Bayesian optimization of peripheral intraneural stimulation protocols to evoke distal limb movements.

Objective.Motor neuroprostheses require the identification of stimulation protocols that effectively produce desired movements. Manual search for these protocols can be very time-consuming and often leads to suboptimal solutions, as several stimulation parameters must be personalized for each subject for a variety of target motor functions. Here, we present an algorithm that efficiently tunes peripheral intraneural stimulation protocols to elicit functionally relevant distal limb movements.Approach.We developed the algorithm using Bayesian optimization (BO) with multi-output Gaussian Processes (GPs) and defined objective functions based on coordinated muscle recruitment. We applied the algorithm offline to data acquired in rats for walking control and in monkeys for hand grasping control and compared different GP models for these two systems. We then performed a preliminary online test in a monkey to experimentally validate the functionality of our method.Main results.Offline, optimal intraneural stimulation protocols for various target motor functions were rapidly identified in both experimental scenarios. Using the model that performed best, the algorithm converged to stimuli that evoked functionally consistent movements with an average number of actions equal to 20% of the search space size in both the rat and monkey animal models. Online, the algorithm quickly guided the observations to stimuli that elicited functional hand gestures, although more selective motor outputs could have been achieved by refining the objective function used.Significance.These results demonstrate that BO can reliably and efficiently automate the tuning of peripheral neurostimulation protocols, establishing a translational framework to configure peripheral motor neuroprostheses in clinical applications. The proposed method can also potentially be applied to optimize motor functions using other stimulation modalities.

A versatile robotic platform for the design of natural, three-dimensional reaching and grasping tasks in monkeys.

OBJECTIVE: Translational studies on motor control and neurological disorders require detailed monitoring of sensorimotor components of natural limb movements in relevant animal models. However, available experimental tools do not provide a sufficiently rich repertoire of behavioral signals. Here, we developed a robotic platform that enables the monitoring of kinematics, interaction forces, and neurophysiological signals during user-defined upper limb tasks for monkeys. APPROACH: We configured the platform to position instrumented objects in a three-dimensional workspace and provide an interactive dynamic force-field. MAIN RESULTS: We show the relevance of our platform for fundamental and translational studies with three example applications. First, we study the kinematics of natural grasp in response to variable interaction forces. We then show simultaneous and independent encoding of kinematic and forces in single unit intra-cortical recordings from sensorimotor cortical areas. Lastly, we demonstrate the relevance of our platform to develop clinically relevant brain computer interfaces in a kinematically unconstrained motor task. SIGNIFICANCE: Our versatile control structure does not depend on the specific robotic arm used and allows for the design and implementation of a variety of tasks that can support both fundamental and translational studies of motor control.

Peripapillary retinal nerve fibre layer thinning rate as a biomarker discriminating stable and progressing relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Peripapillary retinal nerve fibre layer (pRNFL) thickness is a strong candidate as a biomarker of axonal degeneration in multiple sclerosis (MS). The aim was to determine a cut-off value of pRNFL thinning rates in relapsing-remitting MS (RRMS) to discriminate between stable and progressing patients. METHODS: In this 3-year prospective longitudinal study on 141 RRMS patients, annual pRNFL thinning rates (aLpRNFL) were determined by individual linear regression models. The best possible cut-off value discriminating clinically progressing (physical progression or cognitive decline) and stable patients was defined by receiver operating characteristic analysis. Cut-off values were validated using a multivariate logistic regression model. RESULTS: Average aLpRNFL in progressing patients (2.4 µm, SD 2.1) was significantly higher compared to stable patients (0.5 µm, SD 1.2, P < 0.001). At a predefined specificity of 90%, aLpRNFL >1.5 µm was able to distinguish between stable and progressing RRMS with a sensitivity of 76.1%. aLpRNFL >1.5 µm was associated with a 15-fold increased risk of clinically progressing MS (P < 0.001). CONCLUSIONS: A cut-off of aLpRNFL discriminating clinically progressing and stable RRMS was identified. After validation in independent cohorts, this cut-off could be used as a biomarker of axonal degeneration supporting disease monitoring in daily clinical routine.

