Activity in the pontine reticular nuclei scales with handgrip force in humans.

The neural pathways that contribute to force production in humans are currently poorly understood, as the relative roles of the corticospinal tract and brainstem pathways, such as the reticulospinal tract (RST), vary substantially across species. Using functional magnetic resonance imaging (fMRI), we aimed to measure activation in the pontine reticular nuclei (PRN) during different submaximal handgrip contractions to determine the potential role of the PRN in force modulation. Thirteen neurologically intact participants (age: 28 ± 6 yr) performed unilateral handgrip contractions at 25%, 50%, 75% of maximum voluntary contraction during brain scans. We quantified the magnitude of PRN activation from the contralateral and ipsilateral sides during each of the three contraction intensities. A repeated-measures ANOVA demonstrated a significant main effect of force (P = 0.012, [Formula: see text] = 0.307) for PRN activation, independent of side (i.e., activation increased with force for both contralateral and ipsilateral nuclei). Further analyses of these data involved calculating the linear slope between the magnitude of activation and handgrip force for each region of interest (ROI) at the individual-level. One-sample t tests on the slopes revealed significant group-level scaling for the PRN bilaterally, but only the ipsilateral PRN remained significant after correcting for multiple comparisons. We show evidence of task-dependent activation in the PRN that was positively related to handgrip force. These data build on a growing body of literature that highlights the RST as a functionally relevant motor pathway for force modulation in humans.NEW & NOTEWORTHY In this study, we used a task-based functional magnetic resonance imaging (fMRI) paradigm to show that activity in the pontine reticular nuclei scales linearly with increasing force during a handgrip task. These findings directly support recently proposed hypotheses that the reticulospinal tract may play an important role in modulating force production in humans.

White Matter Integrity and Chronic Poststroke Upper Limb Function: An ENIGMA Stroke Recovery Analysis.

BACKGROUND: Integrity of the corticospinal tract (CST) is an important biomarker for upper limb motor function following stroke. However, when structurally compromised, other tracts may become relevant for compensation or recovery of function. METHODS: We used the ENIGMA Stroke Recovery data set, a multicenter, retrospective, and cross-sectional collection of patients with upper limb impairment during the chronic phase of stroke to test the relevance of tracts in individuals with less and more severe (laterality index of CST fractional anisotropy ≥0.25) CST damage in an observational study design. White matter integrity was quantified using fractional anisotropy for the CST, the superior longitudinal fascicle, and the callosal fibers interconnecting the primary motor cortices between hemispheres. Optic radiations served as a control tract as they have no a priori relevance for the motor system. Pearson correlation was used for testing correlation with upper limb motor function (Fugl-Meyer upper extremity). RESULTS: From 1235 available data sets, 166 were selected (by imaging, Fugl-Meyer upper extremity, covariates, stroke location, and stage) for analyses. Only individuals with severe CST damage showed a positive association of fractional anisotropy in both callosal fibers interconnecting the primary motor cortices (r[21]=0.49; P=0.025) and superior longitudinal fascicle (r[21]=0.51; P=0.018) with Fugl-Meyer upper extremity. CONCLUSIONS: Our data support the notion that individuals with more severe damage of the CST depend on residual pathways for achieving better upper limb outcome than those with less affected CST.

The effects of verbal cueing for high intended movement velocity on power, neuromuscular activation, and performance.

