Distinct Cortical Correlates of Perception and Motor Function in Balance Control.

Fluctuations in brain activity alter how we perceive our body and generate movements but have not been investigated in functional whole-body behaviors. During reactive balance, we recently showed that evoked brain activity is associated with the balance ability in young individuals. Furthermore, in PD, impaired whole-body motion perception in reactive balance is associated with impaired balance. Here, we investigated the brain activity during the whole-body motion perception in reactive balance in young adults (9 female, 10 male). We hypothesized that both ongoing and evoked cortical activity influences the efficiency of information processing for successful perception and movement during whole-body behaviors. We characterized two cortical signals using electroencephalography localized to the SMA: (1) the "N1," a perturbation-evoked potential that decreases in amplitude with expectancy and is larger in individuals with lower balance function, and (2) preperturbation ß power, a transient rhythm that favors maintenance of the current sensorimotor state and is inversely associated with tactile perception. In a two-alternative forced choice task, participants judged whether pairs of backward support surface perturbations during standing were in the "same" or "different" direction. As expected, lower whole-body perception was associated with lower balance ability. Within a perturbation pair, N1 attenuation was larger on correctly perceived trials and associated with better balance, but not perception. In contrast, preperturbation ß power was higher on incorrectly perceived trials and associated with poorer perception, but not balance. Together, ongoing and evoked cortical activity have unique roles in information processing that give rise to distinct associations with perceptual and balance ability.

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 ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain-behavior relationships after stroke.

The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large-scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided.

Agonist-Antagonist Coactivation Enhances Corticomotor Excitability of Ankle Muscles.

Spinal pathways underlying reciprocal flexion-extension contractions have been well characterized, but the extent to which cortically evoked motor-evoked potentials (MEPs) are influenced by antagonist muscle activation remains unclear. A majority of studies using transcranial magnetic stimulation- (TMS-) evoked MEPs to evaluate the excitability of the corticospinal pathway focus on upper extremity muscles. Due to functional and neural control differences between lower and upper limb muscles, there is a need to evaluate methodological factors influencing TMS-evoked MEPs specifically in lower limb musculature. If and to what extent the activation of the nontargeted muscles, such as antagonists, affects TMS-evoked MEPs is poorly understood, and such gaps in our knowledge may limit the rigor and reproducibility of TMS studies. Here, we evaluated the effect of the activation state of the antagonist muscle on TMS-evoked MEPs obtained from the target (agonist) ankle muscle for both tibialis anterior (TA) and soleus muscles. Fourteen able-bodied participants (11 females, age: 26.1 ± 4.1 years) completed one experimental session; data from 12 individuals were included in the analysis. TMS was delivered during 4 conditions: rest, TA activated, soleus activated, and TA and soleus coactivation. Three pairwise comparisons were made for MEP amplitude and coefficient of variability (CV): rest versus coactivation, rest versus antagonist activation, and agonist activation versus coactivation. We demonstrated that agonist-antagonist coactivation enhanced MEP amplitude and reduced MEP CVs for both TA and soleus muscles. Our results provide methodological considerations for future TMS studies and pave the way for future exploration of coactivation-dependent modulation of corticomotor excitability in pathological cohorts such as stroke or spinal cord injury.

Targeted Neuromodulation of Abnormal Interhemispheric Connectivity to Promote Neural Plasticity and Recovery of Arm Function after Stroke: A Randomized Crossover Clinical Trial Study Protocol.

