The Alpha Attenuation Test: Assessing Excessive Daytime Sleepiness in Narcolepsy-Cataplexy

Sleep, 20(4):258-266 1997 American Sleep Disorders Association and Sleep Research Society.j The Alpha Attenuation Test: Assessing Excessive Daytime Sleepiness in Narcolepsy-Cataplexy Christi E. D. Alloway, Robert D. Ogilvie and *Colin M. Shapiro Brock University, St. Catharines, and *University of Toronto, The Toronto Hospital, Toronto, Ontario, Canada Summary: Daytime sleep tendency was assessed in 10 drug-free patients with narcolepsy-cataplexy and 10 normals matched for age and gender. Following nocturnal polysomnography, the alpha attenuation test (AAT) and the multiple sleep latency test (MSLT) were administered during five sessions occurring at 2-hour intervals beginning at 0900 and 1000 hours, respectively. For the AAT, participants were polysomnographically recorded for 8 minutes while seated in an illuminated room with their eyes alternately opened and closed. Power spectral analyses of electroencephalograph (EEG) activity at 02-Al (10 second epochs) were calculated using fast Fourier transformations (FFT) within the alpha frequency range (8-12 Hz) to obtain ratios of mean eyes-closed to mean eyes-open alpha power (i.e. the alpha attenuation coefficient, AAC). The narcoleptics were sleepier than the normals as indicated by a significantly smaller mean AAC and a significantly shorter mean latency to stage I on the MSLT. These findings suggest that the AAT may provide a quick and practical objective assessment of the excessive daytime sleepiness (EDS) associated with narcolepsy. Key Words: Narcolepsy-Alpha attenuation test-excessive daytime sleepiness-physiological sleep tendency-eeg power spectral analysis. The multiple sleep latency test (MSLT) (1) is the traditional measure for objectively assessing excessive daytime sleepiness (EDS) in individuals with narcolepsy. Physiological sleep tendency is assessed by measuring the speed at which individuals fall asleep on multiple occasions while lying with their eyes closed in a darkened room (2)-that is, the speed at which the electroencephalograph (EEG) moves from the alpha activity (8-12 Hz) of relaxed eyes-closed wakefulness to the theta activity (4-8 Hz) of the first stage of sleep. A mean sleep latency of 5 minutes or less on the MSLT is considered to represent a pathological degree of sleepiness and in conjunction with the presence of at least two sleep onset rapid eye movement (REM) periods, is considered diagnostic of narcolepsy (3). However, the validity of the MSLT may be questioned due to the confounding of sleepiness with the learned ability to fall asleep (4). Furthermore, the efficacy of the MSLT is limited by a floor effect (near zero latencies) in clinical populations (5) and the failure of EDS patients to show significant improvement in MSLT latencies following subjectively effective pharmacological treatment (6). In addition, Accepted for publication January 1997. Address correspondence and reprint requests to: Christi E. D. Alloway, Psychology Department, Queen's University, Kingston, Ontario K7L 3N6, Canada. 258 the cooperation of the patient in the attempt to fall asleep is essential to the validity of the MSLT, and patients wishing to avoid falling asleep may engage in a variety of behaviors to distort the MSLT results. Furthermore, the MSLT is time-consuming. The MSLT also relies on the presence of a polysomnographer to visually sleep score the EEG concurrently with each nap attempt, introducing a subjective component to an objective measure of sleepiness (7). These shortcomings suggest the need for alternate means of detecting pathological degrees of sleepiness. The technique of EEG power spectral analysis provides a method of quantifying fluctuations in sleepiness and alertness and has the potential to become an alternative to sleep latency testing in the assessment of EDS. Studies (8-9) have demonstrated that as individuals move from alertness toward sleepiness, EEG power in the alpha frequency range decreases when eyes are closed but increases when eyes are open. Based on these findings, the alpha attenuation test (AAT) (10) was developed as a new method of quantifying variations in physiological sleepiness. During the AAT, individuals are asked to repeatedly vary their eyelid position from open to closed while seated in an illuminated room. In a recent validation study, Stampi et al. (7) investigated the ratio of eyes-closed to eyesopen EEG alpha power (referred to as the alpha atten-

