Expanding the repertoire of intermuscular coordination patterns and modulating intermuscular connectivity in stroke-affected upper extremity through electromyogram-guided training: a pilot study.

Abnormal intermuscular coordination is a major stroke-induced functional motor impairment in the upper extremity (UE). Previous studies have computationally identified the abnormalities in the intermuscular coordination in the stroke-affected UE and their negative impacts on motor outputs. Therefore, targeting the aberrant muscle synergies has the potential as an effective approach for stroke rehabilitation. Recently, we verified the modifiability of the naturally expressed muscle synergies of young able-bodied adults in UE through an electromyographic (EMG) signal-guided exercise protocol. This study tested if an EMG-guided exercise will induce new muscle synergies, alter the associated intermuscular connectivity, and improve UE motor outcome in stroke-affected UE with moderate-to-severe motor impairment. The study used the six-week isometric EMG signal-guided exercise protocol that focused on independently activating two specific muscles, the biceps and brachioradialis, to develop new muscle activation groups. The study found that both the stroke and age-matched, able-bodied groups were able to develop new muscle coordination patterns through the exercise while habitual muscle activation was still available, which led to improvements in the motor control of the trained arm. In addition, the results provided preliminary evidence of increased intermuscular connectivity between targeted muscles in the beta-band frequencies for stroke patients after training, suggesting a modulation of the common neural drive. These findings suggest that our isometric exercise protocol has the potential to improve stroke survivors' performance of UE in their activities in daily lives (ADLs) and, ultimately, their quality of life through expanding their repertoire of intermuscular coordination.Clinical Relevance- This study shows the feasibility of expanding the intermuscular coordination pattern in stroke-affected UE through an isometric EMG-guided exercise which positively affects task performance and intermuscular connectivity.

Developing new intermuscular coordination patterns through an electromyographic signal-guided training in the upper extremity.

BACKGROUND: Muscle synergies, computationally identified intermuscular coordination patterns, have been utilized to characterize neuromuscular control and learning in humans. However, it is unclear whether it is possible to alter the existing muscle synergies or develop new ones in an intended way through a relatively short-term motor exercise in adulthood. This study aimed to test the feasibility of expanding the repertoire of intermuscular coordination patterns through an isometric, electromyographic (EMG) signal-guided exercise in the upper extremity (UE) of neurologically intact individuals. METHODS: 10 participants were trained for six weeks to induce independent control of activating a pair of elbow flexor muscles that tended to be naturally co-activated in force generation. An untrained isometric force generation task was performed to assess the effect of the training on the intermuscular coordination of the trained UE. We applied a non-negative matrix factorization on the EMG signals recorded from 12 major UE muscles during the assessment to identify the muscle synergies. In addition, the performance of training tasks and the characteristics of individual muscles' activity in both time and frequency domains were quantified as the training outcomes. RESULTS: Typically, in two weeks of the training, participants could use newly developed muscle synergies when requested to perform new, untrained motor tasks by activating their UE muscles in the trained way. Meanwhile, their habitually expressed muscle synergies, the synergistic muscle activation groups that were used before the training, were conserved throughout the entire training period. The number of muscle synergies activated for the task performance remained the same. As the new muscle synergies were developed, the neuromotor control of the trained muscles reflected in the metrics, such as the ratio between the targeted muscles, number of matched targets, and task completion time, was improved. CONCLUSION: These findings suggest that our protocol can increase the repertoire of readily available muscle synergies and improve motor control by developing the activation of new muscle coordination patterns in healthy adults within a relatively short period. Furthermore, the study shows the potential of the isometric EMG-guided protocol as a neurorehabilitation tool for aiming motor deficits induced by abnormal intermuscular coordination after neurological disorders. TRIAL REGISTRATION: This study was registered at the Clinical Research Information Service (CRiS) of the Korea National Institute of Health (KCT0005803) on 1/22/2021.

Alterations in motor modules and their contribution to limitations in force control in the upper extremity after stroke.

The generation of isometric force at the hand can be mediated by activating a few motor modules. Stroke induces alterations in motor modules underlying steady-state isometric force generation in the human upper extremity (UE). However, how the altered motor modules impact task performance (force production) remains unclear as stroke survivors develop and converge to the three-dimensional (3D) target force. Thus, we tested whether stroke-specific motor modules would be activated from the onset of force generation and also examined how alterations in motor modules would induce changes in force representation. During 3D isometric force development, electromyographic (EMG) signals were recorded from eight major elbow and shoulder muscles in the paretic arm of 10 chronic hemispheric stroke survivors and both arms of six age-matched control participants. A non-negative matrix factorization algorithm identified motor modules in four different time windows: three "exploratory" force ramping phases (Ramps 1-3; 0-33%, 33-67%, and 67-100% of target force magnitude, respectively) and the stable force match phase (Hold). Motor module similarity and between-force coupling were examined by calculating the scalar product and Pearson correlation across the phases. To investigate the association between the end-point force representation and the activation of the motor modules, principal component analysis (PCA) and multivariate multiple linear regression analyses were applied. In addition, the force components regressed on the activation profiles of motor modules were utilized to model the feasible force direction. Both stroke and control groups developed exploratory isometric forces with a non-linear relationship between EMG and force. During the force matching, only the stroke group showed abnormal between-force coupling in medial-lateral and backward-forward and medial-lateral and downward-upward directions. In each group, the same motor modules, including the abnormal deltoid module in stroke survivors, were expressed from the beginning of force development instead of emerging during the force exploration. The PCA and the multivariate multiple linear regression analyses showed that alterations in motor modules were associated with abnormal between-force coupling and limited feasible force direction after stroke. Overall, these results suggest that alterations in intermuscular coordination contribute to the abnormal end-point force control under isometric conditions in the UE after stroke.

