Loss Of Independent Joint Control Research Articles

Manipulating abnormal synergistic coupling of joint torques through force applications at the Hand: A Simulation-Based study

Loss of independent joint control due to abnormal coupling of shoulder and elbow torques (i.e., abnormal synergies) is a common impairment after stroke and has been linked to poor upper-extremity function in stroke survivors. Previous research has shown that the flexor synergy (i.e., shoulder abduction coupled with elbow flexion) can be treated by progressively increasing shoulder abduction loading during elbow extension exercises. However, this finding has not been implemented in planar reaching exercises, as this requires a clear understanding of the relationship between external forces on the hand and elicited joint torques when reaching for different targets on a table. The objective of this study was to model this relationship and determine reach/force combinations that could be used to counteract either the flexor or extensor synergies. We used a musculoskeletal model to compute shoulder and elbow joint torques when reaching for targets on a table against different force directions and magnitudes. We found that force direction modulated the coupling of shoulder and elbow torques and force magnitude scaled each torque uniformly such that the extent of coupling remained the same. Additionally, we found that forces on the hand could be used to gradually increase the magnitude of simultaneous shoulder and elbow torques that counteract either the flexor or extensor synergy. These results provide the foundation to develop therapeutic interventions that address abnormal joint couplings following stroke using forces on the hand during planar reaching. Future studies should examine the therapeutic benefits of these findings in patient populations such as stroke.

Assessing the Usage of Indirect Motor Pathways Following a Hemiparetic Stroke.

A hallmark impairment in a hemiparetic stroke is a loss of independent joint control resulting in abnormal co-activation of shoulder abductor and elbow flexor muscles in their paretic arm, clinically known as the flexion synergy. The flexion synergy appears while generating shoulder abduction (SABD) torques as lifting the paretic arm. This likely be caused by an increased reliance on contralesional indirect motor pathways following damage to direct corticospinal projections. The assessment of functional connectivity between brain and muscle signals, i.e., brain-muscle connectivity (BMC), may provide insight into such changes to the usage of motor pathways. Our previous model simulation shows that multi-synaptic connections along the indirect motor pathway can generate nonlinear connectivity. We hypothesize that increased usage of indirect motor pathways (as increasing SABD load) will lead to an increase of nonlinear BMC. To test this hypothesis, we measured brain activity, muscle activity from shoulder abductors when stroke participants generate 20% and 40% of maximum SABD torque with their paretic arm. We computed both linear and nonlinear BMC between EEG and EMG. We found dominant nonlinear BMC at contralesional/ipsilateral hemisphere for stroke, whose magnitude increased with the SABD load. These results supported our hypothesis and indicated that nonlinear BMC could provide a quantitative indicator for determining the usage of indirect motor pathways following a hemiparetic stroke.

A Method to Quantify Multi-Degree-of-Freedom Lower Limb Isometric Joint Torques in Children with Hemiplegia.

Pediatric hemiplegia, caused by a unilateral brain injury during childhood, can lead to motor deficits such as weakness and abnormal joint torque coupling patterns which may result in a loss of independent joint control. It is hypothesized that these motor impairments are present in the paretic lower extremity, especially at the hip joint where extension may be abnormally coupled with adduction. Previous studies investigating lower extremity isometric joint torques in children with spastic cerebral palsy used tools that limited data collection to one degree of freedom, making it impossible to quantify these coupling patterns. We describe the adaptation of a multi-joint lower extremity isometric torque measurement device to allow for quantification of weakness and abnormal joint torque coupling patterns at the hip in the pediatric population. We also present preliminary data in three children without hemiplegia to highlight how the presence of atypical femoral bony geometry, often observed in childhood hemiplegia, can be accounted for in the Jacobian transformations and affect joint torque measurements at the hip.

Neuromodulatory Inputs to Motoneurons Contribute to the Loss of Independent Joint Control in Chronic Moderate to Severe Hemiparetic Stroke.

