The development of this model was prompted by observations suggesting that OSA presents a relatively specific behavioral and cognitive `footprint.' Thus, we will initially describe cognitive and behavioral sequelae, and then move upstream through the proposed etiologic cascade.

The most heavily investigated and perhaps the most prominent daytime feature of adult OSA is excessive daytime sleepiness, conventionally defined as subjective fatigue or objectively measured sleep propensity. However, adult OSA is also associated with occupational and social failures related to poor planning, disorganization, diminished judgement, rigid thinking, poor motivation, and affective lability (e.g. 39 ; 51 ; 153 ). Childhood OSA is associated with school failure and behaviors reminiscent of attention‐deficit/hyperactivity disorder (ADHD) (e.g. 23 ; 77 ; 89 ; 144 ). Though it is tempting to attribute all of these difficulties to excessive daytime sleepiness, doing so requires expansion of the already multidimensional construct of sleepiness to include conceptually distinct cognitive functions. As will be summarized below, such a conceptual agglomeration is inconsistent with current data on OSA. Moreover, such a stance discourages investigation of the relationships between disordered sleep, subjective sleepiness, sleep propensity, and various aspects of cognitive functioning. In particular, it discourages examination of a clear area of cognitive pathology in OSA – executive dysfunction.

Executive dysfunction and OSA

As defined by neuropsychologists, `executive functioning' refers to the ability to develop and sustain an organized, future‐oriented, and flexible approach to problem situations (44; 59; 72; 119). The executive functions allow individuals to adaptively use their basic skills (e.g. core language skills, visual–perceptual ability, rote memory capacity) in a complex and changing external environment (59; 72). For example, persons of high intellect but poor executive functioning may experience occupational and social failure because their verbal discourse is disorganized and disjointed, marked by `losing track' of what was being said, redundant, at times irrelevant or tangential, rigid, or lacking appropriate emotional overtones.

In this section, we divide the executive function `family' into six members – behavioral inhibition, set‐shifting, self‐regulation of affect and arousal, working memory, analysis/synthesis, and contextual memory. This subdivision is based upon recent theoretical models by 8, 10), 6), 142) and 69, 68). Though we present each executive function individually for heuristic purposes, in fact they are interrelated, and any given `executive functioning test' is likely to tap multiple executive functions (143). Moreover, a given author's definition and subdivision of the executive functions is generally influenced by his or her realm of investigation. Whereas cognitive neuropsychologists have developed sophisticated tasks that can be conducted in controlled laboratory settings with relatively plentiful healthy subjects, clinical neuropsychologists focus on constructs and measures that differentiate neurologically impaired clinical groups in less controlled settings. These approaches are complementary. Current research on the neuropsychological effect of OSA relies on clinical measures, so we use terms derived from clinical neuropsychology. However, we also cite terms that derive from a cognitive neuropsychology tradition, particularly that adopted by 97) in their recent review of the effects of sleep deprivation on decision making.

Following is a summary of each executive function and relevant empirical studies of OSA, particularly the case‐controlled studies recently reviewed by 58). To allow comparisons across domains, and to effectively combine studies that used identical or near identical measures, we report individual or pooled effect size (ES) estimates (120).* Effect size refers to the difference between clinical and control group means, expressed in standard deviation units.

The first executive function in the model is behavioral inhibition. As defined by 8):

Behavioral inhibition refers to three interrelated processes: (a) inhibition of the initial prepotent response to an event; (b) stopping of an ongoing response, which thereby permits a delay in the decision to respond; and (c) the protection of this period of delay and the self‐directed responses that occur within it from disruption by competing events and responses (interference control) (p. 67).

Prepotent responses generally have immediate survival benefit or have been previously met with a favorable risk‐to‐benefit ratio, making them the `default' responses that would occur without behavioral inhibition. Behavioral inhibition, defined in this way, is required for 97) construct of `appreciation of a complex situation while avoiding distractions' (emphasis added). One laboratory measure of behavioral inhibition is the Stroop Color–Word Interference Task, which requires test‐takers to inhibit the prepotent response of word‐reading to name the nonmatching colors in which a series of words are printed (e.g. the word `red' printed in blue ink) (73). Adult patients with untreated OSA perform poorly on this task (ES=0.79, P < 0.05) (136). They also make more impulsive errors than controls on tests of maze completion (ES=1.6 for moderate OSA, 4.38 for severe OSA, both P < 0.01) (12); they often impulsively move into `blind alleys', even after exhortations not to do so.

The second executive function in the model is set shifting. Closely tied to behavioral inhibition, this involves the ability to flexibly move from one cognitive or behavioral strategy to another. This does not necessarily require self‐generation of a new strategy, as patients with frontal lobe lesions may perseverate on a given strategy or behavior while verbalizing a more appropriate response (48; 72; 119). Set shifting is a necessary but not sufficient function underlying the 97) concept of `thinking laterally and being innovative.' Clinical measures of set shifting include the perseveration index of the Wisconsin Card Sorting Test (WCST, 102); and the second subtest of the Trailmaking Test (Trails B, 103). On the WCST, the test taker is required to develop problem‐solving strategies based upon examiner feedback, then to switch strategies without warning when the task contingencies change. The WCST perseveration index relates to the latter task: switching cognitive set. Adults with untreated OSA score poorly on this measure (mean ES=0.55, P < 0.01; 136; 151). Trails B requires the test taker to rapidly alternate between well‐established number and letter cognitive sets on a connect‐the‐dot task (i.e. A‐1–B‐2,…); untreated OSA patients find this difficult (mean ES=0.37, P < 0.001, 12; 84; 111; 136; 151).

