Shoulder position and handedness differentially affect excitability and intracortical inhibition of hand muscles.

Individuals with stroke show distinct differences in hand function impairment when the shoulder is in adduction, within the workspace compared to when the shoulder is abducted, away from the body. To better understand how shoulder position affects hand control, we tested the corticomotor excitability and intracortical control of intrinsic and extrinsic hand muscles important for grasp in twelve healthy individuals. Motor evoked potentials (MEP) using single and paired-pulse transcranial magnetic stimulation were elicited in extensor digitorum communis (EDC), flexor digitorum superficialis (FDS), first dorsal interosseous (FDI), and abductor pollicis brevis (APB). The shoulder was fully supported in horizontal adduction (ADD) or abduction (ABD). Separate mixed-effect models were fit to the MEP parameters using shoulder position (or upper-extremity [UE] side) as fixed and participants as random effects. In the non-dominant UE, EDC showed significantly greater MEPs in shoulder ABD than ADD. In contrast, the dominant side EDC showed significantly greater MEPs in ADD compared to ABD; %facilitation of EDC on dominant side showed significant stimulus intensity x position interaction, EDC excitability was significantly greater in ADD at 150% of the resting threshold. Intrinsic hand muscles of the dominant UE received significantly more intracortical inhibition (SICI) when the shoulder was in ADD compared to ABD; there was no position-dependent modulation of SICI on the non-dominant side. Our findings suggest that these resting-state changes in hand muscle excitabilities reflect the natural statistics of UE movements, which in turn may arise from as well as shape the nature of shoulder-hand coupling underlying UE behaviors.

The effect of time since stroke, gender, age, and lesion size on thalamus volume in chronic stroke: a pilot study.

Recent stroke studies have shown that the ipsi-lesional thalamus longitudinally and significantly decreases after stroke in the acute and subacute stages. However, additional considerations in the chronic stages of stroke require exploration including time since stroke, gender, intracortical volume, aging, and lesion volume to better characterize thalamic differences after cortical infarct. This cross-sectional retrospective study quantified the ipsilesional and contralesional thalamus volume from 69 chronic stroke subjects' anatomical MRI data (age 35-92) and related the thalamus volume to time since stroke, gender, intracortical volume, age, and lesion volume. The ipsi-lesional thalamus volume was significantly smaller than the contra-lesional thalamus volume (t(68) = 13.89, p < 0.0001). In the ipsilesional thalamus, significant effect for intracortical volume (t(68) = 2.76, p = 0.008), age (t(68) = 2.47, p = 0.02), lesion volume (t(68) = - 3.54, p = 0.0008), and age*time since stroke (t(68) = 2.46, p = 0.02) were identified. In the contralesional thalamus, significant effect for intracortical volume (t(68) = 3.2, p = 0.002) and age (t = - 3.17, p = 0.002) were identified. Clinical factors age and intracortical volume influence both ipsi- and contralesional thalamus volume and lesion volume influences the ipsilesional thalamus. Due to the cross-sectional nature of this study, additional research is warranted to understand differences in the neural circuitry and subsequent influence on volumetrics after stroke.

Roles of Lesioned and Nonlesioned Hemispheres in Reaching Performance Poststroke.

Background. Severe poststroke arm impairment is associated with greater activation of the nonlesioned hemisphere during movement of the affected arm. The circumstances under which this activation may be adaptive or maladaptive remain unclear. Objective. To identify the functional relevance of key lesioned and nonlesioned hemisphere motor areas to reaching performance in patients with mild versus severe arm impairment. Methods. A total of 20 participants with chronic stroke performed a reaching response time task with their affected arm. During the reaction time period, a transient magnetic stimulus was applied over the primary (M1) or dorsal premotor cortex (PMd) of either hemisphere, and the effect of the perturbation on movement time (MT) was calculated. Results. For perturbation of the nonlesioned hemisphere, there was a significant interaction effect of Site of perturbation (PMd vs M1) by Group (mild vs severe; P < .001). Perturbation of PMd had a greater effect on MT in the severe versus the mild group. This effect was not observed with perturbation of M1. For perturbation of the lesioned hemisphere, there was a main effect of site of perturbation (P < .05), with perturbation of M1 having a greater effect on MT than PMd. Conclusions. These results demonstrate that, in the context of reaching movements, the role of the nonlesioned hemisphere depends on both impairment severity and the specific site that is targeted. A deeper understanding of these individual-, task-, and site-specific factors is essential for advancing the potential usefulness of neuromodulation to enhance poststroke motor recovery.

