Split-Belt Treadmill Training to Improve Gait Adaptation in Parkinson's Disease.

BACKGROUND: Gait deficits in people with Parkinson's disease (PD) are triggered by circumstances requiring gait adaptation. The effects of gait adaptation training on a split-belt treadmill (SBT) are unknown in PD. OBJECTIVE: We investigated the effects of repeated SBT versus tied-belt treadmill (TBT) training on retention and automaticity of gait adaptation and its transfer to over-ground walking and turning. METHODS: We recruited 52 individuals with PD, of whom 22 were freezers, in a multi-center randomized single-blind controlled study. Training consisted of 4 weeks of supervised treadmill training delivered three times per week. Tests were conducted pre- and post-training and at 4-weeks follow-up. Turning (primary outcome) and gait were assessed over-ground and during a gait adaptation protocol on the treadmill. All tasks were performed with and without a cognitive task. RESULTS: We found that SBT-training improved gait adaptation with moderate to large effects sizes (P < 0.02) compared to TBT, effects that were sustained at follow-up and during dual tasking. However, better gait adaptation did not transfer to over-ground turning speed. In both SBT- and TBT-arms, over-ground walking and Movement Disorder Society-Unified Parkinson's Disease Rating Scale III (MDS-UPDRS-III scores were improved, the latter of which reached clinically meaningful effects in the SBT-group only. No impact was found on freezing of gait. CONCLUSION: People with PD are able to learn and retain the ability to overcome asymmetric gait-speed perturbations on a treadmill remarkably well, but seem unable to generalize these skills to asymmetric gait off-treadmill. Future study is warranted into gait adaptation training to boost the transfer of complex walking skills. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Effect of transcranial direct current stimulation on learning in older adults with and without Parkinson's disease: A systematic review with meta-analysis.

Older adults with and without Parkinson's disease show impaired retention after training of motor or cognitive skills. This systematic review with meta-analysis aims to investigate whether adding transcranial direct current stimulation (tDCS) to motor or cognitive training versus placebo boosts motor sequence and working memory training. The effects of interest were estimated between three time points, i.e. pre-training, post-training and follow-up. This review was conducted according to the PRISMA guidelines (PROSPERO: CRD42022348885). Electronic databases were searched from conception to March 2023. Following initial screening, 24 studies were eligible for inclusion in the qualitative synthesis and 20 could be included in the meta-analysis, of which 5 studies concerned motor sequence learning (total n = 186) and 15 working memory training (total n = 650). Results were pooled using an inverse variance random effects meta-analysis. The findings showed no statistically significant additional effects of tDCS over placebo on motor sequence learning outcomes. However, there was a strong trend showing that tDCS boosted working memory training, although methodological limitations and some heterogeneity were also apparent. In conclusion, the present findings do not support wide implementation of tDCS as an add-on to motor sequence training at the moment, but the promising results on cognitive training warrant further investigations.

Dual Task Turning in Place: A Reliable, Valid, and Responsive Outcome Measure of Freezing of Gait.

BACKGROUND: Freezing of gait (FOG) is a complex symptom in Parkinson's disease (PD) that is both elusive to elicit and varied in its presentation. These complexities present a challenge to measuring FOG in a sensitive and reliable way, precluding therapeutic advancement. OBJECTIVE: We investigated the reliability, validity, and responsiveness of manual video annotations of the turning-in-place task and compared it to the sensor-based FOG ratio. METHODS: Forty-five optimally medicated people with PD and FOG performed rapid alternating 360° turns without and with an auditory stroop dual task, thrice over two consecutive days. The tasks were video recorded, and inertial sensors were placed on the lower back and shins. Interrater reliability between three raters, criterion validity with self-reported FOG, and responsiveness to single-session split-belt treadmill (SBT) training were investigated and contrasted with the sensor-based FOG ratio. RESULTS: Visual ratings showed excellent agreement between raters for the percentage time frozen (%TF) (ICC [intra-class correlation coefficient] = 0.99), the median duration of a FOG episode (ICC = 0.90), and the number of FOG episodes (ICC = 0.86). Dual tasking improved the sensitivity and validity of visual FOG ratings resulting in increased FOG detection, criterion validity with self-reported FOG ratings, and responsiveness to a short SBT intervention. The sensor-based FOG ratio, on the contrary, showed complex FOG presentation-contingent relationships with visual and self-reported FOG ratings and limited responsiveness to SBT training. CONCLUSIONS: Manual video annotations of FOG during dual task turning in place generate reliable, valid, and sensitive outcomes for investigating therapeutic effects on FOG. © 2021 International Parkinson and Movement Disorder Society.

