Neural correlates of insomnia and hyperarousal.

This chapter provides an exhaustive review of the neural substrates associated with insomnia and hyperarousal, considering the chronic disturbance of sleep from the complex perspective of a reciprocal biopsychosocial model. It focuses on several critical abnormalities observed on the structure and function of neuroanatomy, especially the hypersensitive reaction of the amygdala and insular cortex along with reduced reactivity of the prefrontal cortex that results in the development of emotional dysregulation and a continuous feeling of danger. At the circuitry level, it is possible to observe a substantial disturbance of the DMN and ECN connectivity. From a neurochemical point of view, this chapter describes the impact of the imbalances of GABA, serotonergic and noradrenergic systems in specific nuclei, such as the locus coeruleus and the tuberomammillary nucleus, together with HPA-axis overactivation and elevated cortisol levels that cause systemic cortical hyperarousal. As far as electrophysiological markers are concerned, there is a specific increase of beta wave activity in the waking resting-state as well as a decrease of restorative SWS and REM sleep stability. Lastly, this chapter gives some information about clinical relevance, especially about CBT-I, new neuromodulation strategies and brain-region specific pharmacotherapeutic options.