On-Demand Cueing for Freezing of Gait in Parkinson's Disease: A Randomized Controlled Trial.

BACKGROUND: Cueing can alleviate freezing of gait (FOG) in people with Parkinson's disease (PD), but using the same cues continuously in daily life may compromise effectiveness. Therefore, we developed the DeFOG-system to deliver personalized auditory cues on detection of a FOG episode. OBJECTIVES: We aimed to evaluate the effects of DeFOG during a FOG-provoking protocol: (1) after 4 weeks of DeFOG-use in daily life against an active control group; (2) after immediate DeFOG-use (within-group) in different medication states. METHOD: In this randomized controlled trial, 63 people with PD and daily FOG were allocated to the DeFOG or active control group. Both groups received feedback on their daily living step counts using the device, but the DeFOG group also received on-demand cueing. Video-rated FOG severity was compared pre- and post-intervention through a FOG-provoking protocol administered at home off and on-medication, but without using DeFOG. Within-group effects were tested by comparing FOG during the protocol with and without DeFOG. RESULTS: DeFOG-use during the 4 weeks was similar between groups, but we found no between-group differences in FOG-severity. However, the within-group analysis showed that FOG was alleviated by DeFOG (effect size d = 0.57), regardless of medication state. Combining DeFOG and medication yielded an effect size of d = 0.67. CONCLUSIONS: DeFOG reduced FOG considerably in a population of severe freezers both off and on medication. Nonetheless, 4 weeks of DeFOG-use in daily life did not ameliorate FOG during the protocol unless DeFOG was worn. These findings suggest that on-demand cueing is only effective when used, similar to other walking aids. © 2024 International Parkinson and Movement Disorder Society.

The Potential of Transcranial Alternating Current Stimulation to Alleviate Dual-Task Gait Costs in Older Adults: Insights from a Double-Blinded Pilot Study.

BACKGROUND: The performance of an attention-demanding task while walking, i.e., dual-tasking, leads to dual-task costs (e.g., reduced gait speed) in older adults. Previous studies have shown that dual-task costs in gait are associated with future falls and cognitive decline. According to the communication through coherence hypothesis, transcranial alternating current stimulation (tACS) might help alleviate this problem. OBJECTIVE: The aim of this study was to examine the effects of a single session of theta-tACS targeting the left fronto-parietal network (L-FPN) on dual-task walking and cognitive function compared to sham stimulation and transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex, a node within the L-FPN. METHODS: Twenty older adults completed a four-visit, double-blinded, within-subject, cross-over study in which usual-walking, dual-task walking, and cognitive function were evaluated before and immediately after 20 min of tACS, tDCS, or sham (order randomized) stimulation. Dual-task costs to gait speed (primary outcome) and other measures were analyzed. RESULTS: The dual-task cost to gait speed tended to be lower (i.e., better) after tACS (p = 0.067, Cohen's d = 0.433∼small); tDCS significantly reduced this dual-task cost (p = 0.012, Cohen's d = 0.618∼medium), and sham stimulation had no effect (p = 0.467). tACS significantly reduced the dual-task cost to step length (p = 0.037, Cohen's d = 0.502∼medium); a trend was seen after tDCS (p = 0.069, Cohen's d = 0.443∼small). No statistical differences were found for other measures of gait or cognitive function. CONCLUSIONS: The positive effects of tACS on dual-task gait speed and step length were roughly similar to those seen with tDCS. These results suggest that tACS affects the fronto-parietal network and, similar to tDCS, tACS may improve dual-tasking. Nonetheless, to achieve larger benefits and differentiate the effects of tACS and tDCS on brain function and dual-task walking in older adults, other stimulation montages and protocols should be tested.

An Educational Program for Remote Training and Supervision of Home-Based Transcranial Electrical Stimulation: Feasibility and Preliminary Effectiveness.

