Distinct Corticospinal and Reticulospinal Contributions to Voluntary Control of Elbow Flexor and Extensor Muscles in Humans with Tetraplegia

Abstract

Humans with cervical spinal cord injury (SCI) often recover voluntary control of elbow flexors and, to a much lesser extent, elbow extensor muscles. The neural mechanisms underlying this asymmetrical recovery remain unknown. Anatomical and physiological evidence in animals and humans indicates that corticospinal and reticulospinal pathways differentially control elbow flexor and extensor motoneurons; therefore, it is possible that reorganization in these pathways contributes to the asymmetrical recovery of elbow muscles after SCI. To test this hypothesis, we examined motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the arm representation of the primary motor cortex, maximal voluntary contractions, the StartReact response (a shortening in reaction time evoked by a startling stimulus), and the effect of an acoustic startle cue on MEPs elicited by cervicomedullary stimulation (CMEPs) on biceps and triceps brachii in males and females with and without chronic cervical incomplete SCI. We found that SCI participants showed similar MEPs and maximal voluntary contractions in biceps but smaller responses in triceps compared with controls, suggesting reduced corticospinal inputs to elbow extensors. The StartReact and CMEP facilitation was larger in biceps but similar to controls in triceps, suggesting enhanced reticulospinal inputs to elbow flexors. These findings support the hypothesis that the recovery of biceps after cervical SCI results, at least in part, from increased reticulospinal inputs and that the lack of these extra inputs combined with the loss of corticospinal drive contribute to the pronounced weakness found in triceps.

Corticospinal vs Rubrospinal Revisited: An Evolutionary Perspective for Sensorimotor Integration

“…These studies support the idea that after CS tract damage, the muscles with the greatest CM influence show greater weakness, and there may be RM involvement in compensatory (rebalancing) mechanisms for motor alterations (Palmer and Ashby, 1992;Belhaj-Saïf and Cheney, 2000;Zaaimi et al, 2012;Ludolph et al, 2020;Sangari and Perez, 2020). In this way, more recently it has been described in Celsr3| Emx1 mutant mice model, where CST is specifically and fully absent, that axonal projections from RN to the spinal cord are increased and lesions of the RS tract lead to defective forelimb use, with almost no recovery.…”

“…Ludolph et al (2020) compared strength between elbow extensors (triceps) and flexors (biceps), reporting greater relative weakness in flexors relative to elbow extensors; in addition, they also reported greater relative weakness of extensors vs hand flexors. Similarly, in participants with cervical spinal cord damage (tetraplegia) who received transcranial magnetic stimulation, motor-evoked potentials were smaller in triceps relative to controls, suggesting that there is less CS input to the elbow extensors (Sangari and Perez, 2020). Furthermore, in monkeys with CS tract lesions, Zaaimi et al (2012) reported increased facilitation of motor neurons related to elbow flexors but not in those with connections to extensors.…”

Plasticity in Cervical Motor Circuits following Spinal Cord Injury and Rehabilitation

“…For example, a recent study has shown adaptive strategies of motor unit recruitment from the contralesional RST following stroke that prioritize elbow, wrist, and finger flexion synergy over dextrous digit manipulation, which limits functional recovery [112]. Similarly, muscle groups with spared RST input following SCI have been shown to be stronger than those without [113].…”

Age-Related Differences in Corticospinal Excitability and Anticipatory Postural Adjustments of the Trunk

“…Evidence suggests subcortical neural circuits, such as reticulospinal pathways, also contributing to postural adjustments (Prentice and Drew, 2001;Schepens and Drew, 2004;Takakusaki, 2017). Research has shown the reticulospinal inputs being upgraded after spinal cord injury and in ageing as a compensatory mechanism to maintain motor control (Sangari and Perez, 2020;Maitland and Baker, 2021). Although the role of the reticulospinal circuits in modulating corticospinal excitability profile during the APA window remains unknown, it is possible that the reticulospinal circuits influence the control of APAs.…”