Objective:We conducted a prospective study in human patients undergoing awake craniotomies to examine whether the effects of cortical stimulation in hand primary motor cortex (M1) can be (1) frequency dependent and (2) inhibitory. Methods:In 11 participants undergoing clinically indicated awake craniotomies, we delivered bursts of 1-333 Hz stimulation during a finger-flexion task. Synchronized electrocorticography (ECoG), finger joint kinematics, electromyography (EMG), and video were recorded. Results:Inability to flex the index finger during subthreshold stimulation was noted in 3 participants at frequencies >250 Hz when the electrodes were in locations that induced extension of the forefinger at higher amplitudes. Other than these trials, all stimulation events either induced muscle contractions or had no measurable effect. Conclusion:Data presented here represent the first evidence of (1) movement inhibition of the human hand caused by electrical stimulation of M1, as well as (2) the frequency-dependence of net downstream effects of hand M1 stimulation during task. Our findings support the hypothesis that the mechanism of movement inhibition may be activation of indirect, net-inhibitory mechanisms, as opposed to direct inhibition of the stimulated motor neurons. Significance:There is growing interest in using continuous electrical stimulation of the brain to remap anatomical-functional relationships away from invasive lesions. Achieving this type of neuroplasticity requires a better understanding of the direct and indirect effects of cortical stimulation. Here we demonstrate the frequency-dependent effects of cortical M1 stimulation on volitional finger movement.

Abstract Greater motor output variability (MOV, inconsistency and unsteadiness) during submaximal tasks post stroke is associated with poorer motor performance. However, little is known about MOV during maximal tasks and relationships with clinical measures of motor performance among stroke survivors. This study determined inconsistency (across discrete attempts) and unsteadiness (within a single attempt) during knee extension maximal voluntary isometric contractions (MVICs) in stroke survivors and neurotypical controls. Forty‐three stroke survivors (28 female) and 31 age‐matched neurotypical controls (15 female) performed a minimum of five knee extension MVICs with paretic and non‐paretic legs (stroke) or dominant leg (controls). Inconsistency was calculated as coefficient of variation between maximal torque values of each MVIC. Unsteadiness was calculated as the average from coefficient of variation of the torque values during each MVIC. The paretic leg of stroke survivors had greater MVIC inconsistency (7.61 ± 4.31% vs. 4.94 ± 2.77%, p = 0.014) and unsteadiness (7.00 ± 3.16% vs. 3.44 ± 1.68%, p < 0.001) than the dominant leg of neurotypical controls. Greater MVIC inconsistency (rs = −0.374, p = 0.016) and unsteadiness (rs = −0.445, p = 0.004) of stroke survivors' paretic leg were associated with lower Fugl‐Meyer Assessment‐Lower Extremity motor scores. Stroke increases MOV during a single session of MVIC measurements with multiple attempts and is associated with poorer clinical measures of motor performance.

IntroductionDegenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults and a major contributor to balance impairment and gait instability. Surgical decompression halts disease progression, but predicting post-surgical functional recovery remains challenging. Conventional MRI poorly reflects spinal cord microstructural integrity, limiting its ability to quantify sensorimotor deficits or predict outcomes. Diffusion tensor imaging (DTI) provides quantitative measures of tract-specific microstructure and may serve as a more sensitive biomarker for functional impairment and recovery in DCM.MethodsIn a prospective longitudinal cohort of 57 DCM patients undergoing surgical decompression, pre-operative spinal cord DTI was acquired at 3T. DTI metrics: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), and filtered apparent diffusion coefficient (Daxial) were extracted from dorsal, lateral, and ventral funiculi and gray matter at the C2 level. Functional outcomes included the Berg Balance Scale (BBS), Functional Gait Assessment (FGA), 10-Meter Walk Test (10MWT), and Eyes Closed Feet Together (ECFT) test, assessed pre-operatively and at 3 months post-surgery. General linear models examined baseline DTI–function associations; linear mixed-effects models assessed DTI prediction of post-operative improvement. Covariates were selected by pre-screening at p < 0.10.ResultsDorsal column FA (p = 0.034, q = 0.086) and RD (p = 0.025, q = 0.086) were associated with baseline BBS. Dorsal column MD (p = 0.010, q = 0.026) and RD (p = 0.009, q = 0.026) predicted post-operative BBS improvement. Lateral funiculi Daxial (p = 0.008, q = 0.038) predicted post-operative FGA improvement. Gray matter FA was associated with baseline FGA (p = 0.014, q = 0.070). Ventral funiculi metrics showed no significant associations. Forty-nine participants completed 3-month follow-up.ConclusionPre-operative C2-level DTI metrics demonstrate tract-specific associations with balance and gait function in DCM. Dorsal column microstructure was most strongly associated with static balance, while lateral funiculi and gray matter microstructure related more closely to dynamic balance and gait. These findings support spinal cord DTI as a quantitative imaging biomarker for functional prognostication and post-surgical outcome prediction in DCM.

