The subthalamic nucleus (STN) is thought to be a central regulator of behavioral inhibition, which is thought to be a major determinant of impulsivity. Thus, it would be reasonable to hypothesize that STN function is related to impulsivity. However, it has been difficult to test this hypothesis because of the challenges in noninvasively and accurately measuring this structure's signal in humans. We utilized a novel approach for STN signal localization that entails identifying this structure directly on fMRI images for each individual participant in native space. Using this approach, we measured STN responses during the stop signal task in a sample of healthy adult participants. We confirmed that the STN exhibited selective activation during “Stop” trials. Furthermore, the magnitude of STN activation during successful Stop trials inversely correlated with individual differences in trait impulsivity as measured by a personality inventory. Time course analysis revealed that early STN activation differentiated successful from unsuccessful Stop trials, and individual differences in the magnitude of STN activation inversely correlated with stop signal RT, an estimate of time required to stop. These results are consistent with the STN playing a central role in inhibition and related behavioral proclivities, with implications for both normal range function and clinical syndromes of inhibitory dyscontrol. Moreover, the methods utilized in this study for measuring STN fMRI signal in humans may be gainfully applied in future studies to further our understanding of the role of the STN in regulating behavior and neuropsychiatric conditions.

The ability to proactively control motor responses, particularly to overcome overlearned or automatic actions, is an essential prerequisite for adaptive, goal-oriented behavior. The substantia nigra (SN), an element of the BG, has figured prominently in current models of response selection. However, because of its small size and proximity to functionally distinct subcortical structures, it has been challenging to test the SN's involvement in response selection using conventional in vivo functional neuroimaging approaches. We developed a new fMRI localization method for directly distinguishing, on echo-planar images, the SN BOLD signal from that of neighboring structures, including the subthalamic nucleus (STN). Using this method, we tested the hypothesis that the SN supports the proactive control of response selection. We acquired high-resolution EPI volumes at 3 T from 16 healthy participants while they completed the Preparing to Overcome Prepotency task of proactive control. There was significantly elevated delay period signal selectively during high- compared with low-control trials in the SN. The STN did not show delay period activity in either condition. SN delay period signal was significantly inversely associated with task performance RTs across participants. These results suggest that our method offers a novel means for measuring SN BOLD responses, provides unique evidence of SN involvement in cognitive control in humans, and suggests a novel mechanism for proactive response selection.

When predicting where a target or reward will be, participants tend to choose each location commensurate with the true underlying probability (i.e., probability match). The strategy of probability matching involves independent sampling of high and low probability locations on separate trials. In contrast, models of probabilistic spatial attention hypothesize that on any given trial attention will either be weighted toward the high probability location or be distributed equally across all locations. Thus, the strategies of probabilistic sampling by choice decisions and spatial attention appear to differ with regard to low-probability events. This distinction is somewhat surprising because similar brain mechanisms (e.g., pFC-mediated cognitive control) are thought to be important in both functions. Thus, the goal of the current study was to examine the relationship between choice decisions and attentional selection within single trials to test for any strategic differences, then to determine whether that relationship is malleable to manipulations of catecholamine-modulated cognitive control with the drug modafinil. Our results demonstrate that spatial attention and choice decisions followed different strategies of probabilistic information selection on placebo, but that modafinil brought the pattern of spatial attention into alignment with that of predictive choices. Modafinil also produced earlier learning of the probability distribution. Together, these results suggest that enhancing cognitive control mechanisms (e.g., through prefrontal cortical function) leads spatial attention to follow choice decisions in selecting information according to rule-based expectations.