Neurorehabilitation and Neural Repair

BackgroundAccumulating results suggest that reticulospinal tract (RST) excitability increases after stroke. While animal studies suggest this hyperexcitability may compensate for corticospinal tract (CST) damage, its role in motor function in people with stroke (PwS) remains debated. This study aimed to: (1) replicate findings of RST hyperexcitability in PwS using the StartReact paradigm, measuring acceleration of motor response to a startling auditory stimulus; (2) examine the relationship between RST hyperexcitability and motor impairments after stroke; and (3) explore whether RST hyperexcitability provides functional benefits in severely impaired PwS. MethodsForty-six PwS completed the StartReact paradigm and motor assessments (Fugl-Meyer, ARAT, grip strength, Modified Ashworth Scale). PwS were categorized into high StartReact effect and typical StartReact effect subgroups based on comparisons with a healthy control group (n=37). Severe impairment was defined as ARAT [≤]10. ResultsPwS exhibited significantly greater StartReact effects than controls. The high StartReact effect subgroup showed worse motor function, weaker grip strength, and higher spasticity. Among severely impaired PwS, high StartReact effect was not associated with improved grip strength. ConclusionsThese findings confirm the existence of RST hyperexcitability after stroke and suggest it is associated with poorer motor outcomes, likely due to reduced cortical input to the brainstem. The absence of functional benefit in severely impaired individuals supports the interpretation that RST hyperexcitability is a maladaptive rather than a compensatory reaction to brain damage. These findings provide insight into the neurophysiological mechanisms underlying motor impairments after stroke and do no imply direct clinical or therapeutic applications.

Many individuals with limb apraxia after left-hemisphere stroke exhibit a lack of awareness of their tool-related action errors, i.e., unawareness of apraxia (UA; also called anosognosia of apraxia). Little is known about the prevalence of UA, the relationship between UA and apraxia severity, or its underlying mechanisms. Here, we assessed both the causes and consequences of UA. Based on a mechanistic model, we hypothesized that UA may arise because of deficits in representations signaling how tool-related movements should look and feel--a component of action knowledge--and that degradation of this knowledge impedes the detection of mismatches between planned and actual tool-related actions. We further predicted that a consequence of UA is a reduction in error-correction attempts. Fifty-six individuals with chronic LCVA gestured to show how to use tools. Immediately after the gesture production task, participants were asked if they made any errors. All participants also completed an action knowledge task to measure the integrity of tool-related movement goals. Individuals were denoted as exhibiting UA if they performed below a normative cutoff for apraxia yet reported making no errors. Our sample included 21 individuals with apraxia; of these, nearly half (48%) exhibited UA. These two groups made a comparable number of gesture errors and were of equivalent stroke severity, yet individuals with UA had significantly more impaired action knowledge. Additionally, individuals with UA were less likely to attempt to correct their errors compared to individuals who were aware of their apraxia. These data support the hypothesis that action knowledge (how tool actions look and feel) serves a key role in error detection and awareness of apraxia and may contribute to the difficulties with everyday tasks experienced by many people with apraxia.

