Neurorehabilitation and neural repair最新文献

Background. Conventional physical therapy following neurological injury is an arduous task met with minimal returns and quickly plateauing recovery. Unconventional therapies, such as robotic assisted gait training (RAGT) have not produced the robust clinical gains that we all had hoped. Rodent RAGT is a nascent field, but it works on the same principles as the clinical counterpart. Objective. We have previously investigated the ability of RAGT to enhance the recovery of rats following a cervical spinal cord injury and found that training in a resistive field is detrimental, and training in a negative viscosity field is better than actively guiding the limbs through a healthy stepping pattern. Unfortunately, none of these treatments are particularly good at restoring unassisted overground locomotion. Previously we grouped animals based on the RAGT treatment they received. Upon further reflection, these groups are not based on what the animals actually experienced, but how the robot was programmed. Methods. In the work presented here we regrouped and reanalyzed our existing data bi-directionally (does level of overground recovery predict RAGT force profile experienced? does force profile predict recovery?). Results. This method allowed us to uncover a training force profile that optimized overground recovery, specifically, low overall forces (<±6 N), positive Fy and negative Fx during swing, and minimal forces during stance (<±2 N). Conclusions. This work provides new insights into the importance of the specific forces used in rehabilitation, a major shift in current clinical RAGT techniques, and could lead to improvements in patients' lives.

BackgroundCompromised dual-task walking ability reduces functional independence in community-dwelling individuals after stroke. Objective. To examine the influence of mobility task and cognitive task type and complexity, and their interaction on dual-task level-ground walking and obstacle-crossing after stroke.MethodsNinety-three individuals with chronic stroke (mean [SD] age = 62.4 [6.7] years, stroke duration = 67.7 [53.5] months) participated in this observational study with repeated measures. For each dual-task testing condition, a mobility task (level-ground walking or obstacle-crossing) was performed concurrently with 1 of 5 cognitive tasks (serial-subtractions, category naming, clock test, auditory discrimination, and shopping-list recall). Each cognitive task involved low and high complexity levels, yielding 20 dual-task conditions in total. Dual-task effect (DTE = [single-task - dual-task]×100/single-task) on walking distance (mobility-DTE) and number of correct responses (cognitive-DTE) were calculated for each dual-task condition.ResultsMedium to large interaction effects were observed between cognitive task type and complexity on cognitive (F = 12.0-15.8, P < .001, ηp² = 0.12-0.15) and mobility performance (F = 3.2-5.5, P < .05, ηp² = 0.03-0.06) during dual-task level-ground walking and obstacle-crossing. Among the cognitive tasks, serial-subtraction had the greatest interference effect on both cognitive (Mean DTE = -9.2 to -21.5%) and mobility performance (Mean DTE = -18.7 to -19.1%). Overall, "mobility interference" (decrement in walking distance without a decrement in cognitive performance) was the most common dual-task effect pattern observed.ConclusionThe type and complexity level of the mobility and cognitive tasks interact to influence the degree and pattern of dual-task effects, with the serial-subtraction task inducing the greatest effect. Standardized assessments involving distinct cognitive domains are necessary for profiling dual-task interference during walking among individuals with chronic stroke.

BackgroundVariability in movement is critical for performance under dynamic conditions. Stroke causes focal injury to the motor system, disrupts voluntary motor control, and leads to less smooth and more variable upper extremity movements. Few studies have characterized trial-by-trial variation in upper extremity movement smoothness and its clinical and neuroanatomic correlates in the first week post-stroke.ObjectiveTo evaluate trial-by-trial variation in upper extremity movement smoothness during planar reaching and relate it to clinical outcomes and neuroanatomical injury after acute stroke.MethodsTwenty-two patients (4.4 ± 1.7 days post-stroke) and 22 able-bodied adults completed a planar center-out reaching task. Smoothness was quantified with spectral arc length (SPARC). Median and interquartile range (IQR, a quantification of trial-by-trial variation) of SPARC values were assessed. Patients completed a clinical assessment battery acutely and at 90 days post-stroke. MRI-derived stroke lesions were analyzed to estimate basal ganglia, motor cortex, and corticospinal tract injury. Intraclass correlation, Spearman's correlation, and multivariate regression evaluated trial-by-trial variation and its relation to clinical assessments, outcomes, and neuroanatomical injury.ResultsPost-stroke reaching was less smooth and more variable (larger IQR) compared to able-bodied adults. Variability in post-stroke smoothness was primarily driven by within-subject, trial-by-trial variation. More variable smoothness, even after controlling for median smoothness, related to worse performance on clinical assessments and 90-day outcomes. More variable smoothness related to greater corticospinal tract injury (ρ = 0.537, P = .011), but not to basal ganglia or motor cortex injury.ConclusionTrial-by-trial variation of movement is valuable for understanding sensorimotor control post-stroke and has implications for targeted neurorehabilitation.