Non-Invasive Brain Stimulation to Enhance Upper Limb Motor Practice Poststroke: A Model for Selection of Cortical Site.

Motor practice is an essential part of upper limb motor recovery following stroke. To be effective, it must be intensive with a high number of repetitions. Despite the time and effort required, gains made from practice alone are often relatively limited, and substantial residual impairment remains. Using non-invasive brain stimulation to modulate cortical excitability prior to practice could enhance the effects of practice and provide greater returns on the investment of time and effort. However, determining which cortical area to target is not trivial. The implications of relevant conceptual frameworks such as Interhemispheric Competition and Bimodal Balance Recovery are discussed. In addition, we introduce the STAC (Structural reserve, Task Attributes, Connectivity) framework, which incorporates patient-, site-, and task-specific factors. An example is provided of how this framework can assist in selecting a cortical region to target for priming prior to reaching practice poststroke. We suggest that this expanded patient-, site-, and task-specific approach provides a useful model for guiding the development of more successful approaches to neuromodulation for enhancing motor recovery after stroke.

Neural coupling between homologous muscles during bimanual tasks: effects of visual and somatosensory feedback.

While the effects of sensory feedback on bimanual tasks have been studied extensively at two ends of the motor control hierarchy, the cortical and behavioral levels, much less is known about how it affects the intermediate levels, including neural control of homologous muscle groups. We investigated the effects of somatosensory input on the neural coupling between homologous arm muscles during bimanual tasks. Twelve subjects performed symmetric elbow flexion/extension tasks under different types of sensory feedback. The first two types involve visual feedback, with one imposing stricter force symmetry than the other. The third incorporated somatosensory feedback via a balancing apparatus that forced the two limbs to produce equal force levels. Although the force error did not differ between feedback conditions, the somatosensory feedback significantly increased temporal coupling of bilateral force production, indicated by a high correlation between left/right force profiles (P < 0.001). More importantly, intermuscular coherence between biceps brachii muscles was significantly higher with somatosensory feedback than others (P = 0.001). Coherence values also significantly differed between tasks (flexion/extension). Notably, whereas feedback type mainly modulated coherence in the α- and γ-bands, task type only affected ß-band coherence. Similar feedback effects were observed for triceps brachii muscles, but there was also a strong phase effect on the coherence values (P < 0.001) that could have diluted feedback effects. These results suggest that somatosensory feedback can significantly increase neural coupling between homologous muscles. Additionally, the between-task difference in ß-band coherence may reflect different neural control strategies for the elbow flexor and extensor muscles. NEW & NOTEWORTHY: This study investigated the effects of somatosensory feedback during bimanual tasks on the neural coupling between arm muscles, which remains largely unexplored. Somatosensory feedback using a balancing apparatus, compared with visual feedback, significantly increased neural coupling between homologous muscles (indicated by intermuscular coherence values) and improved temporal correlation of bilateral force production. Notably, feedback type modulated coherence in the α- and γ-bands (more subcortical pathways), whereas task type mainly affected ß-band coherence (corticospinal pathway).

Right hemisphere grey matter structure and language outcomes in chronic left hemisphere stroke.

