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In interventional clinical trials for persons with spinal cord injury (SCI), the influence of experimental biological, pharmacological, or device-related interventions must be differentiated from that of physical and occupational therapy interventions, as rehabilitation influences motor-related outcomes. The International Spinal Cord Injury (ISCI) Physical Therapy–Occupational Therapy Basic Data Set (PT-OT BDS) was developed with the intent to track the content and time of rehabilitation interventions that are delivered concurrently with experimental interventions. We assessed the reliability of the PT-OT BDS based on agreement between users. Following an online training session, physical therapists (PTs) and occupational therapists (OTs) from 10 SCI clinical centers across 7 countries participated. At each center, pairs of therapists (a treating therapist and an observing therapist; PT/PT, OT/OT, or PT/OT) used the PT-OT BDS to record the content and time of therapy sessions for 20 patients. Data were analyzed to determine agreement between therapist pairs regarding the content of the therapy session. The influence of therapist characteristics (professional discipline [PT/OT], years of experience working with individuals with SCI), patient characteristics (level [tetraplegia/paraplegia] and severity [complete/incomplete] of injury), setting (inpatient/outpatient), and whether the center was U.S.- versus non-U.S.-based were also analyzed. There was high agreement for five of seven categories and medium agreement for the remaining two categories. For six of the seven intervention categories, there were no significant differences between the treating and the observing therapists in the percentage of instances that a specific category was selected. Characteristics of the therapists, characteristics of the patient, therapy setting, and global location of the center had no meaningful influence on level of agreement between therapist pairs. The BDS is reliable for use acr

STUDY DESIGN Multicentre-observational study. OBJECTIVES The 6-minute walk test (6mWT) is an established assessment of walking function in individuals with spinal cord injury (SCI). However, walking 6 min can be demanding for severely impaired individuals. The 2-minute walk test (2mWT) could be an appropriate alternative that has already been validated in other neurological disorders. The aim of this study was to assess construct validity and test-rest reliability of the 2mWT in individuals with SCI. In addition, the influence of walking performance on sensitivity to change of the 2mWT was assessed. SETTING Swiss Paraplegic Center Nottwil, Switzerland; Balgrist University Hospital, Zürich, Switzerland. METHODS Fifty individuals (aged 18-79) with SCI (neurological level of injury: C1-L3, AIS: A-D) were assessed on two test days separated by 1 to 7 days. The first assessment consisted of a 2mWT familiarization, followed by a 2mWT and 10-meter walk test (10MWT) (including the Walking Index for Spinal Cord Injury (WISCI II)) in randomized order. The second assessment consisted of 2mWT and 6mWT in randomized order. Tests were separated by at least 30 min of rest. RESULTS The interclass correlation coefficient between the 2mWT assessed on the first and second test day was excellent (r = 0.980, p < 0.001). The 2mWT correlated very strongly with the 6mWT (r = 0.992, p < 0.001) and the 10MWT (r = 0.964, p < 0.001), and moderately with the WISCI II (r = 0.571, p < 0.001). Sensitivity to change was slightly affected by walking performance. CONCLUSION The 2mWT is a valid and reliable alternative to the 6mWT to measure walking function in individuals with SCI. TRIAL REGISTRATION NCT04555759.

It has been proposed that a form of cortical reorganization (changes in functional connectivity between brain areas) can be assessed with resting-state (rs) functional MRI (fMRI). Here, we report a longitudinal data set collected from 19 patients with subcortical stroke and 11 controls. Patients were imaged up to five times over 1 year. We found no evidence, using rs-fMRI, for longitudinal poststroke cortical connectivity changes despite substantial behavioral recovery. These results could be construed as questioning the value of resting-state imaging. Here, we argue instead that they are consistent with other emerging reasons to challenge the idea of motor-recovery-related cortical reorganization poststroke when conceived of as changes in connectivity between cortical areas.NEW & NOTEWORTHY We investigated longitudinal changes in functional connectivity after stroke. Despite substantial motor recovery, we found no differences in functional connectivity patterns between patients and controls, nor any changes over time. Assuming that rs-fMRI is an adequate method to capture connectivity changes between cortical regions after brain injury, these results provide reason to doubt that changes in cortico-cortical connectivity are the relevant mechanism for promoting motor recovery.

