Relationship Between Obstructive Sleep Apnea Severity and Brain Activation During a Sustained Attention Task

OBSTRUCTIVE SLEEP APNEA (OSA) IS CHARACTERIZED BY REPEATED EPISODES OF UPPER AIRWAY OBSTRUCTION DURING SLEEP, RESULTING IN INTERMITTENT hypoxemia with periodic arousals.1 Prevalence estimates for OSA in adults range from 9% to 28% for at least mild severity and 2% to 14% for at least moderate severity.2 OSA is recognized as a significant public health problem that imposes substantial cardiovascular3 and neurocognitve morbidities.4 Patients with OSA commonly exhibit excessive daytime sleepiness and show vigilance and attention deficits and slowed reaction times (RT).5 Previous studies have shown that sleep-apnea severity (as measured by the number of respiratory events per hour of sleep, the apnea hypopnea index [AHI]) is associated with attention and response speed. Specifically, increased AHI has been associated with prolonged RT (eg6), impaired sustained attention, and monitoring of information.7,8 Cheshire et al9 found that increased AHI was associated with impaired response speed, sustained attention, vigilance, distractibility, and processing capacity and that the number of arousals was related to performance on a simple RT task. In addition, findings from event-related potential studies of increased P300 latency in OSA (eg10) support the behavioral findings of attention deficits in OSA. Importantly, impaired attention and slowed RTs in patients with OSA are related to a diminished driving ability and risk for road accidents.11,12 Although there is discrepancy across studies with respect to the relative importance of nocturnal hypoxia versus arousals in the pathogenesis of the cognitive deficits in OSA, disturbances in executive function seem to show stronger correlations with measures of hypoxia, whereas alterations in vigilance, alertness, and processing speed correlate more with measures of sleep disruption and arousals.9,13,14 Despite the considerable data about impaired performance and prolonged P300 latency in OSA, much less is known about the changes in the brain substrates underlying these impairments. Although a variety of studies have shown morphologic changes and changes in cerebral blood flow and cerebral metabolites in patients with OSA (for a review see15), only a few studies have assessed brain function in OSA and its association with changes in cognitive functioning.16–18 Using functional magnetic resonance imaging (fMRI) Thomas et al18 reported slower working memory speed on a 2-back task in individuals with OSA, compared with control subjects. This impaired performance was accompanied by reduced activation within anterior cingulate, dorsolateral prefrontal cortex, and posterior parietal cortex of the OSA group compared to the control group. They also reported that hypoxic patients showed slightly reduced responses in 3 regions relative to nonhypoxic patients but not within their primary regions of interest. Our group17 found higher false positive rates in patients with OSA accompanied by impaired cerebral activation during a response inhibition task relative to control subjects. In particular, the OSA group showed diminished response in regions involved with conflict monitoring, attention, motor function, and decision making. Given the obvious attention demands in the tasks utilized in these previous studies, those findings are consistent with (although not conclusive of) the notion of impairment in attention-related brain regions in OSA. Since very little is known about the functional cerebral correlates of nocturnal hypoxia and arousals, the current study aimed to examine the cerebral substrates underlying attention and RT in individuals with OSA and their association with OSA severity. Using a sustained-attention task, patients with OSA and control subjects were compared on measures of performance and brain activation. In addition, the association of AHI, nocturnal hypoxia, and arousals with RT and fMRI measures of brain function during the attention task were assessed. We hypothesized that patients with OSA would show prolonged RTs and decreased cerebral activation compared with control subjects; that prolonged RTs would be related to increased OSA severity, particularly the number of nocturnal arousals; and, given that relationship, a negative relationship between nocturnal arousals and cerebral activation in task-related brain regions.