Altered resting-state network effects in patients after stroke following cortico-cortical target transcranial...

The brain operates through large-scale, distributed networks, which are disrupted after stroke. Cortico-cortical paired associative stimulation (ccPAS) is a novel neuromodulation technique designed to induce spike-timing-dependent plasticity in specific pathways. However, its effects on large-scale resting-state networks (RSNs) in stroke patients remain unclear. In this randomized, double-blind, sham-controlled study, 31 chronic stroke patients (mean age: 49.4 ± 11.8 years) with unilateral supratentorial lesions and upper limb motor dysfunction were recruited. Participants received a 12-day intervention of either active ccPAS (n = 16) or sham stimulation (n = 15) targeting the supplementary motor area (SMA) and primary motor cortex (M1) with a +6 ms interval, and routine rehabilitation. Resting-state functional MRI was acquired pre- and post-intervention. Independent component analysis was used to identify RSNs, and functional network connectivity (FNC) was assessed. Compared to the sham group, the ccPAS group exhibited significantly integrated functional connectivity within three visual networks, the bilateral frontoparietal network, dorsal attention network, default mode network, the sensorimotor network and auditory network (P < 0.001). FNC analysis revealed a reduced time lag between the primary visual network and the sensorimotor network post-ccPAS (P < 0.05). ccPAS targeting the SMA-M1 pathway induces widespread reorganization of RSNs, enhancing connectivity within and between networks subserving attention, visuospatial processing and sensorimotor integration. This pattern of change is consistent with mechanisms of adaptive neuroplasticity and suggests that ccPAS can facilitate recovery by modulating higher-order, distributed brain networks in chronic stroke patients. Chinese Clinical Trial Registry: ChiCTR2000036685.