Exploring the effects of dopamine on sensorimotor inhibition and mobility in older adults.

Dopaminergic activity decreases in older adults (OAs) with normal aging and is further reduced in Parkinson's disease (PD), affecting cortical motor and sensorimotor pathways. Levodopa is the prevailing therapy to counter dopamine loss in PD, though not all PD motor signs improve with levodopa. The purpose of this preliminary study was to explore the effects of levodopa on sensorimotor inhibition, gait and quiet standing in OAs and to investigate the relationships between sensorimotor inhibition and both gait and standing balance both OFF- and ON-levodopa. Fifteen OA males completed a gait, balance and sensorimotor assessments before and 1 h after they were given a 100 mg dose of levodopa. Short-latency afferent inhibition quantified sensorimotor inhibition. Wearable sensors characterized gait (two-minute walk) and standing balance (1-min stance). No sensorimotor inhibition, gait, or standing balance measures changed from OFF- to ON-levodopa. When OFF-levodopa, worse inhibition significantly related to increased double stance (r = 0.62; p = 0.01), increased jerkiness of sway (r = 0.57; p = 0.03) and sway area (r = 0.58; p = 0.02). While ON-levodopa, worse inhibition related to increased arm swing range of motion (r = 0.63; p = 0.01) and jerkiness of sway (r = 0.53; p = 0.04). The relationship between SAI and arm swing excursion significantly changed from OFF- to ON-levodopa (z = - 3.05; p = 0.002; 95% confidence interval = - 0.95, - 0.21). Sensorimotor inhibition relationships to both gait and balance may be affected by dopamine in OAs. Cortical restructuring due to the loss of dopamine may be responsible for the heterogeneity of levodopa effect in people with PD and OAs.

"Look, Your Muscles Are Firing!": A Qualitative Study of Clinician Perspectives on the Use of Surface Electromyography in Neurorehabilitation.

OBJECTIVE: To examine the perceived value, benefits, drawbacks, and ideas for technology development and implementation of surface electromyography recordings in neurologic rehabilitation practice from clinical stakeholder perspectives. DESIGN: A qualitative, phenomenological study was conducted. In-depth, semistructured interviews and focus groups were completed. Sessions included questions about clinician perspectives and demonstrations of surface electromyography systems to garner perceptions of specific system features. SETTING: The study was conducted at hospital systems in a large metropolitan area. PARTICIPANTS: Adult and pediatric physical therapists, occupational therapists, and physiatrists from inpatient, outpatient, and research settings (N=22) took part in the study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Interviews and focus groups were audio-recorded, transcribed verbatim, then coded for analysis into themes. RESULTS: Four major themes emerged: (1) low-tech clinical practice and future directions for rehabilitation; (2) barriers to surface electromyography uptake and potential solutions; (3) benefits of surface electromyography for targeted populations; and (4) essential features of surface electromyography systems. CONCLUSIONS: Surface electromyography systems were not routinely utilized for assessment or intervention following neurologic injury. Despite recognition of potential clinical benefits of surface electromyography use, clinicians identified limited time and resources as key barriers to implementation. Perspectives on design and surface electromyography system features indicated the need for streamlined, intuitive, and clinically effective applications. Further research is needed to determine feasibility and clinical relevance of surface electromyography in rehabilitation intervention.

Systemic AAV8-Mediated Gene Therapy Drives Whole-Body Correction of Myotubular Myopathy in Dogs.

X-linked myotubular myopathy (XLMTM) results from MTM1 gene mutations and myotubularin deficiency. Most XLMTM patients develop severe muscle weakness leading to respiratory failure and death, typically within 2 years of age. Our objective was to evaluate the efficacy and safety of systemic gene therapy in the p.N155K canine model of XLMTM by performing a dose escalation study. A recombinant adeno-associated virus serotype 8 (rAAV8) vector expressing canine myotubularin (cMTM1) under the muscle-specific desmin promoter (rAAV8-cMTM1) was administered by simple peripheral venous infusion in XLMTM dogs at 10 weeks of age, when signs of the disease are already present. A comprehensive analysis of survival, limb strength, gait, respiratory function, neurological assessment, histology, vector biodistribution, transgene expression, and immune response was performed over a 9-month study period. Results indicate that systemic gene therapy was well tolerated, prolonged lifespan, and corrected the skeletal musculature throughout the body in a dose-dependent manner, defining an efficacious dose in this large-animal model of the disease. These results support the development of gene therapy clinical trials for XLMTM.

