Imaging biomarkers for primary motor outcome after stroke – should we include information from beyond the primary motor system?

Hemiparesis is a common consequence of stroke to the primary motor system. Previous studies suggested that damage to additional brain areas might play a causal role in occurrence and severity of hemiparesis and its recovery. Imaging biomarkers to predict post stroke outcome thus might also account for damage to these non-primary motor areas. The study aimed to evaluate if damage to areas outside of the primary motor system is predictive of hemiparesis, and if this damage plays a causal role in its occurrence. In 102 patients with unilateral stroke, the neural correlates of acute and chronic upper limb paresis were mapped by univariate and multivariate lesion behaviour mapping. Following the same approach, CST lesion biomarkers were mapped, and resulting topographies of both analyses were compared. All mapping analyses of acute or chronic upper limb paresis implicated areas outside of the primary motor system. Likewise, mapping CST lesion biomarkers ‒ that, by definition, are only causally related to damage of the CST ‒ implicated several areas outside of the CST with high correspondence to areas associated with upper limb paresis. Damage to areas outside of the primary motor system might not play a causal role in hemiparesis, while still providing predictive value. This finding suggests that simple theory-based biomarkers or qualitative rules to infer post-stroke outcome from imaging data might perform sub-optimally, as they do not consider the complexity of lesion data. Instead, high-dimensional models with data-driven feature selection strategies might be required.