Neurorehabilitation and Neural Repair最新文献

Background: Transauricular vagus nerve stimulation (taVNS) is being studied as a feasible intervention for stroke, but the mechanisms by which this non-invasive technique acts in the cortex are still broadly unknown.

Objectives: This study aimed to systematically review the current pre-clinical evidence in the auricular vagus nerve stimulation (aVNS) neuroplastic effects in stroke.

Methods: We searched, in December of 2022, in Medline, Cochrane, Embase, and Lilacs databases. The authors executed the extraction of the data on Excel. The risk of bias was evaluated by adapted Cochrane Collaboration's tool for animal studies (SYRCLES's RoB tool).

Results: A total of 8 studies published between 2015 and 2022 were included in this review, including 391 animal models. In general, aVNS demonstrated a reduction in neurological deficits (SMD = -1.97, 95% CI -2.57 to -1.36, I² = 44%), in time to perform the adhesive removal test (SMD = -2.26, 95% CI -4.45 to -0.08, I² = 81%), and infarct size (SMD = -1.51, 95% CI -2.42 to -0.60, I² = 58%). Regarding the neuroplasticity markers, aVNS showed to increase microcapillary density, CD31 proliferation, and BDNF protein levels and RNA expression.

Conclusions: The studies analyzed show a trend of results that demonstrate a significant effect of the auricular vagal nerve stimulation in stroke animal models. Although the aggregated results show high heterogeneity and high risk of bias. More studies are needed to create solid conclusions.

Background: Transcranial direct current stimulation (tDCS) can be used to improve post-stroke aphasia. However, given the mixed evidence for its efficacy, individual differences may moderate the relative benefit of this strategy. In planned exploratory subgroup analyses, we examined whether age, education, sex, brain-derived neurotrophic factor status, and baseline performance individually impacted improvement in picture naming between baseline and 1 week after the end of the therapy, then whether the combination of factors that predicted recovery of naming and discourse differed for those who received concurrent tDCS.

Objective: Examine whether individual differences influenced the effect of tDCS on language recovery.

Methods: In this randomized, double-blind, sham-controlled, efficacy study of tDCS combined with language therapy for subacute post-stroke aphasia, patients completed an evaluation including the Philadelphia Naming Test and Cookie Theft picture description, which was analyzed for Content Units (CU) and Syllables/CU. Individual factors were examined using linear models including the interaction between treatment group and subgroup.

Results: Significant interactions were observed between tDCS group and both age and education. The predictors of a positive response to tDCS differed from the predictors of a positive response to language treatment alone. While baseline performance was an important predictor of future performance regardless of treatment group, responses to treatment without tDCS were influenced by age whereas responses to treatment with tDCS were not.

Conclusions: Age and education influence the efficacy of different treatment strategies. Refinement of treatment selection is important to the overall individualization and optimization of post-stroke patient care.

Trial registration: ClinicalTrials.gov NCT02674490.

Background: Microglial-induced inflammation plays a crucial role in the pathophysiological process of nervous system injury, however, still lacks effective therapeutic agents. Previously, we discovered that the inhibition of histone deacetylase 3 (HDAC3) exerts anti-inflammatory effects after traumatic spinal cord injury (SCI), whereas little is known about its underlying mechanism. Therefore, the present study aimed to explore the effects and potential mechanisms of HDAC3 on neuroinflammation and microglial function.

Methods: Rats were randomized into 4 groups: sham group, SCI group, SCI + vehicle group, and SCI + RGF966 group. To examine the effect of HDAC3 on neurological deficit after SCI, we gathered data using the Basso Beattie Bresnahan locomotion scale, the inclined plane test, the blood-spinal cord barrier, junction protein expression, and Nissl staining. We also evaluated microglial activation and inflammatory factor levels. Immunofluorescence analysis, immunohistochemical analysis, western blotting, and quantitative real-time polymerase chain reaction were performed to examine the regulation of the Sirtuin 1 (SIRT1)/nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway.

Results: The results showed that HDAC3 inhibition significantly ameliorated Basso-Beattie-Bresnahan (BBB) permeability, brain edema, and improved neurological functions and junction protein levels. Additionally, HDAC3 inhibition significantly inhibited microglial activation, thereby reducing the levels of SCI-induced pro-inflammatory factors. Moreover, HDAC3 inhibition dramatically enhanced the expression of SIRT1 and increased both Nrf2 nuclear accumulation and transcriptional activity, thereby increasing downstream heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1 expression.

Conclusions: The results of this study suggest that HDAC3 inhibition protects the spinal cord from injury following SCI by inhibiting SCI-induced microglial activation and the subsequent inflammatory response via SIRT1/Nrf2 signaling pathway, highlighting HDAC3 as a potential therapeutic target for the treatment of SCI.