The third executive function in the model is self‐regulation of affect and arousal. This component, which refers to the internal modulation of affective and arousal states to meet a goal (10), is implied in 97) `maintaining interest in outcome' and, in combination with behavioral inhibition, underlies their construct `controlling mood and uninhibited behavior.' Self‐regulation of affect, motivation, and arousal is difficult to assess in a laboratory situation, though anecdotal reports of irritability and affective lability are consistent with a weakness in this executive function. Clinically, the continuous performance tests (CPTs) are relevant, as they require sustained vigilance to a monotonous task over time. Poor CPT performance has been well‐documented among individuals with OSA (e.g. 115), and is more prominent towards the end of such tasks than their beginning (ES=0.76, P=0.01 vs. ES=0.22, P > 0.20; 151). This suggests problems sustaining effort and attention, rather than poor initiation or short‐term maintenance of attention.

Working memory (8, 10; 143, 142) is an active, extremely short‐term memory system, sometimes referred to as a `sketch pad' for visual information and a `phonological loop' for auditory/verbal information (4). It has both a retrospective function, in which recent information is held `on line' for a brief period, and a prospective function, which actively maintains anticipated events – a necessary feature for effective planning (68). This underlies 97) concept of `keeping track of events and developing and updating strategies' (emphasis added) and, to a lesser degree, `assessing risk – anticipating range of consequences.' The ability to repeat back digit strings or visual sequences, and the ability to mentally reverse the sequences, reflects working memory capacity. Untreated adult patients with OSA perform poorly on such tasks (mean ES=0.75, P < 0.001; 84; 136; 151).

The fifth executive function in the model is analysis/synthesis. This involves mentally dismantling old experience/information and synthesizing these pieces in novel ways (8, 10). This is the foundation for creative, goal‐directed thought and problem solving. Together with set‐shifting, analytic/synthetic skills parallel 97) `thinking laterally and being innovative.' This divergent thought process is difficult to measure on formal tests, but neuropsychologists sometimes use fluency tasks. For exam 2;ple, the ability to quickly provide words that start with a given letter, when compared with verbal lexicon and general mental processing speed, indirectly measures mental flexibility and analytic/synthetic skills. Adults with untreated OSA have poor verbal fluency (mean ES=0.55, P < 0.001; 12; 84; 111; 136), even when their language skills are otherwise normal (12; 136).

Finally, `contextual memory' places information into a meaningful time (temporal memory) and space (source memory) context (142). Contextual memory allows the individual to remember when and in what situation information has been learned, which can be dissociated from the content of what has been learned. Temporal source memory corresponds to 97) `remembering when rather than what' concept. We are unaware of any published studies that examine contextual memory in individuals with OSA. However, we include it in the present model because of its known relationship to prefrontal cortical functioning, and because temporal memory is adversely affected by sleep deprivation (97, 98).

Sleepiness and executive function Conventionally defined sleepiness cannot account for the executive functioning deficits displayed by patients with OSA. Executive functioning deficits correlate better with the degree of blood gas abnormalities and sleep fragmentation than with either self‐reported or objectively measured sleepiness (12; 34). Though it is often held that the effect of sleepiness is most evident on long monotonous tasks (49), many of the executive functioning deficits cited above were found on brief tasks. Moreover, as summarized in the next section, patients whose sleep has been normalized with CPAP may nonetheless continue to display executive functioning deficits. It is also worth noting that prepubertal children with OSA are less likely to manifest daytime sleepiness unless their disease is moderately severe to severe (79), yet they frequently display executive function deficits (80). Thus, although excessive daytime sleepiness is an important consideration in the neurobehavioral manifestations of OSA, it is likely that its effects are rapidly reversible with sleep recovery during treatment, and as such cannot account for the more persistent executive dysfunction of OSA. If this assumption is further supported by studies designed to examine this issue, then we need to consider the possibility that neurological damage has occurred as a result of sleep‐disordered breathing, and that this damage may be only partially reversible. This has major implications for the approach to diagnosis and treatment of patients with OSA.

Summary of past findings Individuals with untreated OSA display executive dysfunction that is not attributable to simple sleepiness. In fact, aside from sleepiness, executive dysfunction appears to be the most prominent area of cognitive impairment in untreated sleep‐disordered breathing. Studies that have included multiple cognitive tests have generally found poorer performances of untreated adults on measures of executive functioning than on measures of visual ability (12; 84), verbal ability (12; 84; 101; 136), and long‐term memory (12; 40; 62; 101; 136; 152). Recent data from our laboratories further extend such observations to the pediatric age. Children with OSA perform more poorly on a composite executive functioning measure than on measures of verbal or visual ability (80). Though we are only beginning to use formal neuropsychological tests to assess the effects of pediatric OSA, children with sleep‐disordered breathing are reported by their parents to be unusually inattentive, hyperactive, impulsive, aggressive, and rebellious (1; 167). Findings from such psychiatrically focused behavior rating scales are indicators of adverse daytime effects rather than the mediating factor of executive functioning. Even so, these findings are consistent with poor behavioral inhibition and diminished self‐regulation of affective and arousal state. A similar pattern of behavior ratings is found in ADHD, a neurodevelopmental disorder that centrally involves executive dysfunction (7a, 8, 10). Though application of effective CPAP treatment during sleep has been reported to improve daytime functioning, residual deficits on tests of executive functioning remain particularly evident (11; 13; 62; 136). Similarly, though preliminary studies of childhood OSA have also suggested that improvements occur in post‐treatment daytime behavior regulation (1; 76; 87; 149; 167), most of these studies entailed uncontrolled clinical trials or were subject to rater biases. There is some evidence that residual learning deficits may occur long after sleep‐disordered breathing has resolved in children (78).