Neurorehabilitation and neural repair最新文献

Background: Combining vagus nerve stimulation (VNS) with rehabilitation represents an emerging treatment for a range of neurological disorders, and identifying stimulation parameters that maximize the effects of VNS may provide a means to optimize this therapy. Prior studies show that varying the intensity of stimulation, which influences activity of the locus coeruleus and nucleus basalis in response to VNS, determines the strength of VNS-dependent enhancement of synaptic plasticity in cortical circuits. Objective: The impact of the temporal parameters of stimulation, such as frequency and distribution of pulses within a stimulation train, remains underexplored. In this study, we evaluated how varying these temporal parameters impacts the magnitude of VNS-directed plasticity.

Methods: In the first experiment, rats received trains of VNS at 1 of 3 moderate pulse frequencies (20, 30, or 45 Hz) concurrent with a simple motor task. After 5 days of training, we evaluated cortical movement representations using intracortical microstimulation. In a second experiment, we used a similar paradigm to explore whether burst stimulation (125 ms of 30 Hz pulses, repeated 4 times over 2000 ms), would enhance VNS-dependent plasticity.

Results: All 3 moderate pulse frequencies produced equivalent increases in cortical representation of the paired movement compared to sham stimulation. Unexpectedly, both burst stimulation or a matched number of pulses distributed evenly in time failed to produce significant enhancement of plasticity compared to sham stimulation, whereas moderate pulse frequency stimulation did.

Conclusions: These findings illustrate the importance of the temporal dynamics of stimulation in determining the effects of VNS and provide guidelines for designing novel VNS sequences.

BackgroundIndividuals with prolonged symptoms after a mild traumatic brain injury (mTBI) report requiring more effort to complete complex and sustained activities. However, the relationship between cognitive workload and patient-reported symptoms is unclear.ObjectiveTo compare the cognitive workload between middle-aged and older adults with persistent symptoms after mTBI and controls during a sustained visual attention task and to examine the relationship between workload and patient-reported symptoms.MethodsIn this cross-sectional study, 48 adults (24 with persistent symptoms after mTBI (mean age = 54.92 ± 9.1 years) and 24 age-matched controls (mean age = 55.00 ± 8.7 years) completed the Dot Cancellation (DC) test. Outcome measures included performance measured by time to completion and number of errors on the test, objective workload measured by the Index of Cognitive Activity (ICA), subjective workload measured by the National Aeronautics and Space Administration Task Load Index (NASA-TLX), and patient-reported outcomes of symptom severity measured by the Post-Concussion Symptom Scale (PCSS), and mental fatigue measured by the Mental Fatigue Scale (MFS).ResultsIndividuals with mTBI symptoms took longer to complete the DC test (P = .002) and had higher scores on the NASA-TLX (mTBI = 37.5 [20.4, 50.8] compared to controls 10.4 [5, 27.5], P < .001). No differences in ICA were noted between the groups after accounting for DC time. Moderate correlations were observed between NASA-TLX and PCSS (ρ = .58, P < .001) and NASA-TLX and MFS (ρ = .58, P < .001).ConclusionsIndividuals with persistent symptoms following mTBI exhibit greater subjective cognitive workload and take longer to complete a sustained visual attention task compared to age-matched controls. However, objective measures of cognitive workload did not differ significantly once task duration was controlled. Perceived cognitive workload experienced by this population is influenced by symptom severity and mental fatigue.

