Design and evaluation of an independent 4-week, exosuit-assisted, post-stroke community walking program.

Chronic impairment in the paretic ankle following stroke often requires that individuals use compensatory patterns such as asymmetric propulsion to achieve effective walking speeds needed for community engagement. Ankle exosuit assistance can provide ankle biomechanical benefit in the lab, but such environments inherently limit the amount of practice available. Community walking studies without exosuits can provide massed practice and benefit walking speed but are limited in their ability to assist proper mechanics. In this study, we combined the positive aspects of community training with those of exosuit assistance. We developed and evaluated a community Robotic Exosuit Augmented Locomotion (cREAL) program. Four participants in the chronic stage of stroke independently used our community ankle exosuit for walking in the community 3-5 days/week for 4 weeks. We performed lab evaluations before and after the 4-week program. Two participants significantly improved their unassisted paretic propulsion by an average of 27% after the program and walked on average 4001 steps/day more in the week following the program. Despite the small number of participants, this study provides preliminary evidence for the potential of exosuits to augment gait training and rehabilitation in the community.

Opportunities and challenges in the development of exoskeletons for locomotor assistance.

Exoskeletons can augment the performance of unimpaired users and restore movement in individuals with gait impairments. Knowledge of how users interact with wearable devices and of the physiology of locomotion have informed the design of rigid and soft exoskeletons that can specifically target a single joint or a single activity. In this Review, we highlight the main advances of the past two decades in exoskeleton technology and in the development of lower-extremity exoskeletons for locomotor assistance, discuss research needs for such wearable robots and the clinical requirements for exoskeleton-assisted gait rehabilitation, and outline the main clinical challenges and opportunities for exoskeleton technology.

Reducing the energy cost of walking with low assistance levels through optimized hip flexion assistance from a soft exosuit.

As we age, humans see natural decreases in muscle force and power which leads to a slower, less efficient gait. Improving mobility for both healthy individuals and those with muscle impairments/weakness has been a goal for exoskeleton designers for decades. In this work, we discover that significant reductions in the energy cost required for walking can be achieved with almost 50% less mechanical power compared to the state of the art. This was achieved by leveraging human-in-the-loop optimization to understand the importance of individualized assistance for hip flexion, a relatively unexplored joint motion. Specifically, we show that a tethered hip flexion exosuit can reduce the metabolic rate of walking by up to 15.2 ± 2.6%, compared to locomotion with assistance turned off (equivalent to 14.8% reduction compared to not wearing the exosuit). This large metabolic reduction was achieved with surprisingly low assistance magnitudes (average of 89 N, ~ 24% of normal hip flexion torque). Furthermore, the ratio of metabolic reduction to the positive exosuit power delivered was 1.8 times higher than ratios previously found for hip extension and ankle plantarflexion. These findings motivated the design of a lightweight (2.31 kg) and portable hip flexion assisting exosuit, that demonstrated a 7.2 ± 2.9% metabolic reduction compared to walking without the exosuit. The high ratio of metabolic reduction to exosuit power measured in this study supports previous simulation findings and provides compelling evidence that hip flexion may be an efficient joint motion to target when considering how to create practical and lightweight wearable robots to support improved mobility.

Slowed Luminance Reaction Times in Cervical Dystonia: Disordered Superior Colliculus Processing.

BACKGROUND: Abnormal temporal discrimination in cervical dystonia is hypothesized to be attributable to disrupted processing in the superior colliculus. The fast, luminance-based, retinotectal pathway, projects to the superior colliculus; chromatic stimuli responses, by the retino-geniculo-calcarine pathway, are up to 30 ms longer. OBJECTIVES: We sought to interrogate visual processing and reaction times in patients with cervical dystonia compared with healthy controls. We hypothesized that cervical dystonia patients would have impaired reaction times to luminance based stimuli accessing the retino-tectal pathway in comparison to healthy control participants. METHODS: In 20 cervical dystonia and 20 age-matched control participants, we compared reaction times to two flashing visual stimuli: (1) a chromatic annulus and (2) a luminant, noncolored annulus. Participants pressed a joystick control when they perceived the annulus flashing. RESULTS: Reaction times in control participants were 20 ms significantly faster in the luminant condition than the chromatic (P = 0.017). Patients with cervical dystonia had no reaction time advantage in response to the luminant stimulus. CONCLUSION: Cervical dystonia patients (compared to control participants) demonstrated no reduction in their reaction time to luminant stimuli, processed through the retinotectal pathway. This finding is consistent with superior colliculus dysfunction in cervical dystonia. © 2020 International Parkinson and Movement Disorder Society.

