Test-Retest reliability and measurement error of the uncontrolled manifold analysis: A step towards the clinical translation.

The uncontrolled manifold (UCM) analysis has gained broad application in biomechanics and neuroscience for investigating the structure of motor variability in functional tasks. The UCM utilizes inter-trial analysis to partition the variance of elemental variables (e.g., finger forces, joint angles) that affect (VORT) and do not affect (VUCM) a performance variable (e.g., total force, end-effector position). However, to facilitate the translation of UCM into clinical settings, it is crucial to demonstrate the reliability of UCM estimates: VORT, VUCM, and their normalized difference, ΔV. This study aimed to determine the test-retest reliability using the intraclass correlation coefficient (ICC3,K), Bland-Altman plots, the standard error of measurement (SEM), and the minimal detectable change (MDC) of UCM estimate. Fifteen healthy individuals (24.8 ± 1.2 yrs old) performed a finger coordination task, with sessions separated by one hour, one day, and one week. Excellent reliability was found for VORT (ICC3,K = 0.97) and VUCM (ICC3,K = 0.92), whereas good reliability was observed for ΔV (ICC3,K = 0.84). Bland-Altman plots reveled no systematic differences. SEM% values were 24.57 %, 26.80 % and 12.49 % for VORT, VUCM and ΔV respectively, while the normalized MDC% values were 68.12 %, 74.30 % and 34.61 % for VORT, VUCM and ΔV respectively. Our results support the use of UCM as a reliable method for investigating the structure of movement variability. The excellent measurement properties make the UCM a promising tool for tracking changes in motor behavior over time (i.e., effects of interventions in prospective studies).

Brain-computer interface combined with mental practice and occupational therapy enhances upper limb motor recovery, activities of daily living, and participation in subacute stroke.

Background: We investigated the effects of brain-computer interface (BCI) combined with mental practice (MP) and occupational therapy (OT) on performance in activities of daily living (ADL) in stroke survivors. Methods: Participants were randomized into two groups: experimental (n = 23, BCI controlling a hand exoskeleton combined with MP and OT) and control (n = 21, OT). Subjects were assessed with the functional independence measure (FIM), motor activity log (MAL), amount of use (MAL-AOM), and quality of movement (MAL-QOM). The box and blocks test (BBT) and the Jebsen hand functional test (JHFT) were used for the primary outcome of performance in ADL, while the Fugl-Meyer Assessment was used for the secondary outcome. Exoskeleton activation and the degree of motor imagery (measured as event-related desynchronization) were assessed in the experimental group. For the BCI, the EEG electrodes were placed on the regions of FC3, C3, CP3, FC4, C4, and CP4, according to the international 10-20 EEG system. The exoskeleton was placed on the affected hand. MP was based on functional tasks. OT consisted of ADL training, muscle mobilization, reaching tasks, manipulation and prehension, mirror therapy, and high-frequency therapeutic vibration. The protocol lasted 1 h, five times a week, for 2 weeks. Results: There was a difference between baseline and post-intervention analysis for the experimental group in all evaluations: FIM (p = 0.001, d = 0.56), MAL-AOM (p = 0.001, d = 0.83), MAL-QOM (p = 0.006, d = 0.84), BBT (p = 0.004, d = 0.40), and JHFT (p = 0.001, d = 0.45). Within the experimental group, post-intervention improvements were detected in the degree of motor imagery (p < 0.001) and the amount of exoskeleton activations (p < 0.001). For the control group, differences were detected for MAL-AOM (p = 0.001, d = 0.72), MAL-QOM (p = 0.013, d = 0.50), and BBT (p = 0.005, d = 0.23). Notably, the effect sizes were larger for the experimental group. No differences were detected between groups at post-intervention. Conclusion: BCI combined with MP and OT is a promising tool for promoting sensorimotor recovery of the upper limb and functional independence in subacute post-stroke survivors.