Objective:Neuropsychological symptoms in people with brain tumors are common; however, they are often incompletely explained by tumor variables (such as anatomical location, size, or grade) and may be more directly related to changes in large-scale functional network connectivity. Here we examine these relationships. Methods:Fifty-one participants underwent pre-operative resting-state functional MRIs and three neuropsychological tests-Trail Making Test-Part-B (TMT-B), WAIS-IV Digit-Span Sequencing (WAIS-DS), and Controlled Oral Word Association Test (COWAT). Within-network functional connectivity of the central executive (CEN), default mode (DMN), language (LANG), and salience (SN) networks were compared to healthy controls. Spearman correlations (ρ) were calculated between neuropsychological z-scores, abnormal (>2 standard deviations from control means) within-network connectivity, and tumor variables while controlling for multiple comparisons. Exploratory, statistical mediation analyses then evaluated if relevant tumor variables affected neuropsychological performance via changes in functional connectivity. Results:Significant correlations included: (1) WAIS-DS performance to lesional-SN (ρ = 0.53, P = 0.006), lesional-CEN (ρ = 0.42, P = 0.023), and right-SN (ρ = 0.42, P = 0.023) connectivity; (2) COWAT performance to right-SN (ρ = 0.50, P = 0.012), lesional-SN connectivity (ρ = 0.45, P =0 .017), and lesion laterality (ρ =  0.47, P = 0.017); and (3) TMT-B to lesional-LANG (ρ =  0.46, P =0 .017), right-CEN (ρ = 0.45, P = 0.017), and bilateral-LANG (ρ =  0.42, P = 0.024) connectivity. Mediation analyses revealed the following effects: (1) lesion laterality on TMT-B was fully mediated via right-CEN connectivity (path a*b; β = 0.696 [0.13, 1.419]); (2) IDH-status on WAIS-DS was fully mediated via lesional-CEN connectivity (path a*b; β = 0.251 [0.015, 0.588]); and (3) lesion laterality on COWAT was partially mediated via right-SN connectivity (path a*b; β = 0.333 [0.004-0.72]). Conclusions:Our data support the hypothesis that functional network connectivity may explain some neuropsychological heterogeneity across otherwise anatomically and oncologically similar cases. Notably, more abnormal connectivity correlated with better performance, suggesting compensatory reorganization may be at least partially responsible.

Many stroke survivors cannot walk effectively, even after rehabilitation. Causes include impaired muscle activation, poor interlimb coordination, and limited restorative interventions. To address this, we developed CUped (pronounced “cupid”), a motorized split-crank pedaling device designed to compel use of the paretic limb and retrain interlimb coordination. We examined its within-session effects, comparing three proportional control schemes—assist (A), resist (R), and assist plus resist (A + R)—to identify which best promotes recovery-related movement. Nineteen individuals with stroke and eleven controls pedaled in 5-min bouts, one per control scheme. Each bout included pre-test, exposure, and post-test periods. Participants were instructed to maintain a 180º interlimb phase relationship. Interlimb coordination and paretic limb use were quantified as the mean and standard deviation of phasing error (µE, σE) and net mechanical work (Wₙₑₜ), respectively. ANOVA was used to assess the effects of group, time, and control scheme; regression examined relationships between variables and conditions. Between-limb differences in pedaling velocity (Vdif) were also calculated and served as interpretive measures. In stroke, all control schemes reduced µE, with the largest reduction observed under A + R (p ≤ 0.019; ES: A − 15º, R − 11º, A + R − 21º). Only A + R reduced σE (p = 0.039; ES: −10º). Effects diminished with sustained exposure to control schemes (p < 0.001) and exceeded pre-test when they were terminated (p ≤ 0.027; np2 µE = 0.24, np2 σE = 0.49 ). This “rebound” was associated with an increase in Vdif from pre- to post-test (p < 0.001. np2≥0.53). There was an inverse relationship between baseline phasing error and changes in µE and σE during exposure, where greater baseline error was associated with larger improvements (p < 0.001, R² µE = 0.74, R² σE = 0.69). The R scheme increased Wₙₑₜ, whereas A and A + R reduced it (p ≤ 0.026; ES: A − 8.8 J, R 2.9 J, A + R − 5.8 J). These changes were inversely related to changes in µE (p = 0.002, R²: 0.69). Responses to CUped were similar in controls. CUped improved interlimb phasing and paretic limb use, though effects were not enduring, and gains in one reduced the other, with the A + R scheme performing the best overall. Results support CUped’s potential to enhance recovery-related movement and provide insight into motor adaptation post-stroke.