OBJECTIVES: There has been recent interest in the administration of transcranial electrical stimulation (tES) by a caregiver, family member, or patient themselves while in their own homes (HB-tES). The need to properly train individuals in the administration of HB-tES is essential, and the lack of a uniform training approach across studies has come to light. The primary aim of this paper is to present the HB-tES training and supervision program, a tele-supervised, instructional, and evaluation program to teach laypersons how to administer HB-tES to a participant and to provide a standardized framework for remote monitoring of participants by teaching staff. The secondary aim is to present early pilot data on the feasibility and effectiveness of the training portion of the program based on its implementation in 379 sessions between two pilot clinical trials. MATERIALS AND METHODS: The program includes instructional materials, standardized tele-supervised hands-on practice sessions, and a system for remote supervision of participants by teaching staff. Nine laypersons completed the training program. Data on the feasibility and effectiveness of the program were collected. RESULTS: No adverse events were reported during the training or any of the HB-tES sessions after the training. All laypersons successfully completed the training. The nine laypersons reported being satisfied with the training program and confident in their tES administration capabilities. This was consistent with laypersons requiring technical assistance from teaching staff very infrequently during the 379 completed sessions. The average adherence rate between all administrators was >98%, with seven of nine administrators having 100% adherence to the scheduled sessions. CONCLUSIONS: These findings indicate that the HB-tES program is effective and is associated with participant satisfaction. SIGNIFICANCE: We hope that the remote nature of this training program will facilitate increased accessibility to HB-tES research for participants of different demographics and locations. This program, designed for easy adaptation to different HB-tES research applications and devices, also is accessible online. The adoption of this program is expected to facilitate uniformity of study methods among future HB-tES studies and thereby accelerate the pace of tES intervention discovery.

Targeted tDCS Mitigates Dual-Task Costs to Gait and Balance in Older Adults.

OBJECTIVE: Among older adults, the ability to stand or walk while performing cognitive tasks (ie, dual-tasking) requires coordinated activation of several brain networks. In this multicenter, double-blinded, randomized, and sham-controlled study, we examined the effects of modulating the excitability of the left dorsolateral prefrontal cortex (L-DLPFC) and the primary sensorimotor cortex (SM1) on dual-task performance "costs" to standing and walking. METHODS: Fifty-seven older adults without overt illness or disease completed 4 separate study visits during which they received 20 minutes of transcranial direct current stimulation (tDCS) optimized to facilitate the excitability of the L-DLPFC and SM1 simultaneously, or each region separately, or neither region (sham). Before and immediately after stimulation, participants completed a dual-task paradigm in which they were asked to stand and walk with and without concurrent performance of a serial-subtraction task. RESULTS: tDCS simultaneously targeting the L-DLPFC and SM1, as well as tDCS targeting the L-DLPFC alone, mitigated dual-task costs to standing and walking to a greater extent than tDCS targeting SM1 alone or sham (p < 0.02). Blinding efficacy was excellent and participant subjective belief in the type of stimulation received (real or sham) did not contribute to the observed functional benefits of tDCS. INTERPRETATION: These results demonstrate that in older adults, dual-task decrements may be amenable to change and implicate L-DPFC excitability as a modifiable component of the control system that enables dual-task standing and walking. tDCS may be used to improve resilience and the ability of older results to walk and stand under challenging conditions, potentially enhancing everyday functioning and reducing fall risks. ANN NEUROL 2021;90:428-439.

Combining transcranial direct current stimulation with a motor-cognitive task: the impact on dual-task walking costs in older adults.

