Technology-Assisted Upper Limb Therapy (TAULT): Evaluation of Clinical Practice at a Specialised Centre for Spinal Cord Injury in Switzerland.

(1) Improving upper limb function is essential for people with tetraplegia. Although promising, technology-assisted upper limb training is understudied in this population. This article describes its implementation in a Swiss spinal cord injury rehabilitation centre and reports on the observed changes. (2) A retrospective evaluation of clinical data from January 2018 to June 2020 examined patient characteristics, training parameters, goal-setting practices, goal achievement, and changes in muscle strength over the course of technology-assisted upper limb training. (3) Data analysis included 61 individuals, 68.9% of whom had a spinal cord injury. The ArmeoSpring was the most frequently used device. The typical treatment regimen was three 25 min sessions per week, with evaluations approximately every six weeks. The 1:1 sessions, delivered by specialised staff, focused primarily on improving shoulder movement and the ability to eat and drink. Functional goals were set using a grid. Performance on selected goals in the areas of 'body functions' and 'activities & participation' as well as muscle strength, increased over the course of training. (4) The ArmeoSpring has broad applicability. Despite the observed improvements, the isolated effect of technology-assisted upper limb training cannot be concluded due to the lack of a control group and various concurrent interventions.

Reinforcement Learning Is Impaired in the Sub-acute Post-stroke Period.

Background: Neurorehabilitation approaches are frequently predicated on motor learning principles. However, much is left to be understood of how different kinds of motor learning are affected by stroke causing hemiparesis. Here we asked if two kinds of motor learning often employed in rehabilitation, (1) reinforcement learning and (2) error-based adaptation, are altered at different times after stroke. Methods: In a cross-sectional design, we compared learning in two groups of patients with stroke, matched for their baseline motor execution deficit on the paretic side. The early group was tested within 3 months following stroke (N = 35) and the late group was tested more than 6 months after stroke (N = 30). Two types of task were studied: one based on reinforcement learning and the other on error-based learning. Results: We found that reinforcement learning was impaired in the early but not the late group, whereas error-based learning was unaffected compared to controls. These findings could not be attributed to differences in baseline execution, cognitive impairment, gender, age, or lesion volume and location. Conclusions: The presence of a specific impairment in reinforcement learning in the first 3 months after stroke has important implications for rehabilitation. It might be necessary to either increase the amount of reinforcement feedback given early or even delay onset of certain forms of rehabilitation training, e.g., like constraint-induced movement therapy, and instead emphasize others forms of motor learning in this early time period. A deeper understanding of stroke-related changes in motor learning capacity has the potential to facilitate the development of new, more precise treatment interventions.

Age at Onset of Spinal Cord Injury is Associated with Increased Inpatient Care Needs, Reduced Independence at Discharge and a Higher Risk of Institutionalization after Primary Inpatient Rehabilitation.

OBJECTIVE: To investigate the influence of age at onset of spinal cord injury on length of stay, inpatient therapy and nursing hours, independence at discharge and risk of institutionalization. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 250 patients with a newly acquired traumatic or non-traumatic spinal cord injury undergoing primary inpatient rehabilitation in a Swiss spinal cord injury specialized clinic between 2017 and 2019. METHODS: Multiple regression analysis was used to determine if age, in addition to clinical characteristics (co-morbidities, secondary complications and spinal cord injury severity), affects inpatient rehabilitation parameters (length of stay, daily nursing hours and daily therapy hours), independence at discharge (Spinal Cord Independence Measure III) and place of discharge (private residence vs institution). RESULTS: Chronological age correlated with the number of co-morbidities and secondary complications. Older age was associated with increased daily nursing care and reduced independence at discharge. However, both were also influenced by co-morbidities, secondary complications and severity of spinal cord injury. Length of stay and daily therapy hours were age-independent. Odds for institutionalization after discharge increased significantly, by 1.03-fold per year of age. CONCLUSION: Age at onset of spinal cord injury predicted inpatient nursing care, independence at discharge and the risk of institutionalization after primary inpatient rehabilitation. Co-morbidities, secondary complications and severity of spinal cord injury were also important influencing factors.

