Abnormal synergies and associated reactions post-hemiparetic stroke reflect muscle activation patterns of brainstem motor pathways

Well, what the fuck do stroke survivors do with this knowledge to get recovered? Do the goddamned research properly and create protocols that deliver such recovery.

Abnormal synergies and associated reactions post-hemiparetic stroke reflect muscle activation patterns of brainstem motor pathways

Laura M. McPherson^1,2,3 and Julius P. A. Dewald^4,5,6*

• ¹Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO, United States
• ²Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
• ³Program in Neurosciences, Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States
• ⁴Department of Biomedical Engineering, Northwestern University, Chicago, IL, United States
• ⁵Department of Physical Therapy and Human Movement Sciences, The Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
• ⁶Department of Physical Medicine and Rehabilitation, The Feinberg School of Medicine, Northwestern University, Chicago, IL, United States

Individuals with moderate-to-severe post-stroke hemiparesis cannot control proximal and distal joints of the arm independently because they are constrained to stereotypical movement patterns called flexion and extension synergies. Accumulating evidence indicates that these synergies emerge because of upregulation of diffusely projecting brainstem motor pathways following stroke-induced damage to corticofugal pathways. During our recent work on differences in synergy expression among proximal and distal joints, we serendipitously observed some notable characteristics of synergy-driven muscle activation. It seemed that: paretic wrist/finger muscles were activated maximally during contractions of muscles at a different joint; differences in the magnitude of synergy expression occurred when elicited via contraction of proximal vs. distal muscles; and associated reactions in the paretic limb occurred during maximal efforts with the non-paretic limb, the strength of which seemed to vary depending on which muscles in the non-paretic limb were contracting. Here we formally investigated these observations and interpreted them within the context of the neural mechanisms thought to underlie stereotypical movement patterns. If upregulation of brainstem motor pathways occurs following stroke-induced corticofugal tract damage, then we would expect a pattern of muscle dependency in the observed behaviors consistent with such neural reorganization. Twelve participants with moderate-to-severe hemiparetic stroke and six without stroke performed maximal isometric torque generation in eight directions: shoulder abduction/adduction and elbow, wrist, and finger flexion/extension. Isometric joint torques and surface EMG were recorded from shoulder, elbow, wrist, and finger joints and muscles. For some participants, joint torque and muscle activation generated during maximal voluntary contractions were lower than during maximal synergy-induced contractions (i.e., contractions about a different joint), particularly for wrist and fingers. Synergy-driven contractions were strongest when elicited via proximal joints and weakest when elicited via distal joints. Associated reactions in the wrist/finger flexors were stronger than those of other paretic muscles and were the only ones whose response depended on whether the non-paretic contraction was at a proximal or distal joint. Results provide indirect evidence linking the influence of brainstem motor pathways to abnormal motor behaviors post-stroke, and they demonstrate the need to examine whole-limb behavior when studying or seeking to rehabilitate the paretic upper limb.

Introduction

Stereotypical movement patterns that emerge in the upper limb of individuals with moderate-to-severe post-stroke hemiplegia present a substantial barrier to completing functional tasks because they interfere with the ability to control proximal and distal joints independently. These obligatory movement patterns are described clinically as the flexion synergy (shoulder abduction coupled with elbow, wrist, and finger flexion) and the extension synergy (shoulder adduction coupled with elbow extension, wrist flexion or extension, and finger flexion) (1–5). They emerge as a result of an increased influence of diffusely projecting brainstem motor pathways following stroke-induced damage to the corticospinal pathway (6–10).

Over the last decade, we have extensively characterized the flexion and extension synergies at the shoulder, elbow, wrist, and fingers (1, 4, 5), extending the laboratory's previous work that focused on the proximal manifestation of the synergies at the shoulder and elbow joints (3, 11–15). Recently, we found that some characteristics of flexion and extension synergy expression differ among shoulder, elbow, wrist, and finger muscles (1), expanding our growing body of knowledge that provides the foundation for the development of targeted rehabilitation strategies. During the analysis of data from that study (1), we serendipitously observed some additional characteristics of synergy-driven muscle activation that occurred frequently enough to warrant further exploration.

