Neurocomputational mechanisms of serotonin, sustained stress, and mental effort allocation

Project Summary/Abstract Human beings have a remarkable capacity for exerting cognitive control to achieve their goals, even though performing such tasks can be stressful (e.g., getting into college, landing a job or promotion). Although the ability to exert cognitive control to achieve goals in the face of ongoing stress is highly significant for determining one’s

productivity, health, and well-being, the neurocomputational mechanisms by which cognitive control is evaluated are poorly understood. Recent research suggests that people consider the controllability of a sustained stressor in deciding how to strategically allocate mental effort, yet how people perform this strategic adjustment is unclear.

Whereas substantial research has examined how acute stress (e.g., cold pressor) influences mental effort, less is known about how the contingencies of sustained stress (e.g., ongoing controllable vs. uncontrollable shocks) drive different strategies for mental effort allocation (e.g., attentional focus or response caution). This proposal

will investigate the serotonergic influence on neural and computational processes that underlie how individuals exert mental effort in the face of sustained and uncontrollable stressors (shock). I will leverage our novel Stressor Controllability and Cognitive Control (SCCC) model, psychopharmacology, and pharmaco-fMRI to identify these

neurocomputational mechanisms and test whether serotonin interacts with the aversiveness and controllability of ongoing stressors to bias distinct effort strategies for control allocation. Aim 1 (K99) will use the SCCC model to generate predictions for how sustained stressors guide different effort strategies (e.g., focus vs. caution) and

identify separate sub-processes that reflect the (1) aversiveness and (2) controllability of sustained stressors during these decisions. Aim 2 (K99) will use a pharmacological probe (escitalopram) to test if controllability is a key factor determining when and how SSRIs are effective in modulating strategic goal-directed adjustments in

mental effort allocation. Aim 3 (R00) will use pharmaco-fMRI to investigate to what extent distinct brain networks (e.g., dorsal vs. ventral medial prefrontal cortex) underlie stressor controllability and cognitive control, and localize serotonin influences in neural pathways. These Specific Aims support the applicant’s training goals

(computational modeling of stress/affect, psychopharmacology). The training plan includes various workshops, courses, and guided readings to help the applicant gain the expertise to conduct trailblazing research on stress and cognitive control as an independent investigator. The intellectual environment at Brown is rich and highly

interdisciplinary. The applicant will benefit from frequent interactions with world-renowned faculty with substantial expertise in topics related to the proposed research (e.g., computational modeling of stress, affect, and cognitive control). Understanding the computations, networks, and neurotransmitter systems through which sustained

stressors guide mental effort will inform how disrupted neural networks give rise to motivational impairments

(e.g., apathy, amotivation). Clarifying the role of serotonin in stressor controllability and mental effort is significant and can help understand why and when people are vulnerable vs. resilient to stressors in psychiatric disorders.