In chronic hemiparetic stroke, increased shoulder abductor activity causes involuntary increases in elbow, wrist, and finger flexor activation, an abnormal muscle coactivation pattern known as the flexion synergy. Recent evidence suggests that flexion synergy expression may reflect recruitment of contralesional cortico-reticulospinal motor pathways following damage to the ipsilesional corticospinal tract. However, because reticulospinal motor pathways produce relatively weak post-synaptic potentials in motoneurons, it is unknown how preferential use of these pathways could lead to robust muscle activation. Here, we hypothesize that the descending neuromodulatory component of the ponto-medullary reticular formation, which uses the monoaminergic neurotransmitters norepinephrine and serotonin, serves as a gain control mechanism to facilitate motoneuron responses to reticulospinal motor commands. Thus, inhibition of the neuromodulatory component would reduce flexion synergy expression by disfacilitating spinal motoneurons. To test this hypothesis, we conducted a pre-clinical study utilizing two targeted neuropharmacological probes and inert placebo in a cohort of 16 individuals with chronic hemiparetic stroke. Test compounds included Tizanidine (TIZ), a noradrenergic α2 agonist and imidazoline ligand selected for its ability to reduce descending noradrenergic drive, and Isradipine, a dihyropyridine calcium-channel antagonist selected for its ability to post-synaptically mitigate a portion of the excitatory effects of monoamines on motoneurons. We used a previously validated robotic measure to quantify flexion synergy expression. We found that Tizanidine significantly reduced expression of the flexion synergy. A predominantly spinal action for this effect is unlikely because Tizanidine is an agonist acting on a baseline of spinal noradrenergic drive that is likely to be pathologically enhanced post-stroke due to increased reliance on cortico-reticulospinal motor pathways. Although spinal actions of TIZ cannot be excluded, particularly from Group II pathways, our finding is consistent with a supraspinal action of Tizanidine to reduce descending noradrenergic drive and disfacilitate motoneurons. The effects of Isradipine were not different from placebo, likely related to poor central bioavailability. These results support the hypothesis that the descending monoaminergic component of the ponto-medullary reticular formation plays a key role in flexion synergy expression in chronic hemiparetic stroke. These results may provide the basis for new therapeutic strategies to complement physical rehabilitation.

The Increase in Overlap of Cortical Activity Preceding Static Elbow/Shoulder Motor Tasks Is Associated With Limb Synergies in Severe Stroke

The loss of independent joint control, clinically referred to as limb synergies, is prevalent in the paretic upper limb of individuals with chronic hemiparetic stroke. To understand the underlying neural mechanisms, we previously reported that an increased overlap of cortical representations of shoulder/elbow could contribute to the abnormal poststroke synergies. However, these previous results were limited to a fixed time window just before the onset of motor tasks. Questions such as (1) how this overlap develops during motor preparation and (2) whether such development is also linked to upper limb synergies, remain unclear. To answer these questions, we investigated cortical overlap during motor preparation of isometric shoulder and elbow torque generation tasks in healthy individuals (n = 8), and individuals with moderate to severe chronic hemiparesis following a subcortical stroke (n = 12). We found a significant group difference in how the cortical overlap developed. In the healthy control and moderately impaired stroke groups, cortical overlap between shoulder and elbow motor tasks decreased during the motor preparation; however, this overlap increased in individuals with severe stroke. Furthermore, the rate of cortical overlap decrease/increase was linked to the upper limb Fugl-Meyer scores and limb synergies. These results demonstrate, for the first time, that the increase in overlap of the cortical activity during motor preparation is associated with the expression of synergies in the paretic upper limb of severely impaired poststroke individuals.

Progressive Abduction Loading Therapy with Horizontal-Plane Viscous Resistance Targeting Weakness and Flexion Synergy to Treat Upper Limb Function in Chronic Hemiparetic Stroke: A Randomized Clinical Trial.