Myoelectric interface training enables targeted reduction in abnormal muscle co-activation.

BACKGROUND: Abnormal patterns of muscle co-activation contribute to impaired movement after stroke. Previously, we developed a myoelectric computer interface (MyoCI) training paradigm to improve stroke-induced arm motor impairment by reducing the abnormal co-activation of arm muscle pairs. However, it is unclear to what extent the paradigm induced changes in the overall intermuscular coordination in the arm, as opposed to changing just the muscles trained with the MyoCI. This study examined the intermuscular coordination patterns of thirty-two stroke survivors who participated in 6 weeks of MyoCI training. METHODS: We used non-negative matrix factorization to identify the arm muscle synergies (coordinated patterns of muscle activity) during a reaching task before and after the training. We examined the extent to which synergies changed as the training reduced motor impairment. In addition, we introduced a new synergy analysis metric, disparity index (DI), to capture the changes in the individual muscle weights within a synergy. RESULTS: There was no consistent pattern of change in the number of synergies across the subjects after the training. The composition of muscle synergies, calculated using a traditional synergy similarity metric, also did not change after the training. However, the disparity of muscle weights within synergies increased after the training in the participants who responded to MyoCI training-that is, the specific muscles that the MyoCI was targeting became less correlated within a synergy. This trend was not observed in participants who did not respond to the training. CONCLUSIONS: These findings suggest that MyoCI training reduced arm impairment by decoupling only the muscles trained while leaving other muscles relatively unaffected. This suggests that, even after injury, the nervous system is capable of motor learning on a highly fractionated level. It also suggests that MyoCI training can do what it was designed to do-enable stroke survivors to reduce abnormal co-activation in targeted muscles. Trial registration This study was registered at ClinicalTrials.gov (NCT03579992, Registered 09 July 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03579992?term=NCT03579992&draw=2&rank=1 ).

Feasibility of inducing new intermuscular coordination patterns through an electromyographic signal-guided training in the upper extremity: a pilot study.

Abnormal intermuscular coordination has been highlighted in the field of post-stroke upper extremity (UE) rehabilitation. Relatively recent studies have quantified the altered "muscle synergies", distinctive co-activation patterns of a group of muscles, which characterize the stroke-induced abnormal intermuscular coordination. Nonetheless, whether targeting the altered muscle synergy(ies) would ameliorate the stroke-induced motor impairment and improve motor function remains unknown. Our ultimate aim is to design an exercise protocol that modifies abnormal muscle synergies and improves motor function in UE after stroke. In this study, the feasibility of an electromyographic (EMG) signal-guided exercise protocol, which targeted the alteration of an elbow flexor synergy, was tested in healthy subjects. Four neurologically intact adults participated in a six-week isometric exercise to activate two major elbow flexor muscles, biceps and brachioradialis, in isolation. Participants performed an isometric reaching in a virtual three-dimensional (3D) force space to assess any potential changes in muscle synergies during the assessment at week zero, two, four, and six of the training. EMGs of 12 UE muscles and 3D forces were collected simultaneously. A non-negative matrix factorization (NMF) was applied to the EMGs to identify synergies. From the third-to-fourth week of the training, when the participants intended to use the newly learned motor skill, they were able to activate the targeted muscle pair in isolation and induce the formation of newly emerging synergistic muscle groups. As the participants practiced to expand their repertoire of intermuscular coordination patterns, their motor control of the trained UE was improved. These findings suggest that our isometric exercise protocol can potentially modulate impaired muscle coordination in a way that benefits stroke survivor's performance in activities of daily living (ADLs) and, eventually, their quality of life.

Broad nucleotide cofactor specificity of DNA ligase from the hyperthermophilic crenarchaeon Hyperthermus butylicus and its evolutionary significance.

The nucleotide cofactor specificity of the DNA ligase from the hyperthermophilic crenarchaeon Hyperthermus butylicus (Hbu) was studied to investigate the evolutionary relationship of DNA ligases. The Hbu DNA ligase gene was expressed under control of the T7lac promoter of pTARG in Escherichia coli BL21-CodonPlus(DE3)-RIL. The expressed enzyme was purified using the IMPACT™-CN system (intein-mediated purification with an affinity chitin-binding tag) and cation-ion (Arg-tag) chromatography. The optimal temperature for Hbu DNA ligase activity was 75 °C, and the optimal pH was 8.0 in Tris-HCl. The activity was highly dependent on MgCl2 or MnCl2 with maximal activity above 5 mM MgCl2 and 2 mM MnCl2. Notably, Hbu DNA ligase can use ADP and GTP in addition to ATP. The broad nucleotide cofactor specificity of Hbu DNA ligase might exemplify an undifferentiated ancestral stage in the evolution of DNA ligases. This study provides new evidence for possible evolutionary relationships among DNA ligases.