A Basal Forebrain-Cingulate Circuit in Macaques Decides It Is Time to Act

Abstract

The medial frontal cortex has been linked to voluntary action, but an explanation of why decisions to act emerge at particular points in time has been lacking. We show that, in macaques, decisions about whether and when to act are predicted by a set of features defining the animal's current and past context; for example, respectively, cues indicating the current average rate of reward and recent previous voluntary action decisions. We show that activity in two brain areas-the anterior cingulate cortex and basal forebrain-tracks these contextual factors and mediates their effects on behavior in distinct ways. We use focused transcranial ultrasound to selectively and effectively stimulate deep in the brain, even as deep as the basal forebrain, and demonstrate that alteration of activity in the two areas changes decisions about when to act.

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

“…1E). Previous investigations have shown that the timing of the next action that a rat or macaque makes is related to the timing of recent previous actions (5,14). Therefore, in addition to the present context, we also investigated whether the outcomes and action times of recent past trials influenced human participants' action time on the current trial.…”

“…to Act. Having shown that contextual factors influence decision time to act, we next used a Cox proportional hazard model to estimate actTime, at each trial, from present and past contextual factors (5,14). Specifically, we asked how much time (in seconds) would pass before a participant decided to respond, given present and past contextual factors.…”

“…A Subset of Subcortical Structures Encodes Decision Time to Act. To identify potential subcortical structures that track the parametric variation in action time we examined activity in anatomical regions of interest (ROIs), which have been linked to action initiation (5,7,11,13,15,16). The a priori selected ROIs included caudate nucleus (CN), putamen, nucleus accumbens (NAc), globus pallidus (GP), SN, ventral tegmental area (VTA), PPN, HB, and BF (note that because of the close adjacency of several small and diverse nuclei near the nucleus basalis, our BF region focuses on septal nuclei and part of the diagonal band of Broca) (Fig.…”

“…We have recently shown in macaques that a circuit comprising anterior cingulate cortex (ACC) and basal forebrain (BF) integrates past and present contextual information that influences when an action is made (5). However, the interplay between BF and other brain circuits involved in the generation of selfinitiated actions remains unclear.…”

Differential functional connectivity underlying asymmetric reward-related activity in human and nonhuman primates

“…Protocols 2 and 3 in monkeys: Decision to act task. The experimental task used in protocol 2 is described in detail elsewhere (64). Briefly, the task was designed to investigate how contextual factors and internal state, shaped by present and past environment, are integrated to influence whether and when to act.…”