Movement Quality: A Novel Biomarker Based on Principles of Neuroscience.

A major problem in neurorehabilitation is the lack of objective outcomes to measure movement quality. Movement quality features, such as coordination and stability, are essential for everyday motor actions. These features allow reacting to continuously changing environment or to resist external perturbations. Neurological disorders affect movement quality, leading to functionally impaired movements. Recent findings suggest that the central nervous system organizes motor elements (eg, muscles, joints, fingers) into task-specific ensembles to stabilize motor tasks performance. A method to quantify this feature has been previously developed based on the uncontrolled manifold (UCM) hypothesis. UCM quantifies movement quality in a spatial-temporal domain using intertrial analysis of covariation between motor elements. In this point-of-view article, we first describe major obstacles (eg, the need for group analysis) that interfere with UCM application in clinical settings. Then, we propose a process of quantifying movement quality for a single individual with a novel use of bootstrapping simulations and UCM analysis. Finally, we reanalyze previously published data from individuals with neurological disorders performing a wide range of motor tasks, that is, multi-digit pressing and postural balance tasks. Our method allows one to assess motor quality impairments in a single individual and to detect clinically important motor behavior changes. Our solution may be incorporated into a clinical setting to assess sensorimotor impairments, evaluate the effects of specific neurological treatments, or track movement quality recovery over time. We also recommended the proposed solution to be used jointly with a typical statistical analysis of UCM parameters in cohort studies.

Effects of Fencing Training on Motor Performance and Asymmetry Vary With Handedness.

Previous studies showed that motor asymmetries are reduced in left-handers and after a long-term fencing training in right-handers. Interestingly, left-handed athletes are substantially over-represented in elite fencing. These findings have been speculatively explained by imbalance in experience of fighting opposite handedness opponents resulted from skewed distribution of handedness, i.e. lefties encounter more righties than righties encounter lefties. Whereas these assumptions could be accurate, the underlying mechanisms remain ambiguous. In this study, we investigated effects of fencing training on motor performance and asymmetry with respect to handedness. We compared fencing performance of left- and right-handed fencers in both training and combat conditions. In the combat condition, left-handers won seven out of twelve matches consisted of twelve bouts each. They also showed a significantly longer hit detection time, a measure indicating better quality of fencing attack. In the training condition, left-handed fencers completed fencing board tests significantly faster than right-handers. These findings provide additional factor of superior motor performance to be considered when interpreting over-representation of lefties in elite fencing. Furthermore, our left-handers were less lateralized, which could explain that superior motor performance. This idea is consistent with previous findings of reduced asymmetry in right-handed fencers when comparing to non-athletes.

Sloppy, But Acceptable, Control of Biological Movement: Algorithm-Based Stabilization of Subspaces in Abundant Spaces.

In this paper, we develop an algorithm-based approach to the problem of stability of salient performance variables during motor actions. This problem is reformulated as stabilizing subspaces within high-dimensional spaces of elemental variables. Our main idea is that the central nervous system does not solve such problems precisely, but uses simple rules that achieve success with sufficiently high probability. Such rules can be applied even if the central nervous system has no knowledge of the mapping between small changes in elemental variables and changes in performance. We start with a rule "Act on the most nimble" (the AMN-rule), when changes in the local feedback-based loops occur for the most unstable variable first. This rule is implemented in a task-specific coordinate system that facilitates local control. Further, we develop and supplement the AMN-rule to improve the success rate. Predictions of implementation of such algorithms are compared with the results of experiments performed on the human hand with both visual and mechanical perturbations. We conclude that physical, including neural, processes associated with everyday motor actions can be adequately represented with a set of simple algorithms leading to sloppy, but satisfactory, solutions. Finally, we discuss implications of this scheme for motor learning and motor disorders.

Synergies and Motor Equivalence in Voluntary Sway Tasks: The Effects of Visual and Mechanical Constraints.

