Computational neurorehabilitation: modeling plasticity and learning to predict recovery

Despite progress in using computational approaches to inform medicine and neuroscience in the last 30 years, there have been few attempts to model the mechanisms underlying sensorimotor rehabilitation. We argue that a fundamental understanding of neurologic recovery, and as a result accurate predictions at the individual level, will be facilitated by developing computational models of the salient neural processes, including plasticity and learning systems of the brain, and integrating them into a context specific to rehabilitation. Here, we therefore discuss Computational Neurorehabilitation, a newly emerging field aimed at modeling plasticity and motor learning to understand and improve movement recovery of individuals with neurologic impairment. We first explain how the emergence of robotics and wearable sensors for rehabilitation is providing data that make development and testing of such models increasingly feasible. We then review key aspects of plasticity and motor learning that such models will incorporate. We proceed by discussing how computational neurorehabilitation models relate to the current benchmark in rehabilitation modeling – regression-based, prognostic modeling. We then critically discuss the first computational neurorehabilitation models, which have primarily focused on modeling rehabilitation of the upper extremity after stroke, and show how even simple models have produced novel ideas for future investigation. Finally, we conclude with key directions for future research, anticipating that soon we will see the emergence of mechanistic models of motor recovery that are informed by clinical imaging results and driven by the actual movement content of rehabilitation therapy as well as wearable sensor-based records of daily activity

Two Distinct Ipsilateral Cortical Representations for Individuated Finger Movements.

Movements of the upper limb are controlled mostly through the contralateral hemisphere. Although overall activity changes in the ipsilateral motor cortex have been reported, their functional significance remains unclear. Using human functional imaging, we analyzed neural finger representations by studying differences in fine-grained activation patterns for single isometric finger presses. We demonstrate that cortical motor areas encode ipsilateral movements in 2 fundamentally different ways. During unimanual ipsilateral finger presses, primary sensory and motor cortices show, underneath global suppression, finger-specific activity patterns that are nearly identical to those elicited by contralateral mirror-symmetric action. This component vanishes when both motor cortices are functionally engaged during bimanual actions. We suggest that the ipsilateral representation present during unimanual presses arises because otherwise functionally idle circuits are driven by input from the opposite hemisphere. A second type of representation becomes evident in caudal premotor and anterior parietal cortices during bimanual actions. In these regions, ipsilateral actions are represented as nonlinear modulation of activity patterns related to contralateral actions, an encoding scheme that may provide the neural substrate for coordinating bimanual movements. We conclude that ipsilateral cortical representations change their informational content and functional role, depending on the behavioral context

Estimating the Relevance of World Disturbances to Explain Savings, Interference and Long-Term Motor Adaptation Effects

Recent studies suggest that motor adaptation is the result of multiple, perhaps linear processes each with distinct time scales. While these models are consistent with some motor phenomena, they can neither explain the relatively fast re-adaptation after a long washout period, nor savings on a subsequent day. Here we examined if these effects can be explained if we assume that the CNS stores and retrieves movement parameters based on their possible relevance. We formalize this idea with a model that infers not only the sources of potential motor errors, but also their relevance to the current motor circumstances. In our model adaptation is the process of re-estimating parameters that represent the body and the world. The likelihood of a world parameter being relevant is then based on the mismatch between an observed movement and that predicted when not compensating for the estimated world disturbance. As such, adapting to large motor errors in a laboratory setting should alert subjects that disturbances are being imposed on them, even after motor performance has returned to baseline. Estimates of this external disturbance should be relevant both now and in future laboratory settings. Estimated properties of our bodies on the other hand should always be relevant. Our model demonstrates savings, interference, spontaneous rebound and differences between adaptation to sudden and gradual disturbances. We suggest that many issues concerning savings and interference can be understood when adaptation is conditioned on the relevance of parameters

Movement variability in stroke patients and controls performing two upper limb functional tasks: a new assessment methodology

