Corticospinal and Reticulospinal-Associated Measures in Chronic Ischemic Stroke: Associations with Upper Limb Function

Background: Corticospinal tract (CST) damage is the main cause of post-stroke motor impairment. Whilst the output of the reticulospinal tract (RST) is reportedly upregulated, its relation to CST damage post-stroke is unclear. We assessed CST integrity using transcranial magnetic stimulation and RST activity using the StartReact paradigm in chronic ischemic stroke and examined their inter-relationship and associations with upper-limb impairment. Methods: We included 80 patients with chronic ischemic stroke and 15 age-matched healthy controls (HCs). CST function was quantified using the resting motor threshold asymmetry index (RMT-AI); RST function was measured by the StartReact effect (visual-auditory minus visual-startle reaction time) during isometric wrist flexion. Impairment was assessed with the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and affected-side grip strength, with FDR-corrected correlations. Results: Higher RMT-AI was associated with lower FMA-UE (r -0.46, p 0.0038) and weaker grip (rho -0.43, p 0.0065). A larger StartReact effect showed the same pattern (rho -0.35, p 0.0095, FMA-UE; rho -0.41, p 0.00195, grip). All correlations remained significant after FDR correction. RMT-AI and the StartReact effect were uncorrelated (r 0.05, p 0.792). The StartReact effect did not differ between sides (p 0.631) or between patients and HCs (p 0.342) but was larger in patients with FMA-UE less than or equal to median than in HCs (p 0.025), without a side difference (p 0.143). Conclusions: Greater impairment was associated with greater CST damage and RST activity, possibly reflecting cortico-reticular fibre damage. CST and RST measures were unrelated, suggesting cortical input to the reticular formation beyond M1. Severely impaired patients showed greater bilateral reticulospinal involvement.