Progressive abduction loading therapy has emerged as a promising exercise therapy in stroke rehabilitation to systematically target the loss of independent joint control (flexion synergy) in individuals with chronic moderate/severe upper-extremity impairment. Preclinical investigations have identified abduction loading during reaching exercise as a key therapeutic factor to improve reaching function. An augmentative approach may be to additionally target weakness by incorporating resistance training to increase constitutive joint torques of reaching with the goal of improving reaching function by "overpowering" flexion synergy. The objective was, therefore, to determine the therapeutic effects of horizontal-plane viscous resistance in combination with progressive abduction loading therapy. 32 individuals with chronic hemiparetic stroke were randomly allocated to two groups. The two groups had equivalent baseline characteristics on all demographic and outcome metrics including age (59 ± 11 years), time poststroke (10.1 ± 7.6 years), and motor impairment (Fugl-Meyer, 26.7 ± 6.5 out of 66). Both groups received therapy three times/week for 8 weeks while the experimental group included additional horizontal-plane viscous resistance. Quantitative standardized progression of the intervention was achieved using a robotic device. The primary outcomes of reaching distance and velocity under maximum abduction loading and secondary outcomes of isometric strength and a clinical battery were measured at pre-, post-, and 3 months following therapy. There was no difference between groups on any outcome measure. However, for combined groups, there was a significant increase in reaching distance (13.2%, effect size; d = 0.56) and velocity (13.6%, effect size; d = 0.27) at posttesting that persisted for 3 months and also a significant increase in abduction, elbow extension, and external rotation strength at posttesting that did not persist 3 months. Similarly, the clinical battery demonstrated a significant improvement in participant-reported measures of "physical problems" and "overall recovery" across all participants. The strengthening approach of incorporating horizontal-plane viscous resistance did not enhance the reaching function improvements observed in both groups. Data do not support the postulation that one can be trained to "overpower" the flexion synergy with resistance training targeting constitutive joint torques of reaching. Instead, flexion synergy must be targeted with progressive abduction loading to improve reaching function. ClinicalTrials.gov, NCT01548781.

Robotic quantification of upper extremity loss of independent joint control or flexion synergy in individuals with hemiparetic stroke: a review of paradigms addressing the effects of shoulder abduction loading.

Unsupported or “against-gravity” reaching and hand opening movements are greatly impaired in individuals with hemiparetic stroke. The reduction in reaching excursion and hand opening is thought to be primarily limited by abnormal muscle co-activation of shoulder abductors with distal limb flexors, known as flexion synergy, that results in a loss of independent joint control or joint individuation. Our laboratory employs several methods for quantifying this movement impairment, however the most documented techniques are sophisticated and laboratory-based. Here a series of robotic methods that vary in complexity from comprehensive (laboratory-based) to focused (clinically relevant) are outlined in detail in order to facilitate translation and make recommendations for utilization across the translational spectrum as part of Journal of NeuroEngineering and Rehabilitation thematic series, “Technically-advanced assessments in sensory motor rehabilitation.” While these methods focus on our published work utilizing the device, ACT3D, these methods can be duplicated using any mechatronic device with the appropriate characteristics. The common thread and most important aspect of the methods described is addressing the deleterious effects of abduction loading. Distal upper extremity joint performance is directly and monotonically modulated by proximal (shoulder abduction) joint demands. The employment of robotic metrics is the best tool for selectively manipulating shoulder abduction task requirements spanning the individual’s full range of shoulder abduction strength. From the series of methods and the concluding recommendations, scientists and clinicians can determine the ideal robotic quantification method for the measurement of the impact of loss of independent joint control on reaching and hand function.

Neck rotation modulates flexion synergy torques, indicating an ipsilateral reticulospinal source for impairment in stroke

The effect of reticular formation excitability on maximum voluntary torque (MVT) generation and associated muscle activation at the shoulder and elbow was investigated through natural elicitation (active head rotation) of the asymmetric tonic neck reflex (ATNR) in 26 individuals with stroke and 9 age-range-matched controls. Isometric MVT generation at the shoulder and elbow was quantified with the head rotated (face pointing) contralateral and ipsilateral to the paretic (stroke) and dominant (control) arm. Given the dominance of abnormal torque coupling of elbow flexion with shoulder abduction (flexion synergy) in stroke and well-developed animal models demonstrating a linkage between reticular formation and ipsilateral elbow flexors and shoulder abductors, we hypothesized that constituent torques of flexion synergy, specifically elbow flexion and shoulder abduction, would increase with contralateral head rotation. The findings of this investigation support this hypothesis. Increases in MVT for three of four flexion synergy constituents (elbow flexion, shoulder abduction, and shoulder external rotation) were observed during contralateral head rotation only in individuals with stroke. Electromyographic data of the associated muscle coactivations were nonsignificant but are presented for consideration in light of a likely underpowered statistical design for this specific variable. This study not only provides evidence for the reemergence of ATNR following stroke but also indicates a common neuroanatomical link, namely, an increased reliance on ipsilateral reticulospinal pathways, as the likely mechanism underlying the expression of both ATNR and flexion synergy that results in the loss of independent joint control.