Background This study was designed to determine how goal-directed reaching during virtual reality (VR)-based treadmill walking affects dynamic balance in stroke survivors. Frontal-plane whole-body angular momentum (H) was used to quantify dynamic balance during gait. Methods: Twenty individuals with stroke were enrolled in this study, and 16 were included in the analysis. Participants completed three blocks of a VR-based reaching task while walking on a treadmill after familiarization with both the VR system and treadmill walking. Kinematic data were collected using a markerless motion capture system (Theia3D, Theia Markerless Inc., Kingston, ON, Canada). Stride-level frontal-plane range of angular momentum (H R ) was computed, and segmental contributions to H were analyzed. Results: Frontal-plane H R significantly increased during the preparatory, reaching, and post-reaching strides compared with non-reaching strides at three walking speeds. H R was also greater for contralateral than ipsilateral targets. Segmental analysis revealed that the trunk and reaching arm contributed most strongly to changes in H. Reaching was also accompanied by changes in stride time, length, and width. Conclusion: Reaching during walking imposes greater frontal-plane balance demands on stroke survivors, primarily through trunk and reaching-arm contributions. These findings support further investigation of task-specific, internally generated challenges as a component of VR-based gait rehabilitation.

Brain tumors frequently cause impairments in hand dexterity, and we recently demonstrated that standard manual muscle testing greatly underestimates such dysfunction. Because classical anatomical lesioning studies have not fully explained higher order motor performance, there has been recent interest in examining inter-network brain connectivity as a potentially more direct functional-anatomical relationship. 20 patients with contrast enhancing tumors underwent preoperative resting state functional magnetic resonance imaging (rs-fMRI) and a the 9-hole peg test. 9-hole peg test data were normalized to published data accounting for age and sex. A 40-network atlas was used to extract average time series data from the rs-fMRI to calculate functional connectivity. Effects of age, sex, and lesion volume on connectivity were regressed out using a linear model. The functional connectivity between the ipsilesional somatomotor network with the other 39 networks of the brain were entered into a forward stepwise linear regression with alpha set to 0.05 a priori. Data from three participants were excluded because they were unable to complete the 9-hole peg test in <120s. The strongest predictor of declining 9-hole peg test performance was increased connectivity to the ipsilesional salience network (β =-9.70, t=-3.92, p=0.002), followed by decreased connectivity to the contralesional visual network (β =6.62, t=3.33, p=0.005). Together, these connections explained 68.5% of the variance (aR2=0.685, F=18.4, p=0.0001). Increased connectivity between the ipsilesional somatomotor network and the ipsilesional salience network together with decreased connectivity between the somatomotor network and the contralesional visual network correlate strongly with and explain a high percentage of the variance in hand dexterity in patients with brain tumors. Future studies will examine whether interventional rehabilitation strategies targeting these connections might improve long-term outcomes.

