8
The first-night effect may last more than one night O. Le Bon a, *, L. Staner b , G. Hoffmann a , M. Dramaix c , I. San Sebastian a , J.R. Murphy d , M. Kentos a , I. Pelc a , P. Linkowski e a Sleep Center, Centre Hospitalier Universitaire Brugmann, Universite ´ Libre de Bruxelles, Brussels, Belgium b Sleep Laboratory — FORENAP — Centre Hospitalier de Rouffach, France c Ecole de Sante ´ Publique, Universite ´ Libre de Bruxelles, Brussels, Belgium d University of Texas, Health Science Center at Houston, Houston, TX, USA e Cliniques Universitaires Erasme, Universite ´ Libre de Bruxelles, Brussels, Belgium Received 27 November 2000; received in revised form 2 April 2001; accepted 19 April 2001 Abstract The first-night effect in sleep polysomnographic studies is usually considered to last for one night. However, a few observations have indicated that variables associated to rapid eye movement sleep take longer to stabilize. Notwithstanding, current opinion holds that second nights of recording can be used without restriction for research and clinical purposes. The goal of this study was to describe the dynamics of habituation to polysomnography in optimal conditions. Twenty-six young, carefully screened, healthy subjects were recorded in their home for four consecutive full polysomnographies. Repeated measures ANOVA were applied. Between the two first nights, while there were no differences in sleep duration in non-rapid eye movement sleep, marked mod- ifications in corresponding spectral power were observed. The dynamics of adaptation of rapid eye movement sleep appeared to be a process extending up to the fourth night. Similar dynamics in NREMS and REMS homeostasis have been observed in sleep deprivation studies, and it appears that the same mechanisms may be responsible for the FNE. The longer habituation process of REMS in particular has important implications for sleep research in psychiatry. # 2001 Elsevier Science Ltd. All rights reserved. Keywords: REM; REM latency; NREM; FNE; Habituation; Home polysomnography 1. Introduction The first-night effect (FNE) has been recognized in sleep polysomnographic studies since 1964 (Rechtschaf- fen and Verdone) and was later described in more detail (Agnew et al., 1966). Its main characteristics include: less total sleep time (TST) and rapid eye movement sleep (REMS), a lower sleep efficiency index (SEI), more intermittent wake time, longer REMS latency (RL). No clear pattern has been described for Non-REMS (NREMS), on the other hand. The origin of FNE is probably multifactorial and includes: (1) discomfort caused by electrodes; (2) limitation of movements by gauges and cables; (3) potential psychological con- sequences of being under scrutiny. In most cases, studies have been performed in specialized sleep units, which adds yet another factor: (4) the change in environment. The FNE remains a crucial topic in sleep studies, since it could bias any polysomnography (PSG), whether per- formed for clinical or research purposes. Though an unavoidable burden in practice, it can also be seen more positively from a theoretical perspective as representing an adaptation process of the brain to external stress (Hartmann, 1968; Schmidt and Kaelbling, 1971), per- haps comparable to psychophysiological insomnia (Wauquier et al., 1991). The process of returning to steady-state by habitua- tion in sequential PSG has not been studied extensively. In fact, most studies of the FNE considered only two consecutive nights. Two studies compared the first night versus the mean of two consecutive nights (Browman and Cartwright, 1980; Edinger et al, 1997) and a two- week study was performed in healthy controls (Roehrs et al., 1996), but no specific comparison was reported on the differences between night 2 and the nights immedi- ately following. One study focused on the short-term 0022-3956/01/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved. PII: S0022-3956(01)00019-X Journal of Psychiatric Research 35 (2001) 165–172 www.elsevier.com/locate/jpsychires * Corresponding author. Tel.: +32-2-477-25-54; fax: +32-2-477- 25-50. E-mail address: [email protected] (O. Le Bon).