Corticospinal responses of quadriceps are abnormally coupled with hip adductors in chronic stroke survivors

Stroke survivors often lose the ability to move their joints independently, which results in abnormal movement patterns when attempting to perform an isolated motion. For instance, many stroke subjects exhibit unwanted secondary knee extension movement when performing hip adduction. This study aimed at characterizing whether the neural substrates mediating abnormal activation patterns after stroke are of cortical origin. We developed a novel transcranial magnetic stimulation protocol to evaluate the extent of abnormal across-joint coupling of corticospinal responses in chronic stroke survivors. In stroke survivors, we found that the magnitude of motor evoked potentials of the vastus lateralis and vastus medialis during isometric hip adduction were significantly higher than those recorded during knee extension at similar background activity (P=0.03 and P=0.01). Moreover, motor evoked potential coupling ratios of the quadriceps muscles were significantly different than those observed in healthy controls (P=0.005 to P=0.037). No differences in motor evoked potential coupling ratios were observed between the younger and older adults (P=0.474 to P=0.919). These findings provide evidence for the first time that stroke subjects exhibit abnormal excitability of the quadriceps muscle corticospinal neurons when performing isometric hip adduction. Importantly, the abnormal corticospinal responses observed in stroke subjects were not mediated by aging. The results of this study provide new insights into the mechanisms underlying loss of independent joint control after stroke and have meaningful implications for post-stroke interventions. Moreover, the proposed ‘motor evoked potential coupling ratio’ may serve as an effective probe to evaluate cortical contributions to abnormal muscle synergy after stroke.

Cortical overlap of joint representations contributes to the loss of independent joint control following stroke

The loss of independent joint control in the paretic upper limb is a cardinal sign of movement disorders following stroke. However, the underlying neural mechanisms for such a loss following stroke are still largely unknown. In order to investigate the possible contribution of altered sensorimotor cortical activity to the loss of independent joint control, we measured electroencephalographic (EEG) and torque signals during the generation of static shoulder/elbow torques. We found significant increases in the overlap of shoulder and elbow joint representations at the cortical level in stroke subjects as compared to control subjects. Linear regression results demonstrated significant associations between the cortical overlap of joint representations and the degree of the loss of independent joint control. Therefore, we conclude that an increased overlap of cortical representations for shoulder and elbow contributes to the expression of the loss of independent shoulder/elbow control of the paretic upper limb in chronic hemiparetic stroke survivors.

Changing Motor Synergies in Chronic Stroke

Synergies are thought to be the building blocks of vertebrate movements. The inability to execute synergies in properly timed and graded fashion precludes adequate functional motor performance. In humans with stroke, abnormal synergies are a sign of persistent neurological deficit and result in loss of independent joint control, which disrupts the kinematics of voluntary movements. This study aimed at characterizing training-related changes in synergies apparent from movement kinematics and, specifically, at assessing: 1) the extent to which they characterize recovery and 2) whether they follow a pattern of augmentation of existing abnormal synergies or, conversely, are characterized by a process of extinction of the abnormal synergies. We used a robotic therapy device to train and analyze paretic arm movements of 117 persons with chronic stroke. In a task for which they received no training, subjects were better able to draw circles by discharge. Comparison with performance at admission on kinematic robot-derived metrics showed that subjects were able to execute shoulder and elbow joint movements with significantly greater independence or, using the clinical description, with more isolated control. We argue that the changes we observed in the proposed metrics reflect changes in synergies. We show that they capture a significant portion of the recovery process, as measured by the clinical Fugl-Meyer scale. A process of "tuning" or augmentation of existing abnormal synergies, not extinction of the abnormal synergies, appears to underlie recovery.

Upper-Limb Discoordination in Hemiparetic Stroke: Implications for Neurorehabilitation

Clinically, upper-limb discoordination after stroke is evident in the form of stereotypic movement patterns that reflect a loss of independent joint control. These movement abnormalities, in conjunction with our recent quantitative findings under isometric conditions, provide evidence for an impaired capacity to generate certain muscle coactivation patterns in the impaired limb. In this article, we examine the parallels that exist between coordination disturbances observed under isometric and movement conditions. Our results suggest that discoordination in stroke may largely represent a manifestation of additional neural constraints on motor outflow. The neurotherapeutic implications of our findings are discussed.