Background: Despite intensive rehabilitation efforts, most stroke survivors have persistent functional disability of the paretic arm and hand. These motor impairments may be due in part to maladaptive changes in structural and functional connections between brain regions. The following early stage clinical trial study protocol describes a noninvasive brain stimulation approach to target transcallosally mediated interhemispheric connections between the ipsi- and contralesional motor cortices (iM1 and cM1) using corticocortical paired associative stimulation (ihPAS). This clinical trial aims to characterize ihPAS-induced modulation of interhemispheric connectivity and the effect on motor skill performance and learning in chronic stroke survivors. Methods/Design: A repeated-measures, cross-over design study will recruit 20 individuals post-stroke with chronic mild-moderate paretic arm impairment. Each participant will complete an active ihPAS and control ihPAS session. Assessments of cortical excitability and motor skill performance will be conducted prior to and at four time points following the ihPAS intervention. The primary outcome measures will be: TMS-evoked interhemispheric motor connectivity, corticomotor excitability, and response time on a modified serial reaction time task. Discussion/Conclusion: The findings from this single-site early stage clinical trial will provide foundational results to inform the design of larger-scale, multisite clinical trials to evaluate the therapeutic potential of ihPAS-based neuromodulation for upper limb recovery after stroke. This trial is registered with NCT02465034.

Motor Skill Acquisition Promotes Human Brain Myelin Plasticity.

Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI), the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements) using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus). In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults.

Applications of electroencephalography to characterize brain activity: perspectives in stroke.

A wide array of neuroimaging technologies are now available that offer unprecedented opportunities to study the brain in health and disease. Each technology has associated strengths and weaknesses that need to be considered to maximize their utility, especially when used in combination. One imaging technology, electroencephalography (EEG), has been in use for more than 80 years, but as a result of recent technologic advancements EEG has received renewed interest as an inexpensive, noninvasive and versatile technique to evaluate neural activity in the brain. In part, this is due to new opportunities to combine EEG not only with other imaging modalities, but also with neurostimulation and robotics technologies. When used in combination, noninvasive brain stimulation and EEG can be used to study cause-and-effect relationships between interconnected brain regions providing new avenues to study brain function. Although many of these approaches are still in the developmental phase, there is substantial promise in their ability to deepen our understanding of brain function. The ability to capture the causal relationships between brain function and behavior in individuals with neurologic disorders or injury has important clinical implications for the development of novel biomarkers of recovery and response to therapeutic interventions. The goals of this paper are to provide an overview of the fundamental principles of EEG; discuss past, present, and future applications of EEG in the clinical management of stroke; and introduce the technique of combining EEG with a form of noninvasive brain stimulation, transcranial magnetic stimulation, as a powerful synergistic research paradigm to characterize brain function in both health and disease.Video Abstract available (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A87) for more insights from the authors.

Focal hand dystonia: individualized intervention with repeated application of repetitive transcranial magnetic stimulation.

OBJECTIVES: To examine for individual factors that may predict response to inhibitory repetitive transcranial magnetic stimulation (rTMS) in focal hand dystonia (FHD); to present the method for determining optimal stimulation to increase inhibition in a given patient; and to examine individual responses to prolonged intervention. DESIGN: Single-subject design to determine optimal parameters to increase inhibition for a given subject and to use the selected parameters once per week for 6 weeks, with 1-week follow-up, to determine response. SETTING: Clinical research laboratory. PARTICIPANTS: A volunteer sample of subjects with FHD (N = 2). One participant had transcranial magnetic stimulation responses indicating impaired inhibition, and the other had responses within normative limits. INTERVENTIONS: There were 1200 pulses of 1-Hz rTMS delivered using 4 different stimulation sites/intensity combinations: primary motor cortex at 90% or 110% of resting motor threshold (RMT) and dorsal premotor cortex (PMd) at 90% or 110% of RMT. The parameters producing the greatest within-session increase in cortical silent period (CSP) duration were then used as the intervention. MAIN OUTCOME MEASURES: Response variables included handwriting pressure and velocity, subjective symptom rating, CSP, and short latency intracortical inhibition and facilitation. RESULTS: The individual with baseline transcranial magnetic stimulation responses indicating impaired inhibition responded favorably to the repeated intervention, with reduced handwriting force, an increase in the CSP, and subjective report of moderate symptom improvement at 1-week follow-up. The individual with normative baseline responses failed to respond to the intervention. In both subjects, 90% of RMT to the PMd produced the greatest lengthening of the CSP and was used as the intervention. CONCLUSIONS: An individualized understanding of neurophysiological measures can be an indicator of responsiveness to inhibitory rTMS in focal dystonia, with further work needed to determine likely responders versus nonresponders.