Background: The Fugl-Meyer Assessment-Upper Extremity (FMA-UE) is a widely used outcome measure for quantifying motor impairment in stroke recovery. Meaningful change (responsiveness) in the acute to subacute phase of stroke recovery has not been determined.

Objective: Determine responsiveness and sensitivity to change of the FMA-UE from 1-week to 6-weeks (subacute) after stroke in individuals with moderate to severe arm impairment who received standard clinical care.

Methods: A total of 51 participants with resulting moderate and severe UE hemiparesis after stroke had FMA-UE assessment at baseline (within 2 weeks of stroke) and 6-weeks later. Sensitivity to change was assessed using Glass's delta, standardized response means (SRM), standard error of measure (SEM), and minimal detectable change (MDC). Responsiveness was assessed with the minimal clinically important difference (MCID), estimated using receiver operating characteristic curve analysis with patient-reported global rating of change scales (GROC) and a provider-reported modified Rankin Scale (mRS) as anchors.

Results: The MCID estimates were 13, 12, and 9 anchored to the GROC Arm Weakness, GROC Recovery, and mRS. Glass's delta and the SRM revealed large effect sizes, indicating high sensitivity to change, (∆ = 1.24, 95% CI [0.64, 1.82], SRM = 1.10). Results for the SEM and MDC were 2.46 and 6.82, respectively.

Conclusion: The estimated MCID for the FMA-UE for individuals with moderate to severe motor impairment from 1 to 6-weeks after stroke is 13. These estimates will provide clinical context for FMA-UE change scores by helping to identify the change in upper-extremity motor impairment that is both beyond measurement error and clinically meaningful.

Despite the substantial progress in motor rehabilitation, patient involvement and motivation remain major challenges. They are typically addressed with communicational and environmental strategies, as well as with improved goal-setting procedures. Here we suggest a new research direction and framework involving Neuroeconomics principles to investigate the role of Motor Decision-Making (MDM) parameters in motivational component and motor performance in rehabilitation. We argue that investigating NE principles could bring new approaches aimed at increasing active patient engagement in the rehabilitation process by introducing more movement choice, and adapting existing goal-setting procedures. We discuss possible MDM implementation strategies and illustrate possible research directions using examples of stroke and psychiatric disorders.

Background: The cerebellum plays a crucial role in functional movement by influencing sensorimotor coordination and learning. However, the effects of cortico-cerebellar connectivity on the recovery of upper extremity motor function after stroke have not been investigated. We hypothesized that the integrity of the cortico-cerebellar connections would be reduced in patients with a subacute middle cerebral artery (MCA) stroke, and that this reduction may help to predict chronic upper extremity motor function.

Methods: We retrospectively analyzed the diffusion-tensor imaging of 25 patients with a subacute MCA stroke (mean age: 62.2 ± 2.7 years; 14 females) and 25 age- and sex-matched healthy controls. We evaluated the microstructural integrity of the corticospinal tract (CST), dentatothalamocortical tract (DTCT), and corticopontocerebellar tract (CPCT). Furthermore, we created linear regression models to predict chronic upper extremity motor function based on the structural integrity of each tract.

Results: In stroke patients, the affected DTCT and CST showed significantly impaired structural integrity compared to unaffected tracts and the tracts in controls. When all models were compared, the model that used the fractional anisotropy (FA) asymmetry indices of CST and DTCT as independent variables best predicted chronic upper extremity motor function (R² = .506, P = .001). The extent of structural integrity of the CPCT did not significantly differ between hemispheres or groups and was not predictive of motor function.

Conclusions: We found evidence that microstructural integrity of the DTCT in the subacute phase of an MCA stroke helped to predict chronic upper extremity motor function, independent of CST status.

Background: Recovery of quiet standing balance early poststroke has been poorly investigated using repeated measurements.

Objective: To investigate (1) the time course of steady-state balance in terms of postural stability and inter-limb symmetry, and (2) longitudinal associations with lower limb motor recovery in the first 3 months poststroke.

Methods: Forty-eight hemiparetic subjects (age: 58.9 ± 16.1 years) were evaluated at weeks 3, 5, 8, and 12 poststroke. Motor impairments concerned the Fugl-Meyer assessment (FM-LE) and Motricity Index total score (MI-LE) or ankle item separately (MI-ankle). Postural stability during quiet 2-legged stance was calculated as the net center-of-pressure area (COP_Area) and direction-dependent velocities (COP_Vel-ML and COP_Vel-AP). Dynamic control asymmetry (DCA) and weight-bearing asymmetry (WBA) estimated inter-limb symmetries in balance control and loading. Linear mixed models determined (1) time-dependent change and (2) the between- and within-subject associations between motor impairments and postural stability or inter-limb symmetry.