Long-term effects of systemic gene therapy in a canine model of myotubular myopathy.

INTRODUCTION: X-linked myotubular myopathy (XLMTM), a devastating pediatric disease caused by the absence of the protein myotubularin, results from mutations in the MTM1 gene. While there is no cure for XLMTM, we previously reported effects of MTM1 gene therapy using adeno-associated virus (AAV) vector on muscle weakness and pathology in MTM1-mutant dogs. Here, we followed 2 AAV-infused dogs over 4 years. METHODS: We evaluated gait, strength, respiration, neurological function, muscle pathology, AAV vector copy number (VCN), and transgene expression. RESULTS: Four years following AAV-mediated gene therapy, gait, respiratory performance, neurological function and pathology in AAV-infused XLMTM dogs remained comparable to their healthy littermate controls despite a decline in VCN and muscle strength. CONCLUSIONS: AAV-mediated gene transfer of MTM1 in young XLMTM dogs results in long-term expression of myotubularin transgene with normal muscular performance and neurological function in the absence of muscle pathology. These findings support a clinical trial in patients. Muscle Nerve 56: 943-953, 2017.

A Tandem Cycling Program: Feasibility and Physical Performance Outcomes in People With Parkinson Disease.

BACKGROUND AND PURPOSE: Individuals with Parkinson disease (PD) have motor and nonmotor impairments that interfere with exercise participation. The purpose of this study was to examine the feasibility and physical performance outcomes of a community-based indoor tandem cycling program that was designed to facilitate a higher cadence, consistency, and intensity of training. METHODS: Forty-one participants with mild to moderate PD were enrolled. A high-cadence cycling protocol using mechanically augmented (or forced) exercise on a tandem bicycle was adapted for our program. Participants cycled 3 times per week for 10 weeks. Feasibility measures included program retention, attendance, and adverse events, as well as the ability to reach training goals for heart rate (HR) and cadence. Physical performance outcomes included the Berg Balance Scale (BBS), Short Physical Performance Battery (SPPB), Five-Times-Sit-to-Stand (FTSTS) Test, Timed Up and Go (TUG), and gait parameters during usual and fast-paced walking. RESULTS: Program feasibility was demonstrated with a high attendance rate (96%) and retention rate (100%). There were no adverse events. The majority of participants reached their exercise training goals for target HR (87%) and cadence (95%). Statistically significant physical performance improvement (P < 0.05) was observed across domains of gait, balance, and mobility, suggesting a slowing or reversal of functional decline as a result of this cycling program. DISCUSSION AND CONCLUSION: Program feasibility and improved physical performance outcomes were demonstrated in individuals with mild to moderate PD participating in a community-based indoor tandem cycling program.Video Abstract available for more insights from the authors (see supplemental digital content 1, http://links.lww.com/JNPT/A146).

Self-Reported Cognitive Concerns in People With Lower Limb Loss.

OBJECTIVES: To investigate differences between self-reported cognitive concerns in people with lower limb loss (LLL) and normative data derived from the U.S. general population, and secondarily to determine whether there were cognitive differences based on amputation etiology or age. DESIGN: Survey. SETTING: General community. PARTICIPANTS: A volunteer sample of persons with LLL (N=1086) resulting from trauma or dysvascular complications who regularly use a prosthetic limb. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Quality of Life in Neurological Disorders Applied Cognition-General Concerns Short Form version 1.0 (Neuro-QoL ACGC), an 8-item self-report measure of general cognitive concerns. RESULTS: People with LLL reported significantly more cognitive concerns than the Quality of Life in Neurological Disorders normative sample. Mean Neuro-QoL ACGC scores were significantly lower than normative values (P<.001) across subgroups defined by age (ie, <40, 40-49, 50-59, 60-69, and 70+ years) and subgroups defined by etiology (ie, traumatic and dysvascular LLL). However, there were no significant differences in cognitive concerns among age subgroups (P=.84) or between the etiology subgroups (P=.58). CONCLUSIONS: When compared with the Quality of Life in Neurological Disorders normative sample, individuals with LLL report greater concerns with cognitive health. Cognitive concerns were not differentially affected by age or cause of amputation. The presence of cognitive concerns in people with LLL suggests a need to assess perceived cognitive function in order to tailor education and training in prosthetic use and care.