This systematic review and meta-analysis evaluated the effectiveness of virtual reality (VR) rehabilitation in improving functional performance for patients with cervical spinal cord injury (CSCI), which affects both upper and lower limb function. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, electronic databases including PubMed, Medline, Embase, Scopus, and Cochrane Library were searched. Meta-analysis was conducted on studies reporting common functional outcomes, with standardized mean difference (SMD) used to quantify effect sizes. Nine studies were included in the systematic review, and seven were analyzed in the meta-analysis. Three studies focused on upper limb outcomes, and six on lower limb function. Of the seven studies, four included only CSCI patients, while three had mixed injury cohorts (cervical and thoracic). Meta-analysis revealed no statistically significant improvements in function for mixed injury cohorts across various outcomes: Timed-Up and Go test (SMD 0.94 [-0.21, 2.09]), Berg Balance Scale (-0.83 [-1.72, 0.07]), Walking Index for Spinal Cord Injury II (-0.38 [-0.86, 0.09]), Spinal Cord Independence Measure (-0.41 [-0.92, 0.10]), and 10 Meter Walk Test (-1.43 [-3.58, -0.73]). However, the Timed-Up and Go test showed significant results favoring VR-based rehabilitation when excluding mixed cohorts (SMD 2.02 [1.24, 2.79]). VR rehabilitation shows promise for improving lower limb function in CSCI patients, but overall evidence remains inconclusive due to study variability. Standardizing outcome measures and further research on upper limb rehabilitation are essential to enhance the impact of VR-based interventions for CSCI.

Degenerative cervical myelopathy (DCM) is a leading cause of non-traumatic spinal cord disorders in older adults. Gait instability and balance dysfunction are common in DCM, even in the absence of clinically evident lower limb weakness. We hypothesized that subclinical weakness, measured through maximal voluntary isometric contractions (MVICs) of the knee extensors and ankle plantar flexors, is associated with impaired gait and balance in individuals with DCM. Pre-surgical DCM participants with symptoms of DCM and MRI evidence of cervical spinal cord compression were prospectively enrolled in this observational study. Knee extensor and ankle plantar flexor MVICs of the self-reported most-affected leg were measured using a Biodex system. Berg Balance Scale (BBS) scores, gait speed and spatiotemporal gait parameters, and the modified Japanese Orthopedic Association score (mJOA) were recorded. Multivariable regression assessed associations between MVICs and gait/balance outcomes, controlling for age and sex. Data from 32 DCM participants (11 females; mean age 59.1 ± 10.7 years) were analyzed. Knee extensor MVICs showed significant positive correlations with gait speed (r = 0.38, p = 0.001), mJOA lower extremity scores (r = 0.41, p = 0.019), and BBS scores (r = 0.44, p = 0.007). These associations remained significant in multivariable linear regression models adjusted for age and sex. Ankle plantar flexor MVICs were not significantly associated with any outcomes (p > 0.05). Knee extensor MVICs reflect subclinical lower extremity weakness and are associated with impaired gait and balance in DCM. MVIC is a promising objective method to quantify motor impairment in DCM.

Degenerative cervical myelopathy (DCM), the leading cause of non-traumatic spinal cord injury, frequently results in impaired hand dexterity. While surgical decompression is the primary treatment, over 40% of patients report residual hand disability after surgery. There are no therapies to restore hand function after surgery for DCM. In this single-arm clinical trial, post-surgical DCM participants (within 12 months after surgery) underwent a 4-week VR training protocol using the Virtual Keyboard system, which promotes practice of finger individuation. Assessments of hand dexterity were performed at baseline (at week 1), post-training (at week 6) and follow-up (at week 10). The primary outcome measure for hand dexterity assessment was the Jebsen-Taylor Hand Function Test (JTHFT). Twenty-two post-surgical DCM participants were included in the final analysis. Statistically significant improvement in the JTHFT was observed at both post-training (p < 0.001, Δ= -15.21s) and follow-up (p < 0.001, Δ= -17.84s), with changes exceeding the Minimal Clinically Important Difference (MCID) at both time points. VR hand training also produced significant, sustained and clinically meaningful improvements in quantitative hand dexterity tests and health-related quality of life. The results of this uncontrolled, single-arm study demonstrate the feasibility and efficacy of targeted neurorehabilitation to augment post-surgical neurological recovery in people with DCM.