Neural Correlates of Abnormal Temporal Discrimination in Unaffected Relatives of Cervical Dystonia Patients.

Background: An abnormal temporal discrimination threshold in cervical dystonia (CD) is considered to be a mediational endophenotype; in unaffected relatives it is hypothesized to indicate non-manifesting gene carriage. The pathogenesis underlying this condition remains unknown. Investigation of the neural networks involved in disordered temporal discrimination may highlight its pathomechanisms. Objective: To examine resting state brain function in unaffected relatives of CD patients with normal and abnormal temporal discrimination. We hypothesized that the endophenotype, an abnormal temporal discrimination, would manifest as altered connectivity in relatives in regions associated with CD, thereby illuminating the neural substrates of the link between temporal discrimination and CD. Methods: Rs-fMRI data was analyzed from two sex- and age-matched cohorts: 16 unaffected relatives of CD patients with normal temporal discrimination and 16 with abnormal temporal discrimination. Regional and whole brain functional connectivity measures were extracted via Independent Component Analysis (ICA), Regional Homogeneity (ReHo), and Amplitude of Low Frequency (ALFF) analyses. Results: Our ICA analysis revealed increased connectivity within both the executive control and cerebellar networks and decreased connectivity within the sensorimotor network in relatives with abnormal temporal discrimination when compared to relatives with normal temporal discrimination. The ReHo and ALFF analyses complimented these results and demonstrated connectivity differences in areas corresponding to motor planning, movement coordination, visual information processing, and eye movements in unaffected relatives with abnormal temporal discrimination. Conclusion: Disordered connectivity in unaffected relatives with abnormal temporal discrimination illuminates neural substrates underlying endophenotype expression and supports the hypothesis that genetically determined aberrant connectivity, when later coupled with unknown environmental triggers, may lead to disease penetrance.

Comparison of the human-exosuit interaction using ankle moment and ankle positive power inspired walking assistance.

Previous ankle exoskeleton assistance techniques that were able to demonstrate metabolic reductions can be categorized into those that delivered moment profiles similar to the biological ankle moment throughout the stance phase, and others that delivered positive power only during push off. Both assistance techniques and a powered-off condition were compared in treadmill walking (1.5 m s-1) with a soft exosuit. We hypothesized that both techniques can result in a similar metabolic reduction when providing a similar level of average positive exosuit power at each ankle (0.12 W kg-1) and hip (0.02 W kg-1) while the underlying global center-of-mass and local joint biomechanics would be different. We found a similar net metabolic rate reduction of 15% relative to walking with the suit powered-off for both techniques. The ankle moment inspired technique showed larger magnitudes of reductions for biological moment and power at the hip and the ankle. The ankle power inspired technique might benefit from higher biological efficiency, when reducing positive instead of negative power at the knee and when almost keeping the isometric function of the plantarflexors before push-off. Changes at the ankle caused energetic reductions at the knee, hip and the center-of-mass. A major contribution to metabolic reduction might be based on them. As the lower limb biomechanics that led to these reductions were different, we believe that humans alter their gait to maximize their energetic benefit based on the exosuit assistance. For further insights on mechanisms that lead to metabolic reduction, joint mechanics and muscle-tendon dynamics must be analyzed in combination.

Characterizing Brain Network Topology in Cervical Dystonia Patients and Unaffected Relatives via Graph Theory.

Cervical Dystonia (CD) is a neurological movement disorder characterized by intermittent muscle contractions in the head and neck. The pathophysiology and neural networks underpinning this condition are incompletely understood. There is increasing evidence that isolated focal dystonias are due to network-wide functional alterations. An abnormal temporal discrimination threshold (TDT) is believed to be a mediational endophenotype due to its prevalence in unaffected first-degree relatives as well as patients. However the neural correlates linking abnormal TDT and CD remain poorly understood. Probing changes in large-scale network topology via graph theory with resting state fMRI data from relatives and patients may provide further insight into the pathophysiology of CD. In this study, resting state fMRI data were acquired and analyzed from 16 CD patients with abnormal TDT, 32 unaffected first degree relatives (16 with normal TDT and 16 with abnormal TDT) and 16 healthy controls. Graph theory metrics demonstrating network topology were extracted. The results indicate large-scale functional reorganization of networks in relatives (with abnormal TDT) along with a manifestation of topological aberrations similar to patients.

