A critical time window for recovery extends beyond one-year post-stroke.

The impact of rehabilitation on post-stroke motor recovery and its dependency on the patient's chronicity remain unclear. The field has widely accepted the notion of a proportional recovery rule with a "critical window for recovery" within the first 3-6 mo poststroke. This hypothesis justifies the general cessation of physical therapy at chronic stages. However, the limits of this critical window have, so far, been poorly defined. In this analysis, we address this question, and we further explore the temporal structure of motor recovery using individual patient data from a homogeneous sample of 219 individuals with mild to moderate upper-limb hemiparesis. We observed that improvement in body function and structure was possible even at late chronic stages. A bootstrapping analysis revealed a gradient of enhanced sensitivity to treatment that extended beyond 12 mo poststroke. Clinical guidelines for rehabilitation should be revised in the context of this temporal structure. NEW & NOTEWORTHY Previous studies in humans suggest that there is a 3- to 6-mo "critical window" of heightened neuroplasticity poststroke. We analyze the temporal structure of recovery in patients with hemiparesis and uncover a precise gradient of enhanced sensitivity to treatment that expands far beyond the limits of the so-called critical window. These findings highlight the need for providing therapy to patients at the chronic and late chronic stages.

Effect of Specific Over Nonspecific VR-Based Rehabilitation on Poststroke Motor Recovery: A Systematic Meta-analysis.

BACKGROUND: Despite the rise of virtual reality (VR)-based interventions in stroke rehabilitation over the past decade, no consensus has been reached on its efficacy. This ostensibly puzzling outcome might not be that surprising given that VR is intrinsically neutral to its use-that is, an intervention is effective because of its ability to mobilize recovery mechanisms, not its technology. As VR systems specifically built for rehabilitation might capitalize better on the advantages of technology to implement neuroscientifically grounded protocols, they might be more effective than those designed for recreational gaming. OBJECTIVE: We evaluate the efficacy of specific VR (SVR) and nonspecific VR (NSVR) systems for rehabilitating upper-limb function and activity after stroke. METHODS: We conducted a systematic search for randomized controlled trials with adult stroke patients to analyze the effect of SVR or NSVR systems versus conventional therapy (CT). RESULTS: We identified 30 studies including 1473 patients. SVR showed a significant impact on body function (standardized mean difference [SMD] = 0.23; 95% CI = 0.10 to 0.36; P = .0007) versus CT, whereas NSVR did not (SMD = 0.16; 95% CI = -0.14 to 0.47; P = .30). This result was replicated in activity measures. CONCLUSIONS: Our results suggest that SVR systems are more beneficial than CT for upper-limb recovery, whereas NSVR systems are not. Additionally, we identified 6 principles of neurorehabilitation that are shared across SVR systems and are possibly responsible for their positive effect. These findings may disambiguate the contradictory results found in the current literature.

Domiciliary VR-Based Therapy for Functional Recovery and Cortical Reorganization: Randomized Controlled Trial in Participants at the Chronic Stage Post Stroke.

BACKGROUND: Most stroke survivors continue to experience motor impairments even after hospital discharge. Virtual reality-based techniques have shown potential for rehabilitative training of these motor impairments. Here we assess the impact of at-home VR-based motor training on functional motor recovery, corticospinal excitability and cortical reorganization. OBJECTIVE: The aim of this study was to identify the effects of home-based VR-based motor rehabilitation on (1) cortical reorganization, (2) corticospinal tract, and (3) functional recovery after stroke in comparison to home-based occupational therapy. METHODS: We conducted a parallel-group, controlled trial to compare the effectiveness of domiciliary VR-based therapy with occupational therapy in inducing motor recovery of the upper extremities. A total of 35 participants with chronic stroke underwent 3 weeks of home-based treatment. A group of subjects was trained using a VR-based system for motor rehabilitation, while the control group followed a conventional therapy. Motor function was evaluated at baseline, after the intervention, and at 12-weeks follow-up. In a subgroup of subjects, we used Navigated Brain Stimulation (NBS) procedures to measure the effect of the interventions on corticospinal excitability and cortical reorganization. RESULTS: Results from the system's recordings and clinical evaluation showed significantly greater functional recovery for the experimental group when compared with the control group (1.53, SD 2.4 in Chedoke Arm and Hand Activity Inventory). However, functional improvements did not reach clinical significance. After the therapy, physiological measures obtained from a subgroup of subjects revealed an increased corticospinal excitability for distal muscles driven by the pathological hemisphere, that is, abductor pollicis brevis. We also observed a displacement of the centroid of the cortical map for each tested muscle in the damaged hemisphere, which strongly correlated with improvements in clinical scales. CONCLUSIONS: These findings suggest that, in chronic stages, remote delivery of customized VR-based motor training promotes functional gains that are accompanied by neuroplastic changes. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number NCT02699398 (Archived by ClinicalTrials.gov at https://clinicaltrials.gov/ct2/show/NCT02699398?term=NCT02699398&rank=1).