The authors used two analyses developed within the framework of the uncontrolled manifold hypothesis to quantify multimuscle synergies during voluntary body sway: analysis of intertrial variance and analysis of motor equivalence with respect to the center of pressure (COP) trajectory. Participants performed voluntary sway tasks in the anteroposterior direction at 0.33 and 0.66 Hz. Muscle groups were identified in the space of muscle activations and used as elemental variables in the synergy analyses. Changing mechanical and vision feedback-based constraints led to significant changes in indices of sway performance such as COP deviations in the uninstructed, mediolateral direction and indices of spontaneous postural sway. In contrast, there were no significant effects on synergy indices. These findings show that the neural control of performance and of its stability may involve different control variables and neurophysiological structures. There were strong correlations between the indices of motor equivalence and those computed using the intercycle variance analysis. This result is potentially important for studies of patients with movement disorders who may be unable to perform multiple trials (cycles) at any given task, making analysis of motor equivalence of single trials a viable alternative to explore changes in stability of actions.

A method for measuring manual position control.

There is no generally accepted method for measuring manual position control. We developed a method for doing so. We asked university students to hold a handle that had one rotational degree of freedom. The angular position of the handle depended on the degree of pronation-supination of the forearm. The subjects' task was to hold the handle as steadily as possible to keep a needle positioned in a pie-shaped target zone on a computer screen. If the needle remained in the zone for 0.5s, the gain of the feedback loop increased; otherwise the gain decreased or remained at the starting value of 1. Through this adaptive procedure, we estimated the maximum gain that could be achieved at each of the four pronation-supination angles we tested (thumb up, thumb down, thumb in, and thumb out) for each hand. Consistent with previous research on manual control, and so validating our measure, we found that our participants, all of whom were right-handed, were better able to maintain the needle in the target zone when they used the right hand than when they used the left hand and when they used midrange wrist postures (thumb up or in) rather than extreme wrist postures (thumb down or out). The method provides a valid test of manual position control and holds promise for addressing basic-research and practical questions.

Unintentional drifts during quiet stance and voluntary body sway.

We explored unintentional drifts in voluntary whole-body sway tasks following the removal of visual feedback. The main hypothesis was that the unintentional drifts were produced by drifts of referent coordinates for salient performance variables. Young healthy subjects stood quietly on a force platform and also performed voluntary body sway at 0.5 Hz both in the anterio-posterior and medio-lateral directions. Visual feedback on the center of pressure (COP) coordinate was provided and then turned off. During quiet stance trials, the subjects matched the initial COP coordinate with a target shifted by 3 cm anterior, posterior, left, or right from the coordinate during natural standing and activated the right tibialis anterior to 30% of its maximal voluntary contraction. During cyclical voluntary sway task, the nominal sway amplitude was always 4 cm while the midpoint was at one of the four mentioned locations. Removing visual feedback caused COP drifts during quiet stance trials that were consistent across trials performed by a subject but could be in opposite directions across subjects; there was a consistent drop in the activation level of tibialis anterior. During voluntary body sway, removing visual feedback caused a consistent increase in the voluntary sway amplitude and a drift of the midpoint that was consistent within but not across subjects. Motor equivalent and non-motor equivalent inter-cycle motion components were quantified within the space of muscle groups (muscle modes) under visual feedback and at the end of the period without visual feedback. Throughout the trial, there were large motor equivalent motion components, and they increased over the period without visual feedback. The results corroborate the idea that referent coordinate drifts at different levels of the control hierarchy can lead to unintentional drifts in performance. It suggests that directions of COP drifts are defined by two main factors, drift of the body referent coordinate toward the actual coordinate (that can lead to fall) and an opposite drift to ensure body motion to a safer location. Analysis of motor equivalence suggests that postural stability is not compromised during unintentional drifts in performance in contrast to earlier studies of multi-finger tasks. This may be due to the vital importance of postural stability for everyday actions.

