Psychosocial stress exerts deleterious effects on neurocognitive function across the lifespan (de Kloet et al., 2005; Lupien et al., 2009; McEwen et al., 2015). Working memory (WM) is a key executive function that is susceptible to the negative impact of stress (Evans, Farah and Hackman, 2021; Oshri et al., 2019). Extant research suggests that WM deficits associated with uncontrolled stress underlie a wide range of psychopathology (Evans and Schamberg, 2009; Klein et al., 2001; Morgan III, Doran, Steffian, Hazlett, & Southwick, 2006). However, the effects of stress on cognitive functions, including WM, may not be linear. An established hypothesis in biomedical research suggests that the effect of stress on adaptive functioning emerges in a curvilinear, inverted U-shaped dose-response pattern (Calabrese, 2008a, 2008b). The psychosocial hormesis hypothesis (Oshri, 2022) suggests that exposure to low-moderate stress levels induces beneficial adaptation, up to a threshold, from which point, increasingly higher levels of prolonged stress induce functional inefficiency and toxicity. The present study tests the hormesis model of psychosocial stress by examining relations between recent prolonged perceived stress and neurobehavioral response to a WM challenge among a large sample of healthy adults.
Extant research shows linkages between exposure to a range of psychosocial stress (e.g., adverse parenting, work, and poverty) and WM behavioral performance problems in youth and adults (Evans and Schamberg, 2009; Farah et al., 2006; Mika et al., 2012; Noble et al., 2007; Oshri et al., 2019). Studies on youth show that executive functions such as WM are particularly vulnerable to toxic stress, whereas high WM capacity is a potent protective factor from severe psychosocial stress (Gary W Evans and Kim, 2013; Karalunas et al., 2017). WM and other executive functions are critical for goal-directed behavior in general and problem solving and adaptation in particular (Greiff et al., 2015; Wiley and Jarosz, 2012). However, more recent empirically supported theories suggest that stress may also enhance cognitive performance (Frankenhuis and De Weerth, 2013; Sapolsky, 2015). In a small cross-sectional study of 20 healthy young adults, Oei et al. (2006) suggested that psychosocial stress impaired WM performance, but this adverse effect was present only at high-stress levels. Although this study did not directly test the hormesis hypothesis, it provided preliminary evidence that stress exerts a nonlinear effect on cognition.
Psychosocial stress is considered a subjective construct because it is defined as a state in which an organism perceives that its homeostasis is threatened (Chrousos, 2009). Neurobiological and behavioral responses are adaptive when stress is acute and situational (Ursin and Eriksen, 2004). When psychosocial stress is not transitory and perceived to be beyond one's control, the sustained neurobiological impacts may be toxic and behaviorally maladaptive, as described by the allostatic load theory (McEwen et al., 2015). Despite being well-documented, the adverse effects of stress vary as a function of severity and across individuals, with some emerging research reporting benefits of stress on cognitive function and adjustment (Crane et al., 2019; Höltge et al., 2019). The hormetic effect refers to a curvilinear dose-response relation in which a low dose of environmental stress (adversity or toxicity) induces constructive neurobiological and neurobehavioral processes to promote adaptation up to a threshold of stress level (Oshri, 2022). Once this threshold is reached, adjusting to higher stress levels becomes increasingly demanding and may be cognitively deleterious (Calabrese and Baldwin, 2002; Mattson, 2008b). Of note, in the psychosocial hormesis model, we refer to cumulative or prolonged stress levels as opposed to normative acute stress. Emerging research shows the benefits of experiencing prolonged and moderate stress levels on cognition and human adjustment (Crane et al., 2019; Höltge et al., 2019). However, the hormetic process goes beyond the current documentation of benefits related to stress. The hormesis model of psychosocial stress purports (Oshri et al., 2022) that an organism's exposure and attendant preparation for stress is facilitated through a process called preconditioning, which underlies the strengthening effect and contributes stress tolerance and possibly the emergence of neural and psychological adaptation to future stress (Calabrese et al., 1999). Specifically, when exposed to low-moderate stress levels, the organism can strengthen and reorganize in anticipation of exposure to future threats. Based on this hypothesis, preconditioning underlies an inoculation phase in which the organism is cued to