personalized advice from a physiotherapist and trained without cues. Interestingly, the CuPiD group trained significantly less than the control group, but made nevertheless significantly more progress on balance. Both groups improved on single and dual task gait speed. These results point to the difficulty of delivering cueing in a clinically meaningful fashion and that more study is needed to understand this complex intervention.