Corticospinal and corticoreticulospinal projections benefit motor behaviors in chronic stroke.

After corticospinal tract (CST) stroke, several motor deficits in the upper extremity (UE) emerge, including diminished muscle strength, motor control, and muscle individuation. Both the ipsilesional CST and contralesional corticoreticulospinal tract (CReST) innervate the paretic UE and may have different innervation patterns for the proximal and distal UE segments. These patterns may underpin distinct pathway relationships to separable motor behaviors. In this cross-sectional study of 15 chronic stroke patients and 28 healthy subjects, we examined two key questions: (1) whether segmental motor behaviors differentially relate to ipsilesional CST and contralesional CReST projection strengths, and (2) whether motor behaviors segmentally differ in the paretic UE. We measured strength, motor control, and muscle individuation in a proximal (biceps, BIC) and distal muscle (first dorsal interosseous, FDI) of the paretic UE. We measured the projection strengths of the ipsilesional CST and contralesional CReST to these muscles using transcranial magnetic stimulation (TMS). Stroke subjects had abnormal motor control and muscle individuation despite strength comparable to healthy subjects. In stroke subjects, stronger ipsilesional CST projections were linked to superior motor control in both UE segments, whereas stronger contralesional CReST projections were linked to superior muscle strength and individuation in both UE segments. Notably, both pathways also shared associations with behaviors in the proximal segment. Motor control deficits were segmentally comparable, but muscle individuation was worse for distal motor performance. These results suggest that each pathway has specialized contributions to chronic motor behaviors but also work together, with varying levels of success in supporting chronic deficits. Key points summary: Individuals with chronic stroke typically have deficits in strength, motor control, and muscle individuation in their paretic upper extremity (UE). It remains unclear how these altered behaviors relate to descending motor pathways and whether they differ by proximal and distal UE segment.In this study, we used transcranial magnetic stimulation (TMS) to examine projection strengths of the ipsilesional corticospinal tract (CST) and contralesional corticoreticulospinal tract (CReST) with respect to quantitated motor behaviors in chronic stroke.We found that stronger ipsilesional CST projections were associated with better motor control in both UE segments, whereas stronger contralesional CReST projections were associated with better strength and individuation in both UE segments. In addition, projections of both pathways shared associations with motor behaviors in the proximal UE segment.We also found that deficits in strength and motor control were comparable across UE segments, but muscle individuation was worse with controlled movement in the distal UE segment.These results suggest that the CST and CReST have specialized contributions to chronic motor behaviors and also work together, although with different degrees of efficacy.

A novel biomechanical indicator for impaired ankle dorsiflexion function during walking in individuals with chronic stroke.

BACKGROUND: Ankle dorsiflexion function during swing phase contributes to foot clearance and plays an important role in walking ability post-stroke. Commonly used biomechanical measures such as foot clearance and ankle joint excursion have limited ability to accurately evaluate impaired dorsiflexor function. RESEARCH QUESTION: Can ankle angular velocity and acceleration be used as reliable measurers of dorsiflexion function in post-stroke gait? METHODS: Using linear regression and Pearson's correlation we retrospectively compared peak ankle angular velocity (AωP), peak ankle angular acceleration (AαP), peak dorsiflexion angle (DFAP) and peak foot clearance (FCLP) as direct measures for swing phase dorsiflexor function in 60 chronic stroke survivors. Intraclass correlation coefficient (ICC) analysis was used for test-retest reliability of AωP and AαP. RESULTS: Linear regression models revealed that AωP, AαP, DFAP, FCLP had a significant relationship (p < 0.05) with impaired dorsiflexion function. AαP and DFAP accounted for the most variance of dorsiflexion function. AωP, AαP, FCLP, correlated significantly with all clinical outcome measures of walking ability. DFAP had a positive correlation only with FMA-LE. Post-hoc William's t-tests, used to compare the magnitude of difference between two non-independent correlations, revealed that the correlation between all clinical measures and DFAP were significantly weaker than with AωP and AαP. Correlation between FMA-LE and FCLP was weaker than with AωP and AαP. Excellent test-retest reliability for both AωP (ICC = 0.968) and AαP (ICC = 0.947) was observed. SIGNIFICANCE: These results suggest that DFAP may only be associated with dorsiflexion function during non-task specific isolated movements, but not during walking. FCLP is associated with dorsiflexion function and walking ability measures but not as strongly as AωP and AαP possibly because FCLP is influenced by contribution from hip and knee joint movements. Therefore, AωP and AαP are reliable measures and represent dorsiflexion function more accurately than DFAP, and FCLP.

