Technology-enhanced learning frequency and perceived academic acceleration in AI-mediated digital learning environments: self-efficacy as an indirect pathway and learning motivation as a boundary cond

Stress is implicated in the etiology of mood and anxiety disorders including major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) (, ). These conditions share many core features, including diminished ability to experience pleasure or positive emotions (anhedonia), social avoidance, and sleep disruption (), suggesting a shared pathophysiology. The overlap in symptomatology illustrates potential benefits of using Research Domain Criteria (RDoC) principles () to focus research on translationally-relevant features (e.g., social avoidance) that cut across multiple conditions rather than on narrow diagnostic categories that even highly skilled clinicians may struggle to differentiate in humans (, ). These symptoms are persistent, debilitating, and resistant to treatment, contributing to profound economic and social burdens (, ). Stress can produce neuroadaptive responses (alterations in gene and protein expression) that contribute to persistent and often maladaptive changes in behavior (, ). While these neuroadaptations occur throughout the brain, work focusing on the nucleus accumbens (NAc) provides strong evidence that stress produces changes in behavior via effects on CREB (cAMP response element binding protein) (, , , ), a transcription factor that regulates expression of myriad genes (). A variety of stressors (forced swimming, footshock, social defeat) activate CREB in the NAc, which elevates expression of the opioid peptide dynorphin (DYN), which in turn causes depressive behaviors via activation of kappa-opioid receptors (KORs) (, ). A key mechanism of this effect is that increased DYN acts upon KORs expressed on the terminals and cell bodies of ventral tegmental area (VTA) dopamine (DA) neurons (, ), producing inhibition of mesolimbic system function. The ability of KOR antagonists to relieve this inhibitory tone is a putative neural mechanism of their antidepressant- and anxiolytic-like effects (, ). Increased CREB and KOR function are implicated in despair/learned helplessness (), anxiety/avoidance behavior (), disrupted attention (), anhedonia and fear (), and sleep dysregulation (, ). Collectively, these studies suggest that a common pathophysiology within the NAc explains a broad assortment of features that are frequently co-morbid in stress-related disorders. An improved understanding of mechanism may enable development of new treatments that, by targeting the NAc and its specific cell populations, could dramatically improve outcomes by relieving numerous signs of stress-related illnesses simultaneously. The NAc is the ventral aspect of the striatum, which is composed largely of MSNs that segregate into two major populations, defined by expression of DA D1 or D2 receptors (D1Rs and D2Rs, respectively) (). Considerable evidence indicates that DYN in the NAc arises primarily from D1R-expressing MSNs. Specifically, seminal hybridization studies showed that prodynorphin ()—the gene encoding DYN—segregates with D1R–expressing MSNs, whereas proenkephalin ()—encoding enkephalin—marks D2R-expressing MSNs. This pattern was subsequently confirmed in the human NAc (). More recent cell type–specific approaches in mice, including D1/D2 neuronal profiling (), translational profiling (TRAP) (), and single-cell transcriptomics (, ) consistently show that expression of occurs almost exclusively in D1R-MSNs, with little-to-no expression in D2R-MSNs.