ALPHA AITENUATION TEST IN NARCOLEPSY 259 ~\., ~' tl- (~ uation coefficient, AAC) to determine its efficacy as an objective measure of physiological sleepiness. Stampi et al. (7) deprived 10 normal sleepers of sleep for 40 hours. Every 2 hours (for a total of 18 sessions) participants were administered the following battery of tests: subjective sleepiness measures and performance tests (starting on the hour), the AAT (at 20 minutes past the hour), and the MSLT (at 40 minutes past the hour) (7). The AAC was found to be sensitive to increasing sleepiness following one night of sleep loss such that participants were significantly less alert (i.e. had lower AACs) on the 2nd day of testing compared to the I st day (7). Furthermore, the AAC correlated significantly with the MSLT in eight out of 10 participants (i.e. r > 0.72 for four participants, r > 0.62 for three participants and r = 0.53 for one participant), and these correlations were higher than the correlations between the MSLT and the subjective sleepiness and performance measures, suggesting that the AAT provides a valid assessment of physiological sleepiness in sleepy normals (7). To our knowledge, the AAT has yet to be evaluated in patients with narcolepsy. The present study is the first to investigate the utility of the AAT in distinguishing narcoleptics from normals [however, preliminary findings have been reported in abstract form (11)]. On the basis of EEG power spectral studies of sleep-deprived normals (7,9) it was predicted that the ratio of eyes-closed to eyes-open alpha power (i.e. the AAC) would be lower in narcoleptics than normal controls and that, compared to controls, narcoleptics would demonstrate greater eyes-open alpha power and less eyes-closed alpha power. Participants METHODS Five female and five male patients diagnosed with narcolepsy-cataplexy and 10 normal sleepers matched for age and gender were studied. Narcoleptics were drug-free at the time of testing. Narcoleptics ranged in age from 29 to 62 years [mean = 44.3 years, standard deviation (SO) = 11.9 years], and controls ranged from 28 to 56 years (mean = 42.7 years, SO = 10.6 years). All participants gave their written informed consent and received an honorarium for their participation in the study. A screening process ensured that narcoleptics met the American Sleep Disorders Association's diagnostic criteria for narcolepsy (3) and that normal controls did indeed report normal sleep habits (i.e. the normals reported that they had no difficulty in falling or remaining asleep at night, typically slept between 6 and 8.5 hours a night, and were alert during the daytime). All narcoleptics complained of daytime sleepiness and reported taking naps daily or several times weekly. Normals reported that they were generally alert during the day. All narcoleptics had a history of cataplexy, six reported experiencing sleep paralysis and hypnagogic hallucinations at least once a month, and two reported incidents of hypnagogic hallucinations that occurred 1-5 times during their lifetime. No normals reported a history of cataplexy, although two normals reported experiencing incidents of sleep paralysis and four reported incidents of hypnagogic hallucinations occurring 1-5 times during their lifetime. All narcoleptics reported multiple nocturnal awakenings. Four normals reported no nocturnal awakenings, and six reported awakening 1-3 times during the night. Participants were also given a sleep diary in which they recorded their sleep and wake patterns for the 7 days preceding testing. A t test showed that narcoleptics and normals did not differ with respect to the selfreported mean duration of nocturnal sleep. The selfreported mean duration of nocturnal sleep ranged from 4.7 to 10.8 hours for the narcoleptics (mean = 7.9 hours, SD = 2.1 hours) and from 6.2 to 8.6 hours for the normal controls (mean = 7.4 hours, SD = 0.9 hours). Symptoms related to depression (which may elicit sleep onset REM periods) were assessed with the Beck Depression Inventory (BOI) (12), which consists of 21 statements related to depression. Participants rank each statement according to the degree to which it is experienced [i.e. from neutral (0) to maximal severity (3)]. BDI scores may range from 0 to 63. A t test showed that narcoleptics and normals did not differ with respect to the number of depression-related symptoms they reported on the BDl. The scores obtained on the BDI for the narcoleptics ranged from 1.0 to 25.0 (mean = 8.6, SO = 7.47) and for the normals ranged from 1.0 to 16.0 (mean = 4.5, SO = 5.0). Prior to (but not during) testing, nine of