Combined evaluation of personality, risk and coping in MS patients: A step towards individualized treatment choice - The PeRiCoMS-Study I.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory neurological disease requiring disease-modifying treatment (DMT). To provide patients with the optimal individual therapeutic option, treatment recommendations should be based not only on individual disease course and DMT specific benefit-risk estimates, but also on patient's individual characteristics such as personality, risk attitude and coping strategies. However, these characteristics are difficult to objectify in clinical routine practice without the support of appropriate evaluation instruments. OBJECTIVE: To identify and to assemble an objective test battery measuring personality, risk attitude and coping strategies in MS patients. METHODS: A comprehensive literature search was performed to obtain all questionnaires assessing personality, risk attitude and coping strategies. Availability in German language, validation in a published normative collective and a reliability of >0.70 were required for our purposes. Based on these criteria, we chose the Big-Five-Personality Test, UPPS Impulsive Behaviour Scale, Domain-Specific Risk-Taking scale (DOSPERT), Brief-COPE and Stress & Coping Inventory (SCI). Results were compared to published normative controls of the respective questionnaires. RESULTS: Out of 22 MS patients (7 males, 15 females) participating in this study, 19 (86.4%) completed all questionnaires. The median completion time was 45min (min-max range: 25-60min). The median scores of the MS group were within the average range of published control samples in all questionnaires. CONCLUSIONS: We report that traits of personality, risk attitude and coping strategies can be effectively and feasibly tested in MS patients by the instruments used in our exploratory study. There were no differences between MS patients and healthy controls, thus enabling assessment without being influenced by the diagnosis of MS. After validation in a larger cohort the "PeRiCoMS"-battery will be useful as another step towards a more individualized shared-decision-making in every day routine practice.

Long-term usability and bio-integration of polyimide-based intra-neural stimulating electrodes.

Stimulation of peripheral nerves has transiently restored lost sensation and has the potential to alleviate motor deficits. However, incomplete characterization of the long-term usability and bio-integration of intra-neural implants has restricted their use for clinical applications. Here, we conducted a longitudinal assessment of the selectivity, stability, functionality, and biocompatibility of polyimide-based intra-neural implants that were inserted in the sciatic nerve of twenty-three healthy adult rats for up to six months. We found that the stimulation threshold and impedance of the electrodes increased moderately during the first four weeks after implantation, and then remained stable over the following five months. The time course of these adaptations correlated with the progressive development of a fibrotic capsule around the implants. The selectivity of the electrodes enabled the preferential recruitment of extensor and flexor muscles of the ankle. Despite the foreign body reaction, this selectivity remained stable over time. These functional properties supported the development of control algorithms that modulated the forces produced by ankle extensor and flexor muscles with high precision. The comprehensive characterization of the implant encapsulation revealed hyper-cellularity, increased microvascular density, Wallerian degeneration, and infiltration of macrophages within the endoneurial space early after implantation. Over time, the amount of macrophages markedly decreased, and a layer of multinucleated giant cells surrounded by a capsule of fibrotic tissue developed around the implant, causing an enlargement of the diameter of the nerve. However, the density of nerve fibers above and below the inserted implant remained unaffected. Upon removal of the implant, we did not detect alteration of skilled leg movements and only observed mild tissue reaction. Our study characterized the interplay between the development of foreign body responses and changes in the electrical properties of actively used intra-neural electrodes, highlighting functional stability of polyimide-based implants over more than six months. These results are essential for refining and validating these implants and open a realistic pathway for long-term clinical applications in humans.

Alpine Skiing With total knee ArthroPlasty (ASWAP): physical self-concept, pain, and life satisfaction.

