The stressed brain… Impacts on work, business and cognition

Popular media suggest that modern society is afflicted by stress: Google yields 154,000,000 hits for ‘stress’  and 36,700,000 hits for ‘stress epidemic’. Current EU estimates suggest work-related stress (defined as “a pattern of emotional, cognitive, behavioural and physiological reactions to adverse and noxious aspects of work content, work organisation and work environment. Stress is caused by a poor match between our roles at work and outside it, and by not having a reasonable degree of control over our own work and our own life.”) costs €20 billion p.a. in time and health bills; it is the second most common occupational health problem (after back pain).

The physiology of the stress response has become reasonably well-understood over the

GFP+ CA1 neurons, axons extending towards subi...
GFP+ CA1 neurons, axons extending towards subiculum (Photo credit: Functional Neurogenesis)

past few decades. Particular progress has been made in understanding how stress impacts on cognition – and especially on the brain systems that support learning and memory. The hippocampal formation is widely regarded as the substrate for the brain’s ‘cognitive map’ of the world, and is crucial to certain types of memory; its synapses are highly plastic and its structure and functions are especially sensitive to stress.

A contemporary definition suggests stress involves heightened excitability or arousal, a perception of aversiveness and a lack of controllability over outcomes. The stress response is controlled by the hypothalamic-pituitary-adrenal (HPA) axis, which is substantially regulated by the hippocampal formation (HF: entorhinal cortex, dentate gyrus, Areas CA3 & CA1, subiculum). Area CA1 sends its primary projection to the subiculum, which projects to many cortical and subcortical targets (including hypothalamus). Ventral subiculum projects to the hypothalamus via the postcommissural fornix, the medial corticohypothalamic tract and via the amygdala; these projections innervate the medial preoptic area, the ventromedial and dorsomedial nuclei, and ventral premammillary and medial mammillary nuclei. Ventral subicular lesions attenuate the HPA response to systemic and behavioural stressors. The subiculum thus exerts a dynamic and inhibitory influence  on the HPA axis, and substantially orchestrates the stress response: ‘[N]o neural system is so exquisitely poised to limit the activity of the HPA axis, as well as the autonomic and behavioural elements of the stress response to unconditioned stimuli’ as ventral subiculum.

Behavioural stress (e.g., uncontrollable tailshock) and/or systemic stress (e.g., anoxia; infection) triggers the release of corticotropin-releasing hormone (CRH) from the hypothalamus into the portal circulation to the anterior pituitary, which releases adrenocorticotrophic releasing hormone (ACTH) into the bloodstream, causing corticosterone (rat) or cortisol (human) release from the adrenal cortices14. ACTH initiates ‘fight or flight’ responses, mobilizes energy stores, decreases reflex thresholds, and increases respiratory rate, muscle tension and gastric motility. These effects, if short-lived, are generally positive; pathogenic consequences for cognitive neurobiological functions ensue, however, from elevated and prolonged increases in corticosterone levels.

To briefly summarise a complex literature:

Prolonged behavioural and/or systemic stress

(i) inhibits long-term potentiation (LTP; the important biological model of synaptic plasticity and memory);

(ii) causes hippocampal atrophy;

(iii) impairs learning and memory;

(iv) facilitates long-term depression – the inverse of LTP;

(v) contributes to brain ageing;

(vi) causes many generalised behavioural changes;

(vii) is implicated in many neuropsychiatric disorders;

(viii) depresses the immune system;

(ix) modulates neurotrophic factors (especially brain-derived neurotrophic factor – BDNF).

In other words, sustained and unrelenting stress takes a terrible toll on the brain and body. A subsequent post here will deal with some methods that are known to reduce the effects of stress on brain and body.

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Author: Shane O'Mara

Neuroscientist

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