BackgroundFollowing stroke, a growth-promoting response resulting in heightened neuroplasticity occurs during the early subacute stages of recovery, a period during which the brain may be more responsive to therapeutical interventions. Given its central role in regulating neuroplastic processes and brain repair in animal models, brain-derived neurotrophic factor (BDNF) has been targeted as a potential biomarker for stroke recovery in humans, with interventions upregulating BDNF holding therapeutical potential. Cardiovascular exercise (CE) has been recommended for stroke rehabilitation, partly due to its potential to induce neural adaptations, including upregulation of BDNF.ObjectivesTo examine the effects of CE on BDNF in individuals at early subacute stages of recovery.MethodsSeventy-six participants within 3 months of first-ever ischemic stroke were randomly assigned to 8 weeks of either CE plus standard care or standard care alone. To measure the chronic and acute responses to exercise in serum BDNF levels, blood samples were collected before and immediately after a graded exercise test conducted at baseline, 4, and 8 weeks. The potential role of the BDNF Val66Met polymorphism in modulating the BDNF response was also explored. Data were analyzed following an intention-to-treat approach.ResultsDespite clinically important increases in cardiorespiratory fitness, CE did not induce significant chronic or acute changes in serum BDNF. Furthermore, the response to CE was not associated with changes in cardiorespiratory fitness and clinical outcomes or was modulated by Val66Met.ConclusionsThese findings indicate that CE has a limited capacity to upregulate circulating BDNF in subacute stages of stroke recovery.Trial Registration:Exercise and Genotype in Sub-acute Stroke: https://clinicaltrials.gov/study/NCT05076747.

Background: Emerging trials demonstrate that neuromodulation, especially spinal cord stimulation, improves function for those with chronic spinal cord injury. Their design - uncontrolled and unblinded - is justified by the claim that sham conditions are unethical and/or impossible. In the absence of controlled trials, the functional benefits of spinal cord stimulation cannot be distinguished from the effects of placebo.

Objectives: To discuss the validity of the claim that placebo control conditions are infeasible in spinal cord stimulation research, and to propose feasible solutions for including sham conditions that would account for placebo effects.

Results: Placebo effects are likely to occur in spinal cord stimulation studies, given the high levels of participant expectations of an effect, natural fluctuations in symptoms associated with spinal cord injury, regression towards the mean, the Hawthorne effect, presence of concurrent interventions, and the absence of blinding in existing studies. Options for placebo control conditions could include adding an "untreated" control group, using "placebo-resistant" outcomes, adding an active comparator group or sham stimulation, or investing in parasthesia-free stimulation. Additionally, wherever feasible, blinding of both participants and assessors should be pursued.

Conclusions: The current evidence base for spinal cord stimulation is undermined by the lack of rigorous sham controls, and the argument that such controls are unethical or unfeasible do not withstand scrutiny. We propose strategies for the inclusion of placebo controls in future trials and encourage investigators to prioritize these approaches to ensure the true benefit of spinal cord stimulation can be determined.

BackgroundDespite the prevalence of upper extremity (UE) limitations after stroke, few training interventions prioritize fast movement speeds during rehabilitation.ObjectivesTo compare the effects of an equivalent dose (in the number of trials) of speed versus accuracy training in chronic stroke with mild-to-moderate impairments who have no direct cerebellar damage.Patients and MethodsIn this Phase-1 randomized controlled trial, we randomized 42 participants to either a speed or an accuracy arm-movement training condition. Participants moved their paretic hands through complex tracks, with 2080 trials in 4 sessions within a week. Speed and accuracy were manipulated by displaying 5 cm-wide or 1.25 cm-wide tracks or providing feedback based on average speed and accuracy in the Speed and Accuracy groups, respectively. We measured changes in kinematics in a 3-target test, in the speed-accuracy trade-off in a modified Fitts' test of the paretic arm during goal-directed reaching, and clinical outcomes (ie, UE Fugl-Meyer, Action Research Arm Test, and Box and Block Test) at 3 days and 1-month post-training.ResultsSpeed training led to significantly faster and smoother movements with more symmetric reach velocity profiles at the 3-day post-test, consistent with better feedforward control. Speed training temporarily improved the speed-accuracy tradeoff. At 1 month, however, most gains in the 3-target test and in the modified Fitts' test were lost.ConclusionSpeed training led to greater gains in kinematics of goal-directed actions than accuracy training, notably in a 3-day post-test. Our results suggest that training programs with high repetitions of fast movements may improve paretic arm reaching performance. The trial is registered at ClinicalTrials.gov under ID NCT05013762.