A Spatial-Context Effect in Recognition Memory.

We designed a novel experiment to investigate the modulation of human recognition memory by environmental context. Human participants were asked to navigate through a four-arm Virtual Reality (VR) maze in order to find and memorize discrete items presented at specific locations in the environment. They were later on tested on their ability to recognize items as previously presented or new. By manipulating the spatial position of half of the studied items during the testing phase of our experiment, we could assess differences in performance related to the congruency of environmental information at encoding and retrieval. Our results revealed that spatial context had a significant effect on the quality of memory. In particular, we found that recognition performance was significantly better in trials in which contextual information was congruent as opposed to those in which it was different. Our results are in line with previous studies that have reported spatial-context effects in recognition memory, further characterizing their magnitude under ecologically valid experimental conditions.

Counteracting learned non-use in chronic stroke patients with reinforcement-induced movement therapy.

BACKGROUND: After stroke, patients who suffer from hemiparesis tend to suppress the use of the affected extremity, a condition called learned non-use. Consequently, the lack of training may lead to the progressive deterioration of motor function. Although Constraint-Induced Movement Therapies (CIMT) have shown to be effective in treating this condition, the method presents several limitations, and the high intensity of its protocols severely compromises its adherence. We propose a novel rehabilitation approach called Reinforcement-Induced Movement Therapy (RIMT), which proposes to restore motor function through maximizing arm use. This is achieved by exposing the patient to amplified goal-oriented movements in VR that match the intended actions of the patient. We hypothesize that through this method we can increase the patients self-efficacy, reverse learned non-use, and induce long-term motor improvements. METHODS: We conducted a randomized, double-blind, longitudinal clinical study with 18 chronic stroke patients. Patients performed 30 minutes of daily VR-based training during six weeks. During training, the experimental group experienced goal-oriented movement amplification in VR. The control group followed the same training protocol but without movement amplification. Evaluators blinded to group designation performed clinical measurements at the beginning, at the end of the training and at 12-weeks follow-up. We used the Fugl-Meyer Assessment for the upper extremities (UE-FM) (Sanford et al., Phys Ther 73:447-454, 1993) as a primary outcome measurement of motor recovery. Secondary outcome measurements included the Chedoke Arm and Hand Activity Inventory (CAHAI-7) (Barreca et al., Arch Phys Med Rehabil 6:1616-1622, 2005) for measuring functional motor gains in the performance of Activities of Daily Living (ADLs), the Barthel Index (BI) for the evaluation of the patient's perceived independence (Collin et al., Int Disabil Stud 10:61-63, 1988), and the Hamilton scale (Knesevich et al., Br J Psychiatr J Mental Sci 131:49-52, 1977) for the identification of improvements in mood disorders that could be induced by the reinforcement-based intervention. In order to study and predict the effects of this intervention we implemented a computational model of recovery after stroke. RESULTS: While both groups showed significant motor gains at 6-weeks post-treatment, only the experimental group continued to exhibit further gains in UE-FM at 12-weeks follow-up (p<.05). This improvement was accompanied by a significant increase in arm-use during training in the experimental group. CONCLUSIONS: Implicitly reinforcing arm-use by augmenting visuomotor feedback as proposed by RIMT seems beneficial for inducing significant improvement in chronic stroke patients. By challenging the patients' self-limiting believe system and perceived low self-efficacy this approach might counteract learned non-use. TRIAL REGISTRATION: Clinical Trials NCT02657070 .