Background: In the evaluation of upper limb impairment post stroke there remains a gap between detailed kinematic analyses with expensive motion capturing systems and common clinical assessment tests. In particular, although many clinical tests evaluate the performance of functional tasks, metrics to characterise upper limb kinematics are generally not applicable to such tasks and very limited in scope. This paper reports on a novel, user-friendly methodology that allows for the assessment of both signal magnitude and timing variability in upper limb movement trajectories during functional task performance. In order to demonstrate the technique, we report on a study in which the variability in timing and signal magnitude of data collected during the performance of two functional tasks is compared between a group of subjects with stroke and a group of individually matched control subjects. Methods: We employ dynamic time warping for curve registration to quantify two aspects of movement variability: 1) variability of the timing of the accelerometer signals' characteristics and 2) variability of the signals' magnitude. Six stroke patients and six matched controls performed several trials of a unilateral ('drinking') and a bilateral ('moving a plate') functional task on two different days, approximately 1 month apart. Group differences for the two variability metrics were investigated on both days. Results: For 'drinking from a glass' significant group differences were obtained on both days for the timing variability of the acceleration signals' characteristics (p = 0.002 and p = 0.008 for test and retest, respectively); all stroke patients showed increased signal timing variability as compared to their corresponding control subject. 'Moving a plate' provided less distinct group differences. Conclusion: This initial application establishes that movement variability metrics, as determined by our methodology, appear different in stroke patients as compared to matched controls during unilateral task performance ('drinking'). Use of a user-friendly, inexpensive accelerometer makes this methodology feasible for routine clinical evaluations. We are encouraged to perform larger studies to further investigate the metrics' usefulness when quantifying levels of impairment

The strength of the corticospinal tract not the reticulospinal tract determines upper-limb impairment level and capacity for skill-acquisition in the sub-acute post-stroke period

Background. Upper-limb impairment in patients with chronic stroke appears to be partly attributable to an upregulated reticulospinal tract (RST). Here, we assessed whether the impact of corticospinal (CST) and RST connectivity on motor impairment and skill-acquisition differs in sub-acute stroke, using transcranial magnetic stimulation (TMS)–based proxy measures. Methods. Thirty-eight stroke survivors were randomized to either reach training 3-6 weeks post-stroke (plus usual care) or usual care only. At 3, 6 and 12 weeks post-stroke, we measured ipsilesional and contralesional cortical connectivity (surrogates for CST and RST connectivity, respectively) to weak pre-activated triceps and deltoid muscles with single pulse TMS, accuracy of planar reaching movements, muscle strength (Motricity Index) and synergies (Fugl-Meyer upper-limb score). Results. Strength and presence of synergies were associated with ipsilesional (CST) connectivity to the paretic upper-limb at 3 and 12 weeks. Training led to planar reaching skill beyond that expected from spontaneous recovery and occurred for both weak and strong ipsilesional tract integrity. Reaching ability, presence of synergies, skill-acquisition and strength were not affected by either the presence or absence of contralesional (RST) connectivity. Conclusion. The degree of ipsilesional CST connectivity is the main determinant of proximal dexterity, upper-limb strength and synergy expression in sub-acute stroke. In contrast, there is no evidence for enhanced contralesional RST connectivity contributing to any of these components of impairment. In the sub-acute post-stroke period, the balance of activity between CST and RST may matter more for the paretic phenotype than RST upregulation per se

Agreed Definitions and a Shared Vision for New Standards in Stroke Recovery Research: The Stroke Recovery and Rehabilitation Roundtable Taskforce

The first Stroke Recovery and Rehabilitation Roundtable established a game changing set of new standards for stroke recovery research. Common language and definitions were required to develop an agreed framework spanning the four working groups: translation of basic science, biomarkers of stroke recovery, measurement in clinical trials and intervention development and reporting. This paper outlines the working definitions established by our group and an agreed vision for accelerating progress in stroke recovery research

Asymmetric interlimb transfer of concurrent adaptation to opposing dynamic forces