Relationship of multiscale entropy to task difficulty and sway velocity in healthy young adults.

PURPOSE/BACKGROUND: Multiscale entropy (MSE) is a nonlinear measure of postural control that quantifies how complex the postural sway is by assigning a complexity index to the center of pressure (COP) oscillations. While complexity has been shown to be task dependent, the relationship between sway complexity and level of task challenge is currently unclear. This study tested whether MSE can detect short-term changes in postural control in response to increased standing balance task difficulty in healthy young adults and compared this response to that of a traditional measure of postural steadiness, root mean square of velocity (VRMS). METHODS: COP data from 20 s of quiet stance were analyzed when 30 healthy young adults stood on the following surfaces: on floor and foam with eyes open and closed and on the compliant side of a Both Sides Up (BOSU) ball with eyes open. Complexity index (CompI) was derived from MSE curves. RESULTS: Repeated measures analysis of variance across standing conditions showed a statistically significant effect of condition (p < 0.001) in both the anterior-posterior and medio-lateral directions for both CompI and VRMS. In the medio-lateral direction there was a gradual increase in CompI and VRMS with increased standing challenge. In the anterior-posterior direction, VRMS showed a gradual increase whereas CompI showed significant differences between the BOSU and all other conditions. CompI was moderately and significantly correlated with VRMS. CONCLUSIONS: Both nonlinear and traditional measures of postural control were sensitive to the task and increased with increasing difficulty of standing balance tasks in healthy young adults.

The ability of people with Parkinson's disease to modify dual-task performance in response to instructions during simple and complex walking tasks.

Gait impairments are a common and consequential motor symptom in Parkinson's disease (PD). A cognitive strategy that incorporates instructions to concentrate on specific parameters of walking is an effective approach to gait rehabilitation for persons with PD during single-task and simple dual-task walking conditions. This study examined the ability to modify dual-task walking in response to instructions during a complex walking task in people with PD compared to healthy older adults (HOA). Eleven people with PD and twelve HOA performed a cognitive task while walking with either a usual base or a narrow base of support. Dual-task walking and cognitive task performance were characterized under two conditions-when participants were instructed focus on walking and when they were instructed to focus on the cognitive task. During both usual base and narrow base walking, instructions affected cognitive task response latency, with slower performance when instructed to focus on walking compared to the cognitive task. Regardless of task or instructions, cognitive task performance was slower in participants with PD compared to HOA. During usual base walking, instructions influenced gait speed for both people with PD and HOA, with faster gait speed when instructed to focus on walking compared to the cognitive task. In contrast, during the narrow base walking, instructions affected gait speed only for HOA, but not for people with PD. This suggests that among people with PD the ability to modify walking in response to instructions depends on the complexity of the walking task.

Associations between baseline cognitive status and motor outcomes after treadmill training in people with Parkinson's disease: a pilot study.

