Precisely how is this going to get survivors recovered? Useless research without that!
Insights into the dependence of post-stroke motor recovery on the initial from a computational model
Journal of NeuroEngineering and Rehabilitation volume 22, Article number: 8 (2025)
Abstract
There is a consensus that motor recovery post-stroke primarily depends on the degree of the initial connectivity of the ipsilesional corticospinal tract (CST). Indeed, if the residual CST connectivity is sufficient to convey motor commands, the neuromotor system continues to use the CST predominantly, and motor function recovers up to 80%. In contrast, if the residual CST connectivity is insufficient, hand/arm dexterity barely recovers, even as the phases of stroke progress. Instead, the functional upregulation of the reticulospinal tract (RST) often occurs. In this study, we construct a computational model that reproduces the dependence of post-stroke motor recovery on the initial CST connectivity. The model emulates biologically plausible evolutions of primary motor descending tracts, based on activity-dependent or use-dependent plasticity and the preferential use of more strongly connected neural circuits. The model replicates several elements of the empirical evidence presented by the Fugl-Meyer Assessment (FMA) subscores, which evaluate the capabilities for out-of-synergy and in-synergy movements. These capabilities presumably change differently depending on the degree of the initial CST connectivity post-stroke, providing insights into the interactive dynamics of the primary descending motor tracts. We discuss findings derived from the proposed model in relation to the well-known proportional recovery rule. This modeling study aims to present a way to differentiate individuals who can achieve 70 to 80% recovery in the chronic phase from those who cannot by examining the interactive evolution of out-of-synergy and in-synergy movement capabilities during the subacute phase, as assessed by the FMA.
Introduction
Clinical observations suggest that the extent of potential motor recovery following stroke primarily depends on the residual connectivity of the ipsilesional corticospinal tract (CST) observed within the first few weeks [5, 66, 67]. The ipsilesional CST is the primary motor descending pathway that conveys motor commands to motoneurons [49]. Stroke survivors generally fall into two groups: one group significantly recovers to the level of mild impairment with substantial hand/arm dexterity, and the other group remains at the level of severe-to-moderate impairment, limiting the restoration of hand/arm dexterity [11]. The success or failure to retrieve hand/arm dexterity may depend on whether CST connectivity is resilient during the subacute phase where spontaneous motor recovery occurs [62]. If CST connectivity is not resilient, alternative pathways, including the contralesional reticulospinal tract (RST), may be employed, leading to improvements in gross motor function [10, 15, 62].
The proportional recovery (PR) rule was not originally devised to account for the initial CST connectivity in motor recovery post-stroke [68]. However, this rule is known to broadly differentiate individuals with stroke into two groups: one group with sufficient initial CST connectivity (fitters) and one group with insufficient or no initial CST connectivity (non-fitters) [5]. The PR rule describes that individuals spontaneously recover an average of 70–80% from the first week of stroke to the follow-up (typically 3 or 6 months) in terms of the Fugl-Meyer assessment (FMA) total score, regardless of sex, age and race [46, 72, 74]. Though there are questions about the PR rule due to issues such as mathematical coupling [28], this rule emphasizes the influence of the initial connectivity of the CST, distinguishing ‘fitters’ from ‘non-fitters’. Fitters achieve 70 to 80% recovery, typically surpassing the threshold of the FMA total score of 40 ~ 42 [33, 64], achieving substantial spontaneous recovery of hand/arm dexterity upon entering the chronic phase. The CST is assumed to be the dominant motor descending pathway in fitters. Meanwhile, non-fitters fail to achieve 70 to 80% recovery. The main reason may be that out-of-synergy test items that require the sufficient functional capability of the CST are difficult for non-fitters to score well on (i.e. Score “2” for each test item) [18, 39, 64]. The CST in this group barely achieves a functional capability level that allows for restoring of hand/arm dexterity.
In this study, we construct a computational model to explain the differential motor recovery of non-fitters versus fitters. This model evaluates how the degree of the initial CST connectivity impacts motor recovery after stroke. We reproduce several key features of subscore distributions of the FMA for the upper extremity in fitters and non-fitters. This allows us to gain insight into the interactive evolutions of motor tract (i.e. CST and RST) dynamics depending on the degree of the initial CST connectivity post-stroke. The subscores of the FMA, derived from 27 subtests for in-synergy and out-of-synergy movements, reveal clues about the functioning neural substrates, potentially distinguishing uses of the CST and RST. We apply a strict assumption that while the type of in-synergy movements (tested using the flexion synergy and extension synergy test items) is mediated primarily by either the CST or RST, the type of out-of-synergy movements (tested using the synergy-mixing and out-of-synergy test items) is mediated predominantly by the CST. Individuals with no neurological deficit can conduct elbow flexion while performing shoulder abduction (which is considered as an abnormal synergistic movement following a stroke) by exciting the biceps and abductors individually (via the CST); they do not use involuntary coactivation to perform the movement. We incorporate a stochastic gradient descent algorithm into the Hebbian theory to reflect activity- or use-dependent plasticity [19]. This algorithm successfully replicated the evolution of the torque generation of the elbow joint during flexion, indicating upper- extremity functional activity following stroke. It also revealed that more strongly connected motoneurons are optimized with priority (Reinkensmeyer, Guigon, and Maier [56]). We aim to present a way to differentiate individuals who can achieve 70 to 80% recovery in the chronic phase from those who cannot, by examining the interactive evolution of out-of-synergy and in-synergy movement capabilities during the subacute phase, as assessed by the FMA. Our efforts in this study will provide insights into clinically observed motor improvement during the subacute phase and therapy design.
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