BackgroundStroke recovery is often incomplete. There is a need to robustly evaluate evidence for intensive stroke rehabilitation.ObjectiveInvestigate feasibility, safety, and preliminary evidence of effectiveness for Boot Camp; a pragmatic, intensive, group-based, 5-week upper-limb rehabilitation program for individuals with chronic stroke.MethodsA pragmatic randomized cross-over trial allocated individuals with chronic stroke to Boot Camp or usual care. Boot Camp delivered 90 hours of upper-limb rehabilitation in a group setting over 5 weeks. Feasibility was evaluated with recruitment rates, adherence, program completion, acceptability, and safety. Clinical characteristics including time since stroke, age, and corticospinal tract integrity were documented. The primary outcome measure was the Fugl-Meyer Upper Extremity (FM-UE). Secondary measures assessed upper-limb activity, quality of life, and self-efficacy. Interviews at the completion of Boot Camp provided insights into participant experiences.ResultsThirty-nine individuals consented, with 38 completing the program (22 male, age 61.5 ± 14.8 years, 2.8 ± 3.4 years since stroke). Feasibility criteria for recruitment, program completion, acceptability, and safety were met, but not adherence to full therapy amount. Boot Camp led to large gains in the FM-UE scores (10.2 ± 4.8, P < .001), upper-limb activity (7.3 ± 8.7, P < .001), quality of life (9.3 ± 22.1, P = .012), and self-efficacy (6.1 ± 13.5, P = .023). Participants reported themes of intensity matters, variety generally works, peer support, goals are motivating.ConclusionBoot Camp was feasible, safe, and led to large and meaningful gains in upper-limb outcomes in individuals with chronic stroke.

BackgroundPost-stroke aphasia is considered a language network disorder, and neuroimaging may help understand network alterations. However, the prediction of aphasia recovery remains challenging.ObjectiveWe aimed to explore biomarkers for aphasia recovery using a novel clinically feasible method, which we previously reported as useful for evaluating motor recovery, that included the phase synchrony index (PSI) obtained from resting-state 19-channel electroencephalography.MethodsThis longitudinal observational study included patients with left frontal ischemic lesions admitted for post-acute rehabilitation. We recorded electroencephalograms at the time of admission. Recovery was defined as a change in composite speech score. Based on electrode settings, we focused on 4 language-related networks: (1) left front-temporal, (2) right front-temporal, (3) inter-frontal, and (4) inter-temporal networks. We first evaluated the correlation between these network PSIs and recovery scores and then the predictive potential of our method using the receiver operating characteristic curve and multivariable regression analyses.ResultsWe enrolled 24 patients. Electroencephalograms were recorded for a median of 37.0 days after the stroke. The median speech therapy time was 53.7 hours. Inter-temporal PSI (gamma band) was significantly positively correlated with recovery scores (ρ = .642; 95% confidence interval = 0.311-0.834; P = .017). The PSI could predict patients with good recovery (sensitivity = 84.6%; specificity = 90.9%), and the inter-temporal PSIs were useful in predicting recovery (adjusted R² = .545).ConclusionsOur results revealed an association between the posterior language network adaptive response and speech recovery in patients with frontal lesions. The PSI may reflect post-stroke network alterations and may be a biomarker of aphasia recovery.

Background: Corticospinal excitability (CSE) is a surrogate measure of neuroplasticity within the corticospinal tract measured with transcranial magnetic stimulation (TMS). A single bout of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) cardiovascular exercise (CE) have been both demonstrated to transiently augment CSE in people with stroke. However, the effect of multiple sessions of CE and exercise intensity is unknown.

Objectives: We conducted a randomized controlled trial (NCT03614585) to examine the effect of a HIIT vs. MICT CE program on CSE measures obtained using TMS applied on the ipsilesional (ILH) and contralesional (CLH) hemispheres.

Methods: Fifty-six individuals with cortical and/or subcortical stroke lesions in the chronic phase of stroke recovery (>6 months) were randomly assigned to a 12-week HIIT (n = 28) or MICT (n = 28) program. CSE measures were obtained at baseline and post-intervention. Linear mixed model analyses were conducted to compare changes in CSE measures and their respective interhemispheric ratios.

Results: CSE changes were not significantly different between HIIT and MICT but exploratory analyses showed that, when analyzed together, both groups increased resting motor evoked potential (MEP) amplitude (P = .003), decreased resting motor threshold (rMT) (P = .030), and reduced intracortical facilitation (ICF) (P = .049) in the ILH. No CSE changes in the CLH were observed. HIIT and MICT rebalanced interhemispheric rMT (P = .020) and ICF ratios (P = .040), and increased resting MEP amplitude ratio (P = .020).

