Objectives Waiting and stopping are essential and distinct elements of appropriate behavioural control with its dysfunction implicated in various impulsivity related mental disorders. Although rodent and human studies have investigated both phenomena, the role of preparing to stop in waiting impulsivity has rarely been investigated. Furthermore, convergent evidence from multi-modal investigation tools remains a poorly utilized approach in addressing such questions.

Methods Here, we conducted two separate, but hierarchical studies, using functional magnetic resonance imaging (fMRI) to map the neural circuit involved in waiting impulsivity and proactive stopping, and subsequently provide mechanistic and causal evidence of disruption of this circuit by transcranial magnetic stimulation (TMS). We used a validated human version of the 5-Choice Serial Reaction Time (5CSRT) task and developed a novel proactive stopping task.

Results We first show a shared neural network comprising the pre-supplementary motor area and bilateral anterior insula underlying both waiting impulsivity and proactive stopping. We further demonstrate activity in dorsomedial prefrontal cortex and left inferior frontal gyrus (LIFG) negatively correlated with waiting impulsivity in trials with additional target onset delay. A subsequent study applying continuous theta burst stimulation (a TMS inhibitory protocol) to LIFG in fifty-one healthy volunteers in a single-blind, randomized control-design, demonstrated active stimulation of LIFG significantly increased waiting impulsivity.

Conclusions Our findings highlight the relevance of task design in assessing waiting impulsivity with CSRT tasks and highlight the role of LIFG integrity and related neural circuitry in waiting impulsivity.