Evoked potential (EP) waveforms are affected markedly by sleep as illustrated by studies investigating respiratory-related evoked potentials (RREP; Webster and Colrain 1998a; Wheatley and White 1993) and auditory evoked potentials (AEP; Nielsen-Bohlman et al. 1991; Campbell et al. 1992; Van Sweden et al. 1994 ). The late RREP and AEP components present during wakefulness are the N1, P2, N2 and P300. During Stage 2 sleep, the N1 component is diminished considerably, while the P2 peak may be either slightly augmented or attenuated. The endogenous P300, which is thought to be related to attentional memory processes ( Johnson 1993), can be elicited in wakefulness by both respiratory and auditory stimuli. During Stage 2 sleep, the auditory P300 disappears. However, a late positivity peaking at 450 ms can still be elicited by infrequently occurring stimuli. The P450 appears to have a different latency and topographic distribution than the P300 ( Winter et al. 1995 ). Two major negative components also emerge during sleep, the N300 (replacing the wake N2) and the N550 ( Campbell et al. 1992; Webster and Colrain 1998a ).
The RREP has been reported to occlusion stimuli ( Davenport et al. 1986, 1996; Revelette and Davenport 1990; Wheatley and White 1993; Logie et al. 1998; Webster and Colrain 1998a ), and to resistive loads ( Bloch-Salisbury and Harver 1994; Knafelc and Davenport 1997; Webster and Colrain 1998b). It consists of a series of early components within 100 ms of stimulus delivery. A positive component (P1) is seen over central and postcentral scalp regions, and a negative component (Nf) over frontal scalp regions ( Davenport et al. 1996; Webster and Colrain 1998a ). It has recently been determined that these are generated within primary somatosensory and supplementary motor cortices, respectively ( Logie et al. 1998 ). As would be expected for a primary somatosensory cortex component, the P1 is sensitive to the intensity of the eliciting stimulus, with Knafelc and Davenport (1997) reporting a log–log correlation of 0.98 between P1 amplitude and the intensity of the resistive load used as a stimulus. Components very similar to P1 have been observed in S1 cortex following direct simulation of the contralateral phrenic nerve in the cat ( Davenport et al. 1985 ), mechanical stimulation of the intercostal muscle of the cat ( Davenport et al. 1993 ) and electrical stimulation of the intercostal muscle in humans ( Gandevia and Macefield 1989).
Late components resembling the endogenous evoked potential components reported previously in other stimulus modalities have also been produced by occulsion and resistive load stimuli. Harver et al. (1995) showed an increase in amplitude in the late positivity when the stimuli were attended rather than ignored, while Strobel and Daubenspeck (1993) showed marked attenuation of a late positivity when stimuli were applied to every breath. Webster and Colrain (1998a, b) indicated that the late positivity (P300) has the centro-parietal maximum topographic distribution characteristic of AEPs and visual evoked potentials (VEPs). RREP studies have also reported both augmentation of the P300 with attention ( Webster et al. 1997 ) and increased P300 amplitude with decreased probability of stimulus presentation ( Colrain et al. 1998 ).
The purpose of this study was to investigate the cortical response to a physiological event (respiratory occlusion) at the transition from waking to sleeping. Only a small number of studies have examined EPs during sleep onset. Ogilvie et al. (1991) measured subjects’ EPs in response to 1000 Hz tone pips. Subjects’ sleep/wake state was defined by behavioural response patterns, with the absence of a response to an infrequently occurring auditory stimulus being indicative of sleep. The N1 component diminished with increased reaction time and was virtually absent in definitive sleep. The N2/N300 component increased and the P300 decreased in amplitude with the onset of sleep. Similar results were observed by Harsh et al. (1994) , also using a reaction time/sleep-onset protocol. Winter et al. (1995) applied an auditory oddball paradigm and observed that the large N1 and P300 components that were apparent during wakefulness were difficult to identify during Stage 2 sleep. In Stage 1 (termed drowsiness), an N330 and P420 emerged that were both sensitive to the intensity of the auditory stimulus. de Lugt et al. (1996) recorded AEPs in response to 1000 Hz tone pips. The N1 component was attenuated during Stage 1 sleep. However, the N2 was not found to increase in amplitude during sleep onset. Webster and Colrain (1998a) recorded RREPs during Stage 1 sleep. The respiratory stimulus used was an occlusion that completely interrupted breathing at mid-inspiration for about 250 ms. This stimulus was presented every 3–6 breaths (minimum of 12 s between stimuli), making it analogous to a target stimulus in an oddball paradigm. They reported that the N1, P2 and P300 all showed small decreases in amplitude from wakefulness.