It is widely believed that lifting heavy loads slowly, but with a conscious intention to move at high velocity, can produce resistance training (RT) adaptations indicative of rapid movements. This study investigated the effects of verbally cued high "intended" movement velocity (HIMV) during RT on neuromuscular and performance outcomes. 20 untrained volunteers (aged 24.2 ± 3.9 years) participated in 3 weeks of knee extension training. Participants were randomly allocated to receive verbal cues focusing on high intended movement velocity, HIMV, or steady and controlled movement, TRAD (traditional training). All other training variables, including actual movement velocity (30° s-1 ), remained constant. Increase in mean power output at 30° s-1 was greater for TRAD than HIMV (76% and 33%, respectively, P = 0.027). There were main effects for time (but no between-group differences) for maximal isometric force (+14%, P = 0.003), peak torque at 180° s-1 (+22%, P = 0.006), peak torque at 30° s-1 (+29%, P < 0.001), 3-repetition maximum (+20%, P < 0.001), and resting corticospinal excitability (+43%, P = 0.017). There were no differences between groups or across time for voluntary activation (P = 0.793), spinal excitability (P = 0.686), or intracortical inhibition (all P > 0.05). HIMV verbal cueing did not produce additional neurophysiological or performance benefits when compared to traditional cueing. Overall, our results demonstrated that verbal cueing did not alter the principle of velocity-specific adaptation. Cueing that increases the duration of maximal effort may be optimal for maximizing average power output at low speeds.

Size Matters: Package Size Influences Recognition of Serving Size Information.

PURPOSE: To identify the impact of package size on an individual's use of serving size information. The hypothesis was that participants would make more serving size assumption errors on a nutrition facts table (NFT) interpretation task when assessing packages that appear as a single serving but contain multiple servings, compared with products that appear as a multi-serving and contain multiple servings. METHODS: Sixty participants were randomized into 1 of 3 conditions (n = 20 each); products that appeared as a single serving and contain a single serving (SSSS), products that appeared as a single serving and contain multiple servings (SSMS), and products that both appear as a multi-serving and contain multiple servings (MSMS). All 3 conditions were tested on a NFT interpretation task while participants were being presented food items that were appropriate to their given condition. RESULTS: Participants in the SSMS (9.55 ± 7.78) condition made significantly more serving size assumption errors than the SSSS (0.00 ± 0.00; P < 0.001) and MSMS (0.40 ± 0.75; P < 0.001) conditions. CONCLUSIONS: Participants did not address serving size information when they perceived a product to be a single serving. This resulted in people misinterpreting nutritional and caloric content of foods that were single unit foods with multiple servings.

Investigating female versus male differences in white matter neuroplasticity associated with complex visuo-motor learning.

Magnetic resonance imaging (MRI) has increasingly been used to characterize structure-function relationships during white matter neuroplasticity. Biological sex differences may be an important factor that affects patterns of neuroplasticity, and therefore impacts learning and rehabilitation. The current study examined a participant cohort before and after visuo-motor training to characterize sex differences in microstructural measures. The participants (N = 27) completed a 10-session (4 week) complex visuo-motor training task with their non-dominant hand. All participants significantly improved movement speed and their movement speed variability over the training period. White matter neuroplasticity in females and males was examined using fractional anisotropy (FA) and myelin water fraction (MWF) along the cortico-spinal tract (CST) and the corpus callosum (CC). FA values showed significant differences in the middle portion of the CST tract (nodes 38-51) across the training period. MWF showed a similar cluster in the inferior portion of the tract (nodes 18-29) but did not reach significance. Additionally, at baseline, males showed significantly higher levels of MWF measures in the middle body of the CC. Combining data from females and males would have resulted in reduced sensitivity, making it harder to detect differences in neuroplasticity. These findings offer initial insights into possible female versus male differences in white matter neuroplasticity during motor learning. This warrants investigations into specific patterns of white matter neuroplasticity for females versus males across the lifespan. Understanding biological sex-specific differences in white matter neuroplasticity may have significant implications for the interpretation of change associated with learning or rehabilitation.

The effect of tart cherry juice compared to a sports drink on cycling exercise performance, substrate metabolism, and recovery.