Exploring the specific time course of interhemispheric inhibition between the human primary sensory cortices.

The neurophysiological mechanism of interhemispheric inhibition (IHI) between the human primary sensory cortices (S1s) is poorly understood. Here we used a paired median nerve somatosensory evoked potential protocol to observe S1-S1 IHI from the dominant to the nondominant hemisphere with electroencephalography. In 10 healthy, right-handed individuals, we compared mean peak-to-peak amplitudes of five somatosensory evoked potential components (P14/N20, N20/P25, P25/N30, N30/P40, and P40/N60) recorded over the right S1 after synchronous versus asynchronous stimulation of the right and left median nerves. Asynchronous conditioning + test stimuli (CS+TS) were delivered at interstimulus intervals of 15, 20, 25, 30, and 35 ms. We found that, in relation to synchronous stimulation, when a CS to the left S1 preceded a TS to the right S1 at the short intervals (15 and 20 ms) the amplitude of the cortical N20/P25 complex was significantly depressed, whereas at the longer intervals (25, 30, and 35 ms) significant inhibition was observed for the thalamocortical P14/N20 as well as the cortical N20/P25 components. We conclude that the magnitude of S1 IHI appears to depend on the temporal asynchrony of bilateral inputs and the specific timing is likely reflective of a direct transcallosal mechanism. Employing a method that enables direct S1 IHI to be reliably quantified may provide a novel tool to assess potential IHI imbalances in individuals with neurological damage, such as stroke.

Impact of 5-Hz rTMS over the primary sensory cortex is related to white matter volume in individuals with chronic stroke.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that may facilitate mechanisms of motor learning. In a recent single-blind, pseudo-randomized study, we showed that 5-Hz rTMS over ipsilesional primary somatosensory cortex followed by practice of a skilled motor task enhanced motor learning compared with sham rTMS + practice in individuals with chronic stroke. However, the beneficial effect of stimulation was inconsistent. The current study examined how differences in sensorimotor cortex morphology might predict rTMS-related improvements in motor learning in these individuals. High-resolution T1-weighted magnetic resonance images were acquired and processed in FreeSurfer using a newly developed automated, whole brain parcellation technique. Gray matter and white matter volumes of the ipsilesional primary somatosensory and motor cortices were extracted. A significant positive association was observed between the volume of white matter in the primary somatosensory cortex and motor learning-related change, exclusively in the group that received active 5-Hz rTMS. A regression model with age, gray matter and white matter volumes as predictors was significant for predicting motor learning-related change in individuals who received active TMS. White matter volume predicted the greatest amount of variance (47.6%). The same model was non-significant when volumes of the primary motor cortex were considered. We conclude that white matter volume in the cortex underlying the TMS coil may be a novel predictor for behavioral response to 5-Hz rTMS over the ipsilesional primary somatosensory followed by motor practice.

Motor skill learning is associated with diffusion characteristics of white matter in individuals with chronic stroke.