The neural mechanisms underlying recovery of language after left hemisphere stroke remain elusive. Although older evidence suggested that right hemisphere language homologues compensate for damage in left hemisphere language areas, the current prevailing theory suggests that right hemisphere engagement is ineffective or even maladaptive. Using a novel combination of support vector regression-based lesion-symptom mapping and voxel-based morphometry, we aimed to determine whether local grey matter volume in the right hemisphere independently contributes to aphasia outcomes after chronic left hemisphere stroke. Thirty-two left hemisphere stroke survivors with aphasia underwent language assessment with the Western Aphasia Battery-Revised and tests of other cognitive domains. High-resolution T1-weighted images were obtained in aphasia patients and 30 demographically matched healthy controls. Support vector regression-based multivariate lesion-symptom mapping was used to identify critical language areas in the left hemisphere and then to quantify each stroke survivor's lesion burden in these areas. After controlling for these direct effects of the stroke on language, voxel-based morphometry was then used to determine whether local grey matter volumes in the right hemisphere explained additional variance in language outcomes. In brain areas in which grey matter volumes related to language outcomes, we then compared grey matter volumes in patients and healthy controls to assess post-stroke plasticity. Lesion-symptom mapping showed that specific left hemisphere regions related to different language abilities. After controlling for lesion burden in these areas, lesion size, and demographic factors, grey matter volumes in parts of the right temporoparietal cortex positively related to spontaneous speech, naming, and repetition scores. Examining whether domain general cognitive functions might explain these relationships, partial correlations demonstrated that grey matter volumes in these clusters related to verbal working memory capacity, but not other cognitive functions. Further, grey matter volumes in these areas were greater in stroke survivors than healthy control subjects. To confirm this result, 10 chronic left hemisphere stroke survivors with no history of aphasia were identified. Grey matter volumes in right temporoparietal clusters were greater in stroke survivors with aphasia compared to those without history of aphasia. These findings suggest that the grey matter structure of right hemisphere posterior dorsal stream language homologues independently contributes to language production abilities in chronic left hemisphere stroke, and that these areas may undergo hypertrophy after a stroke causing aphasia.

Neural Substrates of Motor Recovery in Severely Impaired Stroke Patients With Hand Paralysis.

In well-recovered stroke patients with preserved hand movement, motor dysfunction relates to interhemispheric and intracortical inhibition in affected hand muscles. In less fully recovered patients unable to move their hand, the neural substrates of recovered arm movements, crucial for performance of daily living tasks, are not well understood. Here, we evaluated interhemispheric and intracortical inhibition in paretic arm muscles of patients with no recovery of hand movement (n = 16, upper extremity Fugl-Meyer Assessment = 27.0 ± 8.6). We recorded silent periods (contralateral and ipsilateral) induced by transcranial magnetic stimulation during voluntary isometric contraction of the paretic biceps and triceps brachii muscles (correlates of intracortical and interhemispheric inhibition, respectively) and investigated links between the silent periods and motor recovery, an issue that has not been previously explored. We report that interhemispheric inhibition, stronger in the paretic triceps than biceps brachii muscles, significantly correlated with the magnitude of residual impairment (lower Fugl-Meyer scores). In contrast, intracortical inhibition in the paretic biceps brachii, but not in the triceps, correlated positively with motor recovery (Fugl-Meyer scores) and negatively with spasticity (lower Modified Ashworth scores). Our results suggest that interhemispheric inhibition and intracortical inhibition of paretic upper arm muscles relate to motor recovery in different ways. While interhemispheric inhibition may contribute to poorer recovery, muscle-specific intracortical inhibition may relate to successful motor recovery and lesser spasticity.

High-Intensity, Unilateral Resistance Training of a Non-Paretic Muscle Group Increases Active Range of Motion in a Severely Paretic Upper Extremity Muscle Group after Stroke.