Conclusions: Chronic CE increases excitatory ILH CSE measures and reduces interhemispheric imbalances but intensity does not have a moderating effect. More studies are needed to determine the functional relevance of exercise-induced changes in CSE in post-stroke recovery.

BackgroundThe aim of clinical trials for spinal cord injury (SCI) is to improve everyday-life activity outcomes, which requires reliable methods for monitoring patient activity. This study evaluates sensor-derived activity metrics in comparison to established clinical assessment methods.MethodsWearable inertial sensors collected data from 69 individuals with acute, traumatic cervical SCI participating in the Nogo-A Inhibition in Spinal Cord Injury trial (NCT03935321), a phase 2b, multicenter, randomized, placebo-controlled trial. During inpatient rehabilitation, participants wore up to 5 inertial sensors for up to 3 consecutive days each week. An estimation of average daily energy expenditure (EE) was used as an indicator of physical activity and compared to the recovery of Upper Extremity Motor Scores (UEMS) and Spinal Cord Independence Measures (SCIM).ResultsParticipants in the verum (n = 41; 59.4%) and placebo (n = 28; 40.6%) groups showed similar initial activity levels, however, the verum group exhibited a significantly greater weekly increase in average daily EE (ΔEE = 11.6 kcal/day/week, 95% CI [1.5, 21.8], P = .025). In contrast, no significant group differences were observed in changes in UEMS (ΔUEMS = 0.1/week, 95% CI [-0.2, 0.3], P = .603) or SCIM (ΔSCIM = 0.2, per week 95% CI [-0.7, 1.1], P = .644).ConclusionContinuous sensor-based activity monitoring offers objective and sensitive insights into changes in physical capabilities, effectively complementing periodic clinical assessments. Thus, sensor-derived outcome measures offer potential for improving the evaluation of clinical studies in individuals with SCI.Clinical Trail Registration:https://clinicaltrials.gov; NCT03935321.

BackgroundInternal and external cueing strategies are often applied to alleviate gait deficits in Parkinson's disease (PD). However, it remains unclear which type of cueing strategy is most effective at different disease stages. The underlying neural mechanisms of response to cueing are also unknown.ObjectiveTo investigate the immediate response of multiple brain cortical regions and gait to internal and external cueing in people at different stages of PD.MethodsPeople with PD (n = 80) were split into groups dependent on their disease stage (Hoehn and Yahr [H&Y] stage I to III). Participants performed a baseline walk without cues followed by randomized cued walking conditions (internal and external [visual, auditory and tactile] cues). A combined functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) system assessed cortical brain activity while walking. Wearable inertial sensors assessed gait.ResultsCue-related gait improvements were not influenced by H&Y stage; moderate or large effect sizes were only observed for internal cueing and external visual cueing. fNIRS findings suggested cortical response was similar across H&Y stages, with increased activity in the prefrontal cortex with internal cues; and increased activity in the primary motor and visual cortices with external cues. However, EEG showed that people with PD in H&YIII had higher parietal alpha power than those in H&YI in the auditory, tactile, and visual cueing conditions.ConclusionGait improvement with cueing was similar across PD stages and underpinned by cognitive, motor, and/or sensory neural processing within selective brain regions that may be influenced by PD stage (i.e., parietal cortex).