Results: Time-dependent improvements were significant for FM-LE, MI-LE, MI-ankle, COP_Area, COP_Vel-ML, and COP_Vel-AP, and tended to plateau by week 8. DCA and WBA did not exhibit significant change. Between-subject analyses yielded significant regression coefficients for FM-LE, MI-LE, and MI-ankle scores with COP_Area, COP_Vel-ML, and COP_Vel-AP up until week 8, and with WBA until week 12. Within-subject regression coefficients of motor recovery with change in COP_Area, COP_Vel-ML, COP_Vel-AP, DCA, or WBA were generally non-significant.

Conclusions: Postural stability improved significantly in the first 8 weeks poststroke, independent of lower limb motor recovery at the most affected side within subjects. Our findings suggest that subjects preferred to compensate with their less affected side, making metrics reflecting inter-limb asymmetries in balance invariant for change early poststroke.Clinical Trial Registration: Clinicaltrials.gov. unique identifier NCT03728036.

Baseline scores after stroke have long been known as a good predictor of post-stroke outcomes. Similarly, the extent of baseline impairment has been shown to strongly correlate with spontaneous recovery in the first 3 to 6 months after stroke, a principle known as proportional recovery. However, recent critiques have proposed that proportional recovery is confounded, most notably by mathematical coupling and ceiling effects, and that it may not be a valid model for post-stroke recovery. This article reviews the current understanding of proportional recovery after stroke, discusses its supposed confounds of mathematical coupling and ceiling effects, and comments on the validity and usefulness of proportional recovery as a model for post-stroke recovery. We demonstrate that mathematical coupling of the true measurement value is not a real statistical confound, but rather a notational construct that has no effect on the correlation itself. On the other hand, mathematical coupling does apply to the measurement error and can spuriously amplify correlation effect sizes, but should be negligible in most cases. We also explain that compression toward ceiling and the corresponding proportional recovery relationship are consistent with our understanding of post-stroke recovery dynamics, rather than being unwanted confounds. However, while proportional recovery is valid, it is not particularly groundbreaking or meaningful as previously thought, just like how correlations between baseline scores and outcomes are relatively common in stroke research. Whether through proportional recovery or baseline-outcome regression, baseline scores are a starting point for investigating factors that determine recovery and outcomes after stroke.

Background: Accumulating evidence suggests that motor performance is affected by the cognitive control abilities of the subject. Performance in motor tasks in populations with cognitive deficits such as older adults and subjects with stroke is therefore expected to deteriorate. The goal of this study is to investigate the relationship between cognitive impairments and motor control and learning impairments in a visuomotor adaptation task in subjects with stroke.

Methods: Twenty-seven post-stroke, 31 age matched controls, and 30 young control subjects completed a sensorimotor adaptation task composed of 2 adaptation blocks separated by a washout block. Explicit learning was assessed by cueing subjects to suppress their strategy. Cognitive assessment was conducted using the Montreal Cognitive Assessment (MoCA) and a verbal learning test. Subjects with stroke performed the task with their unaffected arm.

Results: Despite the cognitive deterioration, the adaptation and savings of the stroke group and age matched controls were comparable. Adaptation and savings were smaller with respect to the young subjects. Savings was associated with a significant improvement in the explicit component across blocks. Finally, the explicit enhancement between blocks was significantly correlated with the MoCA scores in the stroke group and with the results of the verbal learning test in the young controls.

Conclusion: The lack of stroke-induced attenuation on adaptation, despite a correlation between cognitive abilities and explicit learning in adaptation, suggests that subjects with stroke have enough cognitive resources to support sensorimotor adaptation. The availability of cognitive resources for motor learning following brain damage could be utilized in the rehabilitation process.

Background: Atlas-based voxel features have the potential to aid motor outcome prognostication after stroke, but are seldom used in clinically feasible prediction models. This could be because neuroimaging feature development is a non-standardized, complex, multistep process. This is a barrier to entry for researchers and poses issues for reproducibility and validation in a field of research where sample sizes are typically small.

Objectives: The primary aim of this review is to describe the methodologies currently used in motor outcome prediction studies using atlas-based voxel neuroimaging features. Another aim is to identify neuroanatomical regions commonly used for motor outcome prediction.

Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol was constructed and OVID Medline and Scopus databases were searched for relevant studies. The studies were then screened and details about imaging modality, image acquisition, image normalization, lesion segmentation, region of interest determination, and imaging measures were extracted.

Results: Seventeen studies were included and examined. Common limitations were a lack of detailed reporting on image acquisition and the specific brain templates used for normalization and a lack of clear reasoning behind the atlas or imaging measure selection. A wide variety of sensorimotor regions relate to motor outcomes and there is no consensus use of one single sensorimotor atlas for motor outcome prediction.

Conclusion: There is an ongoing need to validate imaging predictors and further improve methodological techniques and reporting standards in neuroimaging feature development for motor outcome prediction post-stroke.