the 10 narcoleptics were taking medications for their symptoms. Six narcoleptics were taking central nervous system stimulants (five took methylphenidate hydrochloride, one took dexamphetamine sulfate) for their excessive daytime sleepiness, three were taking sleeping pills (immovane) to improve their nocturnal sleep, and two were taking REM sleep suppressants (clomipramine) to reduce their cataplexy. Two of the narcoleptics taking methylphenidate hydrochloride were withdrawn for 2 days prior to testing, and the seven remaining medicated narcoleptics were withdrawn from their medications for 7 days prior to testing. All of the normal participants and nine narcoleptics reported consuming caffeinated beverages. On average, normals consumed 2.5 cups of tea/coffee/pop per day (SO = 1.0). Narcoleptics consumed significantly

260 C. E. D. ALLOWAY ET AL. more cups of tea/coffee/pop per day (mean == 5.0, SD == 3.7) [t(18) == 2.13, P = 0.047]. Five normals and three narcoleptics reported consuming alcoholic beverages. On average, normals consumed 1.8 alcoholic drinks per week (SD = 2.7). This did not differ from the average number of alcoholic drinks consumed by narcoleptics (mean = 1.5 drinks weekly, SD = 3.0). None of the normals reported smoking cigarettes or pipes, whereas four narcoleptics smoked an average of 29 cigarettes per day. During testing, these participants were permitted to smoke after each MSLT session. All participants agreed to refrain from alcohol, caffeine, and sleep-related medications during the 24-hours preceding testing. Procedure Participants reported to the sleep lab at 2130 hours for orientation and electrode application. Electrodes were positioned to enable the monitoring of Cz (central) and 02 (right occipital) EEG [referenced to A2 (right mastoid)], submental electromyogram (EMG) and outer canthi electrooculogram (EOG) activity. A 16-channel Neurofax polygraph (Nihon Kohden, Irvine, CA) was used to amplify the polysomnographic recordings. Time constants were set at 0.3 for EEG and EOG recordings and at 0.03 for EMG recordings. High-frequency filters were set at 30 Hz for EEG and EOG and at 70 Hz for EMG. Recording sensitivity was 7 fl V /mm for EEG and EOG and 1-3 fl V /mm for EMG. Polysomnographic data from the polygraph were acquired on paper and on computer using the software program Microcomputer Quantitative Electrophysiology (Imaging Research Inc., under continued development at Brock University, St. Catharines, Ontario, Canada). Participants retired for the night at 2300 hours and slept undisturbed until 0800 hours. The MSLT was administered according to the guidelines for clinical use outlined in the report from the American Sleep Disorders Association (13). Following the nocturnal polysomnography, nap opportunities were given at 1000, 1200, 1400, 1600, and 1800 hours. At the start of each session of the MSLT, participants were instructed to try to fall asleep while lying quietly with their eyes closed in a darkened room. During the MSLT session, EEG, EOG, and EMG were recorded on paper and computer according to the parameters outlined above and were scored in 30 second epochs using the criteria of Rechtschaffen and Kales (14). Sleep onset was defined as the first three consecutive minutes of stages 1, 2, or REM sleep. Each MSLT session was terminated either 15 minutes following the initial onset of sleep or after 20 minutes in bed with no sleep. A mixed two-factor 2 X 5 (group-by-session) analysis of variance (ANOV A) was performed on the latency to stage 1 sleep with session extracted as the within-subjects factor. The 8-minute version of the AAT was administered at 0900, 1100, 1300, 1500, and 1700 hours. Participants were polysomnographically recorded while seated in an illuminated room within 3 feet of a wall upon which an "X" made of black tape had been placed at eye level. Participants were instructed t~ sit quietly with their eyes open and focus on the black tape on the wall. Following 1 minute of artifact-free recording with eyes open, participants were instructed to sit quietly with their eyes closed for 1 minute. Each eyesopen and eyes-closed session was repeated three more times so that a total of eight I-minute samples of artifact-free EEG were obtained. The MSLT and AAT were scheduled 1 hour apart to reduce the likelihood that participating in one task would influence the other. For the AAT, EEG data were digitized using a sampling rate of 102.4 Hz with a digitizer sensitivity of 16 bits for ± 2.83 volts. Power spectral analyses of eyes-open and eyes-closed