Background and Purpose Reactive balance adaptations with training may be task specific and not reflected within traditional clinical balance assessments. Notably, early results from an ongoing clinical trial aimed at improving mobility and balance for people with multiple sclerosis (PwMS) have not demonstrated significant improvements in clinical balance measures for those undergoing reactive balance gait training. Although preliminary, this contradicts previous research demonstrating improvements in reactive balance with training for PwMS, possibly because the clinical measures utilized are anticipatory. Because these assessments quantify a different domain than the training, a task specific assessment of reactive balance may capture training adaptations not reflected with clinical assessments. Methods PwMS were enrolled in a 10-week trial consisting of three 1-hour visits per week with up to 40 minutes of walking in static or dynamic environments. Dynamic environments involved discrete reactive balance perturbations every 20 seconds, while static environments did not. Every 6 visits, participants completed a reactive balance assessment where mediolateral perturbations were applied during gait on a treadmill at linearly increasing velocities and displacements until a “fall”, as defined by > 20% body weight supported by a fall arrest harness, was elicited or the system reached maximum intensity. Markerless motion capture data were processed in Visual3D. Adaptation was assessed using a linear mixed effects model. Results PwMS that completed dynamic training learned to take larger crossover steps (Static Δ0.10m v Dynamic Δ-0.04m, p<0.001), decrease trunk flexion (Static Δ0.85deg v Dynamic Δ-1.40deg, p<0.001) and lateral trunk flexion (Static Δ1.26deg v Dynamic Δ-3.25deg, p<0.001), and improve the normalcy of their whole-body angular momentum trajectory (Static Δ-9.63% v Dynamic Δ4.24, p = 0.016), while PwMS in the static group demonstrated no change. Discussion Despite not being quantified by clinical metrics, PwMS undergoing reactive balance gait training modified their reactive response kinematics, possibly indicating the task specificity of reactive balance adaptations.

PURPOSE:Females have worse motor-related functional outcomes than males post stroke. However, it is unclear whether stroke affects motor performance such as neuromuscular fatigability differently between sexes. This study determined sex differences in the impact of stroke on fatigability. METHODS:Forty-one chronic stroke survivors (23 female, ≥6 months post stroke) and 23 age-matched neurotypical controls (12 female) performed a sustained submaximal (30% of maximum) isometric knee extension contraction with paretic or dominant leg, respectively. Task duration was used to quantify fatigability. Potentiated twitch (Q tw ) and surface electromyography (EMG) were assessed to quantify muscle contractile properties and neuromuscular activation, respectively. Separate two-way analyses of variance (ANOVAs) were performed to determine the main and interaction effects of group and sex on fatigability and neuromuscular measurements. Separate Pearson correlations were performed to explore associations between fatigability and neuromuscular measurements. RESULTS:There was an interaction effect of group and sex on task duration where female stroke survivors had a shorter task duration than neurotypical females (254 ± 121 vs 445 ± 228 s, P < 0.001) whereas this difference was not observed between male stroke survivors (248 ± 132 s) and neurotypical males (260 ± 72 s, P = 0.628). Also, neurotypical females had a longer task duration than neurotypical males ( P = 0.009); however, there were no differences in task duration between male and female stroke survivors ( P = 0.839). Stroke survivors had a shorter task duration than neurotypical controls (251 ± 124 vs 356 ± 193 s, P = 0.008). Males had a shorter task duration than females (253 ± 112 vs 319 ± 186 s, P = 0.027). Stroke survivors had less of a change in Q tw (35 ± 16 vs 51 ± 13% reduction, P < 0.001) and EMG (35 ± 28 vs 98 ± 41% increase, P < 0.001) than neurotypical controls during exercise. Females had less of a change in Q tw (36 ± 14 vs 46 ± 18% reduction, P = 0.020) and EMG (47 ± 39 vs 67 ± 49% increase, P = 0.021) than males during exercise. Within the stroke survivor group, a shorter task duration was associated with less Q tw reduction for female stroke survivors ( r = 0.656, P = 0.001), but a shorter task duration was associated with greater Q tw reduction for male stroke survivors ( r = -0.519, P = 0.039). CONCLUSIONS:Stroke increased fatigability in females but not males during sustained submaximal isometric knee extension exercise. This sex-specific impact of stroke on fatigability is likely due to central versus peripheral mechanisms.