Sensorimotor, Cognitive, and Affective Functions Contribute to the Prediction of Falls in Old Age and Neurologic Disorders: An Observational Study.

OBJECTIVE: To determine whether impairments across cognitive and affective domains provide additional information to sensorimotor deficits for fall prediction among various populations. DESIGN: We pooled data from 5 studies for this observational analysis of prospective falls. SETTING: Community or low-level care facility. PARTICIPANTS: Older people (N=1090; 74.0±9.4y; 579 female); 500 neurologically intact (NI) older people and 3 groups with neurologic disorders (cognitive impairment, n=174; multiple sclerosis (MS), n=111; Parkinson disease, n=305). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Sensorimotor function was assessed with the Physiological Profile Assessment, cognitive function with tests of executive function, affect with questionnaires of depression, and concern about falling with falls efficacy questionnaires. These variables were associated with fall incidence rates, obtained prospectively over 6-12 months. RESULTS: Poorer sensorimotor function was associated with falls (incidence rate ratio [95% CI], 1.46 [1.28-1.66]). Impaired executive function was the strongest predictor of falls overall (2.91 [2.27-3.73]), followed by depressive symptoms (2.07 [1.56-2.75]) and concern about falling (2.02 [1.61-2.55]). Associations were similar among groups, except for a weaker relationship with executive impairment in NI persons and a stronger relationship with concern about falling in persons with MS. Multivariable analyses showed that executive impairment, poorer sensorimotor performance, depressive symptoms, and concern about falling were independently associated with falls. CONCLUSIONS: Deficits in cognition (executive function) and affect (depressive symptoms) and concern about falling are as important as sensorimotor function for fall prediction. These domains should be included in fall risk assessments for older people and clinical groups.

Gait asymmetry and symptom laterality in Parkinson's disease: two of a kind?

BACKGROUND: The laterality of motor symptoms is considered a key feature of Parkinson's disease (PD). Here, we investigated whether gait and turning asymmetry coincided with symptom laterality as determined by the MDS-UPRDS part III and whether it was increased compared to healthy controls (HC). METHODS: We analyzed the asymmetry of gait and turning with and without a cognitive dual task (DT) using motion capture systems and wearable sensors in 97 PD patients mostly from Hoehn & Yahr stage II and III and 36 age-matched HC. We also assessed motor symptom asymmetry using the bilateral sub-items of the MDS-UPDRS-III. Finally, we examined the strength of the association between gait asymmetry and symptom laterality. RESULTS: Participants with PD had increased gait but not more turning asymmetry compared to HC (p < 0.05). Only 53.7% of patients had a shorter step length on the more affected body side as determined by the MDS-UPDRS-III. Also, 54% took more time and 29% more steps during turns toward the more affected side. The degree of asymmetry in the different domains did not correlate with each other and was not influenced by DT-load. CONCLUSIONS: We found a striking mismatch between the side and the degree of asymmetry in different motor domains, i.e., in gait, turning, and distal symptom severity in individuals with PD. We speculate that motor execution in different body parts relies on different neural control mechanisms. Our findings warrant further investigation to understand the complexity of gait asymmetry in PD.

Towards a better understanding of anticipatory postural adjustments in people with Parkinson's disease.