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The first-night effect may last more than one night

O. Le Bona,*, L. Stanerb, G. Hoffmanna, M. Dramaixc, I. San Sebastiana,J.R. Murphyd, M. Kentosa, I. Pelca, P. Linkowskie

aSleep Center, Centre Hospitalier Universitaire Brugmann, Universite Libre de Bruxelles, Brussels, BelgiumbSleep Laboratory — FORENAP — Centre Hospitalier de Rouffach, FrancecEcole de Sante Publique, Universite Libre de Bruxelles, Brussels, Belgium

dUniversity of Texas, Health Science Center at Houston, Houston, TX, USAeCliniques Universitaires Erasme, Universite Libre de Bruxelles, Brussels, Belgium

Received 27 November 2000; received in revised form 2 April 2001; accepted 19 April 2001

Abstract

The first-night effect in sleep polysomnographic studies is usually considered to last for one night. However, a few observations

have indicated that variables associated to rapid eye movement sleep take longer to stabilize. Notwithstanding, current opinionholds that second nights of recording can be used without restriction for research and clinical purposes. The goal of this study wasto describe the dynamics of habituation to polysomnography in optimal conditions. Twenty-six young, carefully screened, healthy

subjects were recorded in their home for four consecutive full polysomnographies. Repeated measures ANOVA were applied.Between the two first nights, while there were no differences in sleep duration in non-rapid eye movement sleep, marked mod-ifications in corresponding spectral power were observed. The dynamics of adaptation of rapid eye movement sleep appearedto be a process extending up to the fourth night. Similar dynamics in NREMS and REMS homeostasis have been observed

in sleep deprivation studies, and it appears that the same mechanisms may be responsible for the FNE. The longer habituationprocess of REMS in particular has important implications for sleep research in psychiatry. # 2001 Elsevier Science Ltd. All rightsreserved.

Keywords: REM; REM latency; NREM; FNE; Habituation; Home polysomnography

1. Introduction

The first-night effect (FNE) has been recognized insleep polysomnographic studies since 1964 (Rechtschaf-fen and Verdone) and was later described in more detail(Agnew et al., 1966). Its main characteristics include:less total sleep time (TST) and rapid eye movementsleep (REMS), a lower sleep efficiency index (SEI), moreintermittent wake time, longer REMS latency (RL). Noclear pattern has been described for Non-REMS(NREMS), on the other hand. The origin of FNE isprobably multifactorial and includes: (1) discomfortcaused by electrodes; (2) limitation of movements bygauges and cables; (3) potential psychological con-sequences of being under scrutiny. In most cases, studieshave been performed in specialized sleep units, which

adds yet another factor: (4) the change in environment.The FNE remains a crucial topic in sleep studies, since itcould bias any polysomnography (PSG), whether per-formed for clinical or research purposes. Though anunavoidable burden in practice, it can also be seen morepositively from a theoretical perspective as representingan adaptation process of the brain to external stress(Hartmann, 1968; Schmidt and Kaelbling, 1971), per-haps comparable to psychophysiological insomnia(Wauquier et al., 1991).

The process of returning to steady-state by habitua-tion in sequential PSG has not been studied extensively.In fact, most studies of the FNE considered only twoconsecutive nights. Two studies compared the first nightversus the mean of two consecutive nights (Browmanand Cartwright, 1980; Edinger et al, 1997) and a two-week study was performed in healthy controls (Roehrset al., 1996), but no specific comparison was reported onthe differences between night 2 and the nights immedi-ately following. One study focused on the short-term

0022-3956/01/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved.

PI I : S0022-3956(01 )00019-X

Journal of Psychiatric Research 35 (2001) 165–172

www.elsevier.com/locate/jpsychires

* Corresponding author. Tel.: +32-2-477-25-54; fax: +32-2-477-

25-50.

E-mail address: [email protected] (O. Le Bon).

Page 2: The first-night effect may last more than one night

stability of five sleep parameters in elderly healthy con-trols (not including REMS variables) and concludedthat an average of 2 weeks was necessary to achievestability for certain measures (Wohlgemuth et al., 1999).Pioneering work on six consecutive nights was per-formed as early as 1971 (Schmidt and Kaelbling), whichdemonstrated that REMS took more than 1 night tostabilize. A more recent and extensive study of about 32healthy subjects in a lab setting demonstrated significantdifferences, specifically between the second and the thirdnight, for REMS latency and REMS time in the firstthird of the night, but not for REMS as a whole (Tous-saint et al., 1995).

Notwithstanding previous findings, present opinionholds that habituation to polysomnography is a matterof the first night of recording and that the second nightcan be used without restriction for research and clinicalpurposes. In practice, a first night (usually referred to asthe habituation night) is spent with partial or full cableand gauge connections but no actual recording, the sec-ond night is then recorded and used for comparisons.