Measurement & Analysis of the Temporal Discrimination Threshold Applied to Cervical Dystonia.

The temporal discrimination threshold (TDT) is the shortest time interval at which an observer can discriminate two sequential stimuli as being asynchronous (typically 30-50 ms). It has been shown to be abnormal (prolonged) in neurological disorders, including cervical dystonia, a phenotype of adult onset idiopathic isolated focal dystonia. The TDT is a quantitative measure of the ability to perceive rapid changes in the environment and is considered indicative of the behavior of the visual neurons in the superior colliculus, a key node in covert attentional orienting. This article sets out methods for measuring the TDT (including two hardware options and two modes of stimuli presentation). We also explore two approaches of data analysis and TDT calculation. The application of the assessment of temporal discrimination to the understanding of the pathogenesis of cervical dystonia and adult onset idiopathic isolated focal dystonia is also discussed.

Disrupted superior collicular activity may reveal cervical dystonia disease pathomechanisms.

Cervical dystonia is a common neurological movement disorder characterised by muscle contractions causing abnormal movements and postures affecting the head and neck. The neural networks underpinning this condition are incompletely understood. While animal models suggest a role for the superior colliculus in its pathophysiology, this link has yet to be established in humans. The present experiment was designed to test the hypothesis that disrupted superior collicular processing is evident in affected patients and in relatives harbouring a disease-specific endophenotype (abnormal temporal discrimination). The study participants were 16 cervical dystonia patients, 16 unaffected first-degree relatives with abnormal temporal discrimination, 16 unaffected first-degree relatives with normal temporal discrimination and 16 healthy controls. The response of participant's superior colliculi to looming stimuli was assessed by functional magnetic resonance imaging. Cervical dystonia patients and relatives with abnormal temporal discrimination demonstrated (i) significantly reduced superior collicular activation for whole brain and region of interest analysis; (ii) a statistically significant negative correlation between temporal discrimination threshold and superior collicular peak values. Our results support the hypothesis that disrupted superior collicular processing is involved in the pathogenesis of cervical dystonia. These findings, which align with animal models of cervical dystonia, shed new light on pathomechanisms in humans.

Continuous sweep versus discrete step protocols for studying effects of wearable robot assistance magnitude.

BACKGROUND: Different groups developed wearable robots for walking assistance, but there is still a need for methods to quickly tune actuation parameters for each robot and population or sometimes even for individual users. Protocols where parameters are held constant for multiple minutes have traditionally been used for evaluating responses to parameter changes such as metabolic rate or walking symmetry. However, these discrete protocols are time-consuming. Recently, protocols have been proposed where a parameter is changed in a continuous way. The aim of the present study was to compare effects of continuously varying assistance magnitude with a soft exosuit against discrete step conditions. METHODS: Seven participants walked on a treadmill wearing a soft exosuit that assists plantarflexion and hip flexion. In Continuous-up, peak exosuit ankle moment linearly increased from approximately 0 to 38% of biological moment over 10 min. Continuous-down was the opposite. In Discrete, participants underwent five periods of 5 min with steady peak moment levels distributed over the same range as Continuous-up and Continuous-down. We calculated metabolic rate for the entire Continuous-up and Continuous-down conditions and the last 2 min of each Discrete force level. We compared kinematics, kinetics and metabolic rate between conditions by curve fitting versus peak moment. RESULTS: Reduction in metabolic rate compared to Powered-off was smaller in Continuous-up than in Continuous-down at most peak moment levels, due to physiological dynamics causing metabolic measurements in Continuous-up and Continuous-down to lag behind the values expected during steady-state testing. When evaluating the average slope of metabolic reduction over the entire peak moment range there was no significant difference between Continuous-down and Discrete. Attempting to correct the lag in metabolics by taking the average of Continuous-up and Continuous-down removed all significant differences versus Discrete. For kinematic and kinetic parameters, there were no differences between all conditions. CONCLUSIONS: The finding that there were no differences in biomechanical parameters between all conditions suggests that biomechanical parameters can be recorded with the shortest protocol condition (i.e. single Continuous directions). The shorter time and higher resolution data of continuous sweep protocols hold promise for the future study of human interaction with wearable robots.