Effects of visual feedback and memory on unintentional drifts in performance during finger-pressing tasks.

This study tested two hypotheses on the nature of unintentional force drifts elicited by removing visual feedback during accurate force production tasks. The role of working memory (memory hypothesis) was explored in tasks with continuous force production, intermittent force production, and rest intervals over the same time interval. The assumption of unintentional drifts in referent coordinate for the fingertips was tested using manipulations of visual feedback: young healthy subjects performed accurate steady-state force production tasks by pressing with the two index fingers on individual force sensors with visual feedback on the total force, sharing ratio, both, or none. Predictions based on the memory hypothesis have been falsified. In particular, we observed consistent force drifts to lower force values during continuous force production trials only. No force drift or drifts to higher forces were observed during intermittent force production trials and following rest intervals. The hypotheses based on the idea of drifts in referent finger coordinates have been confirmed. In particular, we observed superposition of two drift processes: a drift of total force to lower magnitudes and a drift of the sharing ratio to 50:50. When visual feedback on total force only was provided, the two-finger forces showed drifts in opposite directions. We interpret the findings as evidence for the control of motor actions with changes in referent coordinates for participating effectors. Unintentional drifts in performance are viewed as natural relaxation processes in the involved systems; their typical time reflects stability in the direction of the drift. The magnitude of the drift was higher in the right (dominant) hand, which is consistent with the dynamic dominance hypothesis.

Anticipatory postural adjustments and anticipatory synergy adjustments: preparing to a postural perturbation with predictable and unpredictable direction.

We explored two aspects of feed-forward postural control, anticipatory postural adjustments (APAs) and anticipatory synergy adjustments (ASAs) seen prior to self-triggered unloading with known and unknown direction of the perturbation. In particular, we tested two main hypotheses predicting contrasting changes in APAs and ASAs. The first hypothesis predicted no major changes in ASAs. The second hypothesis predicted delayed APAs with predominance of co-contraction patterns when perturbation direction was unknown. Healthy subjects stood on the force plate and held a bar with two loads acting in the forward and backward directions. They pressed a trigger that released one of the loads causing a postural perturbation. In different series, the direction of the perturbation was either known (the same load released in all trials) or unknown (the subjects did not know which of the two loads would be released). Surface electromyograms were recorded and used to quantify APAs, synergies stabilizing center of pressure coordinate (within the uncontrolled manifold hypothesis), and ASA. APAs and ASAs were seen in all conditions. APAs were delayed, and predominance of co-contraction patterns was seen under the conditions with unpredictable direction of perturbation. In contrast, no significant changes in synergies and ASAs were seen. Overall, these results show that feed-forward control of vertical posture has two distinct components, reflected in APAs and ASAs, which show qualitatively different adjustments with changes in predictability of the direction of perturbation. These results are interpreted within the recently proposed hierarchical scheme of the synergic control of motor tasks. The observations underscore the complexity of the feed-forward postural control, which involves separate changes in salient performance variables (such as coordinate of the center of pressure) and in their stability properties.

Interpersonal synergies: static prehension tasks performed by two actors.

We investigated multidigit synergies stabilizing components of the resultant force vector during joint performance of a static prehension task by two persons as compared to similar tasks performed by a single person using both hands. Subjects transferred the instrumented handle from the right hand to the left hand (one-person condition) or passed that handle to another person (two-person condition) while keeping the handle's position and orientation stationary. Only three digits were involved per hand, the thumb, the index finger, and the middle finger; the forces and moments produced by the digits were measured by six-component sensors. We estimated the performance-stabilizing synergies within the uncontrolled manifold framework by quantifying the intertrial variance structure of digit forces and moments. The analysis was performed at three levels: between hands, between virtual finger and virtual thumb (imagined digits producing the same mechanical variables as the corresponding actual digits combined) produced by the two hands (in both interpersonal and intrapersonal conditions), and between the thumb and virtual finger for one hand only. Additionally, we performed correlation and phase synchronization analyses of resultant tangential forces and internal normal forces. Overall, the one-person conditions were characterized by higher amount of intertrial variance that did not affect resultant normal force components, higher internal components of normal forces, and stronger synchronization of the normal forces generated by the hands. Our observations suggest that in two-person tasks, when participants try to achieve a common mechanical outcome, the performance-stabilizing synergies depend on non-visual information exchange, possibly via the haptic and proprioceptive systems. Therefore, synergies quantified in tasks using visual feedback only may not be generalizable to more natural tasks.

