Mobilizing Patient and Public Involvement in the Development of Real-World Digital Technology Solutions: Tutorial.

Although the value of patient and public involvement and engagement (PPIE) activities in the development of new interventions and tools is well known, little guidance exists on how to perform these activities in a meaningful way. This is particularly true within large research consortia that target multiple objectives, include multiple patient groups, and work across many countries. Without clear guidance, there is a risk that PPIE may not capture patient opinions and needs correctly, thereby reducing the usefulness and effectiveness of new tools. Mobilise-D is an example of a large research consortium that aims to develop new digital outcome measures for real-world walking in 4 patient cohorts. Mobility is an important indicator of physical health. As such, there is potential clinical value in being able to accurately measure a person's mobility in their daily life environment to help researchers and clinicians better track changes and patterns in a person's daily life and activities. To achieve this, there is a need to create new ways of measuring walking. Recent advancements in digital technology help researchers meet this need. However, before any new measure can be used, researchers, health care professionals, and regulators need to know that the digital method is accurate and both accepted by and produces meaningful outcomes for patients and clinicians. Therefore, this paper outlines how PPIE structures were developed in the Mobilise-D consortium, providing details about the steps taken to implement PPIE, the experiences PPIE contributors had within this process, the lessons learned from the experiences, and recommendations for others who may want to do similar work in the future. The work outlined in this paper provided the Mobilise-D consortium with a foundation from which future PPIE tasks can be created and managed with clearly defined collaboration between researchers and patient representatives across Europe. This paper provides guidance on the work required to set up PPIE structures within a large consortium to promote and support the creation of meaningful and efficient PPIE related to the development of digital mobility outcomes.

Effects of ageing on responses to stepping-target displacements during walking.

PURPOSE: Human sensory and motor systems deteriorate with age. When walking, older adults may therefore find it more difficult to adjust their steps to new visual information, especially considering that such adjustments require control of balance as well as of foot trajectory. Our study investigates the effects of ageing on lower limb responses to unpredictable target shifts. METHODS: Participants walked on a treadmill with projected stepping targets that occasionally shifted in the medial or lateral direction. The shifts occurred at a random moment during the early half of the swing phase of either leg. Kinematic, kinetic and muscle activity data were collected. RESULTS: Older adults responded later and corrected for a smaller proportion of the shift than young adults. The order in which muscle activation changed was similar in both groups, with responses of gluteus medius and semitendinosus from about 120 to 140 ms after the shift. Most muscles responded slightly later to lateral target shifts in the older adults than in the young adults, but this difference was not observed for medial target shifts. Ageing delayed the behavioural responses more than it did the electromyographic (EMG) responses. CONCLUSIONS: Our study suggests that older adults can adjust their walking to small target shifts during the swing phase, but not as well as young adults. Furthermore, muscle strength probably plays a substantial role in the changes in online adjustments during ageing.

Fast responses to stepping-target displacements when walking.

KEY POINTS: Goal-directed arm movements can be adjusted at short latency to target shifts. We tested whether similar adjustments are present during walking on a treadmill with shifting stepping targets. Participants responded at short latency with an adequate gain to small shifts of the stepping targets. Movements of the feet during walking are controlled in a similar way to goal-directed arm movements if balance is not violated. ABSTRACT: It is well-known that goal-directed hand movements can be adjusted to small changes in target location with a latency of about 100 ms. We tested whether people make similar fast adjustments when a target location for foot placement changes slightly as they walk over a flat surface. Participants walked at 3 km/h on a treadmill on which stepping stones were projected. The stones were 50 cm apart in the walking direction. Every 5-8 steps, a stepping stone was unexpectedly displaced by 2.5 cm in the medio-lateral direction. The displacement took place during the first half of the swing phase. We found fast adjustments of the foot trajectory, with a latency of about 155 ms, initiated by changes in muscle activation 123 ms after the perturbation. The responses corrected for about 80% of the perturbation. We conclude that goal-directed movements of the foot are controlled in a similar way to those of the hand, thus also giving very fast adjustments.

Treatment of metatarsalgia based on claw toe deformity through soft tissue release of the metatarsophalangeal joint and resection of the proximal interphalangeal joint: Evaluation based on foot kinematics and plantar pressure distribution.

