Biological Mechanisms

Acute stress impairs working memory (g+ = -0.20), cognitive flexibility (g+ = -0.30), and cognitive inhibition (g+ = -0.208) while enhancing response inhibition, with effects increasing under high cognitive load.

Norepinephrine and dopamine have inverted-U shaped influences on PFC function: optimal levels enhance working memory and top-down control, high levels (stress) impair PFC by shifting control from reflective dlPFC circuits to reflexive subcortical circuits.

The vmPFC detects controllability and gates the stress response: when stressors are controllable, vmPFC sends glutamatergic projections to GABAergic interneurons in the DRN, suppressing 5-HT neurons and preventing the stress response cascade.

DA output from VTA is gain-controlled at the population level by the vSub -> NAcc -> VP -> VTA pathway, where the hippocampal pathway controls how many DA neurons are available for phasic response and environmental signals (controllability, uncertainty, volatility) modulate this gain.

Hopelessness (negative instrumental beliefs, ACC-mediated, LC-NE modulated) and controllability (vmPFC-DRN-Amy network, 5-HT modulated) are computationally distinct but coupled through LC-to-DRN projections that regulate 5-HT release.

LC neurons exhibit two modes -- phasic (task-focused, exploitation) and tonic (disengaged, exploration) -- implementing the exploration-exploitation tradeoff at the neurobiological level via NE gain modulation.

Neuromodulators (NE, DA, ACh, 5-HT) create flexibilities and vulnerabilities in PFC network synapses -- the same molecular events enabling rapid modulation of mental representations also make PFC uniquely vulnerable to disruption.

Humans maintain parallel actor (controllable) and spectator (uncontrollable) models; uncontrollable stressors bias the controllability inference system itself toward perceiving uncontrollability.