The distribution of transcallosal inhibition to upper extremity muscles is altered in chronic stroke.

OBJECTIVE: To determine if the distribution of transcallosal inhibition (TI) acting on proximal and distal upper extremity muscles is altered in chronic stroke. METHODS: We examined thirteen healthy controls and sixteen mildly to moderately impaired chronic stroke patients. We used transcranial magnetic stimulation (TMS) to probe TI from the contralesional onto ipsilesional hemisphere (assigned in controls). We recorded the ipsilateral silent period in the paretic biceps (BIC) and first dorsal interosseous (FDI). We measured TI strength, distribution gradient (TI difference between muscles), and motor impairment (Fugl-Meyer Assessment). RESULTS: Both groups had stronger TI acting on their FDIs than BICs (p < 0.001). However, stroke patients also had stronger TI acting on their BICs than controls (p = 0.034), resulting in a flatter distribution of inhibition (p = 0.028). In patients, stronger FDI inhibition correlated with less hand impairment (p = 0.031); BIC inhibition was not correlated to impairment. CONCLUSION: TI is more evenly distributed to the paretic FDI and BIC in chronic stroke. The relative increase in proximal inhibition does not relate to better function, as it does distally. SIGNIFICANCE: The results expand our knowledge about segment-specific neurophysiology and its relevance to impairment after stroke.

A novel biomechanical indicator for impaired ankle dorsiflexion function during walking in individuals with chronic stroke.

Ankle dorsiflexion function during swing phase of the gait cycle contributes to foot clearance and plays an important role in walking ability post-stroke. Commonly used biomechanical measures such as foot clearance and ankle joint excursion have limited ability to accurately evaluate dorsiflexor function in stroke gait. We retrospectively evaluated ankle angular velocity and ankle angular acceleration as direct measures for swing phase dorsiflexor function in post-stroke gait of 61 chronic stroke survivors. Our linear regression models revealed that peak ankle angular velocity (AAV P ), peak ankle angular acceleration (AAA P ), peak dorsiflexion angle (DFA P ) and peak foot clearance (FCL P ) during swing had a significant relationship (p < 0.05) with impaired dorsiflexion function. AAA P and DFA P accounted for the most variance of dorsiflexion function. Additionally, AAV P , AAA P , FCL P during swing, correlated significantly with all clinical outcome measures of walking ability. DFA P during swing had a positive correlation only with FMA-LE. Post-hoc William's t -tests, used to compare the magnitude of difference between two non-independent correlations, revealed that the correlation between all clinical measures and DFA P were significantly weaker than with AAV P and AAA P . We also found that correlation between FMA-LE and FCL P was weaker than with AAV P and AAA P . We found an excellent test-retest reliability for both AAV P (ICC = 0.968) and AAA P (ICC = 0.947). These results suggest that DFA P may only be associated with non-task specific isolated dorsiflexion movement, but not during walking. FCL P is associated with dorsiflexion function and walking ability measures but not as strongly as AAV P and AAA P possibly because FCL P is influenced by contribution from hip and knee joint movements during walking. Therefore, we believe that AAV P and AAA P both can be used as reliable measures of impaired dorsiflexion function in post-stroke gait.

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke.

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. METHODS: We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. RESULTS: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (ß = 0.21; 95% CI 0.04-0.38, p = 0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (ß = -0.28; 95% CI -0.41 to -0.15, p < 0.001) and across multiple domains of function (ß = -0.14; 95% CI -0.22 to -0.06, p < 0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI 3%-58%, p = 0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (odds ratio 1.04, 95% CI 1.01-1.08, p = 0.004). DISCUSSION: We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets.

Investigation of in-phase bilateral exercise effects on corticospinal plasticity in relapsing remitting multiple sclerosis: A registered report single-case concurrent multiple baseline design across five subjects.