Physical interface dynamics alter how robotic exosuits augment human movement: implications for optimizing wearable assistive devices.

BACKGROUND: Wearable assistive devices have demonstrated the potential to improve mobility outcomes for individuals with disabilities, and to augment healthy human performance; however, these benefits depend on how effectively power is transmitted from the device to the human user. Quantifying and understanding this power transmission is challenging due to complex human-device interface dynamics that occur as biological tissues and physical interface materials deform and displace under load, absorbing and returning power. METHODS: Here we introduce a new methodology for quickly estimating interface power dynamics during movement tasks using common motion capture and force measurements, and then apply this method to quantify how a soft robotic ankle exosuit interacts with and transfers power to the human body during walking. We partition exosuit end-effector power (i.e., power output from the device) into power that augments ankle plantarflexion (termed augmentation power) vs. power that goes into deformation and motion of interface materials and underlying soft tissues (termed interface power). RESULTS: We provide empirical evidence of how human-exosuit interfaces absorb and return energy, reshaping exosuit-to-human power flow and resulting in three key consequences: (i) During exosuit loading (as applied forces increased), about 55% of exosuit end-effector power was absorbed into the interfaces. (ii) However, during subsequent exosuit unloading (as applied forces decreased) most of the absorbed interface power was returned viscoelastically. Consequently, the majority (about 75%) of exosuit end-effector work over each stride contributed to augmenting ankle plantarflexion. (iii) Ankle augmentation power (and work) was delayed relative to exosuit end-effector power, due to these interface energy absorption and return dynamics. CONCLUSIONS: Our findings elucidate the complexities of human-exosuit interface dynamics during transmission of power from assistive devices to the human body, and provide insight into improving the design and control of wearable robots. We conclude that in order to optimize the performance of wearable assistive devices it is important, throughout design and evaluation phases, to account for human-device interface dynamics that affect power transmission and thus human augmentation benefits.

Menstrual cycle and the temporal discrimination threshold.

The temporal discrimination threshold (TDT) is a proposed pre-clinical biomarker (endophenotype) for adult onset isolated focal dystonia (AOIFD). Age- and sex-related effects on temporal discrimination demonstrate that women, before the age of 40 years, have faster temporal discrimination than men but their TDTs worsen with age at almost three times the rate of men. Thus after 40 years the TDT in women is progressively worse than in men. AOIFD is an increasingly female-predominant disorder after the age of 40; it is not clear whether this age-related sexually-dimorphic difference observed for both the TDT and sex ratio at disease onset in AOIFD is a hormonal or chromosomal effect. The aim of this study was to examine temporal discrimination at weekly intervals during two consecutive menstrual cycles in 14 healthy female volunteers to determine whether physiological hormonal changes affected temporal discrimination. We observed no significant differences in weekly temporal discrimination threshold values during the menstrual cycles and no significant correlation with the menstrual cycle stage. This observed stability of temporal discrimination during cyclical hormonal change raises interesting questions concerning the age-related sexually-dimorphic decline observed in temporal discrimination. Our findings pave the way for future studies exploring potential pathomechanisms for this age-related deterioration.

A comparison of stimulus presentation methods in temporal discrimination testing.