EEG at 02 were calculated using FFT on 10 second epochs within the alpha frequency band (8-12 Hz) using a bin size of 0.1 Hz. The bins were averaged across the 8-12-Hz frequency range to produce an estimate of alpha power in squared microvolts. The ratio of mean eyes-closed to mean eyes-open alpha power (i.e. the AAC) was then calculated. A mixed two-factor 2 X 5 (group-by-session) ANa V A was performed on the AAC, and a mixed three-factor 2 X 2 X 5 (group-by-eyelid-position-by-aat-session) ANOV A was performed on mean alpha power. In both analyses, session was extracted as the within-subjects factor. Subjective sleepiness was assessed using the Stanford sleepiness scale (SSS) (15) and the visual analogue sleepiness scale (VASS) (16). The SSS consists of seven statements describing progressive changes in subjective sleepiness, ranging from" 1. Feeling active and vital; alert; wide awake" to "7. Almost in reverie; sleep onset soon; lost struggle to remain awake". Participants are asked to choose the statement that best represents their present state of sleepiness. The V ASS is a horizontal line approximately 100 mm in length, labeled "Very Alert" on the left and "Very Sleepy" on the right. Participants are asked to draw a vertical mark on the line at the point corresponding to their present state of sleepiness. V ASS scores are obtained by measuring the distance of the mark from the left end of the line (higher scores being associated with more intense feelings of sleepiness). The SSS and V ASS were administered every 1;2 hour during the daytime testing, including immediately prior to and following each MSLT and AAT session. To compare overall differences in subjective sleepiness between

ALPHA AITENUATION TEST IN NARCOLEPSY 261 TABLE 1. Raw data for AAT and MSLT Narcoleptics Session I Session 2 Session 3 Session 4 Session 5 Age EO EC SOL EO EC SOL EO EC SOL EO EC SOL EO EC SOL 62 2.23 1.77 1.5 1.77 1.30 1.0 1.43 1.42 1.7 1.38 1.35 0.7 1.19 1.08 0.8 57 0.90 1.70 11.7 1.15 1.27 9.4 1.10 1.44 3.3 1.19 1.29 0.7 0.93 1.27 2.0 30 1.44 3.28 14.3 1.56 3.29 2.2 1.35 2.85 6.7 1.91 2.52 2.7 1.82 2.26 4.6 59 2.96 2.54 2.9 2.62 2.25 2.1 2.31 2.43 0.5 2.79 2.50 0.7 2.61 2.10 2.9 33 1.04 2.17 2.7 1.07 2.79 2.4 1.09 2.78 3.3 1.34 2.94 4.1 1.15 3.04 8.3 47 2.32 1.97 1.0 2.44 2.39 0.5 1.19 1.59 4.0 2.71 4.28 0.8 3.14 4.78 5.0 45 1.01 2.13 2.1 0.96 1.41 1.0 1.22 1.14 0.8 1.19 2.17 4.8 1.35 1.69 3.9 39 2.14 2.22 0.7 242 2.44 1.2 2.64 2.40 1.2 2.45 2.45 6.9 2.77 2.90 4.2 43 2.14 1.51 2.0 2.06 1.61 0.3 1.36 1.15 1.7 2.43 1.50 1.0 2.39 1.75 1.2 29 1.32 3.93 6.2 1.47 3.75 7.5 1.78 4.78 5.3 1.81 3.35 3.2 2.08 4.92 5.8 Normals Session 1 Session 2 Session 3 Session 4 Session 5 Age EO EC SOL EO EC SOL EO EC SOL EO EC SOL EO EC SOL 56 1.80 7.84 8.0 2.19 6.30 9.3 2.16 4.98 17.2 2.48 6.69 8.9 2.67 4.22 8.8 50 2.09 3.46 1.8 3.04 3.78 5.5 3.06 3.65 4.1 3.10 2.90 1.6 2.65 3.17 6.7 45 1.08 1.24 20.0 0.79 0.91 5.4 0.75 0.91 11.2 0.82 1.00 9.6 0.89 1.09 9.9 39 0.93 4.55 5.7 0.85 4.98 8.5 1.69 5.61 8.7 1.92 5.71 7.5 1.61 5.76 20.0 52 0.94 5.21 20.0 0.97 5.56 6.5 1.21 5.56 8.2 1.15 4.89 10.4 1.13 5.45 20.0 56 1.08 2.31 2.8 1.02 1.80 8.2 1.02 1.97 2.7 0.94 1.88 2.9 0.81 1.54 3.2 38 2.66 3.83 20.0 3.24 3.91 11.1 3.27 3.90 12.2 3.28 3.45 20.0 3.27 3.78 20.0 29 1.75 2.34 6.9 1.81 2.64 6.8 1.79 2.53 5.0 1.71 2.66 7.5 1.44 2.79 17.2 35 a 1.32 4.48 1.7 1.62 4.76 4.0 1.95 7.49 3.7 2.33 6.09 20.0 2.44 6.64 2.2 28 1.20 3.29 12.7 1.55 3.18 5.5 1.37 3.46 6.7 1.78 3.72 20.0 1.54 4.58 20.0 AAT, alpha attenuation test; MSLT, multiple sleep latency test; EO, mean eyes-open alpha power for AAT session in IL y2; EC, mean eyes-closed alpha power for AAT session in IL y2; SOL, latency to stage I for MSLT session in minutes. a R.K. case study (see Discussion). It normals and narcoleptics, mean scores on the SSS and VASS were calculated within each participant, and t tests were used to assess group differences. t tests were also used to assess group differences in SSS and V ASS ratings obtained prior to and following each MSLT and I... Normal-Narcolepticl 3.5,-------=======-------. AAT session. The relationship among the subjective sleepiness ratings and the MSLT and AAT was examined using Pearson correlation coefficients. RESULTS Raw data for each AAT and MSLT session are presented in Table 1. 