Background Learning and learning-related neuroplasticity in motor cortex are potential mechanisms mediating recovery of movement abilities after stroke. These mechanisms depend on dopaminergic projections from midbrain that may encode reward information. Likewise, therapist experience confirms the role of feedback/reward for training efficacy after stroke. Objective To test the hypothesis that rehabilitative training can be enhanced by adding performance feedback and monetary rewards. Methods This multicentric, assessor-blinded, randomized controlled trial used the ArmeoSenso virtual reality rehabilitation system to train 37 first-ever subacute stroke patients in arm-reaching to moving targets. The rewarded group (n = 19) trained with performance feedback (gameplay) and contingent monetary reward. The control group (n = 18) used the same system without monetary reward and with graphically minimized performance feedback. Primary outcome was the change in the two-dimensional reaching space until the end of the intervention period. Secondary clinical assessments were performed at baseline, after 3 weeks of training (15 1-hour sessions), and at 3 month follow-up. Duration and intensity of the interventions as well as concomitant therapy were comparable between groups. Results The two-dimensional reaching space showed an overall improvement but no difference between groups. The rewarded group, however, showed significantly greater improvements from baseline in secondary outcomes assessing arm activity (Box and Block Test at post-training: 6.03±2.95, P = .046 and 3 months: 9.66±3.11, P = .003; Wolf Motor Function Test [Score] at 3 months: .63±.22, P = .007) and arm impairment (Fugl-Meyer Upper Extremity at 3 months: 8.22±3.11, P = .011). Conclusions Although neutral in its primary outcome, the trial signals a potential facilitating effect of reward on training-mediated improvement of arm paresis. Trial registration ClinicalTrials.gov (ID: NCT02257125).

Background Evidence from animal studies suggests that greater reductions in poststroke motor impairment can be attained with significantly higher doses and intensities of therapy focused on movement quality. These studies also indicate a dose-timing interaction, with more pronounced effects if high-intensity therapy is delivered in the acute/subacute, rather than chronic, poststroke period. Objective To compare 2 approaches of delivering high-intensity, high-dose upper-limb therapy in patients with subacute stroke: a novel exploratory neuroanimation therapy (NAT) and modified conventional occupational therapy (COT). Methods A total of 24 patients were randomized to NAT or COT and underwent 30 sessions of 60 minutes time-on-task in addition to standard care. The primary outcome was the Fugl-Meyer Upper Extremity motor score (FM-UE). Secondary outcomes included Action Research Arm Test (ARAT), grip strength, Stroke Impact Scale hand domain, and upper-limb kinematics. Outcomes were assessed at baseline, and days 3, 90, and 180 posttraining. Both groups were compared to a matched historical cohort (HC), which received only 30 minutes of upper-limb therapy per day. Results There were no significant between-group differences in FM-UE change or any of the secondary outcomes at any timepoint. Both high-dose groups showed greater recovery on the ARAT (7.3 ± 2.9 points; P = .011) but not the FM-UE (1.4 ± 2.6 points; P = .564) when compared with the HC. Conclusions Neuroanimation may offer a new, enjoyable, efficient, and scalable way to deliver high-dose and intensive upper-limb therapy.

BACKGROUND Evidence from animal studies suggests that greater reductions in poststroke motor impairment can be attained with significantly higher doses and intensities of therapy focused on movement quality. These studies also indicate a dose-timing interaction, with more pronounced effects if high-intensity therapy is delivered in the acute/subacute, rather than chronic, poststroke period. OBJECTIVE To compare 2 approaches of delivering high-intensity, high-dose upper-limb therapy in patients with subacute stroke: a novel exploratory neuroanimation therapy (NAT) and modified conventional occupational therapy (COT). METHODS A total of 24 patients were randomized to NAT or COT and underwent 30 sessions of 60 minutes time-on-task in addition to standard care. The primary outcome was the Fugl-Meyer Upper Extremity motor score (FM-UE). Secondary outcomes included Action Research Arm Test (ARAT), grip strength, Stroke Impact Scale hand domain, and upper-limb kinematics. Outcomes were assessed at baseline, and days 3, 90, and 180 posttraining. Both groups were compared to a matched historical cohort (HC), which received only 30 minutes of upper-limb therapy per day. RESULTS There were no significant between-group differences in FM-UE change or any of the secondary outcomes at any timepoint. Both high-dose groups showed greater recovery on the ARAT (7.3 ± 2.9 points; P = .011) but not the FM-UE (1.4 ± 2.6 points; P = .564) when compared with the HC. CONCLUSIONS Neuroanimation may offer a new, enjoyable, efficient, and scalable way to deliver high-dose and intensive upper-limb therapy.