Relapsing-remitting Multiple Sclerosis is the most common demyelinating neurodegenerative disease and is characterized by periods of relapses and generation of various motor symptoms. These symptoms are associated with the corticospinal tract integrity, which is quantified by means of corticospinal plasticity which can be probed via transcranial magnetic stimulation and assessed with corticospinal excitability measures. Several factors, such as exercise and interlimb coordination, can influence corticospinal plasticity. Previous work in healthy and in chronic stroke survivors showed that the greatest improvement in corticospinal plasticity occurred during in-phase bilateral exercises of the upper limbs. During in-phase bilateral movement, both upper limbs are moving simultaneously, activating the same muscle groups and triggering the same brain region respectively. Altered corticospinal plasticity due to bilateral cortical lesions is common in MS, yet, the impact of these type of exercises in this cohort is unclear. The aim of this concurrent multiple baseline design study is to investigate the effects of in-phase bilateral exercises on corticospinal plasticity and on clinical measures using transcranial magnetic stimulation and standardized clinical assessment in five people with relapsing-remitting MS. The intervention protocol will last for 12 consecutive weeks (30-60 minutes /session x 3 sessions/week) and include in-phase bilateral movements of the upper limbs, adapted to different sports activities and to functional training. To define functional relation between the intervention and the results on corticospinal plasticity (central motor conduction time, resting motor threshold, motor evoked potential amplitude and latency) and on clinical measures (balance, gait, bilateral hand dexterity and strength, cognitive function), we will perform a visual analysis and if there is a potential sizeable effect, we will perform statistical analysis. A possible effect from our study, will introduce a proof-of-concept for this type of exercise that will be effective during disease progression. Trial registration: ClinicalTrials.gov NCT05367947.

Is there frequency-specificity in the motor control of walking? The putative differential role of alpha and beta oscillations.

Alpha and beta oscillations have been assessed thoroughly during walking due to their potential role as proxies of the corticoreticulospinal tract (CReST) and corticospinal tract (CST), respectively. Given that damage to a descending tract after stroke can cause walking deficits, detailed knowledge of how these oscillations mechanistically contribute to walking could be utilized in strategies for post-stroke locomotor recovery. In this review, the goal was to summarize, synthesize, and discuss the existing evidence on the potential differential role of these oscillations on the motor descending drive, the effect of transcranial alternate current stimulation (tACS) on neurotypical and post-stroke walking, and to discuss remaining gaps in knowledge, future directions, and methodological considerations. Electrophysiological studies of corticomuscular, intermuscular, and intramuscular coherence during walking clearly demonstrate that beta oscillations are predominantly present in the dorsiflexors during the swing phase and may be absent post-stroke. The role of alpha oscillations, however, has not been pinpointed as clearly. We concluded that both animal and human studies should focus on the electrophysiological characterization of alpha oscillations and their potential role to the CReST. Another approach in elucidating the role of these oscillations is to modulate them and then quantify the impact on walking behavior. This is possible through tACS, whose beneficial effect on walking behavior (including boosting of beta oscillations in intramuscular coherence) has been recently demonstrated in both neurotypical adults and stroke patients. However, these studies still do not allow for specific roles of alpha and beta oscillations to be delineated because the tACS frequency used was much lower (i.e., individualized calculated gait frequency was used). Thus, we identify a main gap in the literature, which is tACS studies actually stimulating at alpha and beta frequencies during walking. Overall, we conclude that for beta oscillations there is a clear connection to descending drive in the corticospinal tract. The precise relationship between alpha oscillations and CReST remains elusive due to the gaps in the literature identified here. However, better understanding the role of alpha (and beta) oscillations in the motor control of walking can be used to progress and develop rehabilitation strategies for promoting locomotor recovery.

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis.

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; ß=0.16) but not contralesional (P=0.96; ß=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; ß=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; ß=-0.26) and contralesional (P=0.006; ß=-0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; ß=-0.21) and extent of sensorimotor damage (P=0.003; ß=-0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.

Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide.