'v r. 3 2.5 "N :J: 2 N ~ ~ 1.5 '" 0.5 --------- ------... --- O+-----~----~------+_----~----~r---~ 900 1100 1300 1500 1700 TIME OF DAY (hr) FIG. 1. Mean alpha (8-12 Hz) attenuation coefficient (AAC) on the alpha attenuation test in narcoleptics and normals as a function of time of day. AAT The analysis of the AAC showed no significant group-by-session interaction, but significant main effects of group [F(l,I8) = 4.97, p = 0.039] and session [F(4,72) = 3.28, P = 0.016] were found (see Fig. 1). The ratio of eyes-closed to eyes-open alpha power (AAC) ranged from 0.6 to 3.0 for the narcoleptics, and from 0.9 to 5.9 for the normals. As predicted, collapsing across session, the mean AAC was significantly lower for the narcoieptics (mean = la, SD = 0.7) compared to the normals (mean = 2.5, SD = 104). Collapsing across group, the mean AAC was lowest at the 1500-hours session. The analysis of mean alpha power revealed a significant group by eyelid position interaction [F(l,I8) 6.52, P = 0.020] (see Fig. 2). Eyes-closed alpha

262 C. E. D. ALLOWAY ET AL. I... Normal-Narcolepticl 14r----------=======~~~--------, 12 ", - ---------------- ~.. ~.. ~.. ~.. ~.. '1. -' ~. -':' ~. '~:~""';. ~... ",. ~.".~ ~.: o+-----~----~----_+----_+----~----~ 900 1100 1300 1500 1700 TIME OF DAY (hr) FIG. 2. Mean eyes-open and mean eyes-closed alpha (8-12 Hz) power in f.l V2 on the alpha attenuation test in narcoleptics and normals as a function of time of day. power ranged from 1.1 fj. y2 to 4.9 fj. y2 for the narcoleptics and from 0.9 fj. y2 to 7.8 fj. y2 for the normals. Eyes-open alpha power ranged from 0.9 fj. y2 to 3.1 fj. y2 for the narcoleptics and from 0.7 fj. y2 to 3.3 fj. y2 for the normals. As predicted, during the eyes-closed condition, mean alpha power was significantly lower in the narcoleptics (mean = 2.4 fj. y2, SO = 1.0 fj. y2) than the normals (3.9 fj.y2, SO = 1.8 fj.y2) [t(18) = 2.5, P = 0.022]. However, contrary to predictions, during the eyes-open condition, mean alpha power did not differ between the groups (mean = 1.7 fj. y2, SO = 0.6 fj. y2 for the narcoleptics and mean = 1.7 fj. y2, SO = 0.8 fj.y2 for the normals) [t(18) = 0]. No significant group-by-session, eyelid position-by-session, or groupby-eyelid position-by-session interactions were found for mean alpha power. The main effect of group (i.e. collapsing across eyelid position and session) did not reach significance; however, there was a trend for mean alpha power to be lower in narcoleptics (2.0 fj.y2) compared to normals (2.8 fj.y2) [F(1,18) = 4.01, P = 0.060]. There was a significant main effect for eyelid position [F(1,18) = 19.76, p = 0.001] such that collapsing across group and session, mean eyes-closed alpha power (3.2 fj. y2) was greater than mean eyesopen alpha power (1.7 fj. y2). No session main effect was found for mean alpha power. MSLT The analysis of latency to stage 1 sleep on the MSLT showed no significant group-by-session interaction, but a significant main effect of group was found [F(1,18) = 15.11, P = 0.001] (see Fig. 3). La- C 10 i >- ~ 8 ~,... 6 w Cl ct Iii 4 2 ~------- O+-----~----~----_+-----+----~----~ 1000 1200 1400 1600 1800 TIME OF DAY (hr) FIG. 3. Mean latency in minutes to stage I sleep on the multiple sleep latency test in narcoleptics and normals as a function of time of day. tency to stage 1 ranged from 0.5 to 15.5 minutes for the narcoleptics and from 1.5 to 20.0 minutes for the normals. Mean latency to stage 1 was significantly shorter for narcoleptics (mean = 3.5 minutes, SO = 3.2 min) than normals (mean = 10.3 minutes, SO = 6.4 minutes). The session main effect did not reach significance [F(4,72) = 2.45, p = 0.054]. Narcoleptics experienced a total of 26 REM-containing naps (i.e. sleep onset REM periods) and 24 non-rem (NREM) sleep naps on the MSLT. Eleven of the narcoleptic REM naps contained stages 1, 2, and REM sleep and 15 contained just stage 1 and REM sleep. Twenty-three of the 24 narcoleptic NREM naps contained both stage 1 and stage 2 sleep. A total of six REM naps occurred at the 1200 and 1400 hours naps, five occurred at the 1000 and 1600 hours naps, and four occurred at the 1800 hours nap. Two narcoleptics had REM sleep on all five naps, five other narcoleptics had two or more REM containing naps, and three had only one nap containing REM sleep. Of these three narcoleptics, one had a sleep onset REM period during the nocturnal sleep. Normals experienced a total of 44 NREM sleep naps and six naps with no sleep onset. Thirty of the 44 normal NREM naps contained stage 1 and stage 2 sleep, whereas 14 contained only stage 1 sleep. One of the normal participants (R.K.) had two naps that contained REM sleep: one at 1400 hours and the other at 1600 hours. AAT and MSLT The relationship between the AAT and the MSLT was investigated by calculating for each participant the fl.,..