BACKGROUND AND PURPOSE: Imaging advances allow investigation of white matter after stroke; a growing body of literature has shown links between diffusion-based measures of white matter microstructure and motor function. However, the relationship between these measures and motor skill learning has not been considered in individuals with stroke. The aim of this study was to investigate the relationships between posttraining white matter microstructural status, as indexed by diffusion tensor imaging within the ipsilesional posterior limb of the internal capsule (PLIC), and learning of a novel motor task in individuals with chronic stroke. METHODS: A total of 13 participants with chronic stroke and 9 healthy controls practiced a visuomotor pursuit task across 5 sessions. Change in motor behavior associated with learning was indexed by comparing baseline performance with a delayed retention test. Fractional anisotropy (FA) indexed at the retention test was the primary diffusion tensor imaging-derived outcome measure. RESULTS: In individuals with chronic stroke, we discovered an association between posttraining ipsilesional PLIC FA and the magnitude of change associated with motor learning; hierarchical multiple linear regression analyses revealed that the combination of age, time poststroke, and ipsilesional PLIC FA posttraining was associated with motor learning-related change (R = 0.649; P = 0.02). Baseline motor performance was not related to posttraining ipsilesional PLIC FA. DISCUSSION AND CONCLUSIONS: Diffusion characteristics of posttraining ipsilesional PLIC were linked to the magnitude of change in skilled motor behavior. These results imply that the microstructural properties of regional white matter indexed by diffusion behavior may be an important factor to consider when determining potential response to rehabilitation in persons with stroke. VIDEO ABSTRACT AVAILABLE: (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A59) for more insights from the authors.

Limitations in utilization and prioritization of standardized somatosensory assessments after stroke: A cross-sectional survey of neurorehabilitation clinicians.

BACKGROUND AND PURPOSE: Somatosensory impairments are common after stroke, but receive limited evaluation and intervention during neurorehabilitation, despite negatively impacting functional movement and recovery. OBJECTIVES: Our objective was to understand the scope of somatosensory assessments used by clinicians in stroke rehabilitation, and barriers to increasing use in clinical practice. METHODS: An electronic survey was distributed to clinicians (physical therapists, occupational therapists, physicians, and nurses) who assessed at least one individual with stroke in the past 6 months. The survey included questions on evaluation procedures, type, and use of somatosensory assessments, as well as barriers and facilitators in clinical practice. RESULTS: Clinicians (N = 431) indicated greater familiarity with non-standardized assessments, and greater utilization compared to standardized assessments (p < 0.0001). Components of tactile sensation were the most commonly assessed modality of somatosensation (25%), while proprioception was rarely assessed (1%). Overall, assessments of motor function were prioritized over assessments of somatosensory function (p < 0.0001). DISCUSSION: Respondents reported assessing somatosensation less frequently than motor function and demonstrated a reliance on rapid and coarse non-standardized assessments that ineffectively capture multi-modal somatosensory impairments, particularly for proprioceptive deficits common post-stroke. In general, clinicians were not familiar with standardized somatosensory assessments, and this knowledge gap likely contributes to lack of translation of these assessments into practice. CONCLUSIONS: Clinicians utilize somatosensory assessments that inadequately capture the multi-modal nature of somatosensory impairments in stroke survivors. Addressing barriers to clinical translation has the potential to increase utilization of standardized assessments to improve the characterization of somatosensory deficits that inform clinical decision-making toward enhancing stroke rehabilitation outcomes.

Delayed Cortical Responses During Reactive Balance After Stroke Associated With Slower Kinetics and Clinical Balance Dysfunction.

BACKGROUND: Slowed balance and mobility after stroke have been well-characterized. Yet the effects of unilateral cortical lesions on whole-body neuromechanical control is poorly understood, despite increased reliance on cortical resources for balance and mobility with aging. Objective. We tested whether individuals post stroke show impaired cortical responses evoked during reactive balance, and the effect of asymmetrical interlimb contributions to balance recovery and the evoked cortical response. METHODS: Using electroencephalography, we assessed cortical N1 responses evoked over fronto-midline regions (Cz) during backward support-surface perturbations loading both legs and posterior-lateral directions that preferentially load the paretic or nonparetic leg in individuals' post-stroke and age-matched controls. We tested relationships between cortical responses and clinical balance/mobility function, as well as to center of pressure (CoP) rate of rise (RoR) during balance recovery. RESULTS: Cortical N1 responses were smaller and delayed after stroke (P < .047), regardless of perturbation condition. In contrast to controls, slower cortical response latencies associated with lower clinical function in stroke (Mini Balance Evaluation Systems Test: r = -.61, P = .007; Timed-Up-and-Go: r = .53, P = .024; walking speed: r = -.46, P = .055). Paretic-loaded balance recovery revealed slower CoP RoR (P = .012) that was associated with delayed cortical response latencies (r = -.70, P = .003); these relationships were not present during bilateral and nonparetic-loaded conditions, nor in the older adults control group. CONCLUSIONS: Individuals after stroke may be limited in their balance ability by the slowed speed of their cortical responses to destabilization. In particular, paretic leg loading may reveal cortical response impairments that reflect reduced paretic motor capacity.