INTRODUCTION: This study investigated the effect of operative claw toe correction with release of the metatarsophalangeal (MTP) joint, repositioning of the plantar fat pad and resection of the proximal interphalangeal joint on foot kinematics, plantar pressure distribution and Foot Function Index (FFI). METHODS: Prospective experimental study with pretest-posttest design. The plantar pressure, 3D foot kinematics and the FFI of 15 patients with symptomatic claw toes were measured three months before and 12months after surgery. Mean pressure, peak pressure and pressure time integral per sensor and various foot angles were calculated for the pre- and posttest and compared to a control group (N=15). RESULTS: Claw toe patients have increased pressure under the distal part of the metatarsal head and less pressure under the proximal part of the metatarsal heads compared to healthy controls. After surgery, there was a redistribution of pressure, resulting in a significant decrease of pressure under the distal part and an increase under the proximal part of the metatarsal head, providing a more equal plantar pressure distribution. Except for some small areas under the forefoot, heel and toes, there were no significant differences in pressure distribution between the operated feet and controls. Small, but significant differences between the pre- and postoperative condition were found for the lateral arch angle, calcaneus/malleolus supination and tibio-talar flexion. The score on the FFI improved statistically significant. DISCUSSION: These findings imply that the present operative procedure results in a more equal distribution of the plantar pressure under the forefoot and decrease of pain and offers successful treatment of metatarsalgia based on claw toe deformity.

Is the manual following response an attempt to compensate for inferred self-motion?

If the surrounding of a visual target unexpectedly starts to move during a fast goal-directed hand movement, the hand reflexively moves along with it. This is known as the 'manual following response'. One explanation for this response is that it is a compensation for inferred self-motion in space. Previous studies have shown that background motion gives rise to both postural responses and deviations in goal-directed hand movements. To evaluate whether compensation for inferred self-motion is responsible for the manual responses we examined whether galvanic stimulation of the vestibular system would give rise to similar deviations in hand movements. Standing participants tried to quickly tap on targets that were presented on a horizontal screen. Participants could infer self-motion on some of the trials, either from galvanic vestibular stimulation or from background motion. Both perturbations took place during the hand movement. It took both the head and hand about 45 ms longer to respond to background motion than to respond to galvanic stimulation. The head responded in a similar manner to both types of perturbations. The hand responded about as expected to galvanic stimulation, but much more vigorously to background motion. Thus, the manual response to background motion is probably not a direct consequence of trying to compensate for inferred self-motion. Perhaps the manual following response is a consequence of an error in binding motion information to objects.

Postural responses to target jumps and background motion in a fast pointing task.

When reaching towards an object while standing, one's hand responds very quickly to visual perturbations such as the target being displaced or the background moving. Such responses require postural adjustments. When the background moves, its motion might be attributed to self-motion in a stable world, and thereby induce compensatory postural adjustments that affect the hand. The changes in posture associated with a given hand movement response may, therefore, be different for the two types of perturbations. To see whether they are, we asked standing participants to move their hand in the sagittal direction away from their body to targets displayed on a horizontal screen in front of them. The target displacements and background motion were in the lateral direction. We found hand movement responses that were in line with earlier reports, with a latency that was slightly shorter for target displacements than for background motion, and that was independent of target displacement size or background motion speed. The trunk responded to both perturbations with a modest lateral sway. The two main findings were that the upper trunk responded even before the hand did so and that the head responded to background motion but hardly responded to target displacements. These findings suggest that postural adjustments associated with adjusting the hand movement precede the actual adjustments to the movement of the hand, while at the same time, participants try to keep their head stable on the basis of visual information.

Correction to: Postural responses to target jumps and background motion in a fast pointing task.

The original publication of this paper contained an error. The background motion speeds were actually 20 and 60 cm/s instead of the 2 and 6 cm/s mentioned in the paper (also in figures). It does not affect any of the results, interpretation or conclusion.

30 min of treadmill walking at self-selected speed does not increase gait variability in independent elderly.

Walking is one of the preferred exercises among elderly, but could a prolonged walking increase gait variability, a risk factor for a fall in the elderly? Here we determine whether 30 min of treadmill walking increases coefficient of variation of gait in elderly. Because gait responses to exercise depend on fitness level, we included 15 sedentary and 15 active elderly. Sedentary participants preferred a lower gait speed and made smaller steps than the actives. Step length coefficient of variation decreased ~16.9% by the end of the exercise in both the groups. Stride length coefficient of variation decreased ~9% after 10 minutes of walking, and sedentary elderly showed a slightly larger step width coefficient of variation (~2%) at 10 min than active elderly. Active elderly showed higher walk ratio (step length/cadence) than sedentary in all times of walking, but the times did not differ in both the groups. In conclusion, treadmill gait kinematics differ between sedentary and active elderly, but changes over time are similar in sedentary and active elderly. As a practical implication, 30 min of walking might be a good strategy of exercise for elderly, independently of the fitness level, because it did not increase variability in step and stride kinematics, which is considered a risk of fall in this population.