Validity and reliability of the 2-minute walk test in individuals with spinal cord injury.

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.

Reward During Arm Training Improves Impairment and Activity After Stroke: A Randomized Controlled Trial.

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).

No evidence for motor-recovery-related cortical connectivity changes after stroke using resting-state fMRI.

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.

Comparing a Novel Neuroanimation Experience to Conventional Therapy for High-Dose Intensive Upper-Limb Training in Subacute Stroke: The SMARTS2 Randomized Trial.

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.

Reduced striatal activation in response to rewarding motor performance feedback after stroke.

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.

Rethinking interhemispheric imbalance as a target for stroke neurorehabilitation.

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.

Evidence for a subcortical origin of mirror movements after stroke: a longitudinal study.

Following a stroke, mirror movements are unintended movements that appear in the non-paretic hand when the paretic hand voluntarily moves. Mirror movements have previously been linked to overactivation of sensorimotor areas in the non-lesioned hemisphere. In this study, we hypothesized that mirror movements might instead have a subcortical origin, and are the by-product of subcortical motor pathways upregulating their contributions to the paretic hand. To test this idea, we first characterized the time course of mirroring in 53 first-time stroke patients, and compared it to the time course of activities in sensorimotor areas of the lesioned and non-lesioned hemispheres (measured using functional MRI). Mirroring in the non-paretic hand was exaggerated early after stroke (Week 2), but progressively diminished over the year with a time course that parallelled individuation deficits in the paretic hand. We found no evidence of cortical overactivation that could explain the time course changes in behaviour, contrary to the cortical model of mirroring. Consistent with a subcortical origin of mirroring, we predicted that subcortical contributions should broadly recruit fingers in the non-paretic hand, reflecting the limited capacity of subcortical pathways in providing individuated finger control. We therefore characterized finger recruitment patterns in the non-paretic hand during mirroring. During mirroring, non-paretic fingers were broadly recruited, with mirrored forces in homologous fingers being only slightly larger (1.76 times) than those in non-homologous fingers. Throughout recovery, the pattern of finger recruitment during mirroring for patients looked like a scaled version of the corresponding control mirroring pattern, suggesting that the system that is responsible for mirroring in controls is upregulated after stroke. Together, our results suggest that post-stroke mirror movements in the non-paretic hand, like enslaved movements in the paretic hand, are caused by the upregulation of a bilaterally organized subcortical system.

Does motivation matter in upper-limb rehabilitation after stroke? ArmeoSenso-Reward: study protocol for a randomized controlled trial.

BACKGROUND: Fifty percent of all stroke survivors remain with functional impairments of their upper limb. While there is a need to improve the effectiveness of rehabilitative training, so far no new training approach has proven to be clearly superior to conventional therapy. As training with rewarding feedback has been shown to improve motor learning in humans, it is hypothesized that rehabilitative arm training could be enhanced by rewarding feedback. In this paper, we propose a trial protocol investigating rewards in the form of performance feedback and monetary gains as ways to improve effectiveness of rehabilitative training. METHODS: This multicentric, assessor-blinded, randomized controlled trial uses the ArmeoSenso virtual reality rehabilitation system to train 74 first-ever stroke patients (< 100 days post stroke) to lift their impaired upper limb against gravity and to improve the workspace of the paretic arm. Three sensors are attached to forearm, upper arm, and trunk to track arm movements in three-dimensional space while controlling for trunk compensation. Whole-arm movements serve as input for a therapy game. The reward group (n = 37) will train with performance feedback and contingent monetary reward. The control group (n = 37) uses the same system but without monetary reward and with reduced performance feedback. Primary outcome is the change in the hand workspace in the transversal plane. Standard clinical assessments are used as secondary outcome measures. DISCUSSION: This randomized controlled trial will be the first to directly evaluate the effect of rewarding feedback, including monetary rewards, on the recovery process of the upper limb following stroke. This could pave the way for novel types of interventions with significantly improved treatment benefits, e.g., for conditions that impair reward processing (stroke, Parkinson's disease). TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02257125 . Registered on 30 September 2014.

Elderly adults show higher ventral striatal activation in response to motor performance related rewards than young adults.