There has been some inconsistency in the literature regarding the labelling of the N2/N300 and to a lesser extent, the P300/P450 components. Early AEP research did not differentiate between the wake and sleep ‘N2’ ( Ornitz et al. 1967 ). Research since then has either followed this pattern of nomenclature ( Ogilvie et al. 1991; Wheatley and White 1993; Van Sweden et al. 1994; de Lugt et al. 1996 ), or described the sleep N2 in terms of its latency, such as N300 ( Niiyama et al. 1994 ), N340 ( Nielsen-Bohlman et al. 1991 ) or N350 ( Harsh et al. 1994; Winter et al. 1995 ). In general, the majority of studies investigating the late positive component (appearing between 300 and 500 ms) during wakefulness and sleep have classified this component according to latency of appearance ( Nielson-Bohlman et al. 1991; Ogilvie et al. 1991; Salisbury and Squires 1993; Harsh et al. 1994; Winter et al. 1995 ). The waking late positivity is usually labelled ‘P300’, with the sleep late positivity labelled P420, P430 or P450, depending on its latency in different studies. For nomenclature purposes, the present study will refer to the late negative component in wake as an N2 and in sleep as an N300. The late positive component will be classified as a P300 in wake and a P450 in sleep.
A major problem with the above-mentioned sleep studies is that the transition from waking to sleeping states was generally measured conventionally as Stage 1 sleep. This is problematic as Stage 1 represents a period of oscillation between two different frequency bands, EEG dominated by alpha activity and EEG dominated by theta activity. As such, the definition of subjects state of arousal during sleep onset has not been precise.
There are neurophysiological reasons to anticipate that EEG state during sleep onset would effect EP. The pattern of EP activity observed in a given arousal state will depend on the manner in which thalamic afferent signals are transmitted to the cortex. This transmission is critically dependent on the state of thalamocortical relay cells. According to Coenen (1995), the development of sleep is related to thalamic blocking or gating (and its associated reduction in level of consciousness) and is due at least in part to decreased brainstem reticular formation (BRF) input to the thalamus. EPs recorded at the scalp are different in wake compared with sleep because thalamocortical cells are at different levels of polarization, with the wake level being close to action potential generation threshold and the sleep level being relatively hyperpolarized. Variations in the EEG also reflect variations in the polarization of thalamic neurons, with the movement from faster frequency, low-amplitude EEG (alpha) to slower frequency, higher amplitude EEG (theta) occurring in association with thalamocortical hyperpolarization. We are therefore proposing an ‘EEG alpha/theta-state-dependent’ model of activity such that if the polarization of thalamic neurons determines EP waveforms, then EPs should be dependent on EEG-defined state. The prediction of this model is that EP components will oscillate between wake and sleep levels in association with alpha and theta EEG activity oscillations that are characteristic of the sleep onset period.
Evidence for an EEG alpha/theta-state-dependent model comes from the study of respiratory activity during sleep onset. Alpha/theta-state-specific changes have been found to occur in ventilation ( Colrain et al. 1987, 1990; Trinder et al. 1992 ), upper airway resistance ( Kay et al. 1994, 1995 ), and chemical drive ( Dunai et al. 1996 ). State instability has also been associated with changes in upper airway and pump muscle activity ( Worsnop et al. 1998 ) and the reduced ability to compensate for an inspiratory resistive load ( Gora et al. 1998 ). In each case, the change from alpha- to theta-dominated EEG activity marked the transition in respiratory activity. If the nature of the BRF influence on thalamic circuits is the same as for respiratory and upper airway motoneurons, it would be expected that the transfer of RREP components from a wake- to a sleep-type pattern would occur in association with oscillations from alpha to theta EEG activity during sleep onset.
The aim of this study was to assess the effect of state, as defined by alpha and theta EEG activity during sleep onset, on the presence of RREP components evoked by brief inspiratory occlusions.