Resting-state and task-based centrality of dorsolateral prefrontal cortex predict resilience to inhibitory repetitive transcranial magnetic stimulation

Background Repetitive transcranial magnetic stimulation (rTMS) is used to investigate normal brain function in healthy participants and as a treatment for brain disorders. Various subject factors can influence individual response to rTMS, including brain network properties. Objective/Hypothesis A previous study by our group showed that ‘virtually lesioning’ the left dorsolateral prefrontal cortex (dlPFC; important for cognitive flexibility) using inhibitory rTMS reduced performance on a set-shifting task. We aimed to determine whether this behavioural response was related to topological features of pre-TMS resting-state and task-based functional networks. Methods Inhibitory (1Hz) rTMS was applied to the left dlPFC in 16 healthy participants, and to the vertex in 17 participants as a control condition. Participants performed a set-shifting task during fMRI at baseline and directly after a single rTMS session 1-2 weeks later. Functional network topology measures were calculated from resting-state and task-based fMRI scans using graph theoretical analysis. Results The dlPFC-stimulated group, but not the vertex group, showed reduced set shifting performance after rTMS associated with lower task-based betweenness centrality of the dlPFC at baseline (p=.030) and a smaller reduction in task-based betweenness centrality after rTMS (p=.024). Reduced repeat trial accuracy after rTMS was associated with higher baseline resting state node strength of the dlPFC (p=.017). Conclusions Our results suggest that behavioural response to inhibitory rTMS to the dlPFC is dependent on baseline functional network features. Individuals with more globally integrated stimulated regions show greater resilience to inhibitory rTMS, while individuals with more locally well-connected regions show greater vulnerability. Highlights Functional brain network properties predict behavioural response to 1Hz DLPFC rTMS Globally integrated stimulated regions are resilient to effects of inhibitory rTMS Segregated, locally well-connected regions are vulnerable to inhibitory rTMS Change in performance after rTMS correlates with change in network properties