Feedback on motor performance activates the striatum and boosting ventral striatum activation with rewarding feedback during motor training supports the consolidation of the learned skill. Aging is associated with changes of the reward system, including striatal and extrastriatal loss of dopamine receptors. How these changes interact with the blood oxygenation level dependent (BOLD) response is, however, not yet fully understood. While it is known that reward prediction and reward-based decision-making differ between young and elderly healthy adults, the influence of age on the processing of rewarding feedback on motor performance have not been investigated so far. Nineteen young (26.42±2.84years) and 18 elderly (65.39±6.40years) healthy adults performed an arc-tracking task including performance feedback linked to a monetary reward after half of the trials, while undergoing functional magnetic resonance imaging (fMRI). The BOLD effect was compared in three predefined regions of interest: Ventral and dorsal striatum plus primary motor cortex. Our study demonstrates differences in the processing of motor performance related reward between young and elderly healthy adults. While both groups earned similar amounts of money linked to their own performance, the ventral striatal response to the rewarding feedback was higher in the older group. Deficient prediction about the rewarding feedback, a higher motivational status or compensation for a reduced number of dopamine receptors in the elderly might be possible explanations. How this interacts with the reward-induced improvement of motor skill consolidation, as observed in young subjects, has to be clarified.

Separable systems for recovery of finger strength and control after stroke.

Impaired hand function after stroke is a major cause of long-term disability. We developed a novel paradigm that quantifies two critical aspects of hand function, strength, and independent control of fingers (individuation), and also removes any obligatory dependence between them. Hand recovery was tracked in 54 patients with hemiparesis over the first year after stroke. Most recovery of strength and individuation occurred within the first 3 mo. A novel time-invariant recovery function was identified: recovery of strength and individuation were tightly correlated up to a strength level of ~60% of estimated premorbid strength; beyond this threshold, strength improvement was not accompanied by further improvement in individuation. Any additional improvement in individuation was attributable instead to a second process that superimposed on the recovery function. We conclude that two separate systems are responsible for poststroke hand recovery: one contributes almost all of strength and some individuation; the other contributes additional individuation.NEW & NOTEWORTHY We tracked recovery of the hand over a 1-yr period after stroke in a large cohort of patients, using a novel paradigm that enabled independent measurement of finger strength and control. Most recovery of strength and control occurs in the first 3 mo after stroke. We found that two separable systems are responsible for motor recovery of hand: one contributes strength and some dexterity, whereas a second contributes additional dexterity.

Thermodilution-determined Internal Jugular Venous Flow.

PURPOSE: Cerebral blood flow (CBF) increases ~20% during whole body exercise although a Kety-Schmidt-determined CBF is reported to remain stable; a discrepancy that could reflect evaluation of arterial vs. internal jugular venous (IJV) flow and/or that CBF is influenced by posture. Here we test the hypothesis that IJV flow, as determined by retrograde thermodilution increases during exercise when body position is maintained. METHODS: Introducing retrograde thermodilution, IJV flow was measured in eight healthy humans at supine and upright rest and during exercise in normoxia and hypoxia with results compared with changes in ultrasound-derived IJV flow and middle cerebral artery mean velocity (MCA Vmean). RESULTS: Thermodilution determined IJV flow was in reasonable agreement with values established in a phantom (R = 0.59, P < 0.0001) and correlated to the ultrasound-derived IJV flow (n = 7; Kendall τ, 0.28; P = 0.036). When subjects stood up, IJV blood flow decreased by 9% ± 13% (mean ± SD) (219 ± 57 to 191 ± 73 mL·min; P < 0.0001) and the influence of body position was maintained during exercise (P < 0.0001). Exercise increased both IJV flow and MCA Vmean (P = 0.019 and P = 0.012, respectively) and the two responses were similar (P = 0.50). During hypoxia, however, only MCA Vmean responded with a further increase (P < 0.0001). CONCLUSIONS: As determined by retrograde thermodilution, IJV flow seems little sensitive to hypoxia, but does demonstrate the about 15% reduction in CBF when humans are upright and, provided that body position is maintained, also the increase in CBF during whole body exercise.