INTRODUCTION: Previous studies have shown that anticipatory postural adjustments (APAs) are altered in people with Parkinson's disease but its meaning for locomotion is less understood. This study aims to investigate the association between APAs and gait initiation, gait and freezing of gait and how a dynamic postural control challenging training may induce changes in these features. METHODS: Gait initiation was quantified using wearable sensors and subsequent straight walking was assessed via marker-based motion capture. Additionally, turning and FOG-related outcomes were measured with wearable sensors. Assessments were conducted one week before (Pre), one week after (Post) and 4 weeks after (Follow-up) completion of a training intervention (split-belt treadmill training or regular treadmill training), under single task and dual task (DT) conditions. Statistical analysis included a linear mixed model for training effects and correlation analysis between APAs and the other outcomes for Pre and Post-Pre delta. RESULTS: 52 participants with Parkinson's disease (22 freezers) were assessed. We found that APA size in the medio-lateral direction during DT was positively associated with gait speed (p<0.001) and stride length (p<0.001) under DT conditions at Pre. The training effect was largest for first step range of motion and was similar for both training modes. For the associations between changes after the training (pooled sample) medio-lateral APA size showed a significant positive correlation with first step range of motion (p = 0.033) only in the DT condition and for the non-freezers only. CONCLUSIONS: The findings of this work revealed new insights into how APAs were not associated with first step characteristics and freezing and only baseline APAs during DT were related with DT gait characteristics. Training-induced changes in the size of APAs were related to training benefits in the first step ROM only in non-freezers. Based on the presented results increasing APA size through interventions might not be the ideal target for overall improvement of locomotion.

Neural correlates of weight-shift training in older adults: a randomized controlled study.

Mediolateral weight-shifting is an important aspect of postural control. As it is currently unknown whether a short training session of mediolateral weight-shifting in a virtual reality (VR) environment can improve weight-shifting, we investigated this question and also probed the impact of practice on brain activity. Forty healthy older adults were randomly allocated to a training (EXP, n = 20, age = 70.80 (65-77), 9 females) or a control group (CTR, n = 20, age = 71.65 (65-82), 10 females). The EXP performed a 25-min weight-shift training in a VR-game, whereas the CTR rested for the same period. Weight-shifting speed in both single- (ST) and dual-task (DT) conditions was determined before, directly after, and 24 h after intervention. Functional Near-Infrared Spectroscopy (fNIRS) assessed the oxygenated hemoglobin (HbO2) levels in five cortical regions of interest. Weight-shifting in both ST and DT conditions improved in EXP but not in CTR, and these gains were retained after 24 h. Effects transferred to wider limits of stability post-training in EXP versus CTR. HbO2 levels in the left supplementary motor area were significantly increased directly after training in EXP during ST (change < SEM), and in the left somatosensory cortex during DT (change > SEM). We interpret these changes in the motor coordination and sensorimotor integration areas of the cortex as possibly learning-related.

Lower back muscle activity during weight-shifting is affected by ageing and dual-tasking.

PURPOSE: Postural control deteriorates with age, especially under dual-task conditions. It is currently unknown how a challenging virtual reality weight-shifting task affects lower back muscle activity. Hence, this study investigated erector spinae neuromuscular control during mediolateral weight-shifting as part of an exergame during single- (ST) and dual-task (DT) conditions in young and older adults. METHODS: Seventeen young and 17 older adults performed mediolateral weight-shifts while hitting virtual wasps in a virtual environment with and without a serial subtraction task (DT). Center of mass position was recorded in real-time using 3D motion capturing. Electromyography recorded bilateral activation of the lumbar longissimus and iliocostalis muscles. RESULTS: Weight-shifting (p < 0.03) and targeting the wasps (p < 0.005) deteriorated with age and DT. Relative muscle activation during both quiet stance and weight-shifting increased with age, while the DT-effect did not differ consistently between age-groups. However, bilateral muscle co-contraction decreased with DT in young adults only. When switching direction and targeting the wasps, variability of muscle activation increased with age and DT and proved related to worse targeting performance. These effects were mainly visible at the non-dominant body side. CONCLUSION: Older adults showed a higher erector spinae muscle contribution to perform weight-shifts with increased variability at the end of a shift, whereby muscle activity was modulated less well in older than in young adults in response to DT. Hence, the current findings point to the potential for developing postural training in which older adults learn to fine-tune trunk muscle activity to improve weight-shifting and reduce fall risk.

Test-retest reliability of functional near-infrared spectroscopy during a finger-tapping and postural task in healthy older adults.