BACKGROUND: The performance of a secondary task while walking increases motor-cognitive interference and exacerbates fall risk in older adults. Previous studies have demonstrated that transcranial direct current stimulation (tDCS) may improve certain types of dual-task performance, and, that tDCS delivered during the performance of a task may augment the benefits of stimulation, potentially reducing motor-cognitive interference. However, it is not yet known if combining multi-target tDCS with the simultaneous performance of a task related to the tDCS targets reduces or increases dual-task walking costs among older adults. The objectives of the present work were (1) To examine whether tDCS applied during the performance of a task that putatively utilizes the brain networks targeted by the neuro-stimulation reduces dual-task costs, and (2) to compare the immediate after-effects of tDCS applied during walking, during seated-rest, and during sham stimulation while walking, on dual-task walking costs in older adults. We also explored the impact on postural sway and other measures of cognitive function. METHODS: A double-blind, 'within-subject' cross-over pilot study evaluated the effects of 20 min of anodal tDCS targeting both the primary motor cortex (M1) and the left dorsolateral prefrontal cortex (lDLPFC) in 25 healthy older adults (73.9 ± 5.2 years). Three stimulation conditions were assessed in three separate sessions: (1) tDCS while walking in a complex environment (tDCS + walking), (2) tDCS while seated (tDCS + seated), and (3) walking in a complex environment with sham tDCS (sham + walking). The complex walking condition utilized virtual reality to tax motor and cognitive abilities. During each session, usual-walking, dual-task walking, quiet standing sway, and cognitive function (e.g., Stroop test) were assessed before and immediately after stimulation. Dual-task costs to gait speed and other measures were computed. RESULTS: The dual-task cost to gait speed was reduced after tDCS + walking (p = 0.004) as compared to baseline values. Neither tDCS + seated (p = 0.173) nor sham + walking (p = 0.826) influenced this outcome. Similar results were seen for other gait measures and for Stroop performance. Sway was not affected by tDCS. CONCLUSIONS: tDCS delivered during the performance of challenging walking decreased the dual-task cost to walking in older adults when they were tested just after stimulation. These results support the existence of a state-dependent impact of neuro-modulation that may set the stage for a more optimal neuro-rehabilitation. TRIAL REGISTRATION: Clinical Trials Gov Registrations Number: NCT02954328.

Validation of the Hebrew Version of the Unified Dyskinesia Rating Scale.

BACKGROUND: The Unified Dyskinesia Rating Scale (UDysRS) is a well-established tool for producing comprehensive assessments of severity and disability associated with dyskinesia in patients with Parkinson's disease (PD). The scale was originally developed in English, and a broad international effort has been undertaken to develop and validate versions in additional languages. Our aim was to validate the Hebrew version of the UDysRS. METHODS: We translated the UDysRS into Hebrew, back-translated it into English, and carried out cognitive pretesting. We then administered the scale to non-demented native Hebrew-speaking patients who fulfilled the Brain Bank diagnostic criteria for probable PD (n = 250). Data were compared to the Reference Standard data used for validating UDysRS translations. RESULTS: The different portions of the Hebrew UDysRS showed high internal consistency (α ≥ 0.92). A confirmatory factor analysis in which we compared the Hebrew UDysRS to the Reference Standard version produced a comparative fit index (CFI) of 0.98, exceeding the threshold criterion of CFI > 0.9 indicating factor validity. A secondary exploratory factor analysis provided further support to the consistency between the factor structures of the Hebrew and Reference Standard versions of the UDysRS. CONCLUSION: The UDysRS Hebrew version shows strong clinimetric properties and fulfills the criteria for designation as an official International Parkinson and Movement Disorder Society-approved translation for use in clinical and research settings.

SPARC: a new approach to quantifying gait smoothness in patients with Parkinson's disease.

BACKGROUND: Impairments in biomechanics and neural control can disrupt the timing and muscle pattern activation necessary for smooth gait. Gait is one of the most affected motor characteristics in Parkinson's disease (PD), but its smoothness has not been well-studied. This work applies the recently proposed spectral arc length measure (SPARC) to study, for the first time, gait in patients with PD. We hypothesized that the gait of patients with PD would be less smooth than that of healthy controls, as reflected in the SPARC measures. METHODS: The gait of 101 PD patients and 39 healthy controls was assessed using an inertial sensor. Smoothness of gait was estimated with SPARC (respectively from acceleration and angular velocity signals, SPARC-Acc and SPARC-Gyro) and harmonic ratios. Correlations between SPARC, traditional gait measures and the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) were evaluated. Measurements and analysis were conducted with and without anti-PD medication. RESULTS: SPARC measures were lower (less smooth) in PD than in controls (SPARC-Acc: PD: - 6.11 ± 0.74; CO: -5.17 ± 0.79; p <  0.001). When comparing PD to controls, SPARC-Acc differed more than other measures of gait (i.e., largest effect size, which was > 1). SPARC measures were correlated with UPDRS motor score (r = - 0.65), while they were independent of other measures of gait smoothness. PD gait in the on state was smoother than in the off state (p <  0.001). CONCLUSIONS: SPARC calculated from trunk acceleration and angular velocity signals provide valid measures of walking smoothness in PD. SPARC is sensitive to Parkinson's disease and PD medications and can be used of as another, complementary measure of the motor control of walking in PD.

