Linking impulsivity to activity levels in pre-supplementary motor area during sequential gambling.

Impulsivity refers to the tendency to act prematurely or without forethought, and excessive impulsivity is a key problem in many neuropsychiatric disorders. Since the pre-supplementary motor area (preSMA) has been implicated in inhibitory control, this region may also contribute to impulsivity. Here, we examined whether functional recruitment of preSMA may contribute to risky choice behavior (state impulsivity) during sequential gambling and its relation to self-reported trait impulsivity. To this end, we performed task-based functional MRI (fMRI) after low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of the preSMA. We expected low-frequency rTMS to modulate task-related engagement of the preSMA and, hereby, tune the tendency to make risky choices. Twenty-four healthy volunteers (12 females, 19-52 years) received real or sham rTMS on separate days in counterbalanced order. Thereafter, participants performed a sequential gambling task with concurrently increasing stakes and risk during whole-brain fMRI. In the sham-rTMS session, self-reported trait impulsivity scaled positively with state impulsivity (riskier choice behavior) during gambling. The higher the trait - impulsivity, the lower was the task-related increase in preSMA activity with increasingly risky choices. Following real-rTMS, low-impulsivity participants increased their preference for risky choices, while the opposite was true for high-impulsivity participants resulting in an overall decoupling of trait impulsivity and state impulsivity during gambling. This rTMS-induced behavioral shift was mirrored in the rTMS-induced change in preSMA activation. These results provide converging evidence for a causal link between the level of task-related preSMA activity and the propensity for impulsive risk-taking behavior in the context of sequential gambling. SIGNIFICANCE STATEMENT: Impulsivity is a personal trait characterized by a tendency to act prematurely or without forethought, and excessive impulsivity is a key problem in many neuropsychiatric disorders. Here we provide evidence that the pre-supplementary motor area, preSMA, is causally involved in implementing general impulsive tendencies (trait impulsivity) into actual behavior (state impulsivity). Participants' self-reported impulsivity levels (trait impulsivity) were reflected in their choice behavior (state impulsivity) when involved in a sequential gambling task. This relationship was uncoupled after perturbing the preSMA with repetitive transcranial stimulation (rTMS). This effect was contingent on trait impulsivity and was echoed in rTMS-induced changes in preSMA activity. PreSMA is key in translating trait impulsivity into behavior, possibly by integrating prefrontal goals with cortico-striatal motor control.