Physical self-concept in the elderly is assumed to be structured in terms of different domains and to contribute substantially to life satisfaction. However, little is known about the role of the physical self-concept in older persons that are engaged in physical activity while suffering from typical age-related impairments or chronic diseases. The present study aimed to investigate the structure of physical self-concept in a group of older persons with total knee arthroplasty (TKA), its development throughout a 12-week skiing intervention, and its importance to life satisfaction. Factor analyses of the present data reveal that the physical self-concept consists of four dimensions addressing strength, flexibility/coordination, endurance, and sportiness. One higher order factor extracted by hierarchical factor analyses reflects a global physical self-concept. The 12-week skiing intervention had no substantial impact in terms of an improvement of self-concept. Life satisfaction is best predicted by positive changes in the subjective ratings between pre- and post-test (i.e., global physical self-concept, flexibility and coordination, and perceived sportiness) and not by objective physical performance (isokinetic strength, endurance, or coordination). Results support the assumption that physical self-concept of older people with TKA is only marginally sensitive to a 12-week skiing intervention.

Alpine Skiing With total knee ArthroPlasty (ASWAP): physical activity, knee function, pain, exertion, and well-being.

This study focused on the psychological and quality of life aspects of resuming alpine skiing practice after total knee arthroplasty (TKA) in elderly skilled skiers. Two data pools were used in order to analyze psychological states: (a) at the beginning, at the end, and 8 weeks after a 12-week skiing intervention; and (b) concerning diurnal variations of states (i.e., skiing days compared with everyday life during intervention and retention phase). In particular, effects of skiing on amount of physical activity and perceived exertion, perceived pain and knee function, and subjective well-being were analyzed using a control group design. Results reveal that the skiing intervention substantially increases the amount of physical activity by the intervention group (122.30 ± 32.38 min/day), compared with the control group (75.14 ± 21.27 min/day) [F (2, 32) = 8.22, P < 0.01, η(2) = 0.34)]. Additionally, the analyses of psychological states demonstrated that skiing goes along with enhanced well-being and no significant impact on perceived pain, exertion or knee function. In sum, alpine skiing can be recommended for older persons with TKA with respect to well-being, perceived pain and knee function, and perceived exertion.

Does a skiing intervention influence the psycho-social characteristics of the elderly?

The purpose of this study was to assess whether a guided alpine skiing intervention lasting 12 weeks has an impact on psycho-social dimensions, measured by subjective assessments, of individuals who are 60+ years of age. A number of well-established questionnaires were used to measure well-being, life satisfaction, self-concept, health status, depression and self-efficacy. The physical self-concept in the domain "strength" increased significantly in the intervention group from pre- to post-test and remained stable through the retention test, whereas the control group demonstrated nearly no alteration. A similar effect was obtained in life satisfaction for the dimension "friends and relatives." On the contrary, psycho-social aspects of the elderly were not negatively influenced. The subjects of this study had very high pre-test scores that might reflect a ceiling effect which, in turn, can explain the marginal positive impact of the intervention. The findings of this study argue for recommending a guided alpine skiing intervention for individuals who are 60 years of age and older with high values in psycho-social variables.

Physical self-concept and physical fitness in elderly individuals.

This investigation examined the relations between physical self-concept and physical fitness (endurance, balance, muscle strength, muscle power) for gaining knowledge about the interrelationship between subjective ratings and objective fitness scores in the elderly in three steps: (1) detecting correlations and changes in time, (2) clarifying the influence of gender, and (3) of a skiing intervention lasting 12 weeks. Physical self-concept was assessed using a modified version of the Physical Self-Concepts (PSK) scales (Stiller et al., 2004) reflecting three first-order factors (endurance, strength, general sportiness) and one second-order factor (global fitness). Objective fitness scores were obtained by VO(2 max), counter movement jump, concentric muscle strength, and static balance. The results reveal that elderly individuals' global physical self and general sportiness are mainly linked to VO(2 max) and concentric muscle strength. Global physical self is predicted by VO(2 max) in females and by physical strength (concentric muscle strength) in males, indicating gender differences. Over time, correlations between subjective ratings and objective fitness scores become stronger in the sense of convergent validity in the skiing intervention group, whereas convergent and divergent validity cannot be supported by data of the control group. In sum, physical self-concept is an important factor in the context of physical intervention programs in the elderly.