ALPHA ATTENUATION TEST IN NARCOLEPSY 263 mean AAC and mean latency to stage 1 on the MSLT and then correlating mean AAC and mean MSLT latency for narcoleptics and normals using Pearson correlation coefficients. Mean AAC correlated significantly with mean latency to stage 1 on the MSLT for narcoleptics (r = 0.75, P = 0.006) but not for normals (r = 0.15, P = 0.342). SSS and VASS Overall, mean SSS scores tended to be higher for narcoleptics (mean = 3.2, SO = 1.0) than normals (mean = 2.4, SO = 0.6) [t(18) = 2.09, p = 0.051]. Similarly, mean VASS scores tended to be higher for narcoleptics (mean = 40.7, SO = 19.7) than normals (mean = 25.6, SO = 12.0) [t(18) = 2.06, p = 0.054]. t tests were used to compare narcoleptic and normal subjective sleepiness ratings obtained just prior to and immediately following each AAT and MSLT session. For these analyses, the alpha level was set at 0.01 in order to allow for the fact that more than 20 t tests were computed. As such, p values between 0.01 and 0.05 are reported as indicating trends only. In regard to the pre- and post-aat mean subjective sleepiness ratings, narcoleptics rated themselves as sleepier than normals on the V ASS administered following the AAT session at 1500 hours (narcoleptics: mean = 51.2, SO = 29.9; normals: mean = 25.6, SO = 17.9) [t(18) = 2.32, p = 0.032]. However, no other differences were observed in subjective sleepiness ratings obtained preand post-aat. In regard to the pre- and post-mslt subjective sleepiness ratings, narcoleptics rated themselves as sleepier than normals on the pre-mslt (1000 hours) SSS (narcoleptics: mean = 3.7, SO = 1.8; normals: mean = 2.3, SO = 1.1) [t(18) = 2.15, P = 0.045], the pre-mslt (1200 hours) VASS (narcoleptics: mean = 38.8, SO = 25.9; normals: mean = 16.5, SO = 11.1) [t(18) = 2.50, P = 0.022], the pre-mslt (1400 hours) VASS (narcoleptics: mean = 38.7, SO = 24.2; normals: mean = 19.1, SO = 11.7) [t(18) = 2.31, P = 0.033], the pre-mslt (1600 hours) SSS (narcoleptics: mean = 3.4, SO = 1.3; normals: mean = 2.0, SO = 0.8) [t(18) = 2.94, P = 0.009], the pre MSLT (1600 hours) VASS (narcoleptics: mean = 44.8, SO = 28.4; normals: mean = 19.0, SO = 15.0) [t(18) = 2.54, p = 0.021], the post-mslt (1600 hours) SSS (narcoleptics: mean = 3.9, SO = 1.5; normals: mean = 2.6, SO = 0.8) [t(18) = 2.36, P = 0.030], the post-mslt (1600 hours) VASS (narcoleptics: mean = 52.4, SO = 25.2; normals: mean = 27.7, SO = 14.4) [t(18) = 2.69, P = 0.015], the pre-mslt (1800 hours) SSS (narcoleptics: mean = 3.0, SO = 1.6; normals: mean = 1.8, SO = 0.8) [t(18) = 2.17, P = 0.044], and the post-mslt (1800 hours) SSS (narcoleptics: mean = 3.4, SO = 0.8; normals: mean = 2.5, SO = 0.9) [t(18) = 2.38, P = 0.029]. To examine the relationship between the subjective sleepiness measures and the AAT, mean scores for the SSS and V ASS administered prior to and following each AAT session were first calculated for each participant, then Pearson correlation coefficients were calculated between mean AAC and pre- and post-aat mean SSS and V ASS for narcoleptics and normals (i.e. a total of four correlations were calculated for both narcoleptics and normals). None of these correlations reached significance for narcoleptics. For normals, there was a significant correlation between mean AAC and post-aat mean VASS (r = -0.61, p = 0.032). The relationship of subjective sleepiness measures with the MSLT was investigated in a similar manner. For each participant, mean latency to stage I on the MSLT and pre- and post-mslt mean SSS and V ASS were calculated, then Pearson correlation coefficients were calculated between mean latency and pre- and post-mslt mean SSS and VASS for narcoleptics and normals. None of these correlations reached significance for narcoleptics. For normals there was a significant correlation between mean latency to stage 1 on the MSLT and pre-mslt mean SSS (r = 0.74, p = 0.007). DISCUSSION The present study is the first to demonstrate that the AAT can be used to distinguish a clinical population of excessively sleepy individuals such as narcoleptics from normal controls. As predicted, the ratio of mean eyes-closed to mean eyes-open alpha power (i.e. the AAC) was significantly smaller for narcoleptics than normals, suggesting that increased physiological sleepiness is associated with lower AACs. These findings are consistent with those of Stampi et al. (7) who observed a decrease in AACs in normals throughout 40 hours of sleep deprivation. Studies of experimentally sleep-deprived normals and shiftworkers (9) have demonstrated that, during maximal sleepiness, alpha power is lower during eyes-closed conditions than during eyes-open conditions, and during maximal alertness, alpha power is higher during eyes-closed conditions than during eyes-open conditions. In the present study, it was predicted that narcoleptics would demonstrate lower mean eyes-closed alpha power and higher mean eyes-open alpha power than normals. However, it was found that mean eyes-closed alpha power was significantly reduced in narcoleptics compared to normals; whereas mean eyes-open alpha power did not differ between narcoleptics and normals. It appears that when the eyes were open, the illumination and the task of focusing on a target on the wall