Cognitive function and other non-motor features in non-demented Parkinson's disease motor subtypes.

Among patients with Parkinson's disease (PD), a wide range of non-motor symptoms (NMS) are evident. We assessed markers of NMS and explored their behavioral correlates with the tremor-dominant (TD) and postural instability gait difficulty (PIGD) subtypes. 110 non-demented patients with PD were evaluated and stratified into the PIGD and TD subtypes and, using stricter criteria, into predominant subgroups: p-PIGD (n = 31) and p-TD (n = 32). Non-motor signs that were assessed included cognitive function (pen and paper and a computerized battery), autonomic function (NMSQest and SCOPA-AUT), mood, and sleep. Health-related quality of life was evaluated using the PDQ-39. The p-PIGD subgroup had a higher score on the NMSQest (p = 0.033) and a higher score (i.e., worse) on the PDQ-39 (p-PIGD: 26.28 ± 12.47; p-TD: 16.93 ± 12.22; p = 0.004), compared to the p-TD subgroup, while these measures did not differ in the larger PIGD and TD group. The p-PIGD subgroup used more sleep medications compared to the p-TD subgroup (1.0 ± 1.39 vs. 0.41 ± 0.94, p = 0.05, respectively). Most cognitive scores were similar in both subgroups; however, the visuospatial components of the Montreal Cognitive Assessment and the computerized catch game were significantly worse among the p-PIGD subgroup. Mild associations were found between certain non-motor symptoms, but not cognitive function, and the PIGD score. Non-demented patients from the PIGD subtype experience more non-motor symptoms and poorer quality of life compared to the TD subtype. These findings suggest that the clinical management of non-motor and motor symptoms in patients with PD may be enhanced by a personalized approach.

Identifying axial and cognitive correlates in patients with Parkinson's disease motor subtype using the instrumented Timed Up and Go.

Parkinson's disease (PD) is clinically highly heterogeneous, often divided into tremor dominant (TD) and postural instability gait difficulty (PIGD). To better understand these subtypes and to help stratify patients, we applied an objective marker, i.e., an instrumented version of the traditional "Timed Up and Go" test (iTUG). It is not known whether the iTUG is sensitive to PD motor phenotypes or what are its behavioral and cognitive correlates. Subjects performed the iTUG wearing a body-fixed sensor. Subcomponents were studied including walking, transitions and turning. Gait, balance and cognitive function and the associations between iTUG, behavioral and cognitive domains were assessed. We also compared two representative subtypes, with minimal symptom overlap, referred to here as predominant PIGD (p-PIGD) and predominant TD (p-TD). One hundred and six patients with PD performed the iTUG. Significant correlations were found between iTUG measures and the PIGD score, but not with TD score. Thirty p-PIGD and 31 p-TD patients were identified. Both groups were similar with respect to age and disease duration (p > 0.75). The p-PIGD patients took significantly longer to complete the iTUG (p = 0.026), used more steps (p = 0.031), albeit with similar step duration (p = 0.936). In the sit-to-stand transition, the p-PIGD patients exhibited lower anterior-posterior jerk (p = 0.04) and lower pitch range (p = 0.012). During the turn, the p-PIGD patients had a lower yaw amplitude (p < 0.038). Cognitive domains were correlated with iTUG measures in the p-PIGD patients, but not in the p-TD. These findings demonstrate that a single sensor can identify axial and cognitive correlates using subcomponents of the iTUG and reveals subtle alterations between the PD motor subtypes.

Dual-task training on a treadmill to improve gait and cognitive function in elderly idiopathic fallers.

