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. 24 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. The pre-supplementary motor area (preSMA) has been implicated in inhibitory control. Here, we provide evidence that this region contributes to the implementation of general impulsive tendencies (trait impulsivity) into actual behavior (state impulsivity). When healthy volunteers performed a sequential gambling task, their choice behavior (i.e., state impulsivity) correlated positively with their impulsivity score (i.e, trait impulsivity). Additionally, participants with lower trait impulsivity showed a stronger increase in task-related activity of the preSMA with increasing risk. Both of these relationships were uncoupled after perturbing the preSMA with repetitive transcranial stimulation (rTMS). ### Competing Interest Statement Conflict of interest statement: Al.L.: None. An.L.: speaking fees, Abbvie. H.R.S.: Has received honoraria as speaker from Lundbeck AS, Denmark, Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Lundbeck AS, Denmark and Sanofi Genzyme, Denmark and as senior editor (NeuroImage) and editor-in-chief (Neuroimage Clinical) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany. D.M.: None.