Resting-state brain network features associated with short-term skill learning ability in humans and the influence of N -methyl- d -aspartate receptor antagonism

Graph theoretical functional magnetic resonance imaging (fMRI) studies have demonstrated that brain networks reorganize significantly during motor skill acquisition, yet the associations between motor learning ability, brain network features, and the underlying biological mechanisms remain unclear. In the current study, we applied a visually guided sequential pinch force learning task and graph theoretical analyses to investigate the associations between short-term motor learning ability and resting-state brain network metrics in 60 healthy subjects. We further probed the test-retest reliability ( = 26) and potential effects of the -methyl- -aspartate (NMDA) antagonist ketamine ( = 19) in independent healthy volunteers. Our results show that the improvement of motor performance after short-term training was positively correlated with small-worldness ( = 0.032) and global efficiency ( = 0.025), whereas negatively correlated with characteristic path length ( = 0.014) and transitivity ( = 0.025). In addition, using network-based statistics (NBS), we identified a learning ability–associated ( = 0.037) and ketamine-susceptible ( = 0.027) cerebellar-cortical network with fair to good reliability (intraclass correlation coefficient [ICC] > 0.7) and higher functional connectivity in better learners. Our results provide new evidence for the association of intrinsic brain network features with motor learning and suggest a role of NMDA-related glutamatergic processes in learning-associated subnetworks. Learning a new motor skill prompts immediate reconfigurations of distributed brain networks followed by adaptive changes in intrinsic brain circuits related to synaptic plasticity. Here, we identify global brain network properties and a cerebellar-cortical functional subnetwork that are both significantly associated with motor learning ability in a previously trained visuomotor task in humans. We further show that the associated functional subnetwork connectivity but not the global brain network properties are susceptible to ketamine. Our findings suggest a distinct functional role for learning-related global versus local network metrics and support the idea of a preferential susceptibility of learning-associated subnetworks to -methyl- -aspartate antagonist and plasticity-related consolidation effects.