Introduction: Adults with spinal cord injury (SCI) often experience reduced or lost sensation and movement, impairing the ability of the brain to locate paralyzed body parts, which, in turn, compromises sensorimotor recovery. This disruption of the internal body map of the brain, or mental body representations (MBR), also contributes to neuropathic pain in about 69% of adults with SCI. Medications for neuropathic pain are often ineffective and can cause adverse reactions. Our previous pilot clinical trial showed that Cognitive Multisensory Rehabilitation (CMR), a physical therapy that restores MBR, produced significant, lasting reductions in neuropathic pain, improved sensorimotor function, and enhanced brain function. Building on these results, we examined whether 8 weeks of CMR or adaptive fitness (1) improved sensorimotor function and reduced pain; (2) greater brain activity and connectivity related to sensorimotor function and MBR in adults with SCI. Methods: Sixteen participants (52+/-8 years old, 13+/-10 years post-SCI) were randomized to 8 weeks of CMR or adaptive fitness (45 min, 3x/week). Ten participants had neuropathic pain of 3/10 or greater. Pain and sensorimotor function were assessed at baseline, post-intervention, and 3-month follow-up using the Numeric Pain Rating Scale (NPRS), ASIA Impairment Scale (AIS), and Neuromuscular Recovery Scale (NRS). Functional MRI included resting-state and 4 tasks: imagining feeling the left leg, imagining moving the left leg, whole-body movement imagery, and a sensation task. Results: After CMR, participants improved on AIS with large effect sizes (touch: d=1.54; pinprick: d=1.83; lower limb motor function: d=1.32), while adaptive fitness had small/moderate effects (touch: d=0.49; pinprick: d=0.53; lower limb motor function: d=0.74). CMR also showed larger effect sizes for NRS (core: d=2.19; upper limb: d=0.69; lower limb: d=0.74) than fitness (core: d=0.73; upper limb: d=0.34; lower limb: d=0.00). Benefits persisted at follow-up. Highest neuropathic pain intensity reduced post-CMR and at 3-month follow-up (d=0.48; d=0.63). Pain increased slightly after fitness (n=6; d=-0.19; d=-0.41). CMR increased brain connectivity and activation during the leg imagery task. Increased activation during whole-body imagery was greater after CMR than fitness. Discussion: These preliminary results support the potential of CMR to improve function and reduce neuropathic pain in adults with SCI, warranting larger confirmatory trials. Clinicaltrial.gov: NCT05167032

Objectives: Among individuals attending stroke rehabilitation, we aimed to determine the proportion who participated in cardiorespiratory exercise, identify patient characteristics predicting participation, and describe exercise characteristics. Design, setting, and participants: This was an observational cohort study involving all patients admitted to four stroke rehabilitation centres in Ontario, Canada, during March or October 2019, or over 12 months starting in 2021. Main measures: Patient characteristics extracted during chart review included age, sex, marital status, employment status, date of stroke, time post-stroke at admission, length of stay for rehabilitation, past medical history that could affect exercise participation, Functional Independence Measure, Functional Ambulation Category, mobility aid use, Chedoke-McMaster Stroke Assessment, Montreal Cognitive Assessment, National Institutes of Health Stroke Scale, and details describing cardiorespiratory exercise completed. Results: 40.1% of stroke patients participated in cardiorespiratory exercise, with 26.4% having it included in their treatment plan. Diagnosed cardiac disease (OR=0.74), poor left ventricular function (OR=0.09), history of mental health conditions (OR=0.69), lower functional ambulation ability (OR=0.74), and wheelchair use at rehabilitation admission (OR=0.46) were associated with lower odds of participating in cardiorespiratory exercise after stroke (p-values<0.05). Use of a walker or rollator at rehabilitation admission (OR=3.22), having a cardiorespiratory exercise goal (OR=2.13), and longer lengths of stay (OR=1.01) were associated with higher odds of participating in cardiorespiratory exercise after stroke (p-values<0.05). Only 1.5% of patients (N=9/601) who participated in cardiorespiratory exercise completed it with recommended intensity and duration. Conclusion: Improving participation in cardiorespiratory exercise during stroke rehabilitation may require addressing cardiovascular, mental health, and mobility-related barriers.

Walking impairments in Parkinsons disease (PD), including reduced speed, cadence, and stride length, and increased variability, impair mobility and raise fall risk. Conventional treatments may fail to address these deficits, underscoring the need for complementary non-invasive alternatives. This study examined whether combining rhythmic auditory cueing with transcranial direct current stimulation (tDCS) over the supplementary motor area (SMA), a critical region for internally-generated movement, would enhance gait performance in PD. Thirty-three participants with PD and thirty-two healthy controls completed two sessions (anodal vs. sham tDCS) with gait assessed during stimulation, immediately after stimulation, and 15 minutes after stimulation under two auditory conditions: walking in silence and walking to music paced 10% faster than baseline cadence. Spatiotemporal, variability, and stability gait parameters were analyzed using linear mixed-effects models. Rhythmic auditory cueing significantly increased cadence and speed during, immediately after, and especially 15 minutes after stimulation, suggesting sustained effects of rhythmic entrainment. Anodal tDCS produced faster cadence, as well as lower stride time variability and stride width, particularly in individuals with PD. Although both music and anodal tDCS affected gait, no interaction was observed, indicating independent effects. Individuals with PD had greater gait variability overall, and adjusted temporal gait parameters less to music than healthy controls did. Anodal stimulation reduced walking variability in PD, reducing the group differences observed under sham conditions. These findings suggest that rhythmic cueing and SMA stimulation target complementary mechanisms, highlighting the promise of combined tDCS-music interventions for gait rehabilitation in PD.

