Ellis MD, Drogos J, Carmona C, Keller T, Dewald JP. Neck rotation modulates flexion synergy torques, indicating an ipsilateral reticulospinal source for impairment in stroke. J Neurophysiol 108: 3096 -3104, 2012. First published September 5, 2012 doi:10.1152/jn.01030.2011.-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 agerange-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 welldeveloped 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. flexion synergy; strength; tonic neck reflex; asymmetric tonic neck reflex REACHING FUNCTION FOLLOWING STROKE can be profoundly impaired and has been historically described as being constrained, at least in part, to stereotypic multijoint movement patterns or synergies (Brunnstrom 1970;Foerster 1936;Twitchell 1951). Initial quantitative investigations thoroughly described the phenomena under isometric conditions highlighting the abnormal coactivation of brachialis, biceps brachii, and brachioradialis with deltoid (Dewald et al. 1995). The coactivation manifests as a "flexion synergy" and is significant for abnormal joint torque coupling of elbow flexion during shoulder abduc-

BackgroundProgressive 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.Methods32 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.ResultsThere 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.ConclusionThe 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.Trial Registration, NCT01548781.

Because flexion synergy expression modifies stretch reflexes in involved muscles, interventions that reduce flexion synergy expression may confer the added benefit of reducing spasticity during functional use of the arm.

Objective-Previous studies determined, using between arms position matching assessments, that at least one-half of individuals with stroke have an impaired position sense. We investigated whether individuals with chronic stroke who have impairments mirroring arm positions also have impairments identifying the location of each arm in space.Methods-Participants with chronic hemiparetic stroke and age-matched participants without neurological impairments (controls) performed a between forearms position matching task based on a clinical assessment and a single forearm position matching task, using passive and active movements, based on a robotic assessment.Results-12 out of our 14 participants with stroke who had clinically determined between forearms position matching impairments had greater errors than the controls in both their paretic and non-paretic arm when matching positions during passive movements; yet stroke participants performed comparable to the controls during active movements.Conclusions-Many individuals with chronic stroke may have impairments matching positions in both their paretic and non-paretic arm if their arm is moved for them, yet not within either arm if these individuals control their own movements.Significance-The neural mechanisms governing arm location perception in the stroke population may differ depending on whether arm movements are made passively versus actively.

This work is motivated by our goal of determining why individuals with stroke are impaired when locating their arms in space. We assessed the ability of individuals without neurological impairments to mirror their forearms during various motor tasks so that we could identify baseline performance in an unimpaired population. Nine right-hand dominant participants without neurological impairments mirrored forearm positions bi-directionally (i.e., right forearm mirrors left forearm, vice versa) for three motor tasks (i.e., passive, passive/active, and active) and two position identification modes (i.e., mirroring to a position stored in working memory versus concurrently felt by the opposite arm). During each trial, the participant's reference forearm moved to a flexion ([Formula: see text]) or extension ([Formula: see text]) position, and then, their opposite forearm mirrored the position of their reference forearm. The main finding across all tested conditions is that participants mirrored forearm positions with an average magnitude of error [Formula: see text]. When controlling their forearms' movements (active motor task), participants mirrored forearm positions more accurately by up to, on average, [Formula: see text] at the flexion location than at the extension location. Moreover, participants mirrored forearm positions more accurately by up to, on average, [Formula: see text] when their forearms were moved for them rather than when they controlled their forearms' movements. Task directionality and position identification mode did not significantly affect participant arm mirroring accuracy. These findings are relevant for interpreting in future work the reason why impairments occur, on similar tasks, in individuals with altered motor commands, working memory, and arm impedance, e.g., post-stroke hemiparesis.

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.

This study utilized a novel robotic device, the ACT-4D, to investigate the relationship between the flexion synergy and stretch reflexes in individuals with chronic hemiparetic stroke. Because the flexion synergy influences the amount of elbow flexor muscle activation present in the paretic limb during tasks requiring shoulder abduction loading, it was hypothesized that stretch reflexes may be modulated by expression of this abnormal muscle coactivation pattern. To test this hypothesis, the ACT-4D was used to enable 10 individuals with chronic hemiparetic stroke to generate varying amounts of shoulder abduction torque while concurrently receiving elbow extension position perturbations. It was found that increased expression of the flexion synergy led to greater reflex amplitudes as well as lower reflex velocity thresholds. The physiological basis of the flexion synergy is briefly discussed, as are the implications of the flexion synergy and stretch reflexes for purposeful movement.

Post hemiparetic stroke an individual may face difficulty performing bimanual tasks due to an asymmetry in their arms' strengths. Here, we determined whether participants with a strength asymmetry were impaired bi-directionally when matching torques between arms (i.e., paretic arm matches non-paretic arm, non-paretic arm matches paretic arm). Six participants with chronic hemiparetic stroke and four participants without neurological impairments partook in this study. First, we identified the maximum voluntary torque that participants could generate about each elbow joint (τ). Then, we determined how accurately and precisely participants could match, bidirectionally, submaximal isometric flexion torques (0.25 · τ) between arms. Results demonstrate that task directionality impacted the ability of our participants with stroke who had a strength asymmetry to match torques between arms; specifically, participants were unimpaired matching to a referenced non-paretic arm yet impaired in the opposite direction. Additionally, results reveal that the degree to which participants overshot the target torque when matching with their non-paretic arm could be predicted based on their strength asymmetry (R = 0.67). We propose that individuals with stroke may avoid torque matching impairments during bimanual tasks by matching their paretic arm to their non-paretic arm.