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P < 0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behaviour was associated with a smaller ipsilesional thalamic volume in both early (n = 179; d = 0.68) and subacute (n = 274, d = 0.46) stroke. In chronic stroke (n = 404), worse sensorimotor behaviour was associated with smaller ipsilesional putamen (d = 0.52) and nucleus accumbens (d = 0.39) volumes, and a larger ipsilesional lateral ventricle (d = -0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n = 256) was associated with smaller ipsilesional putamen (d = 0.72) and larger lateral ventricle (d = -0.41) volumes, while several measures of activity limitations (n = 116) showed no significant relationships. In the full cohort across all time (n = 828), sensorimotor behaviour was associated with the volumes of the ipsilesional nucleus accumbens (d = 0.23), putamen (d = 0.33), thalamus (d = 0.33) and lateral ventricle (d = -0.23). We demonstrate significant relationships between post-stroke sensorimotor behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes.

Corticoreticulospinal tract neurophysiology in an arm and hand muscle in healthy and stroke subjects.

KEY POINTS: The corticoreticulospinal tract (CReST) is a descending motor pathway that reorganizes after corticospinal tract (CST) injury in animals. In humans, the pattern of CReST innervation to upper limb muscles has not been carefully examined in healthy individuals or individuals with CST injury. In the present study, we assessed CReST projections to an arm and hand muscle on the same side of the body in healthy and chronic stoke subjects using transcranial magnetic stimulation. We show that CReST connection strength to the muscles differs between healthy and stroke subjects, with stronger connections to the hand than arm in healthy subjects, and stronger connections to the arm than hand in stroke subjects. These results help us better understand CReST innervation patterns in the upper limb, and may point to its role in normal motor function and motor recovery in humans. ABSTRACT: The corticoreticulospinal tract (CReST) is a major descending motor pathway in many animals, but little is known about its innervation patterns in proximal and distal upper extremity muscles in humans. The contralesional CReST furthermore reorganizes after corticospinal tract (CST) injury in animals, but it is less clear whether CReST innervation changes after stroke in humans. We thus examined CReST functional connectivity, connection strength, and modulation in an arm and hand muscle of healthy (n = 15) and chronic stroke (n = 16) subjects. We delivered transcranial magnetic stimulation to the contralesional hemisphere (assigned in healthy subjects) to elicit ipsilateral motor evoked potentials (iMEPs) from the paretic biceps (BIC) and first dorsal interosseous (FDI) muscle. We operationalized CReST functional connectivity as iMEP presence/absence, CReST projection strength as iMEP size and CReST modulation as change in iMEP size by head rotation. We found comparable CReST functional connectivity to the BICs and FDIs in both subject groups. However, the pattern of CReST connection strength to the muscles diverged between groups, with stronger connections to FDIs than BICs in healthy subjects and stronger connections to BICs than FDIs in stroke subjects. Head rotation modulated only FDI iMEPs of healthy subjects. Our findings indicate that the healthy CReST does not have a proximal innervation bias, and its strong FDI connections may have functional relevance to finger individuation. The reversed CReST innervation pattern in stroke subjects confirms its reorganization after CST injury, and its strong BIC connections may indicate upregulation for particular upper extremity muscles or their functional actions.

Athletes after anterior cruciate ligament reconstruction demonstrate asymmetric intracortical facilitation early after surgery.

Quadriceps dysfunction persists after anterior cruciate ligament reconstruction (ACLR), yet the etiology remains elusive. Inhibitory and facilitatory intracortical networks (ie, intracortical excitability) may be involved in quadriceps dysfunction, yet the investigation of these networks early after ACLR is sparse. The purposes of this study were to examine (a) changes in intracortical excitability in athletes after ACLR compared to uninjured athletes during the course of postoperative rehabilitation, (b) the association between intracortical excitability and quadriceps strength in athletes after ACLR. Eighteen level I/II athletes after ACLR between the ages of 18 to 30 years and eighteen healthy sex, age, and activity matched athletes were tested at three-time points: (a) 2 weeks after surgery, (b) achievement of a "quiet knee" defined as full range of motion and minimal effusion, (c) return to running time point defined as achievement of a quadriceps index ≥80% and at least 12 weeks post-ACLR. Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), measured via transcranial magnetic stimulation and isometric quadriceps strength were examined bilaterally at each time point. There was a significant group × limb interaction (P = .017) for ICF. The ACLR group demonstrated asymmetric ICF (greater in the nonsurgical limb) compared to controls and a significant relationship between SICI and quadriceps strength of the surgical limb at the quiet knee time point (P = .018). ACLR individuals demonstrate differential effects on ICF between limbs. Also, SICI is associated with isometric quadriceps strength after ACLR, suggesting increased inhibition of the motor cortex may contribute to impaired quadriceps strength following ACLR.