Background: Moderate- to high-intensity walking training (M-HIT) is an established intervention for improving walking capacity in chronic stroke. Musculoskeletal (MSK) adverse events commonly occur during M-HIT, yet tools to identify individuals at higher risk are limited. Baseline clinical characteristics may provide insight into susceptibility to training-related MSK adverse events during M-HIT. Thus, this study aimed to develop and internally validate a model for predicting MSK adverse events during a 12-week M-HIT program in chronic stroke using baseline clinical characteristics. Methods: Participants (n=100) from HIT-Stroke Trials 1 and 2 were included. Baseline clinical characteristics included measures of orthopedic history, pre-existing pain, motor function, recent exercise history, demographics and health characteristics, stroke chronicity, and psychological health. Logistic regression models evaluated all possible combinations of baseline characteristics with up to three predictors. Leave-one-out cross-validation was used for internal validation to mitigate overfitting. Predictive performance was quantified using the C-statistic, and the candidate model with the highest cross-validated C-statistic was selected as the final model. Results: MSK adverse events occurred in 32.0% of participants. The optimal three-variable model included prior orthopedic condition (Odds ratio [OR] 3.02 [95% CI 1.14-8.64]), Fugl-Meyer lower extremity motor score (OR 1.14 [95% CI 1.02-1.28]), and self-reported participation in regular walking exercise (OR 0.17 [95% CI 0.05-0.49]) at baseline. This model demonstrated moderate discrimination (cross-validated C-statistic = 0.74; apparent C-statistic = 0.78). Conclusions: Participants reporting at least one pre-existing lower extremity or lumbar spine orthopedic condition and those with better lower-extremity motor function exhibited greater odds of experiencing MSK adverse events during M-HIT, while participants reporting participation in regular walking exercise had lower odds. These findings suggest that baseline clinical characteristics may help identify individuals at elevated risk for MSK adverse events during M-HIT who may warrant closer monitoring or risk-reduction strategies. Future studies are needed for external validation. Clinical Trial Registration: https://ClinicalTrials.gov; Unique identifiers: NCT03760016, NCT06268041

Background and purpose: People after mild traumatic brain injury (mTBI) show persistent deficits in reactive balance. Cortical processes engaged during preparation and execution of balance reactions are reflected in distinct cortical activity signatures that can be measured with electroencephalography (EEG). The purpose of this study was to 1) compare preparatory cortical beta activity and evoked cortical N1 responses during balance recovery in people with mTBI and controls, and 2) explore relationships between preparatory and evoked cortical activity. Methods: Participants (age 21-35 years) with symptomatic mTBI (n=5, 27 +/- 13 days post-injury) and controls (n=5) completed the instrumented and modified push & release tests of reactive balance. Cortical activity was recorded using encephalography (EEG). Main outcome measures were 1) preparatory sensorimotor cortical beta-bust power and duration prior to balance perturbation onset (-1s-0s), and 2) cortical N1 response amplitude and latency during the post-perturbation balance recovery (50-250ms). Results: People with mTBI exhibited lower preparatory beta-burst power compared to controls (p=0.044, g=1.18). During balance recovery, cortical N1 responses occurred earlier in people with mTBI compared to controls (p=0.045, g=3.28). Relationships between preparatory and evoked cortical activity were altered after mTBI compared to controls; people after mTBI with greater beta-burst power and longer duration elicited shorter N1 latencies (r's>0.77, p's<0.010). Discussion and conclusion: The results serve as preliminary, hypothesis-generating observations to guide future research directions investigating neural signatures of reactive balance deficits in people after mTBI. The preparatory brain state before reactive balance recovery should be explored as a potential target for post-mTBI balance rehabilitation.

