Limited capacity for ipsilateral secondary motor areas to support hand function post‐stroke

Abstract

Key points Ipsilateral‐projecting corticobulbar pathways, originating primarily from secondary motor areas, innervate the proximal and even distal portions, although they branch more extensively at the spinal cord. It is currently unclear to what extent these ipsilateral secondary motor areas and subsequent cortical projections may contribute to hand function following stroke‐induced damage to one hemisphere. In the present study, we provide both structural and functional evidence indicating that individuals increasingly rely on ipsilateral secondary motor areas, although at the detriment of hand function. Increased activity in ipsilateral secondary motor areas was associated with increased involuntary coupling between shoulder abduction and finger flexion, most probably as a result of the low resolution of these pathways, making it increasingly difficult to open the hand. These findings suggest that, although ipsilateral secondary motor areas may support proximal movements, they do not have the capacity to support distal hand function, particularly for hand opening. Abstract Recent findings have shown connections of ipsilateral cortico‐reticulospinal tract (CRST), predominantly originating from secondary motor areas to not only proximal, but also distal muscles of the arm. Following a unilateral stroke, CRST from the ipsilateral side remains intact and thus has been proposed as a possible backup system for post‐stroke rehabilitation even for the hand. We argue that, although CRST from ipsilateral secondary motor areas can provide control for proximal joints, it is insufficient to control either hand or coordinated shoulder and hand movements as a result of its extensive spinal branching compared to contralateral corticospinal tract. To address this issue, we combined magnetic resonance imaging, high‐density EEG, and robotics in 17 individuals with severe chronic hemiparetic stroke and 12 age‐matched controls. We tested for changes in structural morphometry of the sensorimotor cortex and found that individuals with stroke demonstrated higher grey matter density in secondary motor areas ipsilateral to the paretic arm compared to controls. We then measured cortical activity when participants were attempting to generate hand opening either supported on a table or when lifting against a shoulder abduction load. The addition of shoulder abduction during hand opening increased reliance on ipsilateral secondary motor areas in stroke, but not controls. Crucially, the increased use of ipsilateral secondary motor areas was associated with decreased hand opening ability when lifting the arm as a result of involuntary coupling between the shoulder and wrist/finger flexors. Taken together, this evidence implicates a compensatory role for ipsilateral (i.e. contralesional) secondary motor areas post‐stroke, although with no apparent capacity to support hand function.

Rudimentary Dexterity Corresponds With Reduced Ability to Move in Synergy After Stroke: Evidence of Competition Between Corticoreticulospinal and Corticospinal Tracts?

“…Anatomical and neurophysiological data suggest that this is done primarily through the premotor cortex (PM) and supplementary motor area (SMA), [16][17][18] potentially forming a compensatory backup system. 15,19,20 Evidence for use of the CRST after stroke is still mostly indirect but is accumulating and includes (1) CRST diffusely innervates spinal segments in a way consistent with flexion and extension synergies 21 ; in contrast, CST exhibits a more focal innervation suitable to support of independent arm joint torques.…”

Intervention-induced changes in neural connectivity during motor preparation may affect cortical activity at motor execution

“…Given beta's role in descending layer V pyramidal neurons 57,58 , 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 synergy-induced impairments 59,60 , particularly during tasks involving lifting at the shoulder 29,61,62 , 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 63,64 , especially for independent control of multijoint movements of the upper extreminty 65 .…”

“…Meanwhile, increased use of descending corticospinal tract from the ipsilesional hemisphere has been shown to be crucial for improved function following stroke 63,64 , especially for independent control of multijoint movements of the upper extreminty 65 . Although contralesional corticobulbar pathways can support more proximal paretic arm movements such as reaching 66 , they do not offer sufficient control of independent joints during multijoint movements 62,67,68 . Thus, the ability to maintain ipsilesional recruitment during combined shoulder-hand tasks is critical for potential functional improvement since ipsilesional corticospinal tract, unlike contralesional corticobulbar tracts, has more specific branching in the spinal cord that allows for independent control of the different parts of the arm [68][69][70] .…”

Hybrid dedicated and distributed coding in PMd/M1 provides separation and interaction of bilateral arm signals

“…One candidate hypothesis for the presence of ipsilateral activity has been that it supplies its own independent control signal. There is some evidence that ipsilateral cortex plays an increased role in movement following hemispheric damage (Brinkman and Kuypers, 1973;Hummel and Cohen, 2006;Dancause, 2006;Wilkins et al, 2020), though not necessarily a beneficial or compensatory one. The magnitude of ipsilateral encoding also increases with the degree of movement complexity (Verstynen et al, 2005) and may involve spatially distinct neural populations (Ziemann et al, 1999;Chen et al, 2003).…”

“…Anatomically, the corticospinal tract (CST) is almost entirely contralateral, and the effectiveness of the ipsilateral component has been debated (Lacroix et al, 2004;Rosenzweig et al, 2009;Soteropoulos et al, 2011;Baker et al, 2015). Ipsilateral cortex may also exert its influence via connections made in the reticular formation (Alagona et al, 2001;Baker et al, 2015;Wilkins et al, 2020), which projects to ipsilateral spinal cord. These reticulospinal pathways may also be responsible for preparatory modulation of muscle spindles (Papaioannou and Dimitriou, 2020), which is relevant to the weak emergence of independent activity we observed during the Instruct phase.…”