BackgroundIndividuals with chronic stroke are less active, which is both a consequence of stroke-related impairments and a risk factor for future health complications. The PROWALKS clinical trial found significant gains in real-world walking activity (steps/day) after 12 weeks of a step activity monitoring behavioral intervention, provided either alone (SAM) or with high-intensity gait training (FAST + SAM), but not after high-intensity gait training alone (FAST). Previous research in individuals after stroke suggests that tailored behavioral counseling may lead to better long-term physical activity participation, but no previous work has focused on post-intervention maintenance of walking activity changes.ObjectiveTo investigate whether steps/day changes after training (POST) were maintained at 6 months (6MO) and 12 months (12MO) after baseline. We hypothesized that SAM and FAST + SAM groups would have better maintenance of steps/day changes than the FAST group. Methods. This analysis included all participants who completed the PROWALKS intervention (n = 200, mean[SD] age: 63.27[12.41], 102 male/98 female, >6 months post-stroke). Analysis outcomes were steps/day change from POST-6MO, and from POST-12MO.ResultsAll groups significantly decreased in steps/day from POST-6MO (P = .001, FAST decreased by mean[SE] 160[272], SAM by 1016[270], FAST + SAM by 400[300]), and POST-12MO (P < .001, FAST decreased by 610[280], SAM by 1072[306], FAST + SAM by 568[313]). There were no significant differences between groups.ConclusionsAll intervention groups showed significant declines in steps/day between POST and 6MO and between POST and 12MO. These results add to a growing body of literature suggesting that a behavioral intervention to initiate behavior change may not be sufficient for maintenance of change.Registration:This study is registered at ClinicalTrials.gov, NCT02835313.

Background: Action observation (AO) has emerged as a potentially powerful therapeutic tool to improve stroke rehabilitation. What remains unclear are the underlying visual attention mechanisms that inform gaze strategies during AO. Further, it is unclear whether visual attention is sustained during AO or influenced by the severity of residual functional impairments following stroke.

Objective: This study seeks to explore eye gaze patterns and vigilance during a single session of AO in stroke survivors with varying levels of impairment.

Methods: Twenty stroke survivors with upper limb impairment (Fugl-Meyer Scores ranging 23-54) engaged in AO by watching an actor performing a disc placement task (observation phase), followed by the participant performing the task (execution phase) with their more affected, then less affected limb. Gaze patterns during the observation phase were evaluated for areas of most prominent gaze and compared between varying levels of severity of residual limb impairment.

Results: Gaze during AO prior to movement on the more affected side is focused on hand and object while AO prior to movement on the less affected side is focused on the overall action in the video. These patterns are prevalent for all levels of severity.

Conclusions: This suggests that participants are developing gaze patterns in line with optimal approaches to encode action specifics, especially on the more affected side. This presents valuable understanding of perceptual patterns of AO that may be optimal for studies evaluating AO in stroke.

Introduction: Randomized Controlled Trials (RCTs) are essential to underpin the superiority of novel interventions affecting upper extremity capacity post-stroke. However, many RCTs are underpowered, due to heterogeneity in recovery. Prognostic targeting may help reduce sample sizes while maintaining sufficient power.

Objective: This study investigates the effects of prognostic targeting on the required sample size to achieve 70% to 90% power in early post-stroke RCTs with upper extremity capacity measured with the Action Research Arm Test (ARAT) as the outcome.

Patients and methods: Serial data from 4 prospective cohort studies (N = 372 stroke patients) were pooled, with assessments from week 1 to 6 months post-stroke. Using this dataset, we generated synthetic 6-month ARAT outcomes and analyzed data cross-sectionally and longitudinally, with and without prognostic targeting based on a pre-existing prognostic model predicting 6-month outcome. We then calculated power for different sample sizes and assessed trial efficiency, determined by the estimated sample size and inclusion rate.

Results: Prognostic targeting within 3 weeks post-stroke theoretically reduced the required sample size by up to 56% and improved trial efficiency by 40 to 45% for detecting a 6-point ARAT difference at 6 months. The targeted trials needed 220, 270, and 360 patients vs. 470, 560, and 820 in non-targeted trials for 70% to 90% power. Benefits persisted in longitudinal analyses.

Conclusion: This study demonstrates the benefits of prognostic targeting for improving power and efficiency in early post-stroke upper extremity trials using ARAT as outcome. We strongly recommend its use in future stroke rehabilitation and recovery studies.