PURPOSE: To determine the effect of baseline cognition on gait outcomes after a treadmill training program for people with Parkinson's disease (PD). METHODS: This pilot clinical trial involved people with PD who were classified as having no cognitive impairment (PD-NCI) or mild cognitive impairment (PD-MCI). Baseline executive function and memory were assessed. The intervention was a 10-week gait training program (twice-weekly treadmill sessions), with structured speed and distance progression and verbal cues for gait quality. Response to intervention was assessed by gait speed measured after week 2 (short-term) and week 10 (long-term). RESULTS: Participants (n = 19; 12 PD-NCI, 7 PD-MCI) had a mean (standard deviation) age of 66.5 (6.3) years, disease duration of 8.8 (6.3) years, and MDS-UPDRS III score of 21.3 (10.7). Gait speed increased at short-term and long-term assessments. The response did not differ between PD-NCI and PD-MCI groups; however, better baseline memory performance and milder PD motor severity were independently associated with greater improvements in gait speed in unadjusted and adjusted models. CONCLUSIONS: These findings suggest that memory impairments and more severe motor involvement can influence the response to gait rehabilitation in PD and highlight the need for treatments optimized for people with greater cognitive and motor impairment.IMPLICATIONS FOR REHABILITATIONCognitive deficits in Parkinson's disease (PD) could impact motor learning and gait rehabilitation, yet little is known about the effects of cognitive impairments on the response to rehabilitation in people with PD.This study demonstrates that the response to gait rehabilitation did not differ between people with PD who had no cognitive impairment and those with mild cognitive impairment.Across all participants, better baseline memory was associated with greater improvements in gait speed.Rehabilitation professionals should be mindful of PD severity, as those with more substantial memory and motor impairments may require additional dosing or support to maximize gait training benefits.

Effects of virtual reality environments on overground walking in people with Parkinson disease and freezing of gait.

BACKGROUND: Freezing of gait (FoG) is a common target of rehabilitative interventions for people with Parkinson disease (PD). Virtual reality (VR) holds potential for advancing research and clinical management of FoG through flexible creation of FoG-provoking environments that are not easily or safely replicated in the clinic. OBJECTIVE: The aim of this study was to investigate whether VR environments that replicate FoG-provoking situations would exacerbate gait impairments associated with FoG compared to unobstructed VR and physical laboratory environments. METHODS: Gait characteristics (pace, rhythm, variability, asymmetry, and postural control domains) and festination were measured using motion capture while people with PD walked in VR environments based on FoG-provoking situations (doorway, hallway, and crowd environments) compared to unobstructed VR and physical laboratory environments. The effect of VR environments was assessed using one-way repeated measures ANOVAs with planned contrasts. RESULTS: Ten participants (mean age 74.1 years, 3 females, Hoehn and Yahr stage 2-3) with PD who self-reported FoG participated. Gait speed and step length were reduced in all VR environments compared to the physical laboratory. Step width was wider, step length was more variable, and festination was more common for some of the VR environments compared to the physical laboratory environment. Compared to the unobstructed virtual laboratory environment, step length was more variable in VR crowd and doorway environments. CONCLUSIONS: The exacerbation of gait impairments that are characteristic precursors of FoG in FoG-provoking VR environments supports the potential utility of VR technology in the assessment and treatment of gait impairments in PD.Implications for rehabilitationFreezing increases fall risk and reduces quality of life in Parkinson disease (PD).Virtual reality (VR) can simulate visuospatial environments that provoke freezing.Immersive VR doorway, hallway, and crowd environments were developed.Gait speed slowed when people with PD walked overground in all VR environments.Step variability and festination increased in freeze-provoking environments.

Development of an item bank for measuring prosthetic mobility in people with lower limb amputation: The Prosthetic Limb Users Survey of Mobility (PLUS-M).

BACKGROUND: Achieving mobility with a prosthesis is a common post-amputation rehabilitation goal and primary outcome in prosthetic research studies. Patient-reported outcome measures (PROMs) available to measure prosthetic mobility have practical and psychometric limitations that inhibit their use in clinical care and research. OBJECTIVE: To develop a brief, clinically meaningful, and psychometrically robust PROM to measure prosthetic mobility. DESIGN: A cross-sectional study was conducted to administer previously developed candidate items to a national sample of lower limb prosthesis users. Items were calibrated to an item response theory model and two fixed-length short forms were created. Instruments were assessed for readability, effective range of measurement, agreement with the full item bank, ceiling and floor effects, convergent validity, and known groups validity. SETTING: Participants were recruited using flyers posted in hospitals and prosthetics clinics across the United States, magazine advertisements, notices posted to consumer websites, and direct mailings. PARTICIPANTS: Adult prosthesis users (N = 1091) with unilateral lower limb amputation due to traumatic or dysvascular causes. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Candidate items (N = 105) were administered along with the Patient Reported Outcome Measurement Information System Brief Profile, Prosthesis Evaluation Questionnaire - Mobility Subscale, and Activities-Specific Balance Confidence Scale, and questions created to characterize respondents. RESULTS: A bank of 44 calibrated self-report items, termed the Prosthetic Limb Users Survey of Mobility (PLUS-M), was produced. Clinical and statistical criteria were used to select items for 7- and 12-item short forms. PLUS-M instruments had an 8th grade reading level, measured with precision across a wide range of respondents, exhibited little-to-no ceiling or floor effects, correlated expectedly with scores from existing PROMs, and differentiated between groups of respondents expected to have different levels of mobility. CONCLUSION: The PLUS-M appears to be well suited to measuring prosthetic mobility in people with lower limb amputation. PLUS-M instruments are recommended for use in clinical and research settings.