Tart cherries have low glycemic index, antioxidant and anti-inflammatory properties, and therefore may benefit performance and recovery from exercise. We determined the effects of consuming tart cherry juice versus a high-glycemic index sports drink on cycling performance, substrate oxidation, and recovery of low-frequency fatigue. Using a randomized, counter-balanced cross-over design, with one-month washout, 12 recreational cyclists (8 males and 4 females; 35±16y; VO2peak 38.2±7.4 ml/kg/min) consumed cherry juice or sports drink twice a day (300mL/d) for 4d before and 2d after exercise. On the exercise day, beverages (providing 1g/kg carbohydrate) were consumed 45min before 90min of cycling at 65%VO2peak, followed by a 10km time trial. Blood glucose, lactate, carbohydrate and fat oxidation, respiratory exchange ratio (RER), O2 cost of cycling, and rating of perceived exertion (RPE) were measured during the initial 90min of cycling. Muscle soreness, maximal voluntary contraction (MVC) and low-frequency fatigue were determined at baseline and after the time trial on the exercise day, and 30min after beverage consumption 24 and 48h later. There were no differences for time trial performance (17±3min cherry juice vs. 17±2min sports drink, p = 0.27) or any other measures between drink conditions. There were time main effects (p<0.05) for isometric MVC (decreasing) and low-frequency fatigue (increasing; i.e. decreased force at low relative to high stimulation frequencies), changing significantly from baseline to post-exercise and then returning to baseline at 24h post-exercise. Tart cherry juice was not effective for improving performance, substrate oxidation during exercise, and recovery from exercise, compared to a high-glycemic index sports drink.

Effects of External Pacing Type on the Cross-Education of Motor Skill.

Cross-education (CE) is a phenomenon whereby motor training of one limb leads to improved performance in the opposite untrained limb. External pacing of a motor task can enhance CE; however, the influence of different pacing methods is poorly understood. This study explored how motor training with auditory (AP) and visual pacing (VP) impacts CE with a visuomotor force target task. Sixty-one participants performed a unimanual motor task. Participants were randomized into a visual (n = 31) or auditory (n = 30) pacing stimuli condition. The primary outcome was cumulative error scores for each hand, before and after visuomotor training. Pacing type did not yield different magnitudes of CE. However, after adjusting for baseline differences, a significant hand (trained vs. untrained) × practice side (dominant or non-dominant) interaction (p = .013, ηp2 = .106) and a group main effect (p = .036, ηp2 = .165) were observed. Visual pacing resulted in greater improvements in task performance compared to auditory pacing regardless of hand or practice side, while training the dominant limb resulting in a greater interlimb asymmetry regardless of pacing stimulus. These findings have implications for applying pacing strategies during rehabilitation from unilateral injury or neurological impairment.

Sex differences in patterns of white matter neuroplasticity after balance training in young adults.

Introduction: In past work we demonstrated different patterns of white matter (WM) plasticity in females versus males associated with learning a lab-based unilateral motor skill. However, this work was completed in neurologically intact older adults. The current manuscript sought to replicate and expand upon these WM findings in two ways: (1) we investigated biological sex differences in neurologically intact young adults, and (2) participants learned a dynamic full-body balance task. Methods: 24 participants (14 female, 10 male) participated in the balance training intervention, and 28 were matched controls (16 female, 12 male). Correlational tractography was used to analyze changes in WM from pre- to post-training. Results: Both females and males demonstrated skill acquisition, yet there were significant differences in measures of WM between females and males. These data support a growing body of evidence suggesting that females exhibit increased WM neuroplasticity changes relative to males despite comparable changes in motor behavior (e.g., balance). Discussion: The biological sex differences reported here may represent an important factor to consider in both basic research (e.g., collapsing across females and males) as well as future clinical studies of neuroplasticity associated with motor function (e.g., tailored rehabilitation approaches).

Gamified Practice Improves Paretic Arm Motor Behavior in Individuals With Stroke.