Online adjustments of leg movements in healthy young and old.

Online movement adjustments are crucial for daily life. This is especially true for leg movements in relation to gait, where failed adjustments can lead to falls, especially in elderly. However, most research has focused on reach adjustments following changes in target location. This arm research reports two categories of online adjustments (see Gaveau et al., Neuropsychologia 55:25-40, 2014 for review). Small, frequently undetected, target location shifts invoke fast, automatic adjustments, usually without awareness. In contrast, large target location shifts can lead to slow, voluntary adjustments. These fast and slow adjustments presumably rely on different neural networks, with a possible role for subcortical pathways for the fast responses. Do leg movement adjustments also fall into these two categories? We review the literature on leg movement adjustments and show that it is indeed possible to discern fast and slow adjustments. More specifically, we provide an overview of studies showing adjustments during step preparation, initiation, unobstructed, and obstructed gait. Fast adjustments were found both during stepping and gait. In the extreme case, even step adjustments appear to be further modifiable online, e.g., when avoiding obstacles during tripping. In older adults, movement adjustments are generally slower and of smaller magnitude, consistent with a greater risk of falling. However, fast responses seem less affected by aging, consistent with the idea of independent parallel mechanisms controlling movement adjustments (Gomi, Curr Opin Neurobiol 18:558-567, 2008). Finally, putative neural pathways are discussed.

Two-stage muscle activity responses in decisions about leg movement adjustments during trip recovery.

Studies on neural decision making mostly investigated fast corrective adjustments of arm movements. However, fast leg movement corrections deserve attention as well, since they are often required to avoid falling after balance perturbations. The present study aimed at elucidating the mechanisms behind fast corrections of tripping responses by analyzing the concomitant leg muscle activity changes. This was investigated in seven young adults who were tripped in between normal walking trials and took a recovery step by elevating the tripped leg over the obstacle. In some trials, a forbidden landing zone (FZ) was presented behind the obstacle, at the subjects' preferred foot landing position, forcing a step correction. Muscle activity of the tripped leg gastrocnemius medialis (iGM), tibialis anterior (iTA), rectus femoris (iRF), and biceps femoris (iBF) muscles was compared between normal trips presented before any FZ appearance, trips with a FZ, and normal trips presented in between trips with a FZ ("catch" trials). When faced with a real or expected (catch trials) FZ, subjects shortened their recovery steps. The underlying changes in muscle activity consisted of two stages. The first stage involved reduced iGM activity, occurring at a latency shorter than voluntary reaction, followed by reduced iTA and increased iBF and iGM activities occurring at longer latencies. The fast response was not related to step shortening, but longer latency responses clearly were functional. We suggest that the initial response possibly acts as a "pause," allowing the nervous system to integrate the necessary information and prepare the subsequent, functional movement adjustment.

Slow maturation of planning in obstacle avoidance in humans.

Complex gait (e.g., obstacle avoidance) requires a higher cognitive load than simple steady-state gait, which is a more automated movement. The higher levels of the central nervous system, responsible for adjusting motor plans to complex gait, develop throughout childhood into adulthood. Therefore, we hypothesize that gait strategies in complex gait are likely to mature until adulthood as well. However, little is known about the maturation of complex gait from childhood into adolescence and adulthood. To address this issue, we investigated obstacle avoidance in forty-four 8- to 18-yr-old participants who walked at preferred speed along a 6-m walkway on which a planar obstacle (150% of step length, 1 m wide) was projected. Participants avoided the obstacle by stepping over this projection, while lower body kinematics were recorded. Results showed that step length and speed adjustments during successful obstacle avoidance were similar across all ages, even though younger children modified step width to a greater extent. Additionally, the younger children used larger maximal toe elevations and take-off distances than older children. Moreover, during unsuccessful trials, younger children deployed exaggerated take-off distances, which resulted in obstacle contact upon the consecutive heel strike. These results indicate that obstacle avoidance is not fully matured in younger children, and that the inability to plan precise foot placements is an important factor contributing to failures in obstacle avoidance.

Cutaneous reflex modulation and self-induced reflex attenuation in cerebellar patients.