Dystonia treatment evaluation in cerebral palsy (CP) is limited by the lack of clinician-assessed scales linking dystonia severity to functional impact. We asked 7 pediatric movement disorder specialists to review videos of 27 children with CP while performing an upper extremity task and while walking. Experts rated arm and leg dystonia severity using the Global Dystonia Severity Rating Scale (GDRS) and task-specific functional impact on a five-point scale adapted from the Dyskinetic Cerebral Palsy Functional Impact Scale. Arm GDRS scores correlated with functional impact on the upper extremity task (linear regression R^2=0.48, p=0.0005). Leg GDRS scores correlated with gait impact (R^2=0.43, p=0.001). A four-point increase in total GDRS corresponded to a one-point worsening in combined functional impact. By demonstrating how expert-rated limb dystonia severity correlates with task-specific functional impact in children with CP, these results could help clinically identify functionally-meaningful differences in dystonia severity.

BackgroundBalance instability is a major contributor to disability and falls in people with Parkinsons disease (PwP) and is often insufficiently explained by motor impairment alone. Altered awareness of motor control has been suggested to contribute to sensorimotor dysfunction in PwP, but its relationship with balance performance is poorly understood. ObjectiveTo determine whether awareness of balance control, assessed using a control detection task (CDT), differs between healthy controls (HC) and PwP, and whether CDT performance is associated with balance-related measures. MethodsHealthy older adults (n=20) and PwP (n=22) performed a standing version of the CDT based on center-of-pressure (COP) control, using a force plate. CDT accuracy was used as the primary outcome measure. Static balance during quiet standing was assessed using the COP trajectory length and rectangular area. Dynamic standing balance was assessed using the Index of Postural Stability (IPS). Group differences were examined by independent-samples t-tests. Correlations between CDT accuracy and balance measures were analyzed. ResultsThe PwP group showed significantly lower CDT accuracy. Higher CDT accuracy was associated with better static balance in the HC group and the combined sample, and with higher IPS primarily in the PwP group. ConclusionsMotor awareness during postural tasks is altered in PwP and is associated with balance control. These findings suggest that balance instability in Parkinsons disease may involve altered balance-related action-outcome monitoring in addition to motor dysfunction.

Objective: To develop the first inventory to measure psychosocial concerns about use of the non-preferred hand, toward the long-term goal of identifying the casual factors of left-right hand choices ("hand usage"). Design: Cross-sectional Setting: Online question battery Participants: 181 healthy adults Interventions; Not applicable Main Outcome Measures: Self-reported concerns about emotional and physical consequences of using the non-preferred hand. Results: Emotional and physical consequences reflected internally consistent categories (Cronbach's > 0.9) that were moderately correlated with each other ({rho} = 0.783 p = 0.002). Concerns were activity-dependent in each category ({rho} < 1x10-100). Reliability analysis and principal components analysis were used to reduce the battery to the 51-item Changed Hand Usage Concerns inventory, which encompasses everyday tasks and concerns about physical and emotional consequences of using the non-preferred hand in those tasks. Conclusions: Concerns about emotional vs. physical consequences of non-preferred hand use reflect coherent and internally consistent categories The Changed Hand Usage Concerns inventory allows assessment of psychosocial concerns about usage of the non-preferred hand for future attempts to manipulate hand usage via rehabilitation in patients with unilateral or asymmetric impairment.

