Original ArticleAttention in children with obstructive sleep apnoea: An event-related potentials study
Introduction
Obstructive sleep apnoea (OSA) is a frequent condition, affecting 1–3% of the children [1], [2], [3], [4], [5], [6], which can lead to neurocognitive impairments [7], [1], such as restlessness, aggression, excessive daytime sleepiness, and poor school performance [2], [3]. Furthermore, associations between OSA and attention deficit–hyperactivity disorder (ADHD) have been proposed [4], [5]. Increased brain vulnerability to OSA during childhood and risk for persistent damage if treatment is delayed have been recognised [1], [6], [7]. However, not every child with moderate to severe OSA will develop evidence of cognitive dysfunction, and vice versa [8], [9], [10], [11], [12], [13], [14], [15], [16], [17].
‘Attention’ refers to a variety of phenomena, including concentration, selectivity, automaticity, conscious monitoring, and capacity limitations [9]. Current studies of attention distinguish between selectively attending to perceptual information and higher-order centralised, executive function concerned with planning and organising complex actions [10]. Growing evidence suggests causal association between OSA, inattention [11], [12], [13], [14], and hyperactivity [15], [16]. However, most children with ADHD do not have OSA, and most children with OSA do not have ADHD [17].
Measures of neurocognitive function are based on administration of neurocognitive standardised batteries, which can be labour intensive for children, or on the administration of caregiver-completed questionnaires, providing a second-hand, subjective report. A more objective measure of neurocognitive function is necessary to enable risk and vulnerability stratification during initial evaluation of snoring and to assess cognitive outcomes following treatment. Ideally, this measure would be non-invasive and time efficient relative to polysomnography (NPSG) and provide more objective measures of impairment than those obtained from parental reports, such as an electrophysiological measure [18].
Event-related potential (ERP) recordings are non-invasive and are used across the life span to investigate brain-based correlates of cognition [19]. They provide an ‘exquisitely sensitive’ measure of cognitive processing during wakefulness which is free of constraints of motor activity or the need for the participant to consciously attend to the task at hand [20], making them ideal for use with children. High-density net arrays are well tolerated by young children, providing temporal resolution of electrical activity at the millisecond level [21], [22], [23], [24], while providing excellent spatial resolution of dipoles [25]. ERP is a portion of the continuous electroencephalogram (EEG) that is time-locked to stimulus onset. Multiple presentations of stimuli are averaged, removing random and non-stimulus-related activity. Amplitude of certain peaks, or components, in the brain wave and latency of the wave provide measures of brain activity [26]. For an overview of signal averaging theory in ERP research and its applications in sleep research, see Colrain’s and Campbell’s review [20].
ERP patterns strongly correlate with learning, reading and school performance – areas of daytime functioning known to be impaired in apnoeic children- and has proven highly successful in ADHD [27], [28]. ERP components such as the P300 have been consistently shown to be reduced in amplitude and of an increasing latency with impending sleep and in conditions of total sleep deprivation. Unfortunately, the ERP findings from studies of adults with sleep fragmentation and OSA have been less straightforward [20].
A 2006 study of 12 adult patients with OSA and 12 age-, sex-, and education level-matched controls revealed a delayed and sustained P300 (300–700 ms) in the OSA group relative to the controls [29]. Stimuli consisted of pure tones in a classic oddball paradigm (90% standard tones and 10% deviant). Subjects with OSA did have longer reaction times than their non-OSA counterparts, although this difference was not significant. In general, the control subjects exhibited an earlier and ‘sharper’ P300 compared with those in the OSA group. The OSA group had a sustained P300 with a large amplitude, suggesting that, although the attention resources allocated were sufficient to generate a correct and timely response, a greater amount of attention resources were needed for a longer amount of time compared with controls. There was also a significant between-groups difference in the P3a, which was a component obtained by subtracting responses to standard stimuli from that of deviant stimuli. On this measure, control participants exhibited a larger amplitude of the P3a, which occurred earlier than that in the OSA patients. These results are consistent with previous reports of a delayed and sustained P300 in apnoeic adults, suggesting that the volitional attention resources allocated to the processing of novel stimuli are sufficient in subjects with OSA, but more effortful and delayed relative to controls. The decreased amplitude of the P3a could be the result of a decrease in overall attention resources available for the task at hand. This is in line with the theory that OSA decreases the cognitive reserve available for such tasks. Gosselin further posits that this increased latency in the OSA group could reflect an alteration in P3a generators, possibly switching from the typically strong prefrontal generators to other brain areas such as the cingulate, auditory, and parietal cortices [29]. This is consistent with the literature discussed above, suggesting that the prefrontal cortex is especially susceptible to sleep fragmentation and hypoxia associated with OSA. It is important to note that ERP differences could distinguish between OSA patients and controls, while behaviourally observable phenomena could not.
