Neurorehabilitation and neural repair最新文献

Background: Understanding the impact of timing of post-stroke motor recovery research trials is critical for clinical care.

Objective: To examine and compare differences in Fugl-Meyer Assessment Upper Extremity (FMA-UE) scores at 2 different time points post-stroke on the effectiveness of upper extremity (UE) rehabilitation interventions compared to conventional care or sham therapy controls in stroke rehabilitation randomized controlled trials (RCTs).

Methods: A meta-analysis was conducted in accordance with PRISMA guidelines. Searches were conducted in CINAHL, Embase, PubMed, Scopus, and Web of Science, up to April 1st, 2021. Inclusion criteria were: (1) English RCTs of adults (≥18 years) diagnosed with stroke; (2) examined a single intervention for stroke UE rehabilitation; (3) used conventional care/sham as the control arm; and (4) assessed FMA-UE as one of the outcome measures.

Results: 157 RCTs were included, including 17 types of interventions. In the acute and subacute phases post stroke, 16 interventions were assessed, and the analyses of 11 interventions showed significant beneficial effects. In the chronic post-stroke phase, 9 intervention types were assessed, and 7 of them showed significant improvements. Greater FMA-UE score improvements were found for the same interventions in the acute and subacute post-stroke phases when compared to the chronic phase.

Conclusions: Interventions studied in the acute and subacute phases showed greater magnitude improvements in the FMA-UE scores compared to the chronic phase. The effectiveness of upper extremity rehabilitation interventions may be underestimated when studied exclusively in the chronic phase, with some of the observed differences potentially attributable to variations in baseline severity.

BackgroundAnimal models suggest that intensive physical training may promote neuroplasticity in Parkinson's disease (PD), but its effects in humans remain underexplored.ObjectivesTo investigate the effects of aerobic interval training (AIT) on brain-derived neurotrophic factor (BDNF) levels, striatal [¹⁸F]fluorodopa positron emission tomography/computed tomography (PET/CT) uptake ([¹⁸F]DOPA_PET/CT), electroencephalography (EEG), and motor function, and to explore their interrelations.MethodsThirty PD patients were randomly assigned to a 12-week moderate-intensity AIT group (PD Training Group [PD-TR], n = 15) or a non-training group (PD Non-Training Group, n = 15). Pre- and post-intervention assessments included BDNF levels, striatal [¹⁸F]DOPA_PET/CT, EEG during motor task-evoked desynchronization (ERD_MT) and rest-evoked synchronization (ERS_REST) in primary motor cortex (M1) and supplementary motor area (SMA), and motor function assessed using the Unified PD Rating Scale (UPDRS) Part III and the Manual Bradykinesia Score for the Affected Upper Extremity (MBS-AUE) calculated as the sum of UPDRS items 3.4 to 3.6.ResultsThe PD-TR group showed increased BDNF levels (P < .001) and improved motor scores (UPDRS III and MBS-AUE; P < .05). Both groups exhibited increased EEG-ERS_REST M1 (P < .05) over time, with no changes in striatal [¹⁸F]DOPA_PET/CT uptake. Significant group differences were observed in correlations between changes (Δ = POST minus PRE) in: ΔBDNF with Δ[¹⁸F] DOPA_PET/CT uptake in the putamen and ΔEEG-ERD_MT M1 (P < .001); Δ[¹⁸F]DOPA_PET/CT uptake in the putamen with Δ[¹⁸F]DOPA_PET/CT uptake in the caudate and ΔEEG-ERS_REST SMA (P < .05); ΔMBS-AUE scores with ΔEEG-ERS_REST SMA (P < .001).ConclusionsTwelve-week AIT enhanced BDNF levels and motor function in PD-TR, with central nervous system neuroplasticity supporting motor recovery.

Background: High-intensity interval training (HIIT) has emerged as a potentially effective exercise promoting functional recovery post-stroke.

Objective: This study examined the efficacy of adding HIIT cycling vs. combining unloaded cycling (SHAM) to conventional physiotherapy on exercise capacity, functional ability, disability level, and health-related quality of life (HRQoL) early post-stroke.

Methods: Forty-four acute stroke survivors were randomly assigned to the HIIT cycling or SHAM group for 6 weeks of exercise training, 3 days/week. The primary outcome was exercise capacity (peak work load [WRpeak]) measured by a maximal exercise test. Secondary outcomes included balance: Berg Balance Scale, walking ability: 6-minute and 10-meter walk tests (6MWT and 10mWT), lower-extremity muscle strength: 5-Repetition Sit-To-Stand test, disability level: modified Rankin Scale (mRS), and HRQoL by EuroQOL 5-dimension questionnaire.

Results: The 2-way factorial analysis of variance showed a significant interaction of time × group on WRpeak (P < .001), 6MWT (P < .001), 10mWT (P < .001), and mRS (P = .012). The significant interaction indicates that the change in WRpeak (mean +17.7 W [95% CI, 10.2-25.1]), 6MWT (mean +126.8 m [77.9-175.7]), 10mWT (mean +0.5 m/s [0.3-0.7]), and mRS (mean -0.7 point [-1.2 to -0.2]) after 6-week of training was significantly greater for HIIT cycling versus SHAM. These changes are also significantly greater in the HIIT group vs the SHAM group up to 6 months (P < .001) post-training.

Conclusions: In individuals with acute stroke, individuals, combining HIIT cycling with conventional physiotherapy significantly maximizes recovery of exercise capacity and walking ability, and reduces the level of disability early post-stroke, compared to SHAM.Protocol Registration number:NCT06179173.

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).