BACKGROUND: Stroke is a heterogeneous condition, making choice of treatment, and determination of how to structure rehabilitation outcomes difficult. Individualized goal-directed and repetitive physical practice is an important determinant of motor learning. Yet, many investigations of motor learning after stroke deliver task practice without consideration of individual capability of the learner. OBJECTIVE: We developed a gamified arm rehabilitation task for people with stroke that is personalized to individual capacity for paretic arm movement, provides a high dose of practice, progresses through increasingly difficulty levels that are dependent on the performance of the individual, and is practiced in an engaging environment. The objectives of the current study were to determine if 10 days of gamified, object intercept training using the paretic arm would improve arm movement speed and clinical outcome measures of impairment or function. METHODS: Individuals with chronic stroke and age-matched controls engaged in 10 days of gamified, skilled motor practice of a semi-immersive virtual reality-based intercept and release task. The paretic arm was assessed using the Fugl-Meyer Assessment (motor impairment) and Wolf Motor Function Test (motor function) before and after training. RESULTS: Both groups showed faster arm movement speed with practice; individuals with stroke demonstrated reduced paretic arm motor impairment and increased function after the intervention. Age and sex (for both groups), and time post-stroke were not related to changes in movement speed. CONCLUSIONS: Findings indicate that gamified motor training positively affects paretic arm motor behavior in individuals with mild to severe chronic stroke.

Data-driven biomarkers better associate with stroke motor outcomes than theory-based biomarkers.

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have associated motor outcomes with the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to model chronic motor outcomes after stroke and compares the accuracy of these associations to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients from the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) Stroke Recovery Working Group. Using the explained variance metric to measure the strength of the association between chronic motor outcomes and imaging biomarkers, we compared theory-based biomarkers, like lesion load to known motor tracts, to three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had stronger associations with chronic motor outcomes accuracy than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R 2 = 0.210, P < 0.001), performing significantly better than the theory-based biomarkers of lesion load of the corticospinal tract (R 2 = 0.132, P < 0.001) and of multiple descending motor tracts (R 2 = 0.180, P < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R 2 = 0.200, P < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R 2 = 0.167, P < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved the strength of associations for theory-based and data-driven biomarkers. Combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R 2 = 0.241, P < 0.001. Overall, these results demonstrate that out-of-sample associations between chronic motor outcomes and data-driven imaging features, particularly when lesion data is represented in terms of structural disconnection, are stronger than associations between chronic motor outcomes and theory-based biomarkers. However, combining both theory-based and data-driven models provides the most robust associations.

Females exhibit smaller volumes of brain activation and lower inter-subject variability during motor tasks.

Past work has shown that brain structure and function differ between females and males. Males have larger cortical and sub-cortical volume and surface area (both total and subregional), while females have greater cortical thickness in most brain regions. Functional differences are also reported in the literature, yet to date little work has systematically considered whether patterns of brain activity indexed with functional magnetic resonance imaging (fMRI) differ between females and males. The current study sought to remediate this issue by employing task-based whole brain motor mapping analyses using an openly available dataset. We tested differences in patterns of functional brain activity associated with 12 voluntary movement patterns in females versus males. Results suggest that females exhibited smaller volumes of brain activation across all 12 movement tasks, and lower patterns of variability in 10 of the 12 movements. We also observed that females had greater cortical thickness, which is in alignment with previous analyses of structural differences. Overall, these findings provide a basis for considering biological sex in future fMRI research and provide a foundation of understanding differences in how neurological pathologies present in females vs males.

Exercise prescription and strategies to promote the cross-education of strength: a scoping review.

The cross-education of strength is moderated by exercise design and prescription in clinical and non-clinical populations. This review synthesizes the available evidence regarding exercise design strategies for unilateral resistance training and provides evidence-based recommendations for the prescription of unilateral training to maximize the cross-education of strength. Greater insights regarding the timing and effectiveness of cross-education interventions in clinical scenarios will strengthen the use of unilateral resistance training for individuals who may benefit from its use.

Repeated unilateral handgrip contractions alter functional connectivity and improve contralateral limb response times.