BACKGROUND AND PURPOSE: Daily activities require the ability to dual task (DT), utilizing cognitive resources while walking to negotiate complex environmental conditions. For older adults, these additional cognitive demands often lead to reduced gait quality that increases the risk of falls. The aim of this study was to assess whether a combined intervention, consisting of treadmill training (TT) while performing DT, improves cognitive and motor performance in older adults with a history of multiple falls. METHODS: A repeated measures design was used to evaluate the effects of training in 10 elderly fallers (mean age, 78.1 ± 5.81 y, 7 women). The progressive intensive training sessions included walking on a treadmill while practicing a variety of dual tasks 3 times a week for more than 6 weeks. Cognitive and motor measures were used to assess the effects of the intervention immediately after training and 1 month posttraining. RESULTS: Improvements were observed in Berg Balance Scale (P = 0.02), Dynamic Gait Index (P = 0.03), gait speed during usual walking and while DT (P < 0.05), and cognitive performance as measured by the Trails Making Test B (P = 0.02). Furthermore, quality of life improved (SF-36: P = 0.01) as did physical activity (Physical Activity Scale for Elderly: P = 0.02). At 1 month postintervention, changes were not significant. DISCUSSION AND CONCLUSIONS: After 6 weeks of TT + DT program, elderly fallers demonstrated improved scores on tests of mobility, functional performance tasks, and cognition.Dual task training can be readily implemented by therapists as a component of a fall-risk reduction training program.Video Abstract available. See Video (Supplemental Digital Content 1, http://links.lww.com/JNPT/A81) for more insights from the authors.

Automated detection of missteps during community ambulation in patients with Parkinson's disease: a new approach for quantifying fall risk in the community setting.

BACKGROUND: Falls are a leading cause of morbidity and mortality among older adults and patients with neurological disease like Parkinson's disease (PD). Self-report of missteps, also referred to as near falls, has been related to fall risk in patients with PD. We developed an objective tool for detecting missteps under real-world, daily life conditions to enhance the evaluation of fall risk and applied this new method to 3 day continuous recordings. METHODS: 40 patients with PD (mean age ± SD: 62.2 ± 10.0 yrs, disease duration: 5.3 ± 3.5 yrs) wore a small device that contained accelerometers and gyroscopes on the lower back while participating in a protocol designed to provoke missteps in the laboratory. Afterwards, the subjects wore the sensor for 3 days as they carried out their routine activities of daily living. An algorithm designed to automatically identify missteps was developed based on the laboratory data and was validated on the 3 days recordings. RESULTS: In the laboratory, we recorded 29 missteps and more than 60 hours of data. When applied to this dataset, the algorithm achieved a 93.1% hit ratio and 98.6% specificity. When we applied this algorithm to the 3 days recordings, patients who reported two falls or more in the 6 months prior to the study (i.e., fallers) were significantly more likely to have a detected misstep during the 3 day recordings (p = 0.010) compared to the non-fallers. CONCLUSIONS: These findings suggest that this novel approach can be applied to detect missteps during daily life among patients with PD and will likely help in the longitudinal assessment of disease progression and fall risk.

Acceptability of wearable devices for measuring mobility remotely: Observations from the Mobilise-D technical validation study.

Background: This study aimed to explore the acceptability of a wearable device for remotely measuring mobility in the Mobilise-D technical validation study (TVS), and to explore the acceptability of using digital tools to monitor health. Methods: Participants (N = 106) in the TVS wore a waist-worn device (McRoberts Dynaport MM + ) for one week. Following this, acceptability of the device was measured using two questionnaires: The Comfort Rating Scale (CRS) and a previously validated questionnaire. A subset of participants (n = 36) also completed semi-structured interviews to further determine device acceptability and to explore their opinions of the use of digital tools to monitor their health. Questionnaire results were analysed descriptively and interviews using a content analysis. Results: The device was considered both comfortable (median CRS (IQR; min-max) = 0.0 (0.0; 0-20) on a scale from 0-20 where lower scores signify better comfort) and acceptable (5.0 (0.5; 3.0-5.0) on a scale from 1-5 where higher scores signify better acceptability). Interviews showed it was easy to use, did not interfere with daily activities, and was comfortable. The following themes emerged from participants' as being important to digital technology: altered expectations for themselves, the use of technology, trust, and communication with healthcare professionals. Conclusions: Digital tools may bridge existing communication gaps between patients and clinicians and participants are open to this. This work indicates that waist-worn devices are supported, but further work with patient advisors should be undertaken to understand some of the key issues highlighted. This will form part of the ongoing work of the Mobilise-D consortium.

