Beyond the Motor Cortex: Theta Burst Stimulation of the Anterior Midcingulate Cortex

BACKGROUND: While the facilitatory and inhibitory effects of intermittent theta burst stimulation (iTBS) and continuous TBS (cTBS) protocols have been well documented on motor physiology, the action of TBS protocols on prefrontal functioning remain unclear. Here we asked whether iTBS or cTBS can differentially modulate rewardrelated signaling in the anterior midcingulate cortex (aMCC). METHODS: Across 2 experiments, we used a robot-assisted transcranial magnetic stimulation system, combined with electroencephalogram recordings, to investigate the aftereffects of prefrontal iTBS and cTBS on the reward positivity, an electrophysiological signal believed to index sensitivity of the aMCC to rewards. Twenty adults (age, 18-28 years) participated in experiment 1 in which we used a scalp landmark for TBS targeting, and 14 adults (age, 18-28 years) participated in experiment 2, in which we aimed to increase TBS effectiveness by utilizing cortical thickness maps to select individualized dorsal lateral prefrontal cortex targets. RESULTS: We demonstrated that prefrontal iTBS suppressed reward-related signaling in the aMCC (reduction in reward positivity) and caused a decrease in postfeedback switch choices. cTBS displayed no effect. We replicated and strengthened this effect on the reward positivity by targeting dorsal lateral prefrontal cortex regions displaying maximal cortical thickness. CONCLUSIONS: While these results are inconsistent with reported TBS effects on motor cortex, the present findings offer a novel transcranial magnetic stimulation targeting approach and normative insights into the magnitude and time course of TBS-induced changes in aMCC excitability. By modulating how the aMCC links value to goal-directed behavior, this research opens an exciting new era of investigative possibilities in the understanding of aMCC function and treatment of aMCC dysfunction.