Dynamic adaptation of large-scale brain networks in response to acute stressors (original) (raw)

2014, Trends in Neurosciences

Stress initiates an intricate response that affects diverse cognitive and affective domains, with the goal to improve survival chances in the light of changing environmental challenges. Here, we bridge animal data at cellular and systems levels with human work on brain-wide networks to propose a framework describing how stress-related neuromodulators trigger dynamic shifts in network balance, enabling an organism to comprehensively reallocate its neural resources according to cognitive demands. We argue that exposure to acute stress prompts a reallocation of resources to a salience network, promoting fear and vigilance, at the cost of an executive control network. After stress subsides, resource allocation to these two networks reverses, which normalizes emotional reactivity and enhances higher-order cognitive processes important for long-term survival. Hermans et al.-Network adaptation to stress-Page 3 Stress-induced shifts in neurocognition Stress is a double-edged sword: it causes us to have difficulty focusing our attention, retrieving information from memory, and making decisions that require complex thought. Extreme and prolonged stress can furthermore have pathological sequelae such as post-traumatic stress disorder and depression. Yet, the acute stress response also enables us to rapidly detect threats, respond adequately, restore homeostasis when threats are no longer present, and better prepare the organism for future challenges [1,2]. Stressors (see Glossary and Box 1) trigger a chain of neuroendocrine reactions throughout the body that is highly preserved across species [3,4]. Animal work at the cellular level has detailed how stresssensitive neurotransmitters and hormones such as catecholamines and corticosteroids exert modulatory effects on neural excitability and plasticity that are targeted both in space and time [3,5,6]. Spatial specificity allows for selective alterations in widespread target tissues, while temporal specificity allows for timedependent shifts in these changes. At the systems level, stress-related neuromodulators may therefore trigger coordinated, brain-wide shifts in neural functioning that enable us to reallocate processing resources (Box 2) to meet unstable environmental demands [2,7-9]. Here, we integrate animal data at the cellular and systems levels with an emerging human literature on changes in large-scale network properties that subserve adaptive shifts in cognition and behavior [10,11]. We focus our discussion on two such large-scale networks: the salience processing network and the executive control network [12,13]. After summarizing empirical evidence, we propose a model (Fig. 1) that describes how these two networks are regulated in a biphasic and reciprocal fashion in response to acute stressors. Spatially and temporally specific effects of stress-related neuromodulators at the cellular level Animal work has indicated that acute stressors trigger multiple waves of neurochemical changes (Fig. 1A). The earliest responses to acute stressors are mediated by neuropeptides, such as corticotropin-releasing factor, and by catecholamines, such as norepinephrine and dopamine [3]. These changes initiate almost instantly and normalize within 30-60 min. Stress also triggers activation of the hypothalamic-pituitaryadrenal axis, which leads to a surge of corticosteroid production in the adrenal cortex. Peak concentrations in the brain are not reached within 20 minutes after stressor onset [14], which implies that the role of corticosteroids in the immediate stress response must be limited. As we will detail below, these multiple waves of neuromodulatory changes and their interactions allow for intricately timed modulation of distinct neural circuits. Rapid effects of catecholaminergic activation Acute stress promptly activates the locus coeruleus (LC), the brain's primary source of norepinephrine [15,16]. Neurocomputational studies in monkeys show that this leads to a shift from a phasic towards a tonic mode of LC activity, which is associated with enhanced scanning of the environment for potentially salient information [15,17]. Central catecholaminergic activation is followed by activation of the peripheral sympatho-adrenomedullary system, which triggers release of epinephrine from the adrenal medulla. Hermans et al.-Network adaptation to stress-Page 4 Epinephrine further increases norepinephrine release through ascending vagal projections to the nucleus of the solitary tract (NTS) [9]. Noradrenergic projections are widespread and include the entire cerebral cortex, hypothalamus, thalamus, and amygdala [18]. Effects of stress levels of norepinephrine may be regionally specific due to local differences in receptor distribution. While α2A-adrenoceptors in the prefrontal cortex