Treadmill training with virtual reality to enhance gait and cognitive function among people with multiple sclerosis: a randomized controlled trial.

BACKGROUND: Motor and cognitive impairments impact the everyday functioning of people with MS (pwMS). The present randomized controlled trial (RCT) evaluated the benefits of a combined motor-cognitive virtual reality training program on key motor and cognitive symptoms and related outcomes in pwMS. METHODS: In a single-blinded, two-arm RCT, 124 pwMS were randomized into a treadmill training with virtual reality (TT + VR) group or a treadmill training alone (TT) (active-control) group. Both groups received three training sessions per week for 6 weeks. Dual-tasking gait speed and cognitive processing speed (Symbol Digit Modalities Test, SDMT, score) were the primary outcomes. Secondary outcomes included additional tests of cognitive function, mobility, and patient-reported questionnaires. These were measured before, after, and 3 months after training. RESULTS: Gait speed improved (p < 0.005) in both groups, similarly, by about 10 cm/s. The TT + VR group (n = 53 analyzed per-protocol) showed a clinically meaningful improvement of 4.4 points (95% CI 1.9-6.8, p = 0.001) in SDMT, compared to an improvement of only 0.8 points in the TT (n = 51 analyzed per-protocol) group (95% CI 0.9-2.5 points, p = 0.358) (group X time interaction effect p = 0.027). Furthermore, TT + VR group-specific improvements were seen in depressive symptoms (lowered by 31%, p = 0.003), attention (17%, p < 0.001), and verbal fluency (11.6% increase, p = 0.002). DISCUSSION: These findings suggest that both TT and TT + VR improve usual and dual-task gait in pwMS. Nonetheless, a multi-modal approach based on VR positively impacts multiple aspects of cognitive function and mental health, more than seen after treadmill-treading alone. Trial registered at ClinicalTrials.Gov NCT02427997.

A training program to improve gait while dual tasking in patients with Parkinson's disease: a pilot study.

Impairments in the ability to perform another task while walking (ie, dual tasking [DT]) are associated with an increased risk of falling. Here we describe a program we developed specifically to improve DT performance while walking based on motor learning principles and task-specific training. We examined feasibility, potential efficacy, retention, and transfer to the performance of untrained tasks in a pilot study among 7 patients with Parkinson's disease (PD). Seven patients (Hoehn and Yahr stage, 2.1±0.2) were evaluated before, after, and 1 month after 4 weeks of DT training. Gait speed and gait variability were measured during usual walking and during 4 DT conditions. The 4-week program of one-on-one training included walking while performing several distinct cognitive tasks. Gait speed and gait variability during DT significantly improved. Improvements were also seen in the DT conditions that were not specifically trained and were retained 1 month after training. These initial findings support the feasibility of applying a task-specific DT gait training program for patients with PD and suggest that it positively affects DT gait, even in untrained tasks. The present results are also consistent with the possibility that DT gait training enhances divided attention abilities during walking.

Daily-Living Freezing of Gait as Quantified Using Wearables in People With Parkinson Disease: Comparison With Self-Report and Provocation Tests.

OBJECTIVE: Freezing of gait (FOG) is an episodic, debilitating phenomenon that is common among people with Parkinson disease. Multiple approaches have been used to quantify FOG, but the relationships among them have not been well studied. In this cross-sectional study, we evaluated the associations among FOG measured during unsupervised daily-living monitoring, structured in-home FOG-provoking tests, and self-report. METHODS: Twenty-eight people with Parkinson disease and FOG were assessed using self-report questionnaires, percentage of time spent frozen (%TF) during supervised FOG-provoking tasks in the home while off and on dopaminergic medication, and %TF evaluated using wearable sensors during 1 week of unsupervised daily-living monitoring. Correlations between those 3 assessment approaches were analyzed to quantify associations. Further, based on the %TF difference between in-home off-medication testing and in-home on-medication testing, the participants were divided into those responding to Parkinson disease medication (responders) and those not responding to Parkinson disease medication (nonresponders) in order to evaluate the differences in the other FOG measures. RESULTS: The %TF during unsupervised daily living was mild to moderately correlated with the %TF during a subset of the tasks of the in-home off-medication testing but not the on-medication testing or self-report. Responders and nonresponders differed in the %TF during the personal "hot spot" task of the provoking protocol while off medication (but not while on medication) but not in the total scores of the self-report questionnaires or the measures of FOG evaluated during unsupervised daily living. CONCLUSION: The %TF during daily living was moderately related to FOG during certain in-home FOG-provoking tests in the off-medication state. However, this measure of FOG was not associated with self-report or FOG provoked in the on-medication state. These findings suggest that to fully capture FOG severity, it is best to assess FOG using a combination of all 3 approaches. IMPACT: These findings suggest that several complementary approaches are needed to provide a complete assessment of FOG severity.

