Neural circuit mapping of waiting impulsivity and proactive inhibition with convergent evidence from fMRI and TMS

Waiting and stopping are essential and distinct elements of motor response inhibition. Waiting impulsivity has been traditionally studied in humans with choice serial reaction time tasks. Proactive stopping is one form of stopping relevant to waiting impulsivity and the neural substrates underlying their interaction are not well defined.

We conducted two separate, but hierarchical studies. In the first we used functional magnetic resonance imaging (fMRI), a choice reaction time task and a novel proactive stopping task, in N = 41 healthy volunteers to map the overlapping neural circuit involved in waiting impulsivity and proactive stopping. In the second study, we aimed to provide mechanistic and causal evidence that disruption of this circuit with continuous theta burst stimulation (cTBS; an inhibitory repetitive transcranial magnetic stimulation protocol) affected waiting impulsivity. We recruited N = 51 healthy, right-handed volunteers in a single-blind, randomized, between-subjects design who were randomly allocated to stimulation (N = 26) and sham (N = 25) groups and subsequently performed a choice reaction time task.

In the first study, we showed; 1. a shared neural network comprising the pre- supplementary motor area and bilateral anterior insula underlying both waiting impulsivity and proactive stopping, and 2. activity in dorsomedial prefrontal cortex and left inferior frontal gyrus negatively correlated with waiting impulsivity in trials with additional target onset delay. In the second study, we demonstrated that inactivation of the left inferior frontal gyrus using cTBS significantly increased waiting impulsivity in a choice reaction time task.

Our findings highlight the relevance of task design in assessing motor response inhibition and the role of the left inferior frontal gyrus integrity and related neural circuitry in waiting impulsivity and proactive stopping. We also leverage the use of convergent evidence from multi-modal investigation tools in addressing the causal neural areas underlying distinct forms of impulsivity.