Examination of Corticospinal and Spinal Reflexive Excitability During the Course of Postoperative Rehabilitation After Anterior Cruciate Ligament Reconstruction.

OBJECTIVE: To investigate corticospinal and spinal reflexive excitability and quadriceps strength in healthy athletes and athletes after anterior cruciate ligament reconstruction (ACLR) over the course of rehabilitation. DESIGN: Prospective cohort study. METHODS: Eighteen athletes with ACLR and 18 healthy athletes, matched by sex, age, and activity, were tested at (1) 2 weeks after surgery, (2) the "quiet knee" time point, defined as full range of motion and minimal effusion, and (3) return to running, defined as achieving a quadriceps index of 80% or greater. We measured (1) corticospinal excitability, using resting motor threshold (RMT) and motor-evoked potential amplitude at a stimulator intensity of 120% of RMT (MEP120) to the vastus medialis, (2) spinal reflexive excitability, calculating the ratio of the maximal Hoffmann reflex to the maximal M-wave to the vastus medialis, and (3) isometric quadriceps strength. RESULTS: The ACLR group had higher RMTs in the nonsurgical limb and higher MEP120 in the surgical limb at all time points. The healthy-athlete group did not have interlimb differences. The RMT was positively associated with quadriceps strength 2 weeks after surgery; MEP120 was associated with quadriceps strength at all time points. CONCLUSION: Compared to healthy athletes, athletes after ACLR had altered corticospinal excitability that did not change from 2 weeks after surgery to the time of return to running. J Orthop Sports Phys Ther 2020;50(9):516-522. Epub 1 Aug 2020. doi:10.2519/jospt.2020.9329.

A single high-intensity exercise bout during early consolidation does not influence retention or relearning of sensorimotor locomotor long-term memories.

A single exercise bout has been found to improve the retention of a skill-based upper extremity motor task up to a week post-practice. This effect is the greatest when exercise intensity is high and exercise is administered immediately after motor practice (i.e., early in consolidation). Whether exercise can affect other motor learning types (e.g., sensorimotor adaptation) and tasks (e.g., walking) is still unclear as previous studies have not optimally refined the exercise parameters and long-term retention testing. Therefore, we investigated whether a single high-intensity exercise bout during early consolidation would improve the long-term retention and relearning of sensorimotor adaptation during split-belt treadmill walking. Twenty-six neurologically intact adults attended three sessions; sessions 2 and 3 were 1 day and 7 days after session 1, respectively. Participants were allocated either to Rest (REST) or to Exercise (EXE) group. In session 1, all groups walked on a split-belt treadmill in a 2:1 speed ratio (1.5:0.75 m/s). Then, half of the participants exercised for 5 min (EXE), while the other half rested for 5 min (REST). A short exercise bout during early consolidation did not improve retention or relearning of locomotor memories one or seven days after session 1. This result reinforces previous findings that the effect of exercise on motor learning may differ between sensorimotor locomotor adaptation and skilled-based upper extremity tasks; thus, the utility of exercise as a behavioral booster of motor learning may depend on the type of motor learning and task.

A short bout of high-intensity exercise alters ipsilesional motor cortical excitability post-stroke.