Limited rehabilitation strategies are available for movement restoration when paresis is too severe following stroke. Previous research has shown that high-intensity resistance training of one muscle group enhances strength of the homologous, contralateral muscle group in neurologically intact adults. How this "cross education" phenomenon might be exploited to moderate severe weakness in an upper extremity muscle group after stroke is not well understood. The primary aim of this study was to examine adaptations in force-generating capacity of severely paretic wrist extensors resulting from high intensity, dynamic contractions of the non-paretic wrist extensors. A secondary, exploratory aim was to probe neural adaptations in a subset of participants from each sample using a single-pulse, transcranial magnetic stimulation (TMS) protocol. Separate samples of neurologically intact controls (n = 7) and individuals ≥4 months post stroke (n = 6) underwent 16 sessions of training. Following training, one-repetition maximum of the untrained wrist extensors in the control group and active range of motion of the untrained, paretic wrist extensors in the stroke group were significantly increased. No changes in corticospinal excitability, intracortical inhibition, or interhemispheric inhibition were observed in control participants. Both stroke participants who underwent TMS testing, however, exhibited increased voluntary muscle activation following the intervention. In addition, motor-evoked potentials that were unobtainable prior to the intervention were readily elicited afterwards in a stroke participant. Results of this study demonstrate that high-intensity resistance training of a non-paretic upper extremity muscle group can enhance voluntary muscle activation and force-generating capacity of a severely paretic muscle group after stroke. There is also preliminary evidence that corticospinal adaptations may accompany these gains.

Activation and intermuscular coherence of distal arm muscles during proximal muscle contraction.

In the human upper extremity (UE), unintended effects of proximal muscle activation on muscles controlling the hand could be an important aspect of motor control due to the necessary coordination of distal and proximal segments during functional activities. This study aimed to elucidate the effects of concurrent activation of elbow muscles on the coordination between hand muscles performing a grip task. Eleven healthy subjects performed precision grip tasks while a constant extension or flexion moment was applied to their elbow joints, inducing a sustained submaximal contraction of elbow muscles to counter the applied torque. Activation of four hand muscles was measured during each task condition using surface electromyography (EMG). When concurrent activation of elbow muscles was induced, significant changes in the activation levels of the hand muscles were observed, with greater effects on the extrinsic finger extensor (23.2 % increase under 30 % elbow extensor activation; p = 0.003) than extrinsic finger flexor (14.2 % increase under 30 % elbow flexor activation; p = 0.130). Elbow muscle activation also induced involuntary changes in the intrinsic thumb flexor activation (44.6 % increase under 30 % elbow extensor activation; p = 0.005). EMG-EMG coherence analyses revealed that elbow muscle activation significantly reduced intermuscular coherence between distal muscle pairs, with its greatest effects on coherence in the ß-band (13-25 Hz) (average of 17 % decrease under 30 % elbow flexor activation). The results of this study provide evidence for involuntary, muscle-specific interactions between distal and proximal UE muscles, which may contribute to UE motor performance in health and disease.

Cortical effects of repetitive finger flexion- vs. extension-resisted tracking movements: a TMS study.

While the cortical effects of repetitive motor activity are generally believed to be task specific, the task parameters that modulate these effects are incompletely understood. Since there are differences in the neural control of flexor vs. extensor muscles, the type of muscles involved in the motor task of interest may be one important parameter. In addition, the role each muscle plays in the task, such as whether or not it is the prime mover, is another potentially important task parameter. In the present study, use-dependent cortical plasticity was examined in healthy volunteers performing a robotic waveform tracking task with either the extensor digitorum communis (EDC) or flexor digitorum superficialis (FDS) acting as the prime mover. Transcranial magnetic stimulation was used to measure corticospinal excitability (CE) and short-interval intracortical inhibition of lower and higher threshold corticospinal neurons (SICI(L) and SICI(H), respectively) before and after a flexion- or extension-resisted finger tracking task. After repetitive performance of the tracking task, there was a significant decrease in SICI(L) targeting the EDC, while no change in CE targeting EDC was observed. In contrast, the reverse pattern was observed in the FDS: a significant increase in CE with no change in SICI(L). There was also a tendency toward increased SICI(H) targeting whichever muscle was acting as the prime mover, although this effect did not reach statistical significance. We conclude that there is a difference in patterns of use-dependent plasticity between extrinsic finger flexor and extensor muscles performing the same task.

Mechanisms of short-term training-induced reaching improvement in severely hemiparetic stroke patients: a TMS study.