The objective of the present study was to analyze thedynamics of the habituation process to poly-somnography in optimal conditions. The study coveredfour consecutive nights of recordings performed athome and included a comprehensive set of variables.The sample was very carefully selected and is largerthan in previous studies of young subjects at home(Coates et al., 1981; Sharpley et al., 1988).

2. Subjects and method

2.1. Subjects

Eighty-four volunteers, aged 15–45 (mean 27.8, S.D.9.7, 47 females), were recruited by advertisement andpaid for participation. A comprehensive screening wasmade to ensure selection of individuals with no knownexisting or previous condition which might correlatewith abnormal sleep. Volunteers first answered adetailed questionnaire designed to elicit sleep history byphone. Those meeting questionnaire-based criteria werethen given a structured interview (by O.L. and G.H.),using the ASDA (1990) criteria for sleep disorders andaxis I DSM-IV (American Psychiatric Association,1994) criteria for psychiatric diagnoses (except for sleepdisorders).

Inclusion criteria were: regular sleep schedules,absence of sleep-related complaints or regular naps,regular weekday work or no employment, no previouspolysomnography and completion of informed consent.Exclusion criteria were: DSM-IV axis I disorder; perso-nal or first-degree familial affective disorder (because ofpotential influence on REM latency (Giles et al., 1989));significant somatic condition; excessive daytime sleepiness;

report of periodic limb movements, snoring or sleepapnea; sleep-apnea index (AHI) >= 5 on the initialnight of monitoring; periodic limb movement episodeson the initial night of recording; routine consumption ofmore than 10 alcoholic beverages (10-g units) per week,or consumption of illicit drugs; use of psychotropicdrugs within 3 weeks before the study; and, transmer-idian flights or shift work within 4 weeks preceding thestudy. Subjects were requested not to drink alcohol fora week before entering the protocol and to change theirlife habits as little as possible during the time of thestudy.

The protocol was approved by the hospital’s EthicsCommittee and informed consent was obtained. Thestudy was conducted in accordance with the rules andregulations for the conduct of clinical trials stated bythe World Medical Assembly (Helsinki, Tokyo, Veniceand Hong Kong).

2.2. Methods

Recordings were made between Mondays and Fri-days, in order to avoid the more irregular weekendschedules. The technician went to the subjects’ homearound 9 pm, explained the procedure and answeredquestions. He then placed three pairs of EEG electrodes(FZp1-A1; C4-A1; O2-A1), 1 pair of EOG electrodes, achin and two inferior limb EMG electrodes, thoracicand abdominal gauges for respiratory movements andthermo-resistors around the mouth and the nose. Sub-jects went to bed at their usual sleep time and connectedthe wires, in a very straightforward procedure, to sleepanalyzer Alice (Respironics, Pittsburgh, PA). When thesubjects decided to go to sleep, they launched the poly-somnography and turned out the light. When theyspontaneously woke up in the morning, they stoppedthe recording and removed the electrodes. The samesequence was repeated for all study nights.

Recordings were randomly analyzed by one of twowell-trained technicians, on a 21’’ screen displaying 30-spolysomnograph epochs, with the exception of micro-arousals, which were always scored separately by thesame person. Classical scoring criteria were used(Rechtschaffen and Kales, 1968). Visual scoring was inthree steps: (1) determination of sleep stages; (2) detec-tion and quantification of respiratory sleep events andperiodic limb movements; and (3) detection and quan-tification of microarousals. The inter-rater reliabilitywas measured in another recent protocol and exceeded0.90 for all variables (Le Bon et al., 1997a). Sleep effi-ciency index (SEI) was defined as TST divided by timein bed (TIB). Sleep onset latency (SOL) was defined asthe time between lights out and the first epoch of stage2. Intermittent wake time represents the time spentawake after sleep onset (WASO). A periodic limbmovement episode was defined as five or more periodic

166 O. Le Bon et al. / Journal of Psychiatric Research 35 (2001) 165–172

Page 3: The first-night effect may last more than one night

limb movements during more than 20 s. In a modifica-tion of the criteria established by Bonnet et al. (1992),microarousals were scored as positive only when asso-ciated with EMG increases. REMS latency has receivedseveral operational definitions in the past (Knowles etal., 1982; Reynolds et al., 1983) and none has beenshown to be indisputably superior to the other, thus twodefinitions were used here: RL_A was defined as thetime between the first epoch of stage 2 and the firstepoch of stage REMS; RL_B was defined as the timebetween the first 10 min of stage 2 not interrupted bymore than 1 min of stage 1 or wake and the first 3 minof stage REMS.

