Brain connectivity alterations after additional sensorimotor or motor therapy for the upper limb in the early-phase post stroke: a randomized controlled trial
Authors: De Bruyn Nele , Saenen Leen , Thijs Liselot , Van Gils Annick , Ceulemans Eva , Essers Bea , Alaerts Kaat , Verheyden Geert 
Published: April 2021

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.