The temporal discrimination threshold (TDT) is the shortest time interval at which an individual detects two stimuli to be asynchronous (normal = 30-50 ms). It has been shown to be abnormal in patients with disorders affecting the basal ganglia including adult onset idiopathic focal dystonia (AOIFD). Up to 97% of patients have an abnormal TDT with age- and sex-related penetrance in unaffected relatives, demonstrating an autosomal dominant inheritance pattern. These findings support the use of the TDT as a pre-clinical biomarker for AOIFD. The usual stimulus presentation method involves the presentation of progressively asynchronous stimuli; when three sequential stimuli are reported asynchronous is taken as a participant's TDT. To investigate the robustness of the 'staircase' method of presentation, we introduced a method of randomised presentation order to explore any potential 'learning effect' that may be associated with this existing method. The aim of this study was to investigate differences in temporal discrimination using two methods of stimulus presentation. Thirty healthy volunteers were recruited to the study (mean age 33.73 ± 3.4 years). Visual and tactile TDT testing using a staircase and randomised method of presentation order was carried out in a single session. There was a strong relationship between the staircase and random method for TDT values. This observed consistency between testing methods suggests that the existing experimental approach is a robust method of recording an individual's TDT. In addition, our newly devised randomised paradigm is a reproducible and more efficient method for data acquisition in the clinic setting. However, the two presentation methods yield different absolute TDT results and either of the two methods should be used uniformly in all participants in any one particular study.

Application of virtual reality head mounted display for investigation of movement: a novel effect of orientation of attention.

OBJECTIVE: To date human kinematics research has relied on video processing, motion capture and magnetic search coil data acquisition techniques. However, the use of head mounted display virtual reality systems, as a novel research tool, could facilitate novel studies into human movement and movement disorders. These systems have the unique ability of presenting immersive 3D stimulus while also allowing participants to make ecologically valid movement-based responses. APPROACH: We employed one such system (Oculus Rift DK2) in this study to present visual stimulus and acquire head-turn data from a cohort of 40 healthy adults. Participants were asked to complete head movements towards eccentrically located visual targets following valid and invalid cues. Such tasks are commonly employed for investigating the effects orientation of attention and are known as Posner cueing paradigms. Electrooculography was also recorded for a subset of 18 participants. MAIN RESULTS: A delay was observed in onset of head movement and saccade onset during invalid trials, both at the group and single participant level. We found that participants initiated head turns 57.4 ms earlier during valid trials. A strong relationship between saccade onset and head movement onset was also observed during valid trials. SIGNIFICANCE: This work represents the first time that the Posner cueing effect has been observed in onset of head movement in humans. The results presented here highlight the role of head-mounted display systems as a novel and practical research tool for investigations of normal and abnormal movement patterns.

Exploring the unknown: electrophysiological and behavioural measures of visuospatial learning.

Visuospatial memory describes our ability to temporarily store and manipulate visual and spatial information and is employed for a wide variety of complex cognitive tasks. Here, a visuospatial learning task requiring fine motor control is employed to investigate visuospatial learning in a group of typically developing adults. Electrophysiological and behavioural data are collected during a target location task under two experimental conditions: Target Learning and Target Cued. Movement times (MTs) are employed as a behavioural metric of performance, while dynamic P3b amplitudes and power in the alpha band (approximately 10 Hz) are explored as electrophysiological metrics during visuospatial learning. Results demonstrate that task performance, as measured by MT, is highly correlated with P3b amplitude and alpha power at a consecutive trial level (trials 1-30). The current set of results, in conjunction with the existing literature, suggests that changes in P3b amplitude and alpha power could correspond to different aspects of the learning process. Here it is hypothesized that changes in P3b correspond to a diminishing inter-stimulus interval and reduced stimulus relevance, while the corresponding changes in alpha power represent an automation of response as habituation occurs in participants. The novel analysis presented in the current study demonstrates how gradual electrophysiological changes can be tracked during the visuospatial learning process under the current paradigm.

Young Women do it Better: Sexual Dimorphism in Temporal Discrimination.

The temporal discrimination threshold (TDT) is the shortest time interval at which two sensory stimuli presented sequentially are detected as asynchronous by the observer. TDTs are known to increase with age. Having previously observed shorter thresholds in young women than in men, in this work we sought to systematically examine the effect of sex and age on temporal discrimination. The aims of this study were to examine, in a large group of men and women aged 20-65 years, the distribution of TDTs with an analysis of the individual participant's responses, assessing the "point of subjective equality" and the "just noticeable difference" (JND). These respectively assess sensitivity and accuracy of an individual's response. In 175 participants (88 women) aged 20-65 years, temporal discrimination was faster in women than in men under the age of 40 years by a mean of approximately 13 ms. However, age-related decline in temporal discrimination was three times faster in women so that, in the age group of 40-65 years, the female superiority was reversed. The point of subjective equality showed a similar advantage in younger women and more marked age-related decline in women than men, as the TDT. JND values declined equally in both sexes, showing no sexual dimorphism. This observed sexual dimorphism in temporal discrimination is important for both (a) future clinical research assessing disordered mid-brain covert attention in basal-ganglia disorders, and (b) understanding the biology of this sexual dimorphism which may be genetic or hormonal.