Gait and balance in apolipoprotein Ɛ4 allele carriers in older adults and Parkinson's disease.

Background: Gait and balance impairments are among the most troublesome and heterogeneous in Parkinson's disease (PD). This heterogeneity may, in part, reflect genetic variation. The apolipoprotein E (APOE) gene has three major allelic variants (ε2, ε3 and ε4). Previous work has demonstrated that older adult (OA) APOE ε4 carriers demonstrate gait deficits. This study compared gait and balance measures between APOE ε4 carriers and non-carriers in both OA and PD. Methods: 334 people with PD (81 APOE ε4 carriers and 253 non-carriers) and 144 OA (41 carriers and 103 non-carriers) were recruited. Gait and balance were assessed using body-worn inertial sensors. Two-way analyses of covariance (ANCOVA) compared gait and balance characteristics between APOE ε4 carriers and non-carriers in people with PD and OA, controlling for age, gender, and testing site. Results: Gait and balance were worse in people with PD compared to OA. However, there were no differences between APOE ε4 carriers and non-carriers in either the OA or PD group. In addition, there were no significant group (OA/PD) by APOE ε4 status (carrier/non-carrier) interaction effects for any measures of gait or balance. Conclusions: Although we found expected impairments in gait and balance in PD compared to OA, gait and balance characteristics did not differ between APOE ε4 carriers and non-carriers in either group. While APOE status did not impact gait and balance in this cross-sectional study, future work is needed to determine whether progression of gait and balance deficits is faster in PD APOE Ɛ4 carriers.

The association between sleep deficits and sedentary behavior in people with mild Parkinson disease.

Purpose: Sleep deficits are a common nonmotor symptom of Parkinson disease (PD). People with mild PD also achieve less physical activity (PA) than healthy older adults (HOA), but the relationship between sleep and PA in PD is unclear. This study examined associations between sleep and PA in participants with PD and HOA.Materials and Methods: Secondary analysis of a prospective observational study. Participants wore a commercially available activity monitor for two weeks. Wilcoxon Rank-Sum tests compared nighttime sleep, wakenings after sleep onset, number of wakenings, naps, step count, and PA intensity between PD and HOA groups. Age-adjusted regression models calculated associations between nighttime sleep and PA.Results: Per day, participants with PD slept 75 fewer minutes (p < 0.01), took 5,792 fewer steps (p < 0.001), achieved less PA at all intensities, and had 32% more sedentary time (p < 0.001) compared to HOA. Thirty minutes more sleep was associated with 26 fewer sedentary minutes for HOA (p = 0.01) and 25 fewer sedentary minutes for the PD group (p < 0.001).Conclusions: Sleep and PA are reduced in mild PD compared to HOA. Both groups demonstrated similar associations between reduced sleep and increased sedentary behavior. Results may encourage providers to screen for sleep deficits when promoting PA.IMPLICATIONS FOR REHABILITATIONThe use of a wrist-worn commercial activity and sleep monitor was well tolerated by both healthy older adults and people with mild Parkinson Disease in this study.People with mild Parkinson Disease slept less and were less active than a group of healthy older adults.Less sleep was associated with more sedentary behavior in both groups.The relationship between poor sleep and sedentary behavior in mild Parkinson Disease suggests that rehabilitation interventions may be optimized by targeting both physical activity and sleep deficits.