Erratum to: The visual amplification of goal-oriented movements counteracts acquired non-use in hemiparetic stroke patients.

Unfortunately, in the original version of this article [1] the sentence "This project was supported through ERC project cDAC (FP7-IDEAS-ERC 341196), EC H2020 project socSMCs (H2020-EU.1.2.2. 641321) and MINECO project SANAR (Gobierno de España)" was missing from the acknowledgements.The acknowledgements have been correctly included in full in this erratum.

The visual amplification of goal-oriented movements counteracts acquired non-use in hemiparetic stroke patients.

BACKGROUND: Stroke-induced impairments result from both primary and secondary causes, i.e. damage to the brain and the acquired non-use of the impaired limbs. Indeed, stroke patients often under-utilize their paretic limb despite sufficient residual motor function. We hypothesize that acquired non-use can be overcome by reinforcement-based training strategies. METHODS: Hemiparetic stroke patients (n = 20, 11 males, 9 right-sided hemiparesis) were asked to reach targets appearing in either the real world or in a virtual environment. Sessions were divided into 3 phases: baseline, intervention and washout. During the intervention the movement of the virtual representation of the patients' paretic limb was amplified towards the target. RESULTS: We found that the probability of using the paretic limb during washout was significantly higher in comparison to baseline. Patients showed generalization of these results by displaying a more substantial workspace in real world task. These gains correlated with changes in effector selection patterns. CONCLUSIONS: The amplification of the movement of the paretic limb in a virtual environment promotes the use of the paretic limb in stroke patients. Our findings indicate that reinforcement-based therapies may be an effective approach for counteracting learned non-use and may modulate motor performance in the real world.

Adaptive rehabilitation gaming system: on-line individualization of stroke rehabilitation.

The effects of stroke differ considerably in degree and symptoms for different patients. It has been shown that specific, individualized and varied therapy favors recovery. The Rehabilitation Gaming System (RGS) is a Virtual Reality (VR) based rehabilitation system designed following these principles. We have developed two algorithms to control the level of task difficulty that a user of the RGS is exposed to, as well as providing controlled variation in the therapy. In this paper, we compare the two algorithms by running numerical simulations and a study with healthy subjects. We show that both algorithms allow for individualization of the challenge level of the task. Further, the results reveal that the algorithm that iteratively learns a user model for each subject also allows a high variation of the task.

A biologically based model for the integration of sensory-motor contingencies in rules and plans: a prefrontal cortex based extension of the Distributed Adaptive Control architecture.

Intelligence depends on the ability of the brain to acquire and apply rules and representations. At the neuronal level these properties have been shown to critically depend on the prefrontal cortex. Here we present, in the context of the Distributed Adaptive Control architecture (DAC), a biologically based model for flexible control and planning based on key physiological properties of the prefrontal cortex, i.e. reward modulated sustained activity and plasticity of lateral connectivity. We test the model in a series of pertinent tasks, including multiple T-mazes and the Tower of London that are standard experimental tasks to assess flexible control and planning. We show that the model is both able to acquire and express rules that capture the properties of the task and to quickly adapt to changes. Further, we demonstrate that this biomimetic self-contained cognitive architecture generalizes to planning. In addition, we analyze the extended DAC architecture, called DAC 6, as a model that can be applied for the creation of intelligent and psychologically believable synthetic agents.

Interactive visuo-motor therapy system for stroke rehabilitation.

We present a virtual reality (VR)-based motor neurorehabilitation system for stroke patients with upper limb paresis. It is based on two hypotheses: (1) observed actions correlated with self-generated or intended actions engage cortical motor observation, planning and execution areas ("mirror neurons"); (2) activation in damaged parts of motor cortex can be enhanced by viewing mirrored movements of non-paretic limbs. We postulate that our approach, applied during the acute post-stroke phase, facilitates motor re-learning and improves functional recovery. The patient controls a first-person view of virtual arms in tasks varying from simple (hitting objects) to complex (grasping and moving objects). The therapist adjusts weighting factors in the non-paretic limb to move the paretic virtual limb, thereby stimulating the mirror neuron system and optimizing patient motivation through graded task success. We present the system's neuroscientific background, technical details and preliminary results.