BACKGROUND: The neurophysiological mechanisms underlying improved upper-extremity motor skills have been partially investigated in patients with good motor recovery but are poorly understood in more impaired individuals, the majority of stroke survivors. OBJECTIVE: The authors studied changes in primary motor cortex (M1) excitability (motor evoked potentials [MEPs], contralateral and ipsilateral silent periods [CSPs and ISPs] using transcranial magnetic stimulation [TMS]) associated with training-induced reaching improvement in stroke patients with severe arm paresis (n = 11; Upper-Extremity Fugl-Meyer score (F-M) = 27 ± 6). METHODS: All patients underwent a single session of reaching training focused on moving the affected hand from a resting site to a target placed at 80% of maximum forward reaching amplitude in response to a visual "GO" cue. Triceps contribute primarily as agonist and biceps primarily as antagonist to the trained forward reaching movement. Response times were recorded for each reaching movement. RESULTS: Preceding training (baseline), greater interhemispheric inhibition (measured by ISP) in the affected triceps muscle, reflecting inhibition from the nonlesioned to the lesioned M1, was observed in patients with lower F-M scores (more severe motor impairment). Training-induced improvements in reaching were greater in patients with slower response times at baseline. Increased MEP amplitudes and decreased ISPs and CSPs were observed in the affected triceps but not in the biceps muscle after training. CONCLUSION: These results indicate that along with training-induced motor improvements, training-specific modulation of intrahemispheric and interhemispheric mechanisms occurs after reaching practice in chronic stroke patients with substantial arm impairment.

Maximal voluntary isometric elbow flexion force during unilateral versus bilateral contractions in individuals with chronic stroke.

The purpose of this study was to determine whether the phenomenon of bilateral deficit in muscular force production observed in healthy subjects and mildly impaired stroke patients also exists in patients with more chronic and greater levels of stroke impairment. Ten patients with chronic hemiparesis resulting from stroke performed unilateral and bilateral maximal voluntary isometric contractions of the elbow flexors. When the total force produced by both arms was compared, 12% less force was produced in the bilateral compared with unilateral condition (p=0.01). However, studying the effect of task conditions on each arm separately revealed a significant decline in nonparetic (p=0.01) but not paretic elbow flexor force in the bilateral compared with unilateral condition. Results suggest that a significant bilateral force deficit exists in the nonparetic but not the paretic arm in individuals with chronic stroke. Bilateral task conditions do not seem to benefit or impair paretic arm maximal isometric force production in individuals with moderate-severity chronic stroke.

Interhemispheric inhibition in distal and proximal arm representations in the primary motor cortex.

Interhemispheric inhibitory interactions (IHI) operate between homologous distal hand representations in primary motor cortex (M1). It is not known whether proximal arm representations exhibit comparable effects on their homologous counterparts. We studied IHI in different arm representations, targeting triceps brachii (TB, n = 13), first dorsal interosseous (FDI, n = 13), and biceps brachii (BB, n = 7) muscles in healthy volunteers. Transcranial magnetic stimulation test stimuli (TS) were delivered to M1 contralateral to the target muscle preceded 10 ms by a conditioning stimulus (CS) to the opposite M1 at 110-150% resting motor threshold (RMT). IHI was calculated as the ratio between motor-evoked potential (MEP) amplitudes in conditioned relative to unconditioned trials. Mean RMTs were 38.9, 46.9, and 46.0% of stimulator output in FDI, TB, and BB muscles, respectively. IHI was 0.45 +/- 0.41 (FDI), 0.78 +/- 0.38 (TB), and 0.52 +/- 0.32 (BB, P < 0.01) when test MEP amplitudes were matched and 0.28 +/- 0.17 (FDI) and 0.85 +/- 0.31 (TB, P < 0.05) when TS intensities expressed as percentage RMT were matched. Significant IHI (P < 0.05) was identified with minimal CS intensities (expressed as percentage stimulator output) in the 30 s for FDI, 60 s for TB, and 40 s for BB. Additionally, a CS of roughly 120% RMT suppressed the test MEP but not a test H-reflex in BB, suggesting IHI observed in BB is likely mediated by a supraspinal mechanism. We conclude that IHI differs between different arm muscle representations, comparable between BB and FDI but lesser for TB. This finding suggests the amount of IHI between different arm representations does not strictly follow a proximal-to-distal gradient, but may be related to the role of each muscle in functional movement synergies.