Significance: Functional near-infrared spectroscopy (fNIRS) is increasingly employed in studies requiring repeated measurements, yet test-retest reliability is largely unknown. Aim: To investigate test-retest reliability during a postural and a finger-tapping task with and without cap-removal. Approach: Twenty healthy older adults performed a postural and a finger-tapping task. The tasks were repeated twice in one session and once the next day. A portable fNIRS system measured cortical hemodynamics (HbO2) in five regions of interest for the postural task and in the hand motor region for finger-tapping. Results: Test-retest reliability without cap-removal was excellent for the prefrontal cortex (PFC), the premotor cortex (PMC) and the somatosensory cortex (SSC) (intraclass correlation coefficient (ICC)≥0.78), and fair for the frontal eye fields (FEF) and the supplementary motor area (SMA) (ICC≥0.48). After cap-removal, reliability reduced for PFC and SSC (ICC≥0.50), became poor for SMA (ICC=0.01) and PMC (ICC=0.00) and remained good for FEF (ICC=0.64). Similarly, good reliability (ICC=0.66) was apparent for the hand motor region without cap-removal, which deteriorated after cap-removal (ICC=0.38). Conclusions: Test-retest reliability of fNIRS measurements during two separate motor tasks in healthy older adults was fair to excellent when the cap remained in place. However, removing the fNIRS cap between measurements compromised reliability.

A systematic review on exercise and training-based interventions for freezing of gait in Parkinson's disease.

Freezing of gait (FOG) in Parkinson's disease (PD) causes severe patient burden despite pharmacological management. Exercise and training are therefore advocated as important adjunct therapies. In this meta-analysis, we assess the existing evidence for such interventions to reduce FOG, and further examine which type of training helps the restoration of gait function in particular. The primary meta-analysis across 41 studies and 1838 patients revealed a favorable moderate effect size (ES = -0.37) of various training modalities for reducing subjective FOG-severity (p < 0.00001), though several interventions were not directly aimed at FOG and some included non-freezers. However, exercise and training also proved beneficial in a secondary analysis on freezers only (ES = -0.32, p = 0.007). We further revealed that dedicated training aimed at reducing FOG episodes (ES = -0.24) or ameliorating the underlying correlates of FOG (ES = -0.40) was moderately effective (p < 0.01), while generic exercises were not (ES = -0.14, p = 0.12). Relevantly, no retention effects were seen after cessation of training (ES = -0.08, p = 0.36). This review thereby supports the implementation of targeted training as a treatment for FOG with the need for long-term engagement.

Repeated Gait Perturbation Training in Parkinson's Disease and Healthy Older Adults: A Systematic Review and Meta-Analysis.

Background: Gait impairments are common in healthy older adults (HOA) and people with Parkinson's disease (PwPD), especially when adaptations to the environment are required. Traditional rehabilitation programs do not typically address these adaptive gait demands in contrast to repeated gait perturbation training (RGPT). RGPT is a novel reactive form of gait training with potential for both short and long-term consolidation in HOA and PwPD. The aim of this systematic review with meta-analysis is to determine whether RGPT is more effective than non-RGPT gait training in improving gait and balance in HOA and PwPD in the short and longer term. Methods: This review was conducted according to the PRISMA-guidelines and pre-registered in the PROSPERO database (CRD42020183273). Included studies tested the effects of any form of repeated perturbations during gait in HOA and PwPD on gait speed, step or stride length. Studies using balance scales or sway measures as outcomes were included in a secondary analysis. Effects of randomized controlled trials (RCT) on RGPT were pooled using a meta-analysis of final measures. Results: Of the 4421 studies, eight studies were deemed eligible for review, of which six could be included in the meta-analysis, totaling 209 participants (159 PwPD and 50 HOA). The studies were all of moderate quality. The meta-analysis revealed no significant effects of RGPT over non-RGPT training on gait performance (SMD = 0.16; 95% CI = -0.18, 0.49; Z = 0.92; P = 0.36). Yet, in some individual studies, favorable effects on gait speed, step length and stride length were observed immediately after the intervention as well as after a retention period. Gait variability and asymmetry, signifying more direct outcomes of gait adaptation, also indicated favorable RGPT effects in some individual studies. Conclusion: Despite some promising results, the pooled effects of RGPT on gait and balance were not significantly greater as compared to non-RGPT gait training in PwPD and HOA. However, these findings could have been driven by low statistical power. Therefore, the present review points to the imperative to conduct sufficiently powered RCT's to verify the true effects of RGPT on gait and balance in HOA and PwPD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php? Identifier: CRD42020183273.

Short-Term Effects of Single-Session Split-Belt Treadmill Training on Dual-Task Performance in Parkinson's Disease and Healthy Elderly.