Protocol for the DeFOG trial: A randomized controlled trial on the effects of smartphone-based, on-demand cueing for freezing of gait in Parkinson's disease.

BACKGROUND: Freezing of gait (FOG) is a highly incapacitating symptom that affects many people with Parkinson's disease (PD). Cueing triggered upon real-time FOG detection (on-demand cueing) shows promise for FOG treatment. Yet, the feasibility of implementation and efficacy in daily life is still unknown. Therefore, this study aims to investigate the effectiveness of DeFOG: a smartphone and sensor-based on-demand cueing solution for FOG. METHODS: Sixty-two PD patients with FOG will be recruited for this single-blind, multi-center, randomized controlled phase II trial. Patients will be randomized into either the intervention group or the active control group. For four weeks, both groups will receive feedback about their physical activity using the wearable DeFOG system in daily life. In addition, the intervention group will also receive on-demand auditory cueing and instructions. Before and after the intervention, home-based assessments will be performed to evaluate the primary outcome, i.e., "percentage time frozen" during a FOG-provoking protocol. Secondary outcomes include the training effects on physical activity monitored over 7 days and the user-friendliness of the technology. DISCUSSION: The DeFOG trial will investigate the effectiveness of personalized on-demand cueing in a controlled design, delivered for 4 weeks in the patient's home environment. We anticipate that DeFOG will reduce FOG to a greater degree than in the control group and we will explore the impact of the intervention on physical activity levels. We expect to gain in-depth insight into whether and how patients control FOG using cueing methods in their daily lives. TRIAL REGISTRATION: Clinicaltrials.gov NCT03978507.

Technical validation of real-world monitoring of gait: a multicentric observational study.

INTRODUCTION: Existing mobility endpoints based on functional performance, physical assessments and patient self-reporting are often affected by lack of sensitivity, limiting their utility in clinical practice. Wearable devices including inertial measurement units (IMUs) can overcome these limitations by quantifying digital mobility outcomes (DMOs) both during supervised structured assessments and in real-world conditions. The validity of IMU-based methods in the real-world, however, is still limited in patient populations. Rigorous validation procedures should cover the device metrological verification, the validation of the algorithms for the DMOs computation specifically for the population of interest and in daily life situations, and the users' perspective on the device. METHODS AND ANALYSIS: This protocol was designed to establish the technical validity and patient acceptability of the approach used to quantify digital mobility in the real world by Mobilise-D, a consortium funded by the European Union (EU) as part of the Innovative Medicine Initiative, aiming at fostering regulatory approval and clinical adoption of DMOs.After defining the procedures for the metrological verification of an IMU-based device, the experimental procedures for the validation of algorithms used to calculate the DMOs are presented. These include laboratory and real-world assessment in 120 participants from five groups: healthy older adults; chronic obstructive pulmonary disease, Parkinson's disease, multiple sclerosis, proximal femoral fracture and congestive heart failure. DMOs extracted from the monitoring device will be compared with those from different reference systems, chosen according to the contexts of observation. Questionnaires and interviews will evaluate the users' perspective on the deployed technology and relevance of the mobility assessment. ETHICS AND DISSEMINATION: The study has been granted ethics approval by the centre's committees (London-Bloomsbury Research Ethics committee; Helsinki Committee, Tel Aviv Sourasky Medical Centre; Medical Faculties of The University of Tübingen and of the University of Kiel). Data and algorithms will be made publicly available. TRIAL REGISTRATION NUMBER: ISRCTN (12246987).