Modulation of cutaneous reflexes is important in the neural control of walking, yet knowledge about underlying neural pathways is still incomplete. Recent studies have suggested that the cerebellum is involved. Here we evaluated the possible roles of the cerebellum in cutaneous reflex modulation and in attenuation of self-induced reflexes. First we checked whether leg muscle activity during walking was similar in patients with focal cerebellar lesions and in healthy control subjects. We then recorded cutaneous reflex activity in leg muscles during walking. Additionally, we compared reflexes after standard (computer triggered) stimuli with reflexes after self-induced stimuli for both groups. Biceps femoris and gastrocnemius medialis muscle activity was increased in the patient group compared with the control subjects, suggesting a coactivation strategy to reduce instability of gait. Cutaneous reflex modulation was similar between healthy control subjects and cerebellar patients, but the latter appeared less able to attenuate reflexes to self-induced stimuli. This suggests that the cerebellum is not primarily involved in cutaneous reflex modulation but that it could act in attenuation of self-induced reflex responses. The latter role in locomotion would be consistent with the common view that the cerebellum predicts sensory consequences of movement.

Gait asymmetry during early split-belt walking is related to perception of belt speed difference.

Gait adaptation is essential for humans to walk according to the different demands of the environment. Although locomotor adaptation has been studied in different contexts and in various patient populations, the mechanisms behind locomotor adaptation are still not fully understood. The aim of the present study was to test two opposing hypotheses about the control of split-belt walking, one based on avoidance of limping and the other on avoiding limb excursion asymmetry. We assessed how well cerebellar patients with focal lesions and healthy control participants could sense differences between belt speeds during split-belt treadmill walking and correlated this to split-belt adaptation parameters. The ability to perceive differences between belt speeds was similar between the cerebellar patients and the healthy controls. After combining all participants, we observed a significant inverse correlation between stance time symmetry and limb excursion symmetry during the early phase of split-belt walking. Participants who were better able to perceive belt speed differences (e.g., they had a lower threshold and hence were able to detect a smaller speed difference) walked with the smallest asymmetry in stance time and the largest asymmetry in limb excursion. Our data support the hypothesis that humans aim to minimize (temporal) limping rather than (spatial) limb excursion asymmetry when using their perception of belt speed differences in the early phase of adaptation to split-belt walking.

Adaptation and aftereffects of split-belt walking in cerebellar lesion patients.

To walk efficiently and stably on different surfaces under various constrained conditions, humans need to adapt their gait pattern substantially. Although the mechanisms behind locomotor adaptation are still not fully understood, the cerebellum is thought to play an important role. In this study we aimed to address the specific localization of cerebellar involvement in split-belt adaptation by comparing performance in patients with stable focal lesions after cerebellar tumor resection and in healthy controls. We observed that changes in symmetry of those parameters that were most closely related to interlimb coordination (such as step length and relative double stance time) were similar between healthy controls and cerebellar patients during and after split-belt walking. In contrast, relative stance times (proportions of stance in the gait cycle) were more asymmetric for the patient group than for the control group during the early phase of the post-split-belt condition. Patients who walked with more asymmetric relative stance times were more likely to demonstrate lesions in vermal lobules VI and Crus II. These results confirm that deficits in gait adaptation vary with ataxia severity and between patients with different types of cerebellar damage.

Regional volumes in brain stem and cerebellum are associated with postural impairments in young brain-injured patients.

Many patients with traumatic brain injury (TBI) suffer from postural control impairments that can profoundly affect daily life. The cerebellum and brain stem are crucial for the neural control of posture and have been shown to be vulnerable to primary and secondary structural consequences of TBI. The aim of this study was to investigate whether morphometric differences in the brain stem and cerebellum can account for impairments in static and dynamic postural control in TBI. TBI patients (n = 18) and healthy controls (n = 30) completed three challenging postural control tasks on the EquiTest® system (Neurocom). Infratentorial grey matter (GM) and white matter (WM) volumes were analyzed with cerebellum-optimized voxel-based morphometry using the spatially unbiased infratentorial toolbox. Volume loss in TBI patients was revealed in global cerebellar GM, global infratentorial WM, middle cerebellar peduncles, pons and midbrain. In the TBI group and across both groups, lower postural control performance was associated with reduced GM volume in the vermal/paravermal regions of lobules I-IV, V and VI. Moreover, across all participants, worse postural control performance was associated with lower WM volume in the pons, medulla, midbrain, superior and middle cerebellar peduncles and cerebellum. This is the first study in TBI patients to demonstrate an association between postural impairments and reduced volume in specific infratentorial brain areas. Volumetric measures of the brain stem and cerebellum may be valuable prognostic markers of the chronic neural pathology, which complicates rehabilitation of postural control in TBI.