Background: Dual-tasking is challenging for people with Parkinson's disease and freezing of gait (PD+FOG) and can exacerbate freezing episodes and falls. Split-belt treadmill training (SBT) is a novel tool to train complex gait and may improve dual-task (DT) walking and turning. Objective: To investigate the single-session effects of SBT on DT walking and DT turning performance in PD+FOG and older adults (OA), compared to regular treadmill training. Methods: Forty-five PD+FOG and 36 OA participated in a single training session (30 min). They were randomized into one of four training groups: (A) SB75-steady belt speed ratio 0.75:1; (B) SB50-steady belt speed ratio 0.5:1; (C) SBCR-changing belt speed ratios between 0.75:1 and 0.5:1; and (D) Tied-Belt (TBT). Over-ground straight-line gait and an alternating turning in place task combined with a cognitive dual-task (DT) (auditory Stroop) were assessed pre- and post-training, and the following day (retention). Constrained longitudinal data analysis was used to investigate the training effects for all participants and for PD+FOG alone. Results: DT gait speed improved at post-training for all groups (p < 0.001). However, SBT (SB50 and SBCR) led to larger post-training improvements compared to TBT, which were still visible at retention (SB50). For mean DT turning speed and Stroop response time while walking, only SBT groups showed significant improvements at post-training or retention. DT stride length, peak DT turning speed, and Stroop performance index while walking also showed larger gains in SBT compared to TBT. Results for PD+FOG alone showed similar effects although with smaller effect sizes. Conclusions: A single session of SBT in PD+FOG and OA showed larger short-term effects on DT walking and turning compared to TBT. Cognitive DT performance was also improved in SBT, likely due to reduced cortical control of gait. These results illustrate the potential for SBT to improve DT during complex gait and possibly reduce fall risk in clinical and healthy populations.

The New Freezing of Gait Questionnaire: Unsuitable as an Outcome in Clinical Trials?

BACKGROUND: Freezing of gait (FOG) is a common gait deficit in Parkinson's disease. The New Freezing of Gait Questionnaire (NFOG-Q) is a widely used and valid tool to quantify freezing of gait severity. However, its test-retest reliability and minimal detectable change remain unknown. OBJECTIVE: To determine the test-retest reliability and responsiveness of the NFOG-Q. METHODS: Two groups of freezers, involved in 2 previous rehabilitation trials, completed the NFOG-Q at 2 time points (T1 and T2), separated by a 6-week control period without active intervention. Sample 1 (N = 57) was measured in ON and sample 2 (N = 14) in OFF. We calculated various reliability statistics for the NFOG-Q scores between T1 and T2 as well as correlation coefficients with clinical descriptors to explain the variability between time points. RESULTS: In sample 1 the NFOG-Q showed modest reliability (intraclass correlation coefficient = 0.68 [0.52-0.80]) without differences between T1 and T2. However, a minimal detectable change of 9.95 (7.90-12.27) points emerged for the total score (range 28 points, relative minimal detectable change of 35.5%). Sample 2 showed largely similar results. We found no associations between cognitive-related or disease severity-related outcomes and variability in NFOG-Q scores. CONCLUSIONS: We conclude that the NFOG-Q is insufficiently reliable or responsive to detect small effect sizes, as changes need to go beyond 35% to surpass measurement error. Therefore, we warrant caution in using the NFOG-Q as a primary outcome in clinical trials. These results emphasize the need for robust and objective freezing of gait outcome measures.

Words That Move Us. The Effects of Sentences on Body Sway.

According to the embodied cognition perspective, cognitive systems and perceptuo-motor systems are deeply intertwined and exert a causal effect on each other. A prediction following from this idea is that cognitive activity can result in subtle changes in observable movement. In one experiment, we tested whether reading various sentences resulted in changes in postural sway. Sentences symbolized various human activities involving high, low, or no physical effort. Dutch participants stood upright on a force plate, measuring the body center of pressure, while reading a succession of sentences. High physical effort sentences resulted in more postural sway (greater SD) than low physical effort sentences. This effect only showed up in medio-lateral sway but not anterio-posterior sway. This suggests that sentence comprehension was accompanied by subtle motoric activity, likely mirroring the various activities symbolized in the sentences. We conclude that semantic processing reaches the motor periphery, leading to increased postural activity.