Interest in stimulation-induced neuroplasticity (i.e., “prehabilitation”) is growing. Potential applications include remapping the brain around invasive tumors to extend resections into previously unresectable areas while protecting neurological function. To achieve this goal, focal cortical stimulation must functionally inhibit a portion of the brain so physiotherapy can encourage other parts of the network to assume its function. While clinical stimulation (i.e., 50-60 Hz) of language cortex inhibits function, stimulation of primary motor areas (M1) activates function by inducing clonus or tonus. While there are reports of motor task inhibition by stimulation of “negative” (i.e., supplemental) motor areas, inhibiting “positive” (i.e., primary) motor areas have not been convincingly demonstrated. 10 participants performed an index finger flexion task (i.e., finger individuation) during an awake craniotomy for tumor resection with access to hand M1 A 4x1 electrode strip was then placed over hand M1 and connected to a NeuroPace Responsive Neurostimulation System (RNS). Up to six frequencies from 1-330Hz (device limits) were applied for 5sec bursts at amplitudes just below those that generated motor evoked potentials (i.e., subthreshold), and subjects were prompted to complete the task during the stimulation. Clinical electrocorticography, EMG, and hand kinematic data were recorded and synchronized. In 4 participants, we observed 3 different mechanisms of stimulation-induced disruption: 1) flexor inhibition (250 Hz and 330 Hz), 2) discoordination (10 Hz), and 3) after discharge-related inhibition (250 Hz). Notably, movement disruption was only achieved in cortical locations that caused finger or wrist extension during suprathreshold stimulation. Here we provide initial evidence for the frequency-dependent functional effects of hand M1 stimulation, and we report evidence for at least three distinct mechanisms of frequency-specific task disruption.

BACKGROUND CONTEXT Degenerative cervical myelopathy (DCM) is the leading cause of nontraumatic spinal cord injury globally, with a prevalence of 605 per million in North America and a major cause of elderly morbidity, impaired quality of life, and reduced life expectancy. Unsteady gait and balance dysfunction are common in DCM and are often seen in the absence of clinically detectable weakness in the lower extremities. We hypothesize that subclinical weakness of the lower limbs, measured using quadriceps voluntary isometric contraction (MVIC), contributes to impairments in balance and gait in DCM. PURPOSE To demonstrate that quadriceps maximum voluntary isometric contraction (MVIC), a quantitative measurement of lower extremity strength, is associated with balance and gait function in DCM. STUDY DESIGN/SETTING Prospective observational study at an academic medical center. PATIENT SAMPLE Presurgical subjects with DCM. OUTCOME MEASURES Average MVIC, modified Japanese Orthopedic Association (mJOA) score, Berg Balance Scale (BBS) score, gait speed. METHODS Presurgical DCM participants were enrolled in the study and quadriceps MVIC of self-reported most-affected leg was measured using a Biodex system (Biodex Medical Systems, Shirley, NY) with participants seated at 90° hip and knee angles. A “Go” indicator on the screen prompted participants to exert maximal leg strength for 5 seconds with verbal encouragement. Participants performed at least 3 contractions (within 10% of the mean) with a max of 5, with 1-minute rest in between. Average MVIC for each participant was calculated from the 3 highest trials. Participants also completed the mJOA, BBS, and 10-Meter Walk Test (used to calculate gait speed). Linear regressions were performed for mJOA lower extremity and total scores, BBS, and gait speed (10MWT) using MVIC as the predictor, accounting for age and sex. A Mann-Whitney U test was used to compare quadriceps MVIC between severity groups (mild-moderate and severe DCM groups). RESULTS The study group included 21 participants with DCM (14 men, 7 women). The mean age was 58.1 [9.1] years, with 5 in the severe mJOA group (<12) and 16 in the mild-moderate group (12-17). MVIC was significantly associated with the pre-surgical mJOA score (R² = 0.526, p = 0.006), mJOA lower extremity score (R² = 0.500, p = 0.010), BBS (R² = 0.436, p = 0.019), and gait speed (R² = 0.460, p = 0.013). Mild-moderate DCM participants had significantly (p=0.008) greater MVIC (127.01 [36.43] Nm) than severe DCM participants (72.21 [27.18] Nm). CONCLUSIONS Quadriceps MVIC quantifies subclinical lower extremity weakness in DCM and predicts impairment in balance and gait. Quadriceps MVIC is a promising objective tool for quantifying functional impairments in DCM. FDA Device/Drug Status This abstract does not discuss or include any applicable devices or drugs.

