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

Abstract

Sleep-disordered breathing (SDB) is a common disorder in aging that is associated with cognitive decline, including significant executive dysfunction, for which the neurobiological underpinnings remain poorly understood. Using proton magnetic resonance spectroscopy (1H MRS), this study assessed whether dysregulation of the homeostatic balance of the major inhibitory and excitatory amino acid neurotransmitter systems of γ-aminobutyric acid (GABA) and glutamate, respectively, play a role in SDB. Levels of GABA and those of the combined resonances of glutamate and glutamine (Glx), were measured by 1H MRS in the left dorsolateral prefrontal cortex (l-DLPFC) and bilateral hippocampal regions of 19 older adults (age ± SD: 66.1 ± 1.9 years) with moderate to severe SDB, defined as having an Apnea-Hypopnea Index (AHI) greater than 15 as assessed by polysomnography, and in 14 older adults (age ± SD: 62.3 ± 1.3 years) without SDB (AHI < 5). In subjects with SDB, levels of l-DLPFC GABA, but not Glx, were significantly lower than in control subjects ( < 0.0002). Additionally, there was a negative correlation between l-DLPFC GABA levels, but not Glx, and SDB severity by AHI ( = -0.68, < 0.0001), and a positive correlation between l-DLPFC GABA levels, but not Glx, and minimal oxygen saturation during sleep ( = 0.62, = 0.0005). By contrast, no group differences or oxygenation associations were found for levels of GABA or Glx in right or left hippocampal region. These findings are interpreted in terms of a pathophysiological model of SDB in which hypoxia-mediated inhibitory neurotransmission deficit in DLPFC could lead to hyperexcitability and, potentially neuronal dysfunction and cognitive decline.

Diffusion tensor imaging reveals neuronal microstructural changes in myalgic encephalomyelitis/chronic fatigue syndrome

“…Another study using fMRI on mindfulness showed prefrontal cortex (BA‐9) was associated with attention‐to‐breathing (Doll et al, 2016). A study showed involvement of prefrontal cortex in sleep breathing disorder compared with HCs (Pereira et al, 2017) that is similar to our finding in Resp. The cerebellar tonsil that is part of the cerebellum is involved in cardiovascular and respiratory function (Harper et al, 1998; Paton et al, 1991; Rector et al, 2006).…”

Brain mitochondrial dysfunction and driving simulator performance in untreated obstructive sleep apnea

“…Another study reported significant correlations between NAA/Cho ratios in frontal regions and Cho/Cre ratios in the hippocampus with the arousal index and hypoxemia but found no correlations with cognitive function using a broad range of tests of memory, vigilance (PVT), IQ, inhibition and set‐shifting as well as subjective sleepiness using the ESS (O'Donoghue et al, 2012). Pereira et al (2017), also found associations between prefrontal cortex levels of GABA and glutamate with the AHI and hypoxemia (O 2 nadir) but no significant correlations were observed in the hippocampus, nor was any cognitive function assessed in that study.…”

Sleep quality improves during treatment with repetitive transcranial magnetic stimulation (rTMS) in patients with cocaine use disorder: a retrospective observational study

“…Both high and lowfrequency rTMS can modulate total sleep and total wake times, sleep latency, sleep efficiency, and other aspects of sleep architecture [28,59,60]. Disruption of sleep pattern and CUD [3] might share common neurobiological pathways and mechanisms, which may help explain the improvements observed in our patients [61][62][63][64]. For example, neuroimaging in humans shows that sleep deprivation and psychostimulant intake modulate the responsiveness of dopaminergic signaling within the mesolimbic system [65][66][67][68].…”