Walking speed is widely used to assess gait recovery following stroke, yet it provides limited insight into how walking performance is mechanically organized. This study examined how center of mass (COM) work organization and propulsion-support coupling vary across walking speeds in individuals with post stroke hemiparesis to distinguish recovery of gait organization from recovery of limb level mechanical function. Eleven individuals with post stroke hemiparesis performed treadmill walking across speeds ranging from 0.2 to 0.7 m/s while ground reaction forces were recorded. Limb specific COM power and work were computed using an individual limbs framework, and interlimb asymmetry in net and positive work, along with the propulsion-support ratio (PSR), were quantified. A qualitative transition in gait organization was observed: at lower walking speeds, COM power exhibited a simplified two phase pattern, whereas at higher walking speeds (approximately >=0.5 m/s), a structured four phase COM power pattern emerged, including identifiable push off and preload phases. Despite this recovery of gait organization, interlimb work asymmetry remained elevated and paretic PSR remained reduced across all speeds, indicating persistent limb level mechanical deficits. These findings demonstrate that increases in walking speed and the emergence of typical COM power structure reflect recovery of gait organization rather than restoration of underlying limb level mechanical capacity. Consequently, walking speed alone is insufficient to characterize gait recovery after stroke, and biomechanically informed measures of COM work organization and propulsion-support coupling provide complementary insight by distinguishing organizational recovery from limb-level mechanical recovery.

BackgroundRespiration is a key central nervous system rhythm that modulates sensorimotor function in healthy individuals, but the neurophysiological mechanisms of volitional breathing-mediated sensorimotor modulation and its preservation in stroke patients remain unclear. This study aimed to characterize the effects of volitional fast inspiration on sensorimotor pathway excitability in healthy and stroke populations, and provide a mechanistic basis for respiratory-integrated post-stroke rehabilitation. MethodsA multimodal case-control neurophysiology study was conducted in 52 healthy volunteers (26 {+/-} 3 years, 30 males) and 44 first-ever subacute stroke patients (66 {+/-} 10 years, 30 males). Three complementary experiments assessed transcranial magnetic stimulation-induced motor-evoked potentials (MEPs), peripheral nerve stimulation-induced somatosensory-evoked potentials (SEPs), and functional electrical stimulation -evoked muscle force under three breathing conditions: volitional fast inspiration (IN), fast expiration (EX), and spontaneous breathing (CON). Two-way and one-way repeated measures ANOVA with Bonferroni post hoc tests were used for statistical analysis. ResultsVolitional fast inspiration significantly enhanced sensorimotor pathway excitability and muscle force generation in both groups. Volitional fast inspiration increased MEP amplitudes relative to spontaneous breathing and fast expiration (p {inverted exclamation} 0.05), with further amplification during active muscle contraction (p {inverted exclamation} 0.05). It also elevated SEP amplitudes in healthy parietal/frontal cortical regions and the stroke parietal cortex (p {inverted exclamation} 0.05). Synchronizing volitional fast inspiration with voluntary finger contraction increased muscle force evoked by functional electrical stimulation by 16-18% relative to spontaneous breathing (p {inverted exclamation} 0.05), with non-significant force gains at rest. ConclusionsVolitional fast inspiration bidirectionally enhances corticospinal transmission, somatosensory integration, and functional force generation in both healthy individuals and stroke patients, with preserved respiratory modulation in stroke-damaged neuropathways. By demonstrating preserved respiratory modulation in stroke-damaged neuropathways, our results provide mechanistic support for integrating controlled breathing into low-cost, non-invasive post-stroke rehabilitation paradigms.

Stroke impairs dexterous hand use in daily activities, which may be due to compromised coordination complexity and diminished task-appropriate and individually-distinctive coordination (expressiveness). This loss of complexity and expressiveness, however, has not been elucidated, especially in spatiotemporal coordination. Here, we characterized spatiotemporal coordination in able-bodied and post-stroke hands during finger individuation. We quantified coordination complexity and expressiveness using principal component analysis (PCA) and linear discriminant analysis of 3D isometric forces from all five fingers. Paretic fingers showed reduced complexity (number of PCs) and expressiveness (task-, individual-, and group-specificity), which was associated with greater intrusion of flexor bias in the paretic hand. Higher-variance PCs were characteristic of tasks and groups, while both higher- and lower-variance PCs were characteristic of individual-specific coordination. These findings advance understanding of how stroke affects finger coordination complexity and expressiveness, and may inform the development of targeted therapies to improve task-relevant and individually distinctive coordination post-stroke.

