Significance Many studies have examined plasticity in the primary somatosensory and motor cortex during disuse, but little is known about how disuse impacts the brain outside of primary cortical areas. We leveraged the whole-brain coverage of resting-state functional MRI (rs-fMRI) to discover that disuse drives plasticity of distant executive control regions in the cingulo-opercular network (CON). Two complementary analyses, pulse censoring and pulse addition, demonstrated that increased functional connectivity between the CON and disused motor regions was driven by large, spontaneous pulses of activity appearing during disuse. These results point to a role for the CON in motor plasticity and reveal spontaneous activity pulses as a potential mechanism for maintaining and reorganizing the brain’s functional connections.