Cease or Persist: A multivariate mechanistic account of effortful persistence

Is this worth my effort? Should I persist and push through or give up and move on? We are constantly confronted with this fundamental question. Persisting through effortful endeavors at all costs is often the key to success in modern society.

Reduced or excessive persistence is a hallmark dysfunction in many neuropsychiatric disorders (anxiety, depression, OCD, apathy, etc.) with massive individual and societal cost.

Despite the urgency to better understand this process, how exactly we decide to cease or persist, and which cognitive, neural and neurochemical systems support persistence, remains unclear.

With COPE, I propose a novel neuro-computational theory of effortful persistence, able to predict decisions to Cease or Persist (COPE), and how they emerge from the dynamic multivariate optimization of costs and benefits across momentary and long-term time scales.

I propose that persistence depends on how much reward or punishment we expect, how effective our efforts are, and how surprising and unstable the environment is.

I will 1) establish and test a neuro-computational model able to simulate effortful persistence, and the neural and neurochemical systems involved in supporting it. 2) I will causally test the neural circuit involved in effortful persistence combining transcranial Focused Ultrasound stimulation with advanced neuroimaging protocols designed to capture activity in small brainstem and midbrain nuclei. 3) I will probe the contribution of 3 key neurochemicals Dopamine, Noradrenaline, and Serotonin and use the COPE model as a prediction tool of the impact of pharmacological manipulation on brain systems and behaviour.

COPE integrates the algorithmic, neural and neurochemical levels of explanation in a unifying model of effortful persistence, laying the grounds for phenotyping of abnormal decision-making in psychiatric disorders and personalization of treatment selection.