Background: Lumbar spinal stenosis (LSS) can cause pain and severe walking limitation. Although surgery aims to improve walking, many patients do not achieve clinically meaningful gains. Rehabilitation can improve outcomes, yet existing programmes lack robust evidence and theoretical underpinning. This study aimed to (1) co-design a theory-informed rehabilitation programme to improve walking after LSS surgery, and (2) evaluate feasibility of conducting a future trial and acceptability of the intervention. Methods: A multi-methods study included intervention co-design followed by a single-arm feasibility study. Co-design used an adapted Experience-Based Co-Design approach with patients, carers, and healthcare professionals (n=39), integrating the Behaviour Change Wheel. This resulted in STructured Rehabilitation and InDividualised Exercise and Education (STRIDE), delivered over 12-week pre- and 12-weeks post-surgery, targeting knowledge, expectations, perceived control, physical capability, and fears. Adults aged [&ge;]50 years awaiting LSS surgery were recruited to a before-after feasibility study. Feasibility outcomes included recruitment and retention. Acceptability was assessed using the Theoretical Framework of Acceptability questionnaire (0-5 (high acceptability)) and focus groups. Clinical outcomes measured at baseline, post-prehabilitation, and post-rehabilitation included 6-minute walk distance (6MWD) and mean daily step count over 7 days. Results: Fifteen of 31 eligible participants were recruited (48%; mean age 70 years), with 80% retained to study end (2 decided against surgery, 1 unable to complete final assessment). Acceptability was high (median 5/5, IQR 0). Participants valued the personalised, supportive approach and reported improved motivation and preparation for surgery, though travel was burdensome. Small pre-operative and moderate-to-large post-operative improvements were observed in 6MWD (+49.9 m and +81.6 m) and daily step count (+868 and +1405 steps/day). Conclusions: This co-designed, physiotherapy-led, behaviour-change rehabilitation programme was acceptable to participants, with encouraging recruitment, retention, and signals of improved walking following LSS surgery. The findings support progression to a future trial.

Background: Spinal cord injury (SCI) is associated with widespread reorganisation of cortical sensorimotor circuits. Persistent complications such as spasticity and neuropathic pain suggest that homeostatic plasticity, which normally helps stabilise and constrain activity-dependent changes in sensorimotor circuits, may be disrupted after SCI. Homeostatic plasticity can be probed using repeated blocks of transcranial direct current stimulation (tDCS); in healthy individuals, two closely spaced excitatory blocks typically leads to an inhibitory response, reflected as a reduction in corticomotor excitability. Objective: To determine whether individuals with SCI show reduced homeostatic suppression of corticospinal excitability in response to repeated anodal tDCS, compared with healthy controls. Methods: Twenty adults with thoracic or below SCI and 20 healthy controls completed three counterbalanced sessions. Each session comprised two 10-minute blocks of 2 mA tDCS separated by 5 minutes, with the second block always being anodal tDCS over left primary motor cortex. The first block was either anodal, cathodal, or sham tDCS, yielding 3 condition types: anodal-anodal, cathodal-anodal, and sham-anodal. To assess corticomotor excitability, transcranial magnetic stimulation-evoked motor evoked potentials (MEPs) were elicited at baseline, after priming, and every 5 minutes for 60 minutes after the second block. The primary outcome was percent change in MEP amplitude from baseline. Results: In the anodal-anodal condition, the SCI group showed greater facilitation than controls over 0-30 minutes (estimate = 83.09, 95% CI 49.75 to 116.43, p < 0.001), suggestive of a weaker homeostatic response. The cathodal-anodal condition led to a significant overall facilitatory effect with no between-group difference, while the sham-anodal condition showed no change in MEP amplitude relative to baseline. Within the SCI group, exploratory subgroup analysis suggests that those with neuropathic pain and a traumatic injury showed greater facilitation in the anodal-anodal condition than those without these features, indicative of a weaker homeostatic response. Conclusions: SCI is associated with impairment in the homeostatic regulation of corticomotor excitability following repeated excitatory brain stimulation. Disrupted plasticity stabilisation may be relevant to persistent symptoms such as neuropathic pain.