BACKGROUND:Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) and patients exhibit diffuse white matter alterations and structural remodeling. However, the correlation between these structural changes and brain network properties, or their effect on the efficacy of treatment outcomes in MRI non-lesional IESS patients is not clear. METHOD:This retrospective study was conducted on IESS patients using fixel-based analysis (FBA) of diffusion MRI and graph theory analysis of structural connectivity, involving 26 non-lesional IESS patients aged 2 to 12 months and 120 age-matched controls. We further examined the differences between antiseizure medication (ASM) responders and non-responders within the IESS cohort. FBA was performed across three age groups (2-5, 6-7, and 8-12 months) to evaluate white matter integrity at the micro- and macroscale using fiber density (FD), fiber cross-section (FC), and combined fiber density and cross-section (FDC). Graph theory analysis was used to assess global and local network properties. RESULTS:When compared to the control group, IESS patients exhibited significantly lower FD, FC, and FDC across major white matter tracts, including the corticospinal tract, corpus callosum, superior longitudinal fasciculus, optic radiations, and thalamic radiations (family-wise error-corrected, p < 0.05). Graph theory analysis revealed significant alterations in brain network properties, particularly in the age group of 2-5 months, where IESS patients exhibited a significantly lower mean clustering coefficient (p < 0.001, d = -0.74) and global efficiency (p = 0.001, d = -0.69. Small-world network analysis demonstrated a shift toward a more randomized network structure in IESS patients, particularly in the age group of 6-7 months (p = 0.001, d = -0.6182). In the secondary analysis, ASM treatment responders showed higher FD values in regions critical for seizure control, such as the hippocampus. Meanwhile, the ASM treatment non-responders exhibited increased FC in areas such as the pons and brainstem. Although subgroup differences did not achieve statistical significance, trends suggest that white matter integrity and network organization may influence treatment outcomes. CONCLUSION:The results highlight widespread changes in white matter integrity and network connectivity in non-lesional IESS patients, with preliminary evidence suggesting a relationship between structural brain differences and treatment responsiveness. These findings underscore the potential of advanced neuroimaging analyses to guide personalized interventions in IESS.

When individuals present with hand injuries, clinicians often use the contralateral hand as an internal control. However, subtle differences in baseline dexterous abilities between the dominant and nondominant hands are poorly understood. To address this gap, here we quantified such differences, measured as independence (individuation) and smoothness of finger movements. A cohort of 47 right-hand-dominant healthy adults (22 males and 25 females) moved each finger independently 10 times, while joint angle data were tracked with a dataglove (CyberGlove III, CyberGlove Systems, San Jose, CA). Each finger's performance was compared with its counterpart on the opposite hand using Wilcoxon-signed rank tests. The right hand scored significantly higher than the left on both direct comparison and linear mixed-effect modeling for thumb individuation (P < 0.0001) and smoothness (P < 0.0001), index finger individuation (P = 0.012), and middle finger individuation (P = 0.009). Differences between the hands for index and middle finger individuation scores changed depending on the individuation scoring method used. Sex-based comparisons revealed females had greater asymmetry of thumb (P = 0.044) and ring finger (P = 0.020) individuation scores, as well as ring finger smoothness (P = 0.036) compared with males on both direct comparison and multiple linear regression. Cluster and principal components analysis were performed to detect whole hand differences. Dominant and nondominant hands were separated using smoothness metrics at a 74.5% sensitivity, 66% specificity, 68.6% positive predictive value, and 72.1% negative predictive value. In sum, this represents the largest study to date quantifying naturally occurring differences in hand dexterity between dominant and nondominant hands in healthy, right-handed young adults.NEW & NOTEWORTHY Here we present the largest study to date quantifying differences in finger dexterity between the dominant and nondominant hands in healthy, right-hand-dominant, young adults using finger individuation and smoothness. To our knowledge, we are the first to demonstrate differences between dominant and nondominant thumb, index, and middle finger dexterity metrics. Whole hand analyses indicate the dominant and nondominant hands can be separated based on smoothness with above-chance sensitivity and specificity.