Advantages of timing the duration of a freezing of gait-provoking test in individuals with Parkinson's disease.

Evaluating freezing of gait (FOG) and quantifying its severity in patients with Parkinson's disease (PD) is challenging; objective assessment is not sufficiently established. We aimed to improve the ability to objectively evaluate FOG severity by investigating the value of measuring the duration of the test and its components. Seventy-one patients with PD and FOG completed a previously validated FOG-provoking test. The test was performed under three conditions: (1) usual, single task; (2) dual task (walking while carrying a tray); and (3) triple task (walking while holding a tray and subtracting 7 s). FOG and festination were scored using standard procedures. We evaluated effect sizes based on both the original scoring and the test duration for the motor-cognitive cost and before and after anti-Parkinsonian medication intake. Additionally, video recording of the test and total time frozen were measured. As expected, the original test score and the test duration increased across the three conditions of the task and were higher in OFF than in the ON-medication state (p < 0.036). For motor-cognitive cost, higher effect sizes were observed for the test duration of each condition, compared to the original scoring in OFF state (0.85 vs. 0.68, respectively). Change in effect size category was more pronounced in the ON state vs. OFF (0.87 vs. 0.55, respectively). Test duration was the only independent predictor for the self-report of FOG severity and the total time frozen during the test. These findings suggest that quantifying the duration of each condition of the FOG-provoking test improves its sensitivity to medications and task complexity. Timing can be used to provide immediate, objective feedback of freezing severity, and a clear interpretation of a patient's performance.

Virtual reality training to enhance behavior and cognitive function among children with attention-deficit/hyperactivity disorder: brief report.

Purpose: To examine the feasibility and efficacy of a combined motor-cognitive training using virtual reality to enhance behavior, cognitive function and dual-tasking in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Methods: Fourteen non-medicated school-aged children with ADHD, received 18 training sessions during 6 weeks. Training included walking on a treadmill while negotiating virtual obstacles. Behavioral symptoms, cognition and gait were tested before and after the training and at 6-weeks follow-up. Results: Based on parental report, there was a significant improvement in children's social problems and psychosomatic behavior after the training. Executive function and memory were improved post-training while attention was unchanged. Gait regularity significantly increased during dual-task walking. Long-term training effects were maintained in memory and executive function. Conclusion: Treadmill-training augmented with virtual-reality is feasible and may be an effective treatment to enhance behavior, cognitive function and dual-tasking in children with ADHD.

Treadmill walking reduces pre-frontal activation in patients with Parkinson's disease.

BACKGROUND: Among patients with Parkinson's disease (PD), gait is typically disturbed and less automatic. These gait changes are associated with impaired rhythmicity and increased prefrontal activation, presumably in an attempt to compensate for reduced automaticity. RESEARCH QUESTION: We investigated whether during treadmill walking, when the pace is determined and fixed, prefrontal activation in patients with PD is lower, as compared to over-ground walking. METHODS: Twenty patients with PD (age: 69.8 ±â€¯6.5 yrs.; MoCA: 26.9 ±â€¯2.4; disease duration: 7.9 ±â€¯4.2 yrs) walked at a self-selected walking speed over-ground and on a treadmill. A wireless functional near infrared spectroscopy (fNIRS) system measured prefrontal lobe activation, i.e., oxygenated hemoglobin (Hb02) in the pre-frontal area. Gait was evaluated using 3D-accelerometers attached to the lower back and ankles (Opal™, APDM). Dynamic gait stability was assessed using the maximum Lyapunov exponent to investigate automaticity of the walking pattern. RESULTS: Hb02 was lower during treadmill walking than during over-ground walking (p = 0.001). Gait stability was greater on the treadmill, compared to over-ground walking, in both the anteroposterior and medio-lateral axes (p < 0.001). SIGNIFICANCE: These findings support the notion that when gait is externally paced, prefrontal lobe activation is reduced in patients with PD, perhaps reflecting a reduced need for compensatory cognitive mechanisms.