Background: Peripheral nerve injuries are common, and there is a critical need for the development of novel treatments to complement surgical repair. Conditioning electrical stimulation (ES; CES) is a novel variation of the well-studied perioperative ES treatment paradigm. CES is a clinically attractive alternative because of its ability to be performed at the bedside prior to a scheduled nerve repair surgery.

Objectives: Although 60 minutes of CES has been shown to enhance motor and sensory axon regeneration, the effects of CES on sympathetic regeneration are unknown. We investigated how 2 clinically relevant CES paradigms (10 and 60 minutes) impact sympathetic axon regeneration and distal target reinnervation.

Results: Our results indicate that the growth of sympathetic axons is inhibited by CES at acute time points, and at a longer survival time point post-injury, there is no difference between sham CES and the CES groups. Furthermore, 10-minute CES did not enhance motor and sensory regeneration with a direct repair, and neither 60-minute nor 10-minute CES enhanced motor and sensory regeneration through a graft.

Conclusion: We conclude sympathetic axons may retain some regenerative ability, but no enhancement is exhibited after CES, which may be accounted for by the inability of the ES paradigm to recruit the small-caliber sympathetic axons into activity. Further studies will be needed to optimize ES parameters to enhance the regeneration of all neuron types.

BackgroundCognitive rehabilitation and exercise training are promising approaches for improving cognition in persons with progressive multiple sclerosis (MS). Identifying heterogeneity of change and factors that influence the effects of cognitive rehabilitation and/or exercise training on cognitive outcomes at the individual level have direct relevance for developing tailored and optimized rehabilitation interventions for improving cognition in progressive MS.ObjectiveThis study involved a secondary data analysis from the CogEx trial in progressive MS. This study first described heterogeneity of change in cognitive processing speed (CPS) across the intervention conditions and then identified possible adherence/compliance, baseline performance, and demographic/clinical variables as correlates of rehabilitation-related CPS changes.MethodsA total of 311 persons with progressive MS who were pre-screened for impaired CPS completed 12 weeks of combined cognitive rehabilitation (or sham) and exercise training (or sham). CPS was measured before and after the 12-week period. As potential correlates of CPS changes, we measured adherence/compliance (ie, treatment exposure), performance outcomes at baseline, as well as demographic and clinical characteristics at baseline.ResultsThere was heterogeneity of change in CPS across the 4 intervention conditions. We further identified baseline learning and memory impairment and premorbid intelligence quotient (IQ), but not adherence/compliance, other baseline performance outcomes, or demographic/clinical characteristics as significant correlates of CPS changes across the 4 intervention conditions.ConclusionsThe overall pattern of results suggests that future trials in this area might account for impaired learning and memory and/or premorbid IQ as potential covariates, or more carefully consider the role of reserve within rehabilitation interventions in progressive MS.

Background: Falls are a common challenge for people with Parkinson's disease (PwPD), driven by balance impairments and misaligned perceptions of balance abilities.

Objective: This study investigated the replicability and generalizability of the relationship between balance ability and perception discordance and fall risk.

Methods: Using baseline data from 2 clinical trials involving 171 PwPD, discordance was calculated using the Activities Specific Balance Confidence Scale and Timed Up and Go (TUG) or the Mini Balance Evaluation System's Test (MiniBEST).

Results: Findings supported the replicability of discordance as a predictor of fall risk, with results consistent across measures. While TUG-derived discordance was statistically significant, MiniBEST-derived discordance showed generalizability without statistical inferiority.

Conclusion: These results emphasize the relevance of balance perception and its misalignment with ability as fall risk predictors.