Understanding post-stroke changes in skeletal muscle oxidative metabolism and microvascular reactivity could help create therapeutic targets that optimize rehabilitative interventions. Due to disuse atrophy, we hypothesized that basal muscle oxygen consumption rate and microvascular endothelial function would be impaired in the tibialis anterior (TA) muscle of the affected leg of chronic stroke survivors compared with the nonaffected leg and versus matched controls. Fifteen chronic stroke survivors (10 females) and 15 matched controls (9 females) completed this study. A near-infrared spectroscopy oximeter measured tissue oxygen saturation (StO2) of the TA in both legs of stroke survivors and the dominant leg of controls. A cuff was placed around the thigh and inflated to 225 mmHg for 5 min while StO2 was continuously measured. The rate of change in StO2 was calculated during cuff occlusion and immediately post-cuff release. The rate of oxygen desaturation was similar between the legs of the stroke survivors (paretic -0.12 ± 0.04%·s-1 vs. nonparetic -0.16 ± 011%·s-1; P = 0.49), but the paretic leg had a reduced desaturation rate versus controls (-0.25 ± 0.18%·s-1; P = 0.007 vs. paretic leg). After cuff release, there was a greater oxygen resaturation rate in the nonparetic leg compared with the paretic leg (3.13 ± 2.08%·s-1 vs. 1.60 ± 1.11%·s-1, respectively; P = 0.01). The control leg had a similar resaturation rate versus the nonparetic leg (control = 3.41 ± 1.79%·s-1; P = 0.69) but was greater than the paretic leg (P = 0.003). The TA in the paretic leg had an impaired muscle oxygen consumption rate and reduced microvascular endothelial function compared with controls.NEW & NOTEWORTHY Secondary consequences of stroke are not well described. In this study, we show that basal muscle oxidative consumption and microvascular endothelial function are reduced in the paretic tibialis anterior muscle of chronic stroke survivors compared with matched controls using near-infrared spectroscopy and the vascular occlusion technique. There was a moderately strong correlation between microvascular endothelial function and paretic leg strength.

INTRODUCTION: In addition to baseline muscle weakness, stroke survivors often demonstrate increased neuromuscular fatigability (an acute exercise-induced reduction in power, hereafter referred to as fatigability), which limits endurance during functional tasks. Ischemic conditioning (IC) is a non-invasive and easy-to-administer intervention that can reduce fatigability in stroke survivors during a sustained isometric contraction of their paretic knee extensors. However, IC’s effects on fatigability during dynamic contractions are unknown, despite the greater relevance to everyday activities. Additionally, fatigability is known to be task specific. Thus, the purpose of this study was to quantify the effects of IC on fatigability (percent reduction in power) during dynamic contractions of the paretic knee extensors in stroke survivors. We hypothesized that fatigability would be less after a single session of IC versus IC-sham treatment in stroke survivors. Methods: Eight stroke survivors (66 ± 6 years of age, 6 male) performed 60 maximal voluntary concentric contractions (1 every 4 seconds) with their paretic knee extensors against a resistance of 30% of their maximal voluntary isometric contraction torque through a 60-degree range of motion after receiving a single session of IC and IC-sham treatment on two separate days. IC consisted of 5 sets of 5-minute upper thigh blood flow occlusion at 225 mmHg (25 mmHg for IC-sham) with 5 minutes of no occlusion between each set. The order of the 2 sessions was randomized. All participants visited the laboratory on a different day for functional measurements (Fugl-Meyer Assessment, 10-meter walk test, and 6-minute walk test). Reduction in power was calculated as the difference between the highest average power output from 5 consecutive contractions within the first 15 contractions and the average power output from the last 5 contractions. A paired t-test was used to compare if fatigability during dynamic exercise would differ between the 2 sessions after IC and IC-sham treatment. Pearson correlation was performed to determine the relationship between the difference in fatigability (after IC versus IC-sham treatment) and functional measurements. Results: After a single session of IC treatment, stroke survivors were less fatigable compared to IC-sham treatment (21.9 ± 19.2% power reduction vs. 29.4 ± 19.0%, p = 0.016). Improvement in fatigability after IC versus IC-sham treatment was positively correlated with Fugl-Meyer Assessment lower extremity motor score ( r = 0.82, p = 0.013). CONCLUSION: These preliminary results indicate that IC could serve as a potential intervention to reduce fatigability during dynamic exercise in stroke survivors, especially those who are mildly affected by stroke. Funding Source: American Heart Association Predoctoral Fellowship (903373, ZZ) and Eunice Kennedy Shriver National Institute of Child Health and Human Development R01 Grant (HD099340, AH & MD). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.