BackgroundTheory of Mind (ToM) deficits are well-documented in right-hemisphere stroke but remain understudied in post-stroke aphasia. Prior work suggests that performance on tasks assessing ToM may be relatively preserved in aphasia and dissociable from language impairment, but these findings are based largely on small studies. This study examined performance on nonverbal false-belief tasks in post-stroke aphasia, its relationship with aphasia severity, and whether vascular brain health, operationalized using cerebral small vessel disease (CSVD) markers, contributed to variability in performance. MethodsForty-four individuals with aphasia completed two nonverbal belief-reasoning tasks assessing spontaneous perspective-taking and self-perspective inhibition. Task accuracy served as the primary outcome. Linear regression models examined associations between task performance, aphasia severity (Western Aphasia Battery-Revised Aphasia Quotient), and CSVD markers, including white matter hyperintensities, cerebral microbleeds, lacunes and enlarged perivascular spaces in the basal ganglia and centrum semiovale. ResultsPerformance was heterogeneous across tasks, with reduced performance observed in 23% of participants on the Reality-Unknown task and 36% on the Reality-Known task. Aphasia severity was not associated with task accuracy. Greater cerebral microbleed count was associated with lower accuracy on both tasks, while greater basal ganglia enlarged perivascular spaces burden showed a more selective association with lower performance. ConclusionsPerformance on nonverbal false-belief tasks in aphasia is variable and not explained by aphasia severity alone. These findings suggest that apparent ToM-related difficulties in aphasia may be shaped by broader vascular brain health, supporting a more multidimensional framework for interpreting social-cognitive task performance after stroke.

Stroke is the third leading cause of death and disability combined worldwide and often results in hemiparesis. Functional magnetic resonance imaging (fMRI) is a non-invasive technique used to investigate changes in brain activations during tasks aimed at restoring the lost motor function. Participants with chronic stroke and residual hemiparesis in the upper extremity were recruited for a clinical intervention that included neurofeedback training and fMRI sessions with motor-execution and motor-imagery tasks. The present study provides a baseline characterization of brain activations prior to neurofeedback training. Since lesion site and volume varied across participants, two fMRI preprocessing pipelines were applied. The first one was used for twelve participants with lesions restricted to a single hemisphere and for one participant with small secondary lesions in the contralesional hemisphere, whereas the second one was used for two participants with large bilateral lesions. These were followed by quality control measures and statistical analysis. First-level (i.e., single-participant) analysis returned the strongest and most extensive activation across participants during motor-execution tasks, with clusters identified in the ipsilesional parietal lobe, bilateral occipital lobes, and cerebellum after Family-Wise Error correction. Second-level (i.e., group-level) analysis involving participants who underwent the first fMRI preprocessing pipeline revealed a significant cluster in the cerebellum after False Discovery Rate correction. These results are consistent with previous studies involving participants with chronic stroke performing motor-tasks. Cerebellar recruitment observed consistently across participants could reflect compensatory mechanisms supporting motor control after stroke.

BackgroundTourette Syndrome (TS) is a neurodevelopmental movement disorder involving involuntary motor and vocal tics believed to be characterised by disordered neural inhibition. Cortical representations have previously been manipulated by disruptions in the inhibitory neurotransmitter {gamma}-aminobutyric acid (GABA). However, while facial tics are the most reported motor tic, it is unclear if facial sensorimotor representations differ in TS. MethodsSixteen individuals with Tourette Syndrome (TS) or chronic tic disorder and twenty typically developing (TD) control participants underwent 3-Tesla functional magnetic resonance imaging (fMRI). Blood-oxygenation level-dependent (BOLD) responses were measured during a block-design task comprising cued facial movements of common facial tics (blinking, grimacing and jaw clenching). Activations in bilateral pre- and post-central cortices and supplementary motor areas (SMA) were examined. Conjunction analyses identified voxels commonly and uniquely activated across movements within each group. ResultsBoth groups showed significant activations in the bilateral sensorimotor cortices and SMA in response to blink, grimace and jaw clench movements, with no significant between-group differences. Between-group similarities were lowest for unique blink maps. Common voxel maps also revealed low between-group similarity, with reduced sensorimotor activation and no shared SMA activation across movements in the TS group. ConclusionVoluntary facial sensorimotor representations do not differ between groups. However, low similarities between group unique blink maps may reflect greater prevalence of blinking tics in TS. Additionally, reduced overlap in sensorimotor activation and absent common SMA engagement across cued movements in the TS group may indicate altered motor integration or action initiation.

