Brain connectivity alterations after additional sensorimotor or motor therapy for the upper limb in the early-phase post stroke: a randomized controlled trial

Abstract Somatosensory function plays an important role for upper limb motor learning. However, knowledge about underlying mechanisms of sensorimotor therapy is lacking. We aim to investigate differences in therapy-induced resting-state functional connectivity changes between additional sensorimotor compared with motor therapy in the early-phase post stroke. Thirty first-stroke patients with a sensorimotor impairment were included for an assessor-blinded multi-centre randomized controlled trial within 8 weeks post stroke [13 (43%) females; mean age: 67 ± 13 years; mean time post stroke: 43 ± 13 days]. Patients were randomly assigned to additional sensorimotor (n = 18) or motor (n = 12) therapy, receiving 16 h of additional therapy within 4 weeks. Sensorimotor evaluations and resting-state functional magnetic resonance imaging were performed at baseline (T1), post-intervention (T2) and after 4 weeks follow-up (T3). Resting-state functional magnetic resonance imaging was also performed in an age-matched healthy control group (n = 19) to identify patterns of aberrant connectivity in stroke patients between hemispheres, or within ipsilesional and contralesional hemispheres. Mixed model analysis investigated session and treatment effects between stroke therapy groups. Non-parametric partial correlations were used to investigate brain−behaviour associations with age and frame-wise displacement as nuisance regressors. Connections within the contralesional hemisphere that showed hypo-connectivity in subacute stroke patients (compared with healthy controls) showed a trend towards a more pronounced pre-to-post normalization (less hypo-connectivity) in the motor therapy group, compared with the sensorimotor therapy group (mean estimated difference = −0.155 ± 0.061; P = 0.02). Further, the motor therapy group also tended to show a further pre-to-post increase in functional connectivity strength among connections that already showed hyper-connectivity in the stroke patients at baseline versus healthy controls (mean estimated difference = −0.144 ± 0.072; P = 0.06). Notably, these observed increases in hyper-connectivity of the contralesional hemisphere were positively associated with improvements in functional activity (r = 0.48), providing indications that these patterns of hyper-connectivity are compensatory in nature. The sensorimotor and motor therapy group showed no significant differences in terms of pre-to-post changes in inter-hemispheric connectivity or ipsilesional intrahemispheric connectivity. While effects are only tentative within this preliminary sample, results suggest a possible stronger normalization of hypo-connectivity and a stronger pre-to-post increase in compensatory hyper-connectivity of the contralesional hemisphere after motor therapy compared with sensorimotor therapy. Future studies with larger patient samples are however recommended to confirm these trend-based preliminary findings.