Background: Acute exercise can increase motor cortical excitability and enhance motor learning in healthy individuals, an effect known as exercise priming. Whether it has the same effects in people with stroke is unclear. Objectives: The objective of this study was to investigate whether a short, clinically-feasible high-intensity exercise protocol can increase motor cortical excitability in non-exercised muscles of chronic stroke survivors. Methods: Thirteen participants with chronic, unilateral stroke participated in two sessions, at least one week apart, in a crossover design. In each session, they underwent either high-intensity lower extremity exercise or quiet rest. Motor cortical excitability of the extensor carpi radialis muscles was measured bilaterally with transcranial magnetic stimulation before and immediately after either exercise or rest. Motor cortical excitability changes (post-exercise or rest measures normalized to pre-test measures) were compared between exercise vs. rest conditions. Results: All participants were able to reach the target high-intensity exercise level. Blood lactate levels increased significantly after exercise (p < .001, d = 2.85). Resting motor evoked potentials from the lesioned hemisphere increased after exercise (mean 1.66; 95% CI: 1.19, 2.13) compared to the rest condition (mean 1.23; 95% CI: 0.64, 1.82), p = .046, d = 2.76, but this was not the case for the non-lesioned hemisphere (p = .406, d = 0.25). Conclusions: High-intensity exercise can increase lesioned hemisphere motor cortical excitability in a non-exercised muscle post-stroke. Our short and clinically-advantageous exercise protocol shows promise as a potential priming method in stroke rehabilitation.

Bilateral Assessment of the Corticospinal Pathways of the Ankle Muscles Using Navigated Transcranial Magnetic Stimulation.

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans and can be assessed using transcranial magnetic stimulation (TMS). Given the role of distal leg muscles in upright postural and dynamic tasks, such as walking, a growing research interest in the assessment and modulation of the corticospinal tracts relative to the function of these muscles has emerged in the last decade. However, methodological parameters used in previous work have varied across studies making the interpretation of results from cross-sectional and longitudinal studies less robust. Therefore, use of a standardized TMS protocol specific to the assessment of leg muscles' corticomotor response (CMR) will allow for direct comparison of results across studies and cohorts. The objective of this paper is to present a protocol that provides the flexibility to simultaneously assess the bilateral CMR of two main ankle antagonistic muscles, the tibialis anterior and soleus, using single pulse TMS with a neuronavigation system. The present protocol is applicable while the examined muscle is either fully relaxed or isometrically contracted at a defined percentage of maximum isometric voluntary contraction. Using each subject's structural MRI with the neuronavigation system ensures accurate and precise positioning of the coil over the leg cortical representations during assessment. Given the inconsistency in CMR derived measures, this protocol also describes a standardized calculation of these measures using automated algorithms. Though this protocol is not conducted during upright postural or dynamic tasks, it can be used to assess bilaterally any pair of leg muscles, either antagonistic or synergistic, in both neurologically intact and impaired subjects.

Different Error Size During Locomotor Adaptation Affects Transfer to Overground Walking Poststroke.

BACKGROUND: Studies in neurologically intact subjects suggest that the gradual presentation of small perturbations (errors) during learning results in better transfer of a newly learned walking pattern to overground walking. Whether the same result would be true after stroke is not known. OBJECTIVE: To determine whether introducing gradual perturbations, during locomotor learning using a split-belt treadmill influences learning the novel walking pattern or transfer to overground walking poststroke. METHODS: Twenty-six chronic stroke survivors participated and completed the following walking testing paradigm: baseline overground walking; baseline treadmill walking; split-belt treadmill/adaptation period (belts moving at different speeds); catch trial (belts at same speed); post overground walking. Subjects were randomly assigned to the Gradual group (gradual changes in treadmill belts speed during adaptation) or the Abrupt group (a single, large, abrupt change during adaptation). Step length asymmetry adaptation response on the treadmill and transfer of learning to overground walking was assessed. RESULTS: Step length asymmetry during the catch trial was the same between groups ( P = .195) confirming that both groups learned a similar amount. The magnitude of transfer to overground walking was greater in the Gradual than in the Abrupt group ( P = .041). CONCLUSIONS: The introduction of gradual perturbations (small errors), compared with abrupt (larger errors), during a locomotor adaptation task seems to improve transfer of the newly learned walking pattern to overground walking poststroke. However, given the limited magnitude of transfer, future studies should examine other factors that could impact locomotor learning and transfer poststroke.

A locomotor learning paradigm using distorted visual feedback elicits strategic learning.