Noninvasive cortical stimulation in neurorehabilitation: a review.

The purpose of this special communication is to provide an overview of noninvasive cortical stimulation techniques, the types of mechanistic information they can provide, and the ways their use is contributing to our understanding of current models of neurorehabilitation. The focus is primarily on studies using noninvasive cortical stimulation techniques in the human motor system. Noninvasive cortical stimulation techniques are useful tools in the field of neurorehabilitation that are being actively used to test proposed models of functional recovery after neurologic injury. They can provide insight into the physiologic mechanisms of functional recovery and are under investigation as a possible auxiliary intervention to modulate cortical excitability and enhance training effects.

Exploiting interlimb coupling to improve paretic arm reaching performance in people with chronic stroke.

OBJECTIVE: To determine whether paretic arm reaching performance is improved in bilateral compared with unilateral conditions. DESIGN: Cohort study. SETTING: University human performance laboratory. PARTICIPANTS: Thirty-two subjects with chronic stroke (57+/-14y; on Fugl-Meyer Assessment arm score, 37+/-14). INTERVENTION: Unilateral and bilateral reaching. Bilateral tasks included varying levels of weight on the nonparetic hand. MAIN OUTCOME MEASURES: An electromagnetic tracking system recorded hand peak acceleration, velocity, and movement time. A 2-way repeated-measures analysis of variance and Tukey-adjusted pairwise comparisons were used to analyze the results (alpha=.05). RESULTS: Paretic differed significantly from nonparetic peak acceleration and velocity in unilateral reaching but not bilateral reaching. Within limbs, the paretic arm attained a higher peak acceleration (P<.001) and velocity (P=.03) in the bilateral compared with the unilateral task, but movement time was unchanged between tasks. Nonparetic peak acceleration was higher (P=.015), velocity was unchanged, and movement time increased (P=.005) in the bilateral compared with the unilateral task. The addition of a weight to the nonparetic arm during bilateral reaching did not result in further improvement in paretic arm performance. CONCLUSIONS: Interlimb coupling effects during bilateral reaching are retained even after chronic stroke and can be used to produce an immediate improvement in paretic arm reaching performance.

Improved hemiparetic muscle activation in treadmill versus overground walking.

OBJECTIVE: Treadmill training is a promising tool for retraining gait after stroke. The treadmill induces an immediate shift toward symmetry and longer paretic stance times due to altered muscle activation (active) or the motorized belt (passive). The authors investigated vastus lateralis and medial hamstrings activation differences between treadmill and overground walking in participants with stroke. METHODS: Vastus lateralis and medial hamstrings surface electromyography was recorded during velocity-matched overground and treadmill walking in 19 chronically hemiparetic subjects. Variables from ensemble averages of electromyography included burst onset and offset times (% cycle), duration (% cycle), integrated amplitude (mV.% cycle), and onset relative to foot strike (% cycle). Conditions were compared using paired t-tests (alpha = 0.05). RESULTS: Paretic vastus lateralis onset occurred earlier in the treadmill condition (overground: 47.1%, treadmill: 41.9%, P = 0.01). For nonparetic vastus lateralis in the treadmill condition, onset occurred later (overground: 85.2%, treadmill: 87.6%, P = 0.09), offset occurred earlier (overground: 54.7%, treadmill: 47.8%, P = 0.03), duration was shorter (overground: 69.1%, treadmill: 61.2%, P = 0.01), and integrated amplitude was lower (overground: 14.1, treadmill: 10.6, P = 0.05). Within limbs, paretic vastus lateralis onset occurred earlier relative to paretic foot strike. Nonparetic vastus lateralis onset occurred later relative to nonparetic foot strike. CONCLUSIONS: Treadmill walking induces immediate changes in vastus lateralis, but not medial ham-strings, activation patterns. These alterations (earlier paretic vastus lateralis onset and later nonparetic vastus lateralis onset) during treadmill versus overground walking parallel the increased symmetry in gait patterning.