Objective Cerebral palsy (CP) affects approximately 1 million Americans and 18 million individuals worldwide, yet contemporary US epidemiologic data remains limited. We aimed to use Cerebral Palsy Research Network (CPRN) clinical registry to describe demographics and clinical characteristics of individuals with CP across the US and determine associations with gross motor function and genetic etiology. Methods Registry subjects were included if they had clinician-confirmed CP and prospectively entered data for Gross Motor Function Classification System (GMFCS) Level, gestational age, genetic etiology, CP distribution, and tone/movement types. Logistic regression was used to determine which of these variables plus race, sex, ethnicity, and age were associated with GMFCS level and genetic etiology. Results A total of 9,756 children and adults with CP from 22 CPRN sites met inclusion criteria. Participants were predominantly White (73.0%), male (57.3%), non-Hispanic (87.8%), and younger than 18 years (73.7%). Most were classified as GMFCS levels I-III (55.6%), born preterm (52.8%), had spasticity (83.8%), and had quadriplegia (41.9%); 12.2% were identified as having a genetic etiology. Tone/movement types, CP distribution, and gestational age were significantly associated with both GMFCS level and genetic etiology (p<0.001). Compared to White individuals, Black individuals were more likely to have greater gross motor impairment (p<0.001). Conclusion In this large US cohort, clinical and demographic factors, including race, were associated with gross motor function and genetic etiology in CP. These findings highlight persistent disparities and demonstrate the value of a national clinical registry for informing prognostication, quality improvement efforts, and targeted genetic testing strategies.

Objective: To assess ethnic disparities in time to hospital presentation, use of acute reperfusion therapies, and in-hospital treatment times among patients presenting with stroke in a Dutch emergency department. Methods: In this single-centre observational cohort study, we included patients with a first-ever ischemic stroke between September 2020 and September 2021. Patients were categorized by ethnicity (with or without migration background). Demographic and stroke characteristics were compared between groups. Outcomes included: rates of presentation outside therapeutic time window, acute reperfusion therapy (intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)), and, when applicable, door-to-treatment time (DTTT), with a door-to-needle time (DTNT) and door-to-groin time (DTGT) for IVT and EVT respectively. Univariable and multivariable linear and logistic regression analyses were performed, adjusted for age, sex, and NIHSS at presentation, where appropriate. Results: A total of 232 patients were included, of whom 62 (26.7%) had a migration background. These patients were younger (66.6 vs 71.2 years) and more frequently had diabetes (27.4% vs 15.9%). Sex distribution was similar (59.7% vs 60.6% male). Stroke etiology differed between groups with less cardio-embolism (4.8% vs 15.3%) and more small vessel disease (69.4% vs 48.2%) among patients with a migration background. These latter patients presented more often outside the therapeutic time window (53.2% vs 37.1%; OR 1.90; 95% CI 1.05-3.45). EVT was less frequently performed in patients with a migration background compared to those without (8.1% vs 22.4%; OR 0.28; 95% CI 0.10-0.75). There were no significant differences in treatment times (DTTT 38min vs 30min, DTNT 35min vs 26min, DTGT 64min vs 54min). Conclusion: Patients with a migration background were more likely to present outside the therapeutic time window and had a lower rate of EVT. In order to improve access for these patients, more insight into prehospital and within hospital barriers and facilitators for appropriate management are needed.