Distorted visual feedback (DVF) during locomotion has been suggested to result in the development of a new walking pattern in healthy individuals through implicit learning processes. Recent work in upper extremity visuomotor rotation paradigms suggest that these paradigms involve implicit and explicit learning. Additionally, in upper extremity visuomotor paradigms, the verbal cues provided appear to impact how a behavior is learned and when this learned behavior is used. Here, in two experiments in neurologically intact individuals, we tested how verbal instruction impacts learning a new locomotor pattern on a treadmill through DVF, the transfer of that pattern to overground walking, and what types of learning occur (i.e., implicit vs. explicit learning). In experiment 1, we found that the instructions provided impacted the amount learned through DVF, but not the size of the aftereffects or the amount of the pattern transferred to overground walking. Additionally, the aftereffects observed were significantly different from the baseline walking pattern, but smaller than the behavior changes observed during learning, which is uncharacteristic of implicit sensorimotor adaptation. Thus, experiment 2 aimed to determine the cause of these discrepancies. In this experiment, when VF was not provided, individuals continued using the learned walking pattern when instructed to do so and returned toward their baseline pattern when instructed to do so. Based on these results, we conclude that DVF during locomotion results in a large portion of explicit learning and a small portion of implicit learning. NEW & NOTEWORTHY The results of this study suggest that distorted visual feedback during locomotor learning involves the development of an explicit strategy with only a small component of implicit learning. This is important because previous studies using distorted visual feedback have suggested that locomotor learning relies primarily on implicit learning. This paradigm, therefore, provides a new way to examine a different form of learning in locomotion.

Corticospinal and intracortical excitability differ between athletes early after ACLR and matched controls.

Neuromuscular impairments, such as quadriceps weakness and activation deficits, persist after anterior cruciate ligament reconstruction (ACLR). Recent research demonstrating changes in the function of the primary motor cortex after ACLR posits that quadriceps impairments may be influenced by reduced corticospinal excitability. The purpose of this study was to investigate whether the integrity of the neuromotor axis of the vastus medialis is altered in subjects 2 weeks post-ACLR compared to uninjured control subjects. Eighteen athletes 2 weeks post-ACLR and 18 age and sex matched uninjured control subjects participated in this cross-sectional study. We quantified corticospinal (resting motor threshold, RMT; motor evoked potential amplitudes at 120% RMT, MEP120 ) and intracortical (inhibition and facilitation) excitability using single and paired pulse transcranial magnetic stimulation (TMS), respectively. We assessed spinal-reflex excitability (H-reflex amplitude normalized to maximal M-wave, H/M ratio) using peripheral stimulation. Subjects post-ACLR had higher RMTs (p = 0.001), greater MEP120 amplitudes (p = 0.001), and more asymmetric facilitation (p = 0.041) than the uninjured control subjects. No significant group differences were found for intracortical inhibition (p = 0.289) and H/M ratio (p = 0.332). Our findings indicate that both intracortical and corticospinal excitability of vastus medialis are bilaterally altered in subjects 2 weeks after ACLR. Given persistent neuromuscular deficits seen after ACLR, rehabilitation strategies targeting intracortical and corticospinal deficits may potentially improve clinical outcomes. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2941-2948, 2018.

Characterizing the corticomotor connectivity of the bilateral ankle muscles during rest and isometric contraction in healthy adults.

The investigation of the corticomotor connectivity (CMC) to leg muscles is an emerging research area, and establishing reliability of measures is critical. This study examined the measurement reliability and the differences between bilateral soleus (SOL) and tibialis anterior (TA) CMC in 21 neurologically intact adults. Using single pulse transcranial magnetic stimulation (TMS), each muscle's CMC was assessed twice (7 ±â€¯2 days apart) during rest and active conditions. CMC was quantified using a standardized battery of eight measures (4/condition): motor threshold during resting (RMT), motor evoked potential amplitude and latency (raw and normalized to height) in both conditions, contralateral silent period (CSP) during active. Using two reliability metrics (intraclass correlation coefficient and coefficient of variation of method error; good reliability: ≥0.75 and ≤15, respectively) and repeated-measures ANOVA, we investigated the reliability and Muscle X Body Side interaction. For both muscles, RMT, resting raw and normalized latencies, and active raw latency demonstrated good reliability, while CSP had good reliability only for TA. Amplitude did not demonstrate good reliability for both muscles. SOL CMC was significantly different from TA CMC for all measures but CSP; body side had no significant effect. Therefore, only certain measures may reliably quantify SOL and TA CMC while different CMC (except CSP) between SOL and TA suggests dissimilar corticospinal drive to each muscle regardless of the side.