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.

Concussion: current concepts in diagnosis and management.

Current understanding of the term "concussion" is fraught with misconceptions regarding the extent and nature of brain injury. Despite increasing attention in popular media and within the context of sports, considerable gaps exist in our knowledge of the diagnosis, underlying brain pathology, recovery of function, and optimal interventions for concussion. In this special interest article, we discuss the definition and risk factors associated with concussion, summarize and highlight some of the most widely used assessment tools, and critique the evidence for current principles of concussion management. Our evaluation has identified opportunities for novel neuroimaging techniques to improve the understanding of the pathophysiology of concussion and to evaluate the changes in the recovering brain in response to rehabilitation. In summary, a clear definition of the underlying brain pathology, the potential long-term consequences, and the risk factors of injury and recovery will help guide future research aiming to minimize the impact of injury and develop innovative and successful therapeutic approaches aimed at ameliorating the functional impairments associated with concussion.

Distinct cortical correlates of perception and motor function in balance control.

Fluctuations in brain state alter how we perceive our body and generate movements but have not been investigated in functional whole-body behaviors. During reactive balance control, we recently showed that evoked brain activity is associated with balance ability in healthy young individuals. Further, in individuals with Parkinson's disease, impairments in whole-body motion perception in reactive balance are associated with clinical balance impairment. Here we investigated brain activity during whole-body motion perception in reactive balance in healthy young adults. We hypothesized that flexibility in brain states underlies successful perception and movement during whole-body movement. We characterized two cortical sensorimotor signals using electroencephalography localized to the supplementary motor area: 1) the "N1 response", a perturbation-evoked potential that decreases in amplitude with expectancy and is larger in individuals with lower balance function; and 2) pre-perturbation beta oscillatory activity, a rhythm that favors maintenance of the current sensorimotor state and is inversely associated with perception in seated somatosensory perceptual tasks. In a two-alternative forced choice task, participants judged whether pairs of backward support-surface perturbations during standing were in the "same" or "different" direction. As expected, lower whole-body perception was associated with lower balance ability. Within a perturbation pair, N1 attenuation was larger on correctly perceived trials and associated with better balance, but not perception. In contrast, pre-perturbation beta power was higher on incorrectly perceived trials and associated with poorer perception, but not balance. Taken together, flexibility in different cortical processes influences perceptual accuracy but have distinct associations with balance and perceptual ability.

Delayed cortical engagement associated with balance dysfunction after stroke.

Cortical resources are typically engaged for balance and mobility in older adults, but these resources are impaired post-stroke. Although slowed balance and mobility after stroke have been well-characterized, the effects of unilateral cortical lesions due to stroke on neuromechanical control of balance is poorly understood. Our central hypothesis is that stroke impairs the ability to rapidly and effectively engage the cerebral cortex during balance and mobility behaviors, resulting in asymmetrical contributions of each limb to balance control. Using electroencephalography (EEG), we assessed cortical N1 responses evoked over fronto-midline regions (Cz) during balance recovery in response to backward support-surface perturbations loading both legs, as well as posterior-lateral directions that preferentially load the paretic or nonparetic leg. Cortical N1 responses were smaller and delayed in the stroke group. While older adults exhibited weak or absent relationships between cortical responses and clinical function, stroke survivors exhibited strong associations between slower N1 latencies and slower walking, lower clinical mobility, and lower balance function. We further assessed kinetics of balance recovery during perturbations using center of pressure rate of rise. During backward support-surface perturbations that loaded the legs bilaterally, balance recovery kinetics were not different between stroke and control groups and were not associated with cortical response latency. However, lateralized perturbations revealed slower kinetic reactions during paretic loading compared to controls, and to non-paretic loading within stroke participants. Individuals post stroke had similar nonparetic-loaded kinetic reactions to controls implicating that they effectively compensate for impaired paretic leg kinetics when relying on the non-paretic leg. In contrast, paretic-loaded balance recovery revealed time-synchronized associations between slower cortical responses and slower kinetic reactions only in the stroke group, potentially reflecting the limits of cortical engagement for balance recovery revealed within the behavioral context of paretic motor capacity. Overall, our results implicate individuals after stroke may be uniquely limited in their balance ability by the slowed speed of their cortical engagement, particularly under challenging balance conditions that rely on the paretic leg. We expect this neuromechanical insight will enable progress toward an individualized framework for the assessment and treatment of balance impairments based on the interaction between neuropathology and behavioral context.

