Dorsolateral prefrontal cortex GABA deficit in older adults with sleep-disordered breathing

Significance Sleep-disordered breathing (SDB), characterized by intermittent hypoxia and sleep fragmentation during sleep, is common in the elderly and can contribute to cognitive decline, with significant impairment of executive function, including mental flexibility, problem solving, and working memory, which are under dorsolateral prefrontal cortex (DLPFC) control. The results of the present study suggest a potential mechanism of SDB in which a hypoxia-driven deficit of DLPFC γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter, disrupts the neural excitation/inhibition balance which could lead to hyperexcitability, and potentially neuronal damage and cognitive decline. If validated, these findings, along with the proposed model, would represent a significant advance toward achieving a better understanding of the neurobiology of SDB and novel targets for interventions for the disorder.