To assess whether Action Observation Training (AOT) modifies brain dynamic functional network connectivity (dFNC) in healthy controls (HC) and multiple sclerosis (MS) patients with right (R) upper limb impairment.

In this blind, controlled study, 87 R-handed subjects were randomized into 2 experimental groups (HC-AOT n=23; MS-AOT n=20) and 2 control groups (HC-C n=23; MS-C n=21). The 2-weeks training consisted of 10 sessions of 45 minutes. AOT-groups watched 3 daily-life actions videos alternated by their execution with the R hand; C-groups performed the same tasks watching landscape videos. At baseline (t0) and after 2 weeks (w2), resting state fMRI was obtained. Independent component analysis identified 41 FC networks. Between-group differences and dFNC changes over-time in each group were evaluated using a dynamic approach, i.e., assessing FC on small temporal segments using sliding windows, and then grouping FC correlation matrices into recurrent FC states.

After training, MS groups improved in right upper limb functions. Two recurrent FC states were detected: State1, showing strong inter-network connectivity; and State2, with weak inter-network connectivity. At t0, MS patients showed a consistent dFNC decrease vs HC, especially in State1, mainly involving basal ganglia, cerebellar and default mode networks (DMN), and some increase of dFNC of visual, executive and attention networks. DFNC was significantly increased over time in both MS groups, especially in State1, with more effects in MS-AOT than in MS-C, and an involvement of sensorimotor, visual, basal ganglia, DMN and attention networks. Conversely, HC-groups showed a decrease of dFNC at w2 vs t0, with a prevalent involvement of sensorimotor, basal ganglia, cerebellar and attention networks in HC-AOT, and of DMN and attention network in HC-C.

Two-weeks of AOT modulated dFNC of several functional networks in MS patients.