reorganize, prepare, and behaviorally cope with subsequent stress more effectively. Fig. 1 presents a generic conceptual model of the hormetic relation between stress severity (i.e., perceived stress level in the past month) and neurocognitive functioning. Neurobiological, cognitive, and behavioral changes are triggered as a function of stress severity, ranging between low and moderate under normal circumstances. In this range, stress kindles adaptive long-term neurocognitive changes that may serve as an increased capacity to maintain neurocognitive functioning, despite future stress that may exceed moderate levels. This strengthening area occurs up to a threshold of stress severity at the apex of the inverted U curve (Calabrese and Mattson, 2017). At the threshold stress level, cognitive performance starts to decrease as a function of increased stress. Beyond this critical threshold, in the buffering/protective phase, the positive effect related to increasing stress ends while a decline in cognitive performance is predicted. Yet, this adaptive neuropsychobiological process still serves to buffer the full impact of stress on cognitive performance, compared to minimal stress. At very high stress levels, adverse neuropsychobiological effects eclipse beneficial cognitive processes. Beyond this point, the effect of higher stress severity become increasingly harmful and is hence referred to as the damaging/toxic phase. Thus, the hormetic process is comprised of strengthening and protective phases that may function to promote long-term adaptation and protection from moderate-to-high levels of stress (Calabrese, 2016, Calabrese and Mattson, 2017).
Testing the hormetic model at the neural level adds conceptual and applied utility. Conceptually, there is inherent value to cognitive neuroscience to better understand the interactions of neural and behavioral systems. Neuroimaging studies of the cognitive effects of stress may provide cognitive and behavioral science knowledge beyond “where” questions to address “how” questions – how neural activity in specialized regions may subserve specific behavioral functions necessary to sustain environmental stress. The potential applied benefits of the hormetic model are also promising. The effects of stress on WM neural systems have been increasingly demonstrated as important links in models of risk prevention and intervention. Measuring these effects on neural systems and how they link to functional outcomes, such as WM performance, may advance discovery of opportunities for model-driven targets of prevention and intervention (Melby-Lervåg and Hulme, 2013; Snider et al., 2018). For example, understanding how adversity is linked to WM performance can later be examined as a cognitive resource for resilience. Moreover, understanding neural mechanisms may also yield specific novel neuromarkers that can be used to quantify risk and assess the efficacy of stress-related interventions (Snider et al., 2018). Such neuromarkers have been complimentary in other research areas, such as decision-making and addiction, providing added predictive utility over behavioral measures (Gowin et al., 2014; Krakauer et al., 2017; Paulus et al., 2005) and revealing sustained neuroprotective effects against the negative consequences of adversity (Rosen et al., 2018).
Despite the potential for protective long-term hormetic effects of low-moderate stress, research shows significant interindividual variability in response to stress, which has been linked to access to protective psychosocial resources. The beneficial effects of psychosocial assets have been explained by the cognitive-behavioral theory (Bandura, 1993). As personal and interpersonal assets (e.g., self-efficacy, social capital and friendship, meaning and purpose) attenuate adverse effects of stressors (Jain et al., 2012), they might be critical to establishing and maintaining an individual's location along the hormetic curve. For example, higher levels of self-efficacy, larger social capital, and higher levels of perceived purpose in life are associated with more effective coping and more positive outcomes following psychosocial stress (Cassidy, 2015; Murray Nettles, Mucherah and Jones, 2000; Rutten et al., 2013; Rutter, 1987; Schwarzer and Warner, 2013). According to Bandura (1982), higher levels of personal resources, such as self-efficacy, empower individuals to more effectively achieve goals, despite challenging stress, through cognitive strategies such as attention shifting, re-focusing, and reorganizing. This body of literature converges to suggest that psychosocial assets might help attenuate the levels of stress perceived by individuals, and thus constitute putatively critical contexts to examine when testing the hormetic effects of stress on cognition and behavior.