The ventral striatum is believed to encode the subjective value of cost/benefit options; however, this effect has strikingly been absent during choices that involve physical effort. Prior work in freely-moving animals has revealed opposing striatal signals, with greater response to increasing effort demands and reduced responses to rewards requiring effort. Yet, the relationship between these conflicting signals remains unknown. Using fMRI with a naturalistic, effort-based navigation paradigm, we identified functionally-segregated regions within ventral striatum that separately encoded action, effort, and discounting of rewards by effort. Strikingly, these sub-regions mirrored results from a large-sample connectivity-based parcellation of the striatum. Moreover, individual differences in striatal effort activation and effort discounting signals predicted striatal responses to effort-related choices during an independent fMRI task. Taken together, our results suggest that a dorsomedial region primarily associated with action may instead represent the effort cost of actions, and raises fundamental questions regarding the interpretation of striatal “reward” signals in the context of effort demands.

Stress is a major risk factor for the development of mental illness, including major depressive disorder (MDD), yet the underlying biological mechanisms remain unclear. Particular challenges lie in disentangling adaptive versus maladaptive responses to repeated stress exposure. Preclinically, stress-induced changes in glutamatergic function have been frequently observed in the medial prefrontal cortex (mPFC), a key region for mediating adaptive stress responses. Here, we examined stress-induced changes in mPFC glutamate using magnetic resonance spectroscopy (MRS) in four human samples varying in perceived stress exposure. Changes in mPFC glutamate following an acute stressor were reliably moderated by recent perceived stress in healthy controls. This adaptive glutamate response was absent in unmedicated individuals with MDD and was associated with excessively pessimistic beliefs as assessed via ecological momentary assessments over a 1-month follow-up period. Taken together, these data provide novel evidence for glutamatergic adaptation to stress in mPFC that is significantly disrupted in MDD.