Transcranial focused ultrasound to rIFG improves response inhibition through modulation of the P300 onset latency

Response inhibition is important to avoid undesirable behavioral action consequences. Neuroimaging and lesion studies point to a locus of inhibitory control in right inferior frontal gyrus (rIFG). Electrophysiology studies have implicated a downstream event-related potential from rIFG, the fronto-central P300, as a putative neural marker of the success and timing of inhibition over behavioral responses. However, it remains to be established whether rIFG effectively drives inhibition as represented by the P300 activity, and whether rIFG contributions to inhibition are conveyed through either the P300 timing or amplitude. Here, we aimed to causally uncover the connection between rIFG and P300 for inhibition by using transcranial focused ultrasound (tfUS) to target rIFG of human subjects while they performed a Stop-Signal task. By applying tFUS simultaneous with different task events, we found behavioral inhibition was improved only when applied to rIFG simultaneous with a ‘stop’ signal. Applying tFUS simultaneous with the ‘go’ signal or control regions had no impact on behavior. The improvement in inhibition performance caused by tFUS to rIFG during stop conditions occurred through faster stopping times that were paired with significantly shorter P300 latencies, whereas amplitude was not affected. These results reveal a causal connection between rIFG in driving response inhibition in that it may regulate the speed of stopping directly, as indexed by the reduced P300 onset latency during tFUS. Our tFUS-EEG approach provides a causal connection, in healthy humans, between prefrontal rIFG regions and downstream P300 production in service of inhibitory control.