Human decisions about when to act originate within a basal forebrain-nigral circuit

Decisions about when to act are critical for survival in humans as in animals, but how a desire is translated into the decision that an action is worth taking at any particular point in time is incompletely understood. Here we show that a simple model developed to explain when animals decide it is worth taking an action also explains a significant portion of the variance in timing observed when humans take voluntary actions. The model focuses on the current environment's potential for reward, the timing of the individual's own recent actions, and the outcomes of those actions. We show, by using ultrahigh-field MRI scanning, that in addition to anterior cingulate cortex within medial frontal cortex, a group of subcortical structures including striatum, substantia nigra, basal forebrain (BF), pedunculopontine nucleus (PPN), and habenula (HB) encode trial-by-trial variation in action time. Further analysis of the activity patterns found in each area together with psychophysiological interaction analysis and structural equation modeling suggested a model in which BF integrates contextual information that will influence the decision about when to act and communicates this information, in parallel with PPN and HB influences, to nigrostriatal circuits. It is then in the nigrostriatal circuit that action initiation per se begins.