State-dependent interhemispheric inhibition reveals individual differences in motor behavior in chronic stroke.

OBJECTIVE: To investigate state-dependent interhemispheric inhibition (IHI) in chronic stroke survivors compared to neurotypical older adult controls, and test whether abnormal IHI modulation was associated with upper extremity motor behavior. METHODS: Dual-coil transcranial magnetic stimulation (TMS) measured IHI bi-directionally, between non-lesioned and lesioned motor cortex (M1) in two activity states: (1) at rest and (2) during contralateral isometric hand muscle contraction. IHI was tested by delivering a conditioning stimulus 8-msec or 50-msec prior to a test stimulus over contralateral M1. Paretic motor behavior was assessed by clinical measures of impairment, strength, and dexterity, and mirroring activity in the non-paretic hand. RESULTS: Stroke survivors demonstrated reduced IHI at rest, and less IHI modulation (active - rest) compared to controls. Individual differences in IHI modulation were related to motor behavior differences where greater IHI modulation was associated with greater motor impairment and more mirroring. In contrast, there were no relationships between IHI at rest and motor behavior. CONCLUSIONS: Abnormal state-dependent interhemispheric circuit activity may be more sensitive to post-stroke motor deficits than when assessed in a single motor state. SIGNIFICANCE: Characterizing state-dependent changes in neural circuitry may enhance models of stroke recovery and inform rehabilitation interventions.

Associations between myelin water imaging and measures of fall risk and functional mobility in multiple sclerosis.

BACKGROUND AND PURPOSE: Myelin water fraction (MWF) deficits as measured by myelin water imaging (MWI) have been related to worse motor function in persons with multiple sclerosis (PwMS). However, it is unknown if measures from MWI metrics in motor areas relate to fall risk measures in PwMS. The objective of this study was to examine the relationship between MWI measures in motor areas to performance on clinical measures of fall risk and disability in PwMS. METHODS: Sixteen individuals with relapsing-remitting MS participated (1 male, 15 female; age 47.1 years [12.3]; Expanded Disability Status Scale 4.0 [range 0-6.5]) and completed measures of walking and fall risk (Timed 25 Foot Walk [T25FW] and Timed Up and Go). MWF and the geometric mean of the intra-/extracellular water T2 (geomT2IEW ) values reflecting myelin content and contribution of large-diameter axons/density, respectively, were assessed in three motor-related regions. RESULTS: The geomT2IEW of the corticospinal tract (r = -.599; p = .018) and superior cerebellar peduncles (r = -.613; p = .015) demonstrated significant inverse relationships with T25FW, suggesting that decreased geomT2IEW was related to slower walking. Though not significant, MWF in the corticospinal tract and superior cerebellar peduncles also demonstrated fair relationships with the T25FW, suggesting that worse performance on the T25FW was associated with lower MWF values. CONCLUSIONS: MWI of key motor regions was associated with walking performance in PwMS. Further MWI studies are needed to identify relationships between pathology and clinical function in PwMS to guide targeted rehabilitation therapies aimed at preventing falls.