In humans, motor learning is underpinned by changes in sensorimotor network functional connectivity (FC). Unilateral contractions increase FC in the ipsilateral primary motor cortex (M1) and supplementary motor area (SMA); areas involved in motor planning and execution of the contralateral hand. Therefore, unilateral contractions are a promising approach to augment motor performance in the contralateral hand. In a within-participant, randomized, cross-over design, 15 right-handed adults had two magnetic resonance imaging (MRI) sessions, where functional-MRI and MR-Spectroscopic Imaging were acquired before and after repeated right-hand contractions at either 5% or 50% maximum voluntary contraction (MVC). Before and after scanning, response times (RTs) were determined in both hands. Nine minutes of 50% MVC contractions resulted in decreased handgrip force in the contracting hand, and decreased RTs and increased handgrip force in the contralateral hand. This improved motor performance in the contralateral hand was supported by significant neural changes: increased FC between SMA-SMA and increased FC between right M1 and right Orbitofrontal Cortex. At a neurochemical level, the degree of GABA decline in left M1, left and right SMA correlated with subsequent behavioural improvements in the left-hand. These results support the use of repeated handgrip contractions as a potential modality for improving motor performance in the contralateral hand.

Improved processing speed and decreased functional connectivity in individuals with chronic stroke after paired exercise and motor training.

After stroke, impaired motor performance is linked to an increased demand for cognitive resources. Aerobic exercise improves cognitive function in neurologically intact populations and may be effective in altering cognitive function post-stroke. We sought to determine if high-intensity aerobic exercise paired with motor training in individuals with chronic stroke alters cognitive-motor function and functional connectivity between the dorsolateral prefrontal cortex (DLPFC), a key region for cognitive-motor processes, and the sensorimotor network. Twenty-five participants with chronic stroke were randomly assigned to exercise (n = 14; 66 ± 11 years; 4 females), or control (n = 11; 68 ± 8 years; 2 females) groups. Both groups performed 5-days of paretic upper limb motor training after either high-intensity aerobic exercise (3 intervals of 3 min each, total exercise duration of 23-min) or watching a documentary (control). Resting-state fMRI, and trail making test part A (TMT-A) and B were recorded pre- and post-intervention. Both groups showed implicit motor sequence learning (p < 0.001); there was no added benefit of exercise for implicit motor sequence learning (p = 0.738). The exercise group experienced greater overall cognitive-motor improvements measured with the TMT-A. Regardless of group, the changes in task score, and dwell time during TMT-A were correlated with a decrease in DLPFC-sensorimotor network functional connectivity (task score: p = 0.025; dwell time: p = 0.043), which is thought to reflect a reduction in the cognitive demand and increased automaticity. Aerobic exercise may improve cognitive-motor processing speed post-stroke.

Data-driven biomarkers outperform theory-based biomarkers in predicting stroke motor outcomes.

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have predicted motor outcomes based on the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to predict chronic motor outcomes after stroke and compares the accuracy of these predictions to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients (293 female/496 male) from the ENIGMA Stroke Recovery Working Group (age 64.9±18.0 years; time since stroke 12.2±0.2 months; normalised motor score 0.7±0.5 (range [0,1]). The out-of-sample prediction accuracy of two theory-based biomarkers was assessed: lesion load of the corticospinal tract, and lesion load of multiple descending motor tracts. These theory-based prediction accuracies were compared to the prediction accuracy from three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had better prediction accuracy - as measured by higher explained variance in chronic motor outcomes - than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R2 = 0.210, p < 0.001), performing significantly better than predictions using the theory-based biomarkers of lesion load of the corticospinal tract (R2 = 0.132, p< 0.001) and of multiple descending motor tracts (R2 = 0.180, p < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R2 =0.200, p < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R2 =0.167, p < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved prediction accuracy for theory-based and data-driven biomarkers. Finally, combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R2 = 0.241, p < 0.001. Overall, these results demonstrate that models that predict chronic motor outcomes using data-driven features, particularly when lesion data is represented in terms of structural disconnection, perform better than models that predict chronic motor outcomes using theory-based features from the motor system. However, combining both theory-based and data-driven models provides the best predictions.