Mirror Training Augments the Cross-education of Strength and Affects Inhibitory Paths.

PURPOSE: Unilateral strength training strengthens not only the muscles on the trained side but also the homologous muscles on the untrained side; however, the magnitude of this interlimb cross-education is modest. We tested the hypothesis that heightened sensory feedback by mirror viewing the exercising hand would augment cross education by modulating neuronal excitability. METHODS: Healthy adults were randomized into a mirror training group (MG, N = 11) and a no-mirror training group (NMG, N = 12) and performed 640 shortening muscle contractions of the right wrist flexors at 80% maximum voluntary contraction (MVC) during 15 sessions for 3 wk. Maximal strength and specific transcranial magnetic stimulation metrics of neuronal excitability, measured in the mirror and no-mirror setup at rest and during unilateral contractions at 60% MVC, were assessed before and after the strength intervention. RESULTS: Trained wrist flexor MVC increased 72% across groups, whereas cross-education was higher for the MG (61%) than NMG (34%, P = 0.047). The MG showed a reduction (15%-16%) in the contralateral silent period duration measured from the contracting left-untrained flexor carpi radialis, whereas the NMG showed an increase (12%, P ≤ 0.030). Interhemispheric inhibition, measured from the trained to the untrained primary motor cortex, increased in the MG (11%) but decreased in the NMG (15%) when measured in the mirror setup at rest (P = 0.048). Other transcranial magnetic stimulation measures did not change. CONCLUSION: Viewing the exercising hand in a mirror can augment the cross-education effect. The use of a mirror in future studies can potentially accelerate functional recovery from unilateral impairment due to stroke or upper limb fracture.

Force-stabilizing synergies in motor tasks involving two actors.

We investigated the ability of two persons to produce force-stabilizing synergies in accurate multi-finger force production tasks under visual feedback on the total force only. The subjects produced a time profile of total force (the sum of two hand forces in one-person tasks and the sum of two subject forces in two-person tasks) consisting of a ramp-up, steady-state, and ramp-down segments; the steady-state segment was interrupted in the middle by a quick force pulse. Analyses of the structure of inter-trial finger force variance, motor equivalence, anticipatory synergy adjustments (ASAs), and the unintentional drift of the sharing pattern were performed. The two-person performance was characterized by a dramatically higher amount of inter-trial variance that did not affect total force, higher finger force deviations that did not affect total force (motor equivalent deviations), shorter ASAs, and larger drift of the sharing pattern. The rate of sharing pattern drift correlated with the initial disparity between the forces produced by the two persons (or two hands). The drift accelerated following the quick force pulse. Our observations show that sensory information on the task-specific performance variable is sufficient for the organization of performance-stabilizing synergies. They suggest, however, that two actors are less likely to follow a single optimization criterion as compared to a single performer. The presence of ASAs in the two-person condition might reflect fidgeting by one or both of the subjects. We discuss the characteristics of the drift in the sharing pattern as reflections of different characteristic times of motion within the subspaces that affect and do not affect salient performance variables.

Unintentional movements produced by back-coupling between the actual and referent body configurations: violations of equifinality in multi-joint positional tasks.