Virtual reality doorway and hallway environments alter gait kinematics in people with Parkinson disease and freezing.

BACKGROUND: Many people with Parkinson disease (PD) experience freezing of gait (FoG), a transient gait disturbance associated with increased fall risk and reduced quality of life. Head-mounted virtual reality (VR) systems allow overground walking and can create immersive simulations of physical environments that induce FoG. RESEARCH QUESTION: For people with PD who experience FoG (PD+FoG), are kinematic gait changes observed in VR simulations of FoG-provoking environments? METHODS: In a cross-sectional experiment, people with PD+FoG walked at their self-selected speed in a physical laboratory and virtual laboratory, doorway, and hallway environments. Motion analysis assessed whole-body kinematics, including lower extremity joint excursions, swing phase toe clearance, trunk flexion, arm swing, sagittal plane inclination angle, and spatiotemporal characteristics. One-way repeated measures analysis of variance was conducted to examine the effects of environment on gait variables, with planned contrasts between laboratory environments and the virtual doorway and hallway. RESULTS: Twelve participants with PD+FoG (mean age [standard deviation]=72.8 [6.5] years, disease duration=8.8 [8.9] years, 3 females) completed the protocol. The environment had significant and widespread effects on kinematic and spatiotemporal variables. Compared to the physical laboratory, reduced joint excursions were observed in the ankle, knee, and hip when walking in the virtual doorway and in the knee and hip when walking in the virtual hallway. In both the virtual doorway and hallway compared to the physical laboratory, peak swing phase toe clearance, arm swing, and inclination angle were reduced, and walking was slower, with shorter, wider steps. SIGNIFICANCE: Virtual doorway and hallway environments induced kinematic changes commonly associated with FoG episodes, and these kinematic changes are consistent with forward falls that are common during FoG episodes. Combined with the flexibility of emerging VR technology, this research supports the potential of VR applications designed to improve the understanding, assessment, and treatment of FoG.

Cognition as a mediator for gait and balance impairments in GBA-related Parkinson's disease.

The extent to which the heterogeneity of gait and balance problems in PD may be explained by genetic variation is unknown. Variants in the glucocerebrosidase (GBA) gene are the strongest known genetic risk factor for PD and are associated with greater motor and cognitive severity. However, the impact of GBA variants on comprehensive measures of gait and balance and their relationship to cognition remains unknown. We aimed to determine differences in gait and balance impairments in those with and without GBA variants (mutation carriers and E326K polymorphism) and explore direct and indirect effects of GBA status on gait, balance, and cognition. 332 participants, 43 of whom had GBA variants, were recruited. Participants completed a comprehensive, objective assessment of gait and standing balance using body-worn inertial sensors. Group differences in gait and balance between PD with and without GBA variants were assessed with linear regression, adjusting for age, gender, clinical testing site, disease duration, and apolipoprotein E (APOE) ɛ4 status. Structural equation modeling (SEM) explored direct relationships between GBA status and gait and balance and indirect relationships between GBA status and gait and balance via cognition. The GBA variant group had more impaired gait (pace and variability) and balance (sway area/jerk and sway velocity), than the non-GBA variant group. SEM demonstrated cognition as a mediator of GBA status on gait and balance. The close relationships among GBA, gait/balance, and cognition suggest potential for novel therapeutics to target the GBA pathway and/or cognition to improve mobility in PD GBA variants.

Validity of Instrumented 360° Turn Test in Older Adults with Cognitive Impairment.

AIMS: To examine concurrent and construct validity of inertial sensor 360°turn measures in relation with motion capture and mobility assessments in cognitively impaired older adults. METHODS: Data was collected in 31 participants, mean age 85.2 (SD 5.2), during clockwise (CW) and counter clockwise (CCW) 360° turns using (1) APDM body-worn inertial sensors and (2) Qualisys 8-camera laboratory-based motion capture. RESULTS: Absolute agreement between inertial sensor and motion capture measures was excellent for turn duration and turn peak velocity (ICC = 0.96-0.98). Strong to moderate correlations were present between inertial sensor turn measures and performance on the Timed Up and Go, Short Physical Performance Battery and 90-s Balance Test. ROC curve analysis of CCW 360° turn duration and turn peak velocity distinguished higher risk versus lower risk for mobility disability. CONCLUSIONS: Inertial sensor 360° turn measures demonstrated concurrent and construct validity in relation to motion capture and mobility assessments.

