CHEMCONTROL · Balancing brain chemicals for boosting meta-control

Cognitive control enables us to flexibly adapt behaviour to achieve our goals given a constantly changing environment. It is a hallmark of the human mind and exquisitely vulnerable in health and disease. Cognitive control often implies goal-directed instrumental effort to inhibit unwanted, yet hardwired or overlearnt biases, and is commonly associated with the prefrontal cortex (PFC) and dopamine (DA). However, the mechanisms of the broader construct of flexible cognitive control remain unclear. The urgency of addressing this is evidenced by robust predictive associations between flexible control and consequential life outcomes for health, wealth and well-being. CHEMCONTROL approaches the problem from a novel angle, reconceptualizing it as meta-level decision-making between distinct control strategies. I propose to shift attention away from the classic focus on instrumental effort, implicating PFC and DA, towards a richer meta-control framework that takes into account outcome controllability. CHEMCONTROL radically upgrades the value of an opponent, cognitively effortless strategy that releases hardwired Pavlovian biases, implicating serotonin (5-HT). It redefines PFC function as making meta-level decisions between expensive dopaminergic versus frugal serotonergic strategies based on estimating outcome controllability. We have recently validated a computational procedure for quantifying controllability estimates. I will combine this procedure with (i) high-resolution fMRI to compare neural activity in DA and 5-HT systems and (ii) novel PET designs to compare DA and 5-HT release. Next, I will use (iii) psychopharmacology and (iv) ultrasound neuromodulation, to causally manipulate key model components. CHEMCONTROL will unravel the mechanisms of (boosting) meta-control, revolutionizing strategies for promoting efficacy and resilience in a rapidly changing world.