We tested several predictions of a recent theory that combines the ideas of control with referent configurations, hierarchical control, and the uncontrolled manifold (UCM) hypothesis. In particular, we tested a hypothesis that unintentional changes in hand coordinate can happen following a long-lasting transient perturbation. The subjects grasped a handle with the right hand, occupied an initial position against a bias force produced by the HapticMaster robot, and then tried not to react to changes in the robot-produced force. Changes in the force were smooth and transient; they always ended with the same force as the bias force. The force-change amplitude and the time the force was kept at the new level (dwell time) varied across conditions. After the transient force change was over, the handle rested in a position that differed significantly from the initial position. The amplitude of this unintentional movement increased with the amplitude of transient force change and with the dwell time. In the new position, the across-trials joint configuration variance was mostly confined to a subspace compatible with the average handle coordinate and orientation (the UCMs for these variables). We view these results as the first experimental support for the hypothesis on back-coupling between the referent and actual body configurations during multi-joint actions. The results suggest that even under the instruction "not to react to transient force changes," the subjects may be unable to prevent unintentional drift of the referent configuration. The structure of joint configuration variance after such movements was similar to that in earlier reports on joint configuration variance after intentional movements. We conclude that the intentional and unintentional movements are products of a single neural system that can lead to intentional and unintentional shifts of the referent body configuration.

Postural sway and perceived comfort in pointing tasks.

In this study, we explored relations between indices of postural sway and perceived comfort during pointing postures performed by standing participants. The participants stood on a force plate, grasped a pointer with the dominant (right) hand, and pointed to targets located at four positions and at two distances from the body. We quantified postural sway over 60-s intervals at each pointing posture, and found no effects of target location or distance on postural sway indices. In contrast, comfort ratings correlated significantly with indices of one of the sway components, trembling. Our observations support the hypothesis that rambling and trembling sway components involve different neurophysiological mechanisms. They also suggest that subjective perception of comfort may be more important than the actual posture for postural sway.

Equifinality and its violations in a redundant system: control with referent configurations in a multi-joint positional task.

We tested a prediction that equifinality at the task level may be accompanied by violations of equifinality within the redundant set of elemental variables. Seated subjects grasped a handle, and occupied an initial arm configuration against a bias force produced by a robot. The robot applied a smooth, transient change in the force (perturbation). The subjects were instructed "not to intervene voluntarily" with hand deviations. After the robot force returned to the bias value, the hand returned close to the original position and orientation. Analysis of across-trials variance in the joint configuration space confirmed that most variance of the difference between the initial and final states was compatible with unchanged values of both hand position and orientation. These results provide direct support for the theoretical scheme that combines the ideas of synergies and control with referent configurations.

Internal forces during static prehension: effects of age and grasp configuration.

The authors studied effects of healthy aging on 3 components of the internal force vector during static prehensile tasks. Young and older subjects held an instrumented handle using a 5-digit prismatic grasp under different digit configurations and external torques. Across digit configurations, older subjects showed larger internal normal (grip) and tangential (load-resisting) digit force components and larger internal moment of force. In contrast to earlier reports, safety margin values were not higher in the older subjects. The results show that the increased grip force in older persons is a specific example of a more general age-related problem reflected in the generation of large internal force vectors in prehensile tasks. It is possible that the higher internal forces increase the apparent stiffness of the hand+handle system and, hence, contribute to its stability. This strategy, however, may be maladaptive, energetically wasteful, and inefficient in ensuring safety of hand-held objects.

End-state comfort and joint configuration variance during reaching.