First, we noticed that paretic wrist and finger muscles seemed to be activated maximally while individuals contracted muscles at a different joint, not during a maximal voluntary contraction of the wrist and finger muscles themselves, as is typical. Second, there seemed to be differences in the magnitude of synergy expression when it was elicited via contraction of proximal muscles vs. distal muscles. Third, there seemed to be consistent movement resembling flexion or extension synergy patterns in the paretic limb during maximal efforts with the non-paretic limb (a phenomenon described clinically as an associated reaction). The strength of these associated reactions appeared to differ based on which muscles in the non-paretic limb were being activated. We did not formally investigate these observations for inclusion in that study.

Thus, the goals of this article were to formally investigate the observations, specifically focusing on differences between proximal vs. distal joints and flexor vs. extensor muscles, and to interpret them within the context of the neural mechanisms thought to underlie stereotypical movement patterns. If upregulation of brainstem motor pathways occurs following stroke-induced corticospinal and corticobulbar tract damage, then we would expect a pattern of muscle dependency in the observed behaviors consistent with the ways in which the muscles are impacted by such neural reorganization. Specifically, while all upper limb muscles are controlled by both the precise, sophisticated lateral corticospinal system and the diffusely projecting, comparatively more crude brainstem motor system, the two motor systems have different contributions to neural control of proximal vs. distal muscles. Brainstem motor pathways have the strongest projections to proximal muscles (16–18), which is in line with their role in postural stability. Conversely, the corticospinal pathway has the strongest and most frequent projections to distal muscles (19), which is in line with their role as the predominant muscles for fine motor control. In addition, the reticulospinal pathway, which is the brainstem pathway thought to underlie the flexion synergy (6–10, 14), has bilateral effects in the upper limbs and favors the facilitation of flexor muscles on the ipsilateral side (16, 20–23). Following corticospinal and corticobulbar damage, activity of brainstem pathways may be inadequately balanced due to the reduced activity of the corticospinal tract and/or a loss of oligosynaptic inhibitory cortico-reticular connections (24). As a result, the way that muscles are activated may reflect characteristics of brainstem pathways.

Based on this framework, our study had the following aims and specific predictions. The first aim of the study was to determine which paretic upper limb muscles are activated maximally during contractions of muscles at other joints (i.e., during elicitation of the flexion and extension synergies) rather than during voluntary contractions of the muscles themselves. We predicted that maximal activation of proximal muscles (i.e., those of the shoulder and elbow) would be achieved through voluntary contractions but that maximal activation for the most distal muscles (i.e., those of the wrist and fingers) would occur during synergy-driven contractions.

The second aim of the study was to determine whether the magnitude of flexion and extension synergy expression differs when elicited via maximal contractions of proximal vs. distal muscles in the paretic arm. Because proximal muscles are more heavily innervated by brainstem pathways than distal muscles, we predicted that activation of proximal muscles would result in stronger synergy expression compared with activation of distal muscles.

The third aim of the study was to determine whether the magnitude of associated reactions differs when elicited via maximal contractions of proximal vs. distal muscles of the contralateral (non-paretic) arm. We predicted that activation of proximal muscles, compared with activation of distal muscles, would result in stronger associated reactions, and that the associated reactions would be stronger in flexor compared with extensor muscles. This is because reticulospinal pathways have stronger bilateral projections to proximal compared to distal muscles and flexor compared to extensor muscles.

Our findings were consistent with our predictions. For some participants, joint torque and muscle activation generated during maximal voluntary contractions were lower than during maximal synergy-induced contractions. This was more prevalent and more severe in magnitude at the wrist and fingers than at the shoulder and elbow. Synergy-driven contractions were strongest when elicited via proximal joints and weakest when elicited via distal joints. Associated reactions in the paretic wrist/finger flexors were stronger than those of other paretic muscles and were the only ones whose response depended on whether the contralateral contraction was at a proximal or distal joint.

All data utilized in the analyses presented here were collected as part of the same experiment protocol, which included both ipsilateral and contralateral contractions (see Methods). Some analyses of data from the ipsilateral contractions were reported in McPherson and Dewald (1). Portions of our findings have been reported in the abstract (25) and dissertation (26) forms.

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