Non-parametric bootstrapping method for measuring the temporal discrimination threshold for movement disorders.

OBJECTIVE: Recent studies have proposed that the temporal discrimination threshold (TDT), the shortest detectable time period between two stimuli, is a possible endophenotype for adult onset idiopathic isolated focal dystonia (AOIFD). Patients with AOIFD, the third most common movement disorder, and their first-degree relatives have been shown to have abnormal visual and tactile TDTs. For this reason it is important to fully characterize each participant's data. To date the TDT has only been reported as a single value. APPROACH: Here, we fit individual participant data with a cumulative Gaussian to extract the mean and standard deviation of the distribution. The mean represents the point of subjective equality (PSE), the inter-stimulus interval at which participants are equally likely to respond that two stimuli are one stimulus (synchronous) or two different stimuli (asynchronous). The standard deviation represents the just noticeable difference (JND) which is how sensitive participants are to changes in temporal asynchrony around the PSE. We extended this method by submitting the data to a non-parametric bootstrapped analysis to get 95% confidence intervals on individual participant data. MAIN RESULTS: Both the JND and PSE correlate with the TDT value but are independent of each other. Hence this suggests that they represent different facets of the TDT. Furthermore, we divided groups by age and compared the TDT, PSE, and JND values. The analysis revealed a statistical difference for the PSE which was only trending for the TDT. SIGNIFICANCE: The analysis method will enable deeper analysis of the TDT to leverage subtle differences within and between control and patient groups, not apparent in the standard TDT measure.

A headset method for measuring the visual temporal discrimination threshold in cervical dystonia.

BACKGROUND: The visual temporal discrimination threshold (TDT) is the shortest time interval at which one can determine two stimuli to be asynchronous and meets criteria for a valid endophenotype in adult-onset idiopathic focal dystonia, a poorly penetrant disorder. Temporal discrimination is assessed in the hospital laboratory; in unaffected relatives of multiplex adult-onset dystonia patients distance from the hospital is a barrier to data acquisition. We devised a portable headset method for visual temporal discrimination determination and our aim was to validate this portable tool against the traditional laboratory-based method in a group of patients and in a large cohort of healthy controls. METHODS: Visual TDTs were examined in two groups 1) in 96 healthy control participants divided by age and gender, and 2) in 33 cervical dystonia patients, using two methods of data acquisition, the traditional table-top laboratory-based system, and the novel portable headset method. The order of assessment was randomized in the control group. The results obtained by each technique were compared. RESULTS: Visual temporal discrimination in healthy control participants demonstrated similar age and gender effects by the headset method as found by the table-top examination. There were no significant differences between visual TDTs obtained using the two methods, both for the control participants and for the cervical dystonia patients. Bland-Altman testing showed good concordance between the two methods in both patients and in controls. DISCUSSION: The portable headset device is a reliable and accurate method for visual temporal discrimination testing for use outside the laboratory, and will facilitate increased TDT data collection outside of the hospital setting. This is of particular importance in multiplex families where data collection in all available members of the pedigree is important for exome sequencing studies.

Electrophysiological and behavioral measures of visuo-motor learning for application in movement disorders.

Dystonia is the third most common movement disorder worldwide and drastically reduces the quality of life of those who are affected. Despite its prevalence, very little is known about the underlying pathology of the disorder. Recent literature has suggested that abnormal processing in the superior colliculus (SC) may play a role in Dystonia. The SC is known to be an important hub in the neural network that is used when learning a novel movement and therefore we would postulate that a disorder of SC should result in abnormal movement learning. Here 9 participants completed learning and non-learning movement tasks while behavioural and electrophysiological data were acquired. The results of this study show that there is a significant relationship between the behavioural and electrophysiological data (R(2) = 0.19, F(1, 46) =10.88, p < 0.002) during the learning task but not in the non-learning task (p > 0.05). The developed paradigm is ideally suited for probing the underlying pathology of Dystonia via movement learning.