This study joined two approaches to motor control. The first approach comes from cognitive psychology and is based on the idea that goal postures and movements are chosen to satisfy task-specific constraints. The second approach comes from the principle of motor abundance and is based on the idea that control of apparently redundant systems is associated with the creation of multi-element synergies stabilizing important performance variables. The first approach has been tested by relying on psychophysical ratings of comfort. The second approach has been tested by estimating variance along different directions in the space of elemental variables such as joint postures. The two approaches were joined here. Standing subjects performed series of movements in which they brought a hand-held pointer to each of four targets oriented within a frontal plane, close to or far from the body. The subjects were asked to rate the comfort of the final postures, and the variance of their joint configurations during the steady state following pointing was quantified with respect to pointer endpoint position and pointer orientation. The subjects showed consistent patterns of comfort ratings among the targets, and all movements were characterized by multi-joint synergies stabilizing both pointer endpoint position and orientation. Contrary to what was expected, less comfortable postures had higher joint configuration variance than did more comfortable postures without major changes in the synergy indices. Multi-joint synergies stabilized the pointer position and orientation similarly across a range of comfortable/uncomfortable postures. The results are interpreted in terms conducive to the two theoretical frameworks underlying this work, one focusing on comfort ratings reflecting mean postures adopted for different targets and the other focusing on indices of joint configuration variance.

Association between muscle activation and metabolic cost of walking in young and old adults.

BACKGROUND: The net metabolic cost of walking (C(w)) as well as the level of neural activation of agonist and antagonist leg muscles are higher in healthy old compared with young adults. This study examined the association between C(w) and agonist muscle activity and antagonist coactivity in young and old adults. METHODS: Young and old adults walked at 0.98 m/s on a treadmill set at 6% decline, level, and 6% incline, while C(w) and neural activation of leg muscles were measured. RESULTS: C(w) was 7.0% (incline), 19.2% (level), and 47.3% (decline) higher in old adults (overall 18.3%). Old (67.1%) versus young (40.1%) adults activated their leg muscles 67.3% more during the gait tasks and had 152.8% higher antagonist muscle coactivation (old: 67.1%, young: 19.9%). Agonist muscle activation was unrelated to C(w) on incline, but it explained up to 42% (level), 48% (decline), and 70% (three tasks combined) of variance in C(w). Antagonist coactivation accounted for up to 41% (incline), 45% (level), 59% (decline), 39% (three tasks combined) of variance in C(w). CONCLUSIONS: Age-related adaptations in the recruitment pattern of leg muscles during gait significantly contribute to the high C(w) in old adults. Clinical interventions optimizing the neural control of leg muscles during gait could reduce C(w) consequently the relative effort needed for exercise and activities of daily living in old adults.

Ipsilateral motor cortical responses to TMS during lengthening and shortening of the contralateral wrist flexors.

Unilateral lengthening contractions provide a greater stimulus for neuromuscular adaptation than shortening contractions in the active and non-active contralateral homologous muscle, although little is known of the potential mechanism. Here we examined the possibility that corticospinal and spinal excitability vary in a contraction-specific manner in the relaxed right flexor carpi radialis (FCR) when humans perform unilateral lengthening and shortening contractions of the left wrist flexors at the same absolute force. Corticospinal excitability in the relaxed right FCR increased more during lengthening than shortening at 80% and 100% of maximum voluntary contraction (MVC). Short-interval intracortical inhibition diminished during shortening contractions, and it became nearly abolished during lengthening. Intracortical facilitation lessened during shortening but increased during lengthening. Interhemispheric inhibition to the 'non-active' motor cortex diminished during shortening, and became nearly abolished during lengthening at 90% MVC. The amplitude of the Hoffman reflex in the relaxed right FCR decreased during and remained depressed for 20 s after lengthening and shortening of the left wrist flexors. We discuss the possibility that instead of the increased afferent input, differences in the descending motor command and activation of brain areas that link function of the motor cortices during muscle lengthening vs. shortening may cause the contraction-specific modulation of ipsilateral motor cortical output. In conclusion, ipsilateral motor cortex responses to transcranial magnetic stimulation are contraction-specific; unilateral lengthening and shortening contractions reduced contralateral spinal excitability, but uniquely modulated ipsilateral corticospinal excitability and the networks involved in intracortical and interhemispheric connections, which may have clinical implications.