INTRODUCTION Motor skill learning can help stroke survivors to cope with motor function deficits but requires many repetitions. One factor that keeps patients motivated is obtaining reward upon successfully completing a motor task. It has been suggested that stroke survivors have deficits in reward processing which may negatively impact skill learning. OBJECTIVE To test the hypothesis that stroke survivors have deficient reward processing during motor skill learning evident in reduced activation in the striatum and its subdivisions in functional magnetic resonance imaging as compared with healthy, age-matched control subjects. METHODS Striatal activity in response to performance dependent feedback and monetary reward was measured in 28 subacute stroke patients and 18 age-matched healthy control subjects during the training of visuomotor tracking an arc-shaped trajectory using the wrist (unimpaired side in patients, dominant side in controls) in an fMRI scanner. RESULTS Despite comparable monetary rewards, stroke patients showed reduced activation in the ventral part (p < 0.01), but not in the dorsal part of the striatum (p = 0.11). 14 patients had their lesion extending into the striatum. The nucleus accumbens as part of the ventral striatum was unlesioned in all participants and still showed a marked hypoactivation in stroke patients as compared with controls (p < 0.001), a finding that could not be explained by motivational differences between the groups. CONCLUSION Striatal hypoactivation in stroke survivors may cause impaired consolidation of motor skills. Stronger rewarding stimuli or drug-mediated enhancement may be needed to normalize reward processing after stroke with positive effects on recovery.

OBJECTIVE Patients with chronic stroke have been shown to have failure to release interhemispheric inhibition (IHI) from the intact to the damaged hemisphere before movement execution (premovement IHI). This inhibitory imbalance was found to correlate with poor motor performance in the chronic stage after stroke and has since become a target for therapeutic interventions. The logic of this approach, however, implies that abnormal premovement IHI is causal to poor behavioral outcome and should therefore be present early after stroke when motor impairment is at its worst. To test this idea, in a longitudinal study, we investigated interhemispheric interactions by tracking patients' premovement IHI for one year following stroke. METHODS We assessed premovement IHI and motor behavior five times over a 1-year period after ischemic stroke in 22 patients and 11 healthy participants. RESULTS We found that premovement IHI was normal during the acute/subacute period and only became abnormal at the chronic stage; specifically, release of IHI in movement preparation worsened as motor behavior improved. In addition, premovement IHI did not correlate with behavioral measures cross-sectionally, whereas the longitudinal emergence of abnormal premovement IHI from the acute to the chronic stage was inversely correlated with recovery of finger individuation. INTERPRETATION These results suggest that interhemispheric imbalance is not a cause of poor motor recovery, but instead might be the consequence of underlying recovery processes. These findings call into question the rehabilitation strategy of attempting to rebalance interhemispheric interactions in order to improve motor recovery after stroke. Ann Neurol 2019;85:502-513.

Kai Lutz,1–3 Mario Widmer1,2,41Department of Neurology, University Hospital Zürich, Zürich, 2Cereneo, Center for Neurology and Rehabilitation, Vitznau, 3Division of Neuropsychology, Institute of Psychology, University of Zürich, Zürich, 4Neural Control of Movement Lab, ETH Zürich, Zürich, SwitzerlandAbstract: Since its introduction in 2000, the monetary incentive delay (MID) task has been used extensively to investigate changes in neural activity in response to the processing of reward and punishment in healthy, but also in clinical populations. Typically, the MID task requires an individual to react to a target stimulus presented after an incentive cue to win or to avoid losing the indicated reward. In doing so, this paradigm allows the detailed examination of different stages of reward processing like reward prediction, anticipation, outcome processing, and consumption as well as the processing of tasks under different reward conditions. This review gives an overview of different utilizations of the MID task by outlining the neuronal processes involved in distinct aspects of human reward processing, such as anticipation versus consumption, reward versus punishment, and, with a special focus, reward-based learning processes. Furthermore, literature on specific influences on reward processing like behavioral, clinical and developmental influences, is reviewed, describing current findings and possible future directions.Keywords: reward, punishment, dopamine, reward system