264 C. E. D. ALLOWAY ET AL. may have acted as alerting stimuli for the narcoleptics, enabling the suppression of the latent physiological sleepiness that was observed once they closed their eyes. Thus, the significantly reduced AAC in narcoleptics was mediated almost entirely by the eyesclosed condition of the AAT. The decreased AAC and increased eyes-closed alpha power in narcolepsy mimics the effects of shiftwork and experimentally induced sleep deprivation in normals. However, it must be stressed that in the present study no evidence was found to suggest that the narcoleptics were sleep deprived. Mean nocturnal sleep length did not differ significantly between normals and narcoleptics for either the sleep diary that was completed for 7 days prior testing or the nocturnal polysomnography carried out immediately preceding the daytime testing. Furthermore, the nocturnal polysomnography showed no significant differences between narcoleptics and normals in sleep efficiency or in the percentage of time spent in stages 2, 3, 4, and REM sleep. The only significant differences found between narcoleptics and normal sleepers during the nocturnal polysomnography were that latencies to stage 1 and REM sleep were shorter, and the percentage of time spent in stage 1 was higher for narcoleptics. Thus, there was no evidence to suggest that the reduced AACs observed during seated daytime wakefulness in narcoleptics could be accounted for by the effects of nocturnal-sleep deprivation. In the absence of sleep deprivation in the narcoleptics, some neurophysiological mechanism is producing an elevation in the physiological need for sleep in narcoleptics. The AAC correlated significantly with latency to stage 1 on the MSLT in narcoleptics but not in normals. This result is contrary to the findings of Stampi et al. (7) who demonstrated that the AAC correlated with latency to sleep onset on the MSLT in eight out of 10 sleep-deprived normal participants. However, Stampi et al. (7) measured latency to sleep onset within minutes of measuring eyes-open and eyes-closed alpha power; whereas in the present study, more than 45 minutes separated the two measurements, and neither the normals nor the narcoleptics were experimentally deprived of sleep. We propose that the AAT and MSLT produced relatively independent measures of sleepiness in our nonsleep-deprived normal participants because they were scheduled to begin on alternate hours throughout the day. These tests were not scheduled to run consecutively to avoid both sleepiness priming and sleep inertia effects. It was desirable that participants not become sleepy and fall asleep faster on the MSLT because they had just finished sitting quietly while staring at the wall or closing their eyes and vice versa. Subjective sleepiness ratings obtained just prior to or following four of the AAT sessions did not differ significantly between narcoleptics and normals, but following the AAT session at 1500 hours, narcoleptics tended to rate themselves as sleepier than normals on the V ASS (i.e. p = 0.032). In contrast, although sleepiness ratings obtained just prior to or following the MSLT sessions were more frequently higher for narcoleptics than normals, all but one of these differences failed to reach the 0.01 level of significance. The tendency for subjective sleepiness ratings centered around the MSLT, but not the AAT, to differentiate narcoleptics and normals may have been due in part to the environment in which the subjective sleepiness ratings were obtained. For the AAT, sleepiness ratings were obtained while participants were seated in a chair. By contrast, for the MSLT, sleepiness ratings were obtained while participants were lying down in bed, in anticipation of or just following a nap opportunity. Thus, in situations that promote sleepiness (i.e. lying down for the MSLT vs. sitting in a chair for the AAT), subjective sleepiness ratings tended to be higher for narcoleptics than normals. What is noteworthy is that the AAT successfully differentiated the narcoleptics and normals in the absence of group differences in subjective sleepiness ratings. One of the normal participants in the present study (RK.) presents an interesting case study demonstrating the merit of the AAT in the situation of false-positive MSLT results. RK., age 35 years, is a normal sleeper who reported sleeping an average of 6.9 hours each night during the week before testing and obtained 8.7 hours of sleep the night before testing. RK. reported no need to nap during the day and no history of excessive daytime sleepiness, cataplexy, or sleep paralysis, although he did report having unusual visual or auditory experiences (i.e. hypnagogic hallucinations) one to five times during his lifetime. He was not taking any medications, nor did he demonstrate symptoms of depression (his score was 2 out of 63 on the BDI). RK. experienced two sleep onset REM periods on the MSLT and his mean latency to stage 1 sleep was 3.6 minutes, suggesting that he met the diagnostic criteria for narcolepsy. [The occurrence of sleep onset REM periods in otherwise normal sleepers has been documented by Rosenthal et al. (17) who reported that 15% (i.e. 11 of 73) of their drug-free normal sleepers (asymptomatic for narcolepsy) experienced two or more sleep onset REM periods on the MSLT.] However, RK. subjectively rated himself as alert throughout the day (mean SSS = 1.4, mean VASS = 10.2). Moreover, his AAT results gave no indication of excessive sleepiness. On the contrary, they suggested an above-average degree of physiological alertness. RK. 's mean AAC (3.1) was higher than the average AAC for normals (2.5) as was his mean eyes-closed alpha power (5.9 j.1v2 vs. 3.9 j.1v2). His mean eyes- ~)