The intervals between the end of a REMS period andthe beginning of the next were named RL2 to RL6according to when it occurred during the night.NREMS/REMS cycles include each REMS episode andthe NREMS episode immediately preceding it. EachREMS episode began with the first epoch of REMS andended after the last epoch of REMS was followed by atleast 15 min of NREMS. A NREMS episode is the timespent between two consecutive REMS episodes orbetween a REMS episode and either the beginning orend of the night. No other requirement was necessaryfor the definition of REMS or NREMS episodes, con-sidering that the first REMS episode may be very shortand perhaps even virtual (‘‘aborted first-REMS’’;Dement and Kleitman, 1957).

The spectrogram was computed for all EEG channels.The sampling rate was 100 Hz. Each channel was cre-ated by computing the spectrum every 6 s and each 6-sspectrum was the average of two spectra computed ontwo overlapping windows of 5.12 s (0–5.11 and 0.88–5.99). The signal was multiplied with a 512 point Bar-tlett window after suppressing the mean from each pointin order to remove the 0 Hz component. The FastFourrier Transform was then applied to estimate spec-tral power and was averaged for the two overlappingsegments (mV2/Hz). Six frequency bands were analyzed:Ultra-Slow (0.25–0.8 Hz), Delta (1–3.9 Hz), Theta (4–7.4 Hz), Alpha (7.5–12.4 Hz), Sigma (12.5–17.9 Hz) andBeta (18–25 Hz). The data from frontal, central andoccipital origins were averaged. Spectral analysis datawere analyzed as total power per night, and not byNREMS/REMS cycles, as advocated in a recent study(Preud’homme et al., 2000). The data presented are forthe spectral power corresponding to visually scoredNREMS and REMS.

2.3. Statistics

Three variables required log transformation toachieve normal distributions: WASO, SOL and REMdensity (RD). ANOVAs with two factors (gender andage group) were applied to compare repeated measurescollected over 4 nights (RM-ANOVAS). Two age

groups were created by splitting the sample at 25 years,in order to obtain similar size groups. P-values wereGeisser–Greenhouse corrected. Post-hoc comparisonbetween pairs of nights was performed using simple(forward: night 1 and night 2 (N1–N2); N1–N3; N1–N4; backward: N2–N4) or repeated (N2–N3) contrastsof the RM-ANOVAS. Polynomial contrasts were esti-mated to determine which equation best fitted the evo-lution of the means (linear, quadratic and cubiccontrasts were examined). Bedtime was converted inminutes after at 9 pm. This permitted to enter it as adecimal and positive variable in the RM-ANOVA.Hypotheses tests were two-sided and carried out at the5% significance level. All statistics were computed withSPSS 9 (SPSS Inc., Chicago, IL).

3. Results

3.1. Descriptive values

Eighty-four subjects responded to our advertisement(mean age 27.8, range 15–45 years, S.D. 9.7, 47females). Results from telephone questionnaires andphysician interviews were causes for exclusion of 47individuals (five parasomnias, five irregular sleep sche-dules, seven restless legs or suspicion of periodic limbmovements, 10 snoring problems, five excessive daytimesleepiness, nine anxiety disorders, six affective dis-orders). First night polysomnography resulted in theexclusion of an additional six subjects (two periodiclimb movement and four apneic/hypopneic indices overfive). Thirty-one subjects (36.9%) met inclusion criteriaand were considered to be normal control subjects.Data from five subjects had to be excluded because oftechnical problems (two 800 Mb optical disks seriouslydamaged during storage, for unknown reasons).Twenty-six subjects (mean age 26.7, range 15–45 years,S.D. 9.8, 12 females) completed all aspects of the studyand no missing PSG epochs were observed. The groupwas split in two by age: 14 subjects were < 25 years and12 were >= 25 years. The index of sleep respiratorydisorders in the final 26 subjects was 2.8/h (S.D. 1.49),and no episodes of periodic limb movements wereobserved. Bedtime (mean and range) was respectivelyfor the four nights: 11:16 pm (10:09 pm–01:05 am),11:10 pm (09:42 pm–00:51 am), 11:16 pm (09:31 pm–00:51 am), 11:23 pm (09:53 pm–00:48 am).