In another 2006 study from Gosselin’s group, 13 adults with OSA and 13 controls participated in a passive auditory oddball task while reading [30]. They found that the individuals with OSA exhibited a decreased percentage of rapid-eye-movement (REM) sleep; increased body mass index (BMI); increased sleepiness as assessed by the Epworth sleepiness scale [31]; an increased number of arousals and sleep transitions; and decreased P3a amplitudes compared with controls. The authors concluded that this abnormal P3a amplitude reflected ‘involuntary attention switching’ but relatively preserved automatic processing. The blunted amplitude probably represents the reduced cognitive resources available in patients with OSA for the attention task. Increased hypoxaemia and decreased sleep efficiency were correlated to decreased amplitude of the P3a in frontocentral, central, and parietal electrode sites. However, citing the few ERP studies of OSA in existence, the authors are quick to point out that further research is needed [30]. Furthermore, this study did not use high-density arrays of electrodes. These differences in reports regarding ERPs in patients with OSA could be the result of differences in task demands or protocol or in the components of the EEG that are being isolated for study. Nonetheless, ERP recording is a method that can be used in evaluating the neurocognitive changes associated with OSA and the efficacy of adenotonsillectomy (AT) [32].
We hypothesised that assessment of ERPs using a high-density array during an oddball attention task provides objective and complementary evidence of impaired attention in apnoeic children aged 4–8 years. The theoretical model under study is that children experiencing insufficient or disrupted sleep (as in OSA) are less effective in organising cognitions. Therefore, the activation profiles observed in such children would be more diffuse and poorly localised compared with control counterparts. We hypothesised the performance impacted by OSA can be indexed by increased latencies and decreased amplitudes of specific ERP components and linked with measures of attention, inhibition, and executive functioning. We chose to test the predictive power of identified ERP patterns in apnoeic and control children using the attention and executive functioning and Memory and Learning subscales of the A Developmental NEuroPSYchological Assessment (NEPSY), as these are areas which have been of high interest in the field of paediatric sleep-disordered breathing (SDB) and impairments in attention and attentional switching are most prominent in ERP studies of adults with OSA [20].
Section snippets
Participants
A total of 16 children were originally included in the suspected OSA group; however, two were excluded from the final analyses because they had too many eye-movement artefacts in their electrophysiological data. It should be noted that no families in the Sleep Centre declined to participate secondary to use of the high-density electrode array, and the ERP method was tolerated by all participants. The final sample included 14 children (nine females), 4–8 years of age, evaluated for suspected OSA
Demographic and behavioural
There were no demographic differences between groups, including SES, BMI, or PPVT (Table 1). Significant differences existed for behavioural assessment scores (Table 2). Control children scored higher than apnoeic children on the NEPSY Visual Attention subtest (t = −2.125, p = 0.048) and Memory and Learning percentile scores (t = –2.126, p = 0.043). Significant parent-reported group differences were found on many CBCL scales. The OSA group scored higher on all measures.
PSG
Group means for relevant
Behavioural findings
Children with OSA performed more poorly on Visual Attention and Memory and Learning domains of the NEPSY, and such findings cannot be due to variability in age, sex, SES, or other confounders. The children studied herein not only exemplify the anticipated cross-sectional profile of children around the world, but further confirm previous studies on the presence of behavioural sequelae of OSA in children [2], [3], [50].
Electrophysiological findings
By 108 ms following stimulus onset, OSA children exhibited significantly
Conclusion
We report brain changes associated with OSA that can be used to determine which children might require earlier diagnosis or treatment. Children with OSA exhibit substantial alterations in behavioural tests, ERP temporal trajectories, and localisation patterns during an attention task. Activation in centroparietal areas is selectively impaired in OSA. These findings are remarkably similar to affected brain regions identified in a recent functional magnetic resonance imaging (fMRI) study of
Conflict of interest
The ICMJE Uniform Disclosure Form for Potential Conflict of interest associated with this article can be viewed by clicking on the following link: doi:10.1016/j.sleep.2011.06.007.
Acknowledgements
Research was supported by a dissertation research award from the American Psychological Association, a fellowship from the National Institute of Mental Health (F30MH79531) and the following Grants from the National Institutes of Health: HL070911, HL065270 and HD047083.
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