Smartphone-Based VO2max Measurement With Heart Snapshot in Clinical and Real-world Settings With a Diverse Population: Validation Study.

BACKGROUND: Maximal oxygen consumption (VO2max) is one of the most predictive biometrics for cardiovascular health and overall mortality. However, VO2max is rarely measured in large-scale research studies or routine clinical care because of the high cost, participant burden, and requirement for specialized equipment and staff. OBJECTIVE: To overcome the limitations of clinical VO2max measurement, we aim to develop a digital VO2max estimation protocol that can be self-administered remotely using only the sensors within a smartphone. We also aim to validate this measure within a broadly representative population across a spectrum of smartphone devices. METHODS: Two smartphone-based VO2max estimation protocols were developed: a 12-minute run test (12-MRT) based on distance measured by GPS and a 3-minute step test (3-MST) based on heart rate recovery measured by a camera. In a 101-person cohort, balanced across age deciles and sex, participants completed a gold standard treadmill-based VO2max measurement, two silver standard clinical protocols, and the smartphone-based 12-MRT and 3-MST protocols in the clinic and at home. In a separate 120-participant cohort, the video-based heart rate measurement underlying the 3-MST was measured for accuracy in individuals across the spectrum skin tones while using 8 different smartphones ranging in cost from US $99 to US $999. RESULTS: When compared with gold standard VO2max testing, Lin concordance was pc=0.66 for 12-MRT and pc=0.61 for 3-MST. However, in remote settings, the 12-MRT was significantly less concordant with the gold standard (pc=0.25) compared with the 3-MST (pc=0.61), although both had high test-retest reliability (12-MRT intraclass correlation coefficient=0.88; 3-MST intraclass correlation coefficient=0.86). On the basis of the finding that 3-MST concordance was generalizable to remote settings whereas 12-MRT was not, the video-based heart rate measure within the 3-MST was selected for further investigation. Heart rate measurements in any of the combinations of the six Fitzpatrick skin tones and 8 smartphones resulted in a concordance of pc≥0.81. Performance did not correlate with device cost, with all phones selling under US $200 performing better than pc>0.92. CONCLUSIONS: These findings demonstrate the importance of validating mobile health measures in the real world across a diverse cohort and spectrum of hardware. The 3-MST protocol, termed as heart snapshot, measured VO2max with similar accuracy to supervised in-clinic tests such as the Tecumseh (pc=0.94) protocol, while also generalizing to remote and unsupervised measurements. Heart snapshot measurements demonstrated fidelity across demographic variation in age and sex, across diverse skin pigmentation, and between various iOS and Android phone configurations. This software is freely available for all validation data and analysis code.

Effects of instructed focus and task difficulty on concurrent walking and cognitive task performance in healthy young adults.

Dual task paradigms can be used to examine the interactions between cognition and the control of posture and gait. Measuring and interpreting changes in dual task performance is challenging, however, because many factors can influence performance. This study examined the effects of instructed focus and walking task difficulty, and the interaction between these factors, on dual task performance in healthy young adults. Fifteen participants performed a cognitive task while walking with either a usual base or a narrow base of support. Participants were instructed to focus on either the cognitive task or walking. Trade-offs both within and between tasks were assessed using the modified attention allocation index and the performance operating characteristic. Instructed focus influenced both the cognitive task and walking. Performance on the cognitive task was faster with instructions to focus on the cognitive task, and walking was faster (and more accurate in the narrow-base condition) with instructions to focus on walking. Walking task difficulty did not affect cognitive performance but did affect walking, with faster walking in the usual-base versus narrow-base condition. There was evidence of an interaction, with greater effects of instructed focus on the cognitive task during usual versus narrow-base walking. These results support the idea that the ability to flexibly shift attention allocation and task performance in response to instructions depends on the difficulty of the postural control task. The modified attention allocation index and the performance operating characteristic were instrumental in fully characterizing trade-offs between and within tasks in order to understand dual task performance changes. A clearer understanding of the factors that affect dual task walking and the interactions between these factors has important implications for the assessment of dual task performance in both clinical and research settings.