Quick foot placement adjustments during gait: direction matters.

To prevent falls, adjustment of foot placement is a frequently used strategy to regulate and restore gait stability. While foot trajectory adjustments have been studied during discrete stepping, online corrections during walking are more common in daily life. Here, we studied quick foot placement adjustments during gait, using an instrumented treadmill equipped with a projector, which allowed us to project virtual stepping stones. This allowed us to shift some of the approaching stepping stones in a chosen direction at a given moment, such that participants were forced to adapt their step in that specific direction and had varying time available to do so. Thirteen healthy participants performed six experimental trials all consisting of 580 stepping stones, and 96 of those stones were shifted anterior, posterior or lateral at one out of four distances from the participant. Overall, long-step gait adjustments were performed more successfully than short-step and side-step gait adjustments. We showed that the ability to execute movement adjustments depends on the direction of the trajectory adjustment. Our findings suggest that choosing different leg movement adjustments for obstacle avoidance comes with different risks and that strategy choice does not depend exclusively on environmental constraints. The used obstacle avoidance strategy choice might be a trade-off between the environmental factors (i.e., the cost of a specific adjustment) and individuals' ability to execute a specific adjustment with success (i.e., the associated execution risk).

Effects of aging and dual tasking on step adjustments to perturbations in visually cued walking.

Making step adjustments is an essential component of walking. However, the ability to make step adjustments may be compromised when the walker's attentional capacity is limited. This study compared the effects of aging and dual tasking on step adjustments in response to stepping-target perturbations during visually cued treadmill walking. Fifteen older adults (69.4 ± 5.0 years; mean ± SD) and fifteen young adults (25.4 ± 3.0 years) walked at a speed of 3 km/h on a treadmill. Both groups performed visually cued step adjustments in response to unpredictable shifts of projected stepping targets in forward (FW), backward (BW) or sideward (SW) directions, at different levels of task difficulty [which increased as the available response distance (ARD) decreased], and with and without dual tasking (auditory Stroop task). In both groups, step adjustments were smaller than required. For FW and BW shifts, older adults undershot more under dual-task conditions. For these shifts, ARD affected the age groups differentially. For SW shifts, larger errors were found for older adults, dual tasking and the most difficult ARD. Stroop task performance did not differ between groups in all conditions. Older adults have more difficulty than young adults to make corrective step adjustments while walking, especially under dual-tasking conditions. Furthermore, they seemed to prioritize the cognitive task over the step adjustment task, a strategy that may pose aging populations at a greater fall risk. For comparable task difficulty, the older adults performed considerably worse than the young adults, indicating a decreased ability to adjust steps under time pressure.

Cortical control of normal gait and precision stepping: an fNIRS study.

Recently, real time imaging of the cortical control of gait became possible with functional near-infrared spectroscopy (fNIRS). So far, little is known about the activations of various cortical areas in more complex forms of gait, such as precision stepping. From previous work on animals and humans one would expect precision stepping to elicit extra activity in the sensorimotor cortices (S1/M1), supplementary motor area (SMA), as well as in prefrontal cortices (PFC). In the current study, hemodynamic changes in the PFC, SMA, M1, and S1 were measured with fNIRS. In contrast to previous fNIRS gait studies, the technique was optimized by the use of reference channels (to correct for superficial hemodynamic interference). Eleven subjects randomly performed ten trials of treadmill walking at 3 km/h (normal walking) and ten trials of 3 km/h treadmill walking on predefined spots for the left and right foot presented on the treadmill (precision stepping). The walking trials of approximately 35 seconds were alternated with rest periods of 25-35 seconds consisting of quiet standing. The PFC revealed profound activation just prior to the onset of both walking tasks. There was also extra activation of the PFC during the first half of the task period for precision stepping. The SMA showed mainly increased activation prior to the start of both tasks. In contrast, the sensorimotor cortex did not show a change in activation during either task as compared to a condition of standing. The SMA, M1, and S1 revealed no significant differences between normal walking and precision stepping. It was concluded that fNIRS is suited to record the planning and initiation of gait. The lack of M1/S1 activation during gait suggests that even in the current precision stepping task the control of ongoing gait depended mostly on subcortical automatisms, while motor cortex contributions did not differ between standing and walking.