Acute Effects of High-Intensity Aerobic Exercise on Motor Cortical Excitability and Inhibition in Sedentary Adults.

Transcranial magnetic stimulation studies have demonstrated increased cortical facilitation and reduced inhibition following aerobic exercise, even when examining motor regions separate to the exercised muscle group. These changes in brain physiology following exercise may create favorable conditions for adaptive plasticity and motor learning. One candidate mechanism behind these benefits is the increase in brain-derived neurotropic factor (BDNF) observed following exercise, which can be quantified from a venous blood draw. The aim of this study was to investigate changes in motor cortex excitability and inhibition of the upper limb, and circulating BDNF, following high-intensity interval training (HIIT) on a stationary bicycle. Nineteen sedentary adults participated in a randomized crossover design study involving a single bout of high-intensity interval cycling for 20 min or seated rest. Venous blood samples were collected, and transcranial magnetic stimulation (TMS) was used to stimulate the extensor carpi radialis (ECR), where motor evoked potentials (MEP) were recorded pre- and post-condition. Following exercise, there was a significant increase (29.1%, p < 0.001) in corticospinal excitability measured at 120% of resting motor threshold (RMT) and a reduction in short-interval cortical inhibition (SICI quantified as 86.2% increase in the SICI ratio, p = 0.002). There was a non-significant (p = 0.125) 23.6% increase in BDNF levels. Collectively, these results reflect a net reduction in gamma aminobutyric acid (GABA)ergic synaptic transmission and increased glutamatergic facilitation, resulting in increased corticospinal excitability. This study supports the notion that acute high-intensity exercise provides a potent stimulus for inducing cortical neuroplasticity, which may support enhanced motor learning.

Predicting Individual Treatment Response to rTMS for Motor Recovery After Stroke: A Review and the CanStim Perspective.

Background: Rehabilitation is critical for reducing stroke-related disability and improving quality-of-life post-stroke. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique used as stand-alone or adjunct treatment to physiotherapy, may be of benefit for motor recovery in subgroups of stroke patients. The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) seeks to advance the use of these techniques to improve post-stroke recovery through clinical trials and pre-clinical studies using standardized research protocols. Here, we review existing clinical trials for demographic, clinical, and neurobiological factors which may predict treatment response to identify knowledge gaps which need to be addressed before implementing these parameters for patient stratification in clinical trial protocols. Objective: To provide a review of clinical rTMS trials of stroke recovery identifying factors associated with rTMS response in stroke patients with motor deficits and develop research perspectives for pre-clinical and clinical studies. Methods: A literature search was performed in PubMed, using the Boolean search terms stroke AND repetitive transcranial magnetic stimulation OR rTMS AND motor for studies investigating the use of rTMS for motor recovery in stroke patients at any recovery phase. A total of 1,676 articles were screened by two blinded raters, with 26 papers identified for inclusion in this review. Results: Multiple possible factors associated with rTMS response were identified, including stroke location, cortical thickness, brain-derived neurotrophic factor (BDNF) genotype, initial stroke severity, and several imaging and clinical factors associated with a relatively preserved functional motor network of the ipsilesional hemisphere. Age, sex, and time post-stroke were generally not related to rTMS response. Factors associated with greater response were identified in studies of both excitatory ipsilesional and inhibitory contralesional rTMS. Heterogeneous study designs and contradictory data exemplify the need for greater protocol standardization and high-quality controlled trials. Conclusion: Clinical, brain structural and neurobiological factors have been identified as potential predictors for rTMS response in stroke patients with motor impairment. These factors can inform the design of future clinical trials, before being considered for optimization of individual rehabilitation therapy for stroke patients. Pre-clinical models for stroke recovery, specifically developed in a clinical context, may accelerate this process.