Interlimb transfer of a novel dynamic force has been well documented. It has also been shown that unimanual adaptation to opposing novel environments is possible if they are associated with different workspaces. The main aim of this study was to test if adaptation to opposing velocity dependent viscous forces with one arm could improve the initial performance of the other arm. The study also examined whether this interlimb transfer occurred across an extrinsic, spatial, coordinative system or an intrinsic, joint based, coordinative system. Subjects initially adapted to opposing viscous forces separated by target location. Our measure of performance was the correlation between the speed profiles of each movement within a force condition and an ‘average’ trajectory within null force conditions. Adaptation to the opposing forces was seen during initial acquisition with a significantly improved coefficient in epoch eight compared to epoch one. We then tested interlimb transfer from the dominant to non-dominant arm (D → ND) and vice-versa (ND → D) across either an extrinsic or intrinsic coordinative system. Interlimb transfer was only seen from the dominant to the non-dominant limb across an intrinsic coordinative system. These results support previous studies involving adaptation to a single dynamic force but also indicate that interlimb transfer of multiple opposing states is possible. This suggests that the information available at the level of representation allowing interlimb transfer can be more intricate than a general movement goal or a single perceived directional error

Distinct Haptic Cues Do Not Reduce Interference when Learning to Reach in Multiple Force Fields

Background: Previous studies of learning to adapt reaching movements in the presence of novel forces show that learning multiple force fields is prone to interference. Recently it has been suggested that force field learning may reflect learning to manipulate a novel object. Within this theoretical framework, interference in force field learning may be the result of static tactile or haptic cues associated with grasp, which fail to indicate changing dynamic conditions. The idea that different haptic cues (e.g. those associated with different grasped objects) signal motor requirements and promote the learning and retention of multiple motor skills has previously been unexplored in the context of force field learning. Methodology/Principle Findings: The present study tested the possibility that interference can be reduced when two different force fields are associated with differently shaped objects grasped in the hand. Human subjects were instructed to guide a cursor to targets while grasping a robotic manipulandum, which applied two opposing velocity-dependent curl fields to the hand. For one group of subjects the manipulandum was fitted with two different handles, one for each force field. No attenuation in interference was observed in these subjects relative to controls who used the same handle for both force fields. Conclusions/Significance: These results suggest that in the context of the present learning paradigm, haptic cues on their own are not sufficient to reduce interference and promote learning multiple force fields

Haptic guidance improves the visuo-manual tracking of trajectories

BACKGROUND: Learning to perform new movements is usually achieved by following visual demonstrations. Haptic guidance by a force feedback device is a recent and original technology which provides additional proprioceptive cues during visuo-motor learning tasks. The effects of two types of haptic guidances-control in position (HGP) or in force (HGF)-on visuo-manual tracking ("following") of trajectories are still under debate. METHODOLOGY/PRINCIPALS FINDINGS: Three training techniques of haptic guidance (HGP, HGF or control condition, NHG, without haptic guidance) were evaluated in two experiments. Movements produced by adults were assessed in terms of shapes (dynamic time warping) and kinematics criteria (number of velocity peaks and mean velocity) before and after the training sessions. CONCLUSION/SIGNIFICANCE: These results show that the addition of haptic information, probably encoded in force coordinates, play a crucial role on the visuo-manual tracking of new trajectories

Compensation for Changing Motor Uncertainty

When movement outcome differs consistently from the intended movement, errors are used to correct subsequent movements (e.g., adaptation to displacing prisms or force fields) by updating an internal model of motor and/or sensory systems. Here, we examine changes to an internal model of the motor system under changes in the variance structure of movement errors lacking an overall bias. We introduced a horizontal visuomotor perturbation to change the statistical distribution of movement errors anisotropically, while monetary gains/losses were awarded based on movement outcomes. We derive predictions for simulated movement planners, each differing in its internal model of the motor system. We find that humans optimally respond to the overall change in error magnitude, but ignore the anisotropy of the error distribution. Through comparison with simulated movement planners, we found that aimpoints corresponded quantitatively to an ideal movement planner that updates a strictly isotropic (circular) internal model of the error distribution. Aimpoints were planned in a manner that ignored the direction-dependence of error magnitudes, despite the continuous availability of unambiguous information regarding the anisotropic distribution of actual motor errors