ALPHA ATTENUATION TEST IN NARCOLEPSY 265,"" open alpha power (1.9 IL V2) was comparable with that obtained in narcoleptics and normals (1.7 IL V2). Thus, the present study has documented the ability of the AAT to confirm the presence of physiological alertness in a normal participant matching the MSLT diagnostic criteria for narcolepsy. The AAT may be instrumental in the clinical assessment of excessive daytime sleepiness. It is quick and simple to administer and is free of the serious limitations associated with the assessment of sleepiness via the MSLT-namely, a floor effect in excessively sleepy populations (5), the confounding of sleepiness with the ability to fall asleep (i.e. "sleepability") (4), and the reliance on the presence of a polysomnographer to sleep score the EEG record "on line" during each nap opportunity (7). Furthermore, the AAT is an ideal measure for assessing sleepiness in field studies or in actual work environments because it is nonintrusive (i.e. it does not necessitate a sleepconducive environment, thereby inducing less sleepiness than the MSLT) (7). Although the MSLT is perhaps the best measure for documenting the occurrence of sleep onset REM periods (18), it clearly has the potential to produce misleading evaluations of physiological sleepiness (due to the sleepability confound and floor effects). The inclusion of the AAT in the clinical assessment of patients with sleep-related complaints appears warranted. The AAT may easily be accommodated into the MSLT paradigm by scheduling these two tests to occur on alternate hours throughout the day as was done in the present study. We recommend that future research investigate the efficacy of the AAT in the evaluation of pharmacological-treatment efficacy for excessive daytime sleepiness. Given that studies of subjectively effective stimulant medications in narcoleptics have failed to demonstrate a reduction in sleepiness on the MSLT (6), it would be advantageous for future studies to investigate the ability of the AAT to detect variations in sleepiness/alertness following clinically effective pharmacological treatment. Future research is also needed to test the ability of the AAT to assess sleepiness in clinical populations other than narcoleptics. For example, it is of interest whether the AAT would identify increased physiological sleepiness in sleep onset insomniacs (who would have trouble falling asleep on the MSLT) and in other patients complaining of excessive daytime sleepiness (e.g. patients with central and obstructive sleep apnea). Some researchers have suggested that the AAT may be limited in its ability to assess sleepiness in highalpha producers. Stampi et al. (19) reported in their study of sleep-deprived normals that in individuals who produced extremely high AACs (labeled "high alpha producers"), the AAC tended not to correlate with latency-to-sleep onset on the MSLT. In the study, the MSLT was administered 5 minutes following the administration of the AAT. Stampi et al. (19) reported that although the high alpha producers demonstrated a high level of alertness on the AAT (i.e. high AAC), this degree of alertness was not related to latency to sleep onset on the MSLT. That is, presumably, these high alpha producers were still able to fall asleep within the 20-minute nap opportunity provided by the MSLT. We propose that these findings may reflect more on the sleepability confound of the MSLT rather than on a specific limitation of the AAT. Heitmann et al. (20), in their study of shiftworkers working a nightshift, reported that the AAC correlated best with subjective sleepiness measures in individuals producing "medium"-level AACs. This suggests that the AAT may be less sensitive to subjective sleepiness in individuals who demonstrate extreme levels of alertness or sleepiness on their AACs. However, in the present study, subjective sleepiness ratings administered prior to and following each AAT correlated with the AAC in just four participants (two narcoleptics and two normals), and no apparent pattern was observed for persons having higher or lower level AACs. We suggest that the AAT is a measure of the underlying or latent physiological sleepiness, whereas subjective sleepiness ratings tend to reflect manifest sleepiness, which is influenced by moment-to-moment fluctuations in alerting stimuli within the environment (2); thus the lack of correlation among these measures in some individuals may not present a serious consequence. 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