Assessing the effects of subthalamic nucleus stimulation on gait and mobility in people with Parkinson disease.

PURPOSE: To determine the effects of unilateral and bilateral subthalamic nucleus (STN) stimulation on gait and mobility in persons with Parkinson disease (PD). METHOD: We examined eight individuals with advanced PD who underwent staged stimulator implantation surgeries. Gait and mobility were assessed in the medication-on state with a variety of clinical and laboratory measures (Unified Parkinson Disease Rating Scale items, Timed Up and Go Test, gait speed) at three time points: prior to surgery, after the first surgery (unilateral stimulation) and after the second surgery (bilateral stimulation). RESULTS: Despite overall improvements in motor function and reduction of dyskinesia, there were no significant group effects of unilateral or bilateral stimulation on gait and mobility compared to pre-surgical function. However, there were clinically meaningful changes, both improvements and declines, at the individual level. CONCLUSIONS: Because of the consequences of gait deficits and mobility limitations for people with PD, future research should examine the effects of STN stimulation on gait in the medication-on state using sensitive and specific measures such as gait speed. Accurate assessment of gait changes is necessary to improve the evaluation of STN effects and the prediction of individuals in need of rehabilitation services to manage gait and mobility deficits.

Sensorimotor Inhibition and Mobility in Genetic Subgroups of Parkinson's Disease.

Background: Mobility and sensorimotor inhibition impairments are heterogeneous in Parkinson's disease (PD). Genetics may contribute to this heterogeneity since the apolipoprotein (APOE) ε4 allele and glucocerebrosidase (GBA) gene variants have been related to mobility impairments in otherwise healthy older adult (OA) and PD cohorts. The purpose of this study is to determine if APOE or GBA genetic status affects sensorimotor inhibition and whether the relationship between sensorimotor inhibition and mobility differs in genetic sub-groups of PD. Methods: Ninety-three participants with idiopathic PD (53 non-carriers; 23 ε4 carriers; 17 GBA variants) and 72 OA (45 non-carriers; 27 ε4 carriers) had sensorimotor inhibition characterized by short-latency afferent inhibition. Mobility was assessed in four gait domains (pace/turning, rhythm, trunk, variability) and two postural sway domains (area/jerkiness and velocity) using inertial sensors. Results: Sensorimotor inhibition was worse in the PD than OA group, with no effect of genetic status. Gait pace/turning was slower and variability was higher (p < 0.01) in PD compared to OA. Postural sway area/jerkiness (p < 0.01) and velocity (p < 0.01) were also worse in the PD than OA group. Genetic status was not significantly related to any gait or postural sway domain. Sensorimotor inhibition was significantly correlated with gait variability (r = 0.27; p = 0.02) and trunk movement (r = 0.23; p = 0.045) in the PD group. In PD non-carriers, sensorimotor inhibition related to variability (r = 0.35; p = 0.010) and trunk movement (r = 0.31; p = 0.025). In the PD ε4 group, sensorimotor inhibition only related to rhythm (r = 0.47; p = 0.024), while sensorimotor inhibition related to pace/turning (r = -0.49; p = 0.046) and rhythm (r = 0.59; p = 0.013) in the PD GBA group. Sensorimotor inhibition was significantly correlated with gait pace/turning (r = -0.27; p = 0.04) in the OA group. There was no relationship between sensorimotor inhibition and postural sway. Conclusion: ε4 and GBA genetic status did not affect sensorimotor inhibition or mobility impairments in this PD cohort. However, worse sensorimotor inhibition was associated with gait variability in PD non-carriers, but with gait rhythm in PD ε4 carriers and with gait rhythm and pace in PD with GBA variants. Impaired sensorimotor inhibition had a larger effect on mobility in people with PD than OA and affected different domains of mobility depending on genetic status.