Progressive recruitment of contralesional cortico‐reticulospinal pathways drives motor impairment post stroke

Abstract

A hallmark of hemiparetic stroke is the loss of fine motor control in the contralesional arm and hand and the constraint to a grouped movement pattern known as the flexion synergy. In the flexion synergy, increasing shoulder abductor activation drives progressive, involuntary increases in elbow, wrist and finger flexion. The neural mechanisms underlying this phenomenon remain unclear. Here, across 25 adults with moderate to severe hemiparesis following chronic stroke and 18 adults without neurological injury, we test the overall hypothesis that two inter-related mechanisms are necessary for flexion synergy expression: increased task-dependent activation of the intact, contralesional cortex and recruitment of contralesional motor pathways via ipsilateral reticulospinal projections. First, we imaged brain activation in real time during reaching motions progressively constrained by flexion synergy expression. Using this approach, we found that cortical activity indeed shifts towards the contralesional hemisphere in direct proportion to the degree of shoulder abduction loading in the contralesional arm. We then leveraged the post-stroke reemergence of a developmental brainstem reflex to show that anatomically diffuse reticulospinal motor pathways are active during synergy expression. We interpret this progressive recruitment of contralesional cortico-reticulospinal pathways as an adaptive strategy that preserves low-level motor control at the cost of fine motor control.

Intervention-Induced Changes in Cortical Connectivity and Activity in Severe Chronic Hemiparetic Stroke

“…Given beta's role in descending layer V pyramidal neurons 60,61 , the observed intervention-induced increase in CAR may reflect increased drive and use of remaining descending ipsilesional motor resources during the lifting and opening condition following the intervention, rather than purely an intracortical change. This is significant since reliance on descending tracts from the contralesional hemisphere has been linked with synergyinduced impairments 62,63 , particularly during tasks involving lifting at the shoulder 26,64 , as examined here. Meanwhile, increased use of descending corticospinal tract from the ipsilesional hemisphere has been shown to be crucial for improved function following stroke [65][66][67] , especially for independent control of multijoint movements of the upper extreminty 68 .…”

Statistics and spin: it's time to improve

“…We were interested in the topic of the paper entitled ‘Progressive recruitment of contralesional cortico‐reticulospinal pathways drives motor impairment post stroke’ which was published in The Journal of Physiology (McPherson et al . ). However, our interest decreased when we were unable to find important statistical reporting elements and noted several instances of ‘spin’.…”

“…Given the many P values reported by McPherson et al . () that were just above or below the selected threshold of P < 0.05, it is worth emphasising that a perfect replication study ‒ same protocol and sample size ‒ has only a 50% chance of reproducing effects with P values around 0.05 (e.g. Button et al .…”

“…P values are fickle, especially when study samples are small and heterogeneous, and the true effect being investigated is not large (Hasley et al 2015). Given the many P values reported by McPherson et al (2018) that were just above or below the selected threshold of P < 0.05, it is worth emphasising that a perfect replication study -same protocol and sample size -has only a 50% chance of reproducing effects with P values around 0.05 (e.g. Button et al 2013).…”

Reply from Jacob Graves McPherson, Albert Chen, Michael D. Ellis, Jun Yao, C. J. Heckman and Julius P. A. Dewald

“…With regard to McPherson et al . (), first, we thank Gandevia and Heroux for noticing the accidental omission of the definition of error bars or asterisks in Fig. 2–4.…”