Sleep apnea at the frontier- an integrated multidisciplinary functional framework.

In this review, we propose a systems-motivated approach to sleep apnea, as a well characterized disorder illustrative of the sleep-wake process. We advance a framework with mechanistic underpinning of the insulin-resistant cardiometabolic effects of obesity and its putative bi-directional relationship with sleep apnea. Such a physiological construct affords an integrated perspective where pathophysiological outcomes in the brain and heart can be objectively characterized by imaging methods that index functional derangements, including those related to clinical measures of metabolism and ischemia, as well as to translational indices of neurotransmitter signaling. A provocative complexity-analysis network model is explored as a novel formalism for brain macro-phenomena, such as the sleep-wake process, as an emergent property arising from the collective interactions of its micro-constituent very large number of neurons. Clinical management is highlighted at the intersection of guideline-directed cardiometabolic- and sleep- medicine, biopsychosocial interventions, and incorporation of newer pharmacological therapeutic advancements. Together, these disparate developments herald a new functional/physiological synergistic era in sleep medicine.