3.2. Data analyses

In addition to the descriptive data for each of the 4nights, Table 1 presents the global results of the RM-ANOVAS with gender and age group as cofactors, thecontrasts between pairs of nights and the equations thatbest fitted the curves across the four nights. Statistically

O. Le Bon et al. / Journal of Psychiatric Research 35 (2001) 165–172 167

Page 4: The first-night effect may last more than one night

Table 1

Selected sleep variables and between nights comparisonsa

N1

(mean;S.D.)

N2

(mean;S.D.)

N3

(mean;S.D.)

N4

(mean;S.D.)

RM-ANOVA

(P;d.f.;F)

N1–N2

(P)

N1–N3

(P)

N1–N4

(P)

N2–N3

(P)

N2–N4

(P)

N3–N4

(P)

Slope

TIB (min) 468.1 (37.6) 470.4 (36.7) 466.9 (52.5) 472.3 (43.1) ns

SPT (min) 445.2 (39.9) 456.5 (35.4) 450.1 (53.8) 454.3 (41.7) ns

TST (min) 408.0 (54.2) 434.6 (40.2) 426.0 (56.1) 431.7 (48.5) (0.060;2.6;2.8)

SEI (TST/TIB) (%) 87.0 (7.8) 92.5 (4.6) 91.3 (6.3) 91.4 (6.1) 0.001;2.7;6.7 0.000 0.014 0.002 ns ns ns Lin>quad

SOLb (min) 13.9 (11.6) 9.7 (8.4) 11.6 (20.0) 12.2 (11.4) ns

WASOb (min) 37.2 (27.2) 21.2 (20.1) 24.0 (26.3) 22.5 (28.3) 0.000;2.8;9.1 0.000 0.001 0.000 ns ns ns Lin>quad

Awakenings (#) 8.6 (6.4) 4.7 (4.3) 5.3 (5.6) 4.9 (6.0) 0.002;2.9;5.9 0.001 0.005 0.002 ns ns ns Lin>quad

Microarousals (/h) 11.8 (6.8) 12.1 (6.1) 12.2 (7.8) 12.1 (5.3) ns

Mvt Time (min) 7.1 (4.8) 9.1 (5.0) 9.5 (5.0) 10.1 (4.8) 0.003;2.8;5.5 0.017 0.008 0.003 ns ns ns Lin

Stage Shifts (#) 192.1 (41.0) 197.8 (40.2) 190.3 (38.4) 189.7 (40.3) ns

Stage 1 (min) 49.6 (20.1) 51.2 (17.7) 46.7 (16.4) 52.0 (18.0) ns

Stage 2 (min) 185.1 (39.8) 192.6 (40.8) 184.9 (42.3) 189.4 (49.6) ns

Stage 3 (min) 39.2 (14.5) 43.0 (17.6) 38.4 (13.1) 36.5 (14.5) (0.083;2.8;2.4)

Stage 4 (min) 67.9 (32.4) 62.9 (37.8) 63.7 (34.3) 62.1 (39.0) ns

SWS (min) 107.2 (38.9) 105.9 (44.5) 102.0 (38.5) 97.9 (42.0) ns

NREMS (min) 341.9 (33.6) 349.8 (28.2) 333.8 (38.9) 339.4 (38.1) ns

NREMS-US (mV2/Hz) 43590.3 (26271) 63793.8 (47176) 53320.4 (41444) 48150.4 (27238) 0.041;2.7;3.0 004 ns ns ns (.052) ns Quad

NREMS-Delta (mV2/Hz) 24424.7 (13128) 30398.7 (18248) 28068.6 (16612) 27689.4 (16310) 0.022;3.0;3.9 002 ns ns ns ns ns Quad

NREMS-Theta (mV2/Hz) 2961.5 (1184.3) 3498.2 (1745.2) 3430.9 (1397.0) 3673.7 (2195.7) ns

NREMS-Alpha (mV2/Hz) 1059.9 (411.2) 1208.9 (701.9) 1197.8 (565.9) 1328.4 (969.7) ns

NREMS-Sigma (mV2/Hz) 436.2 (177.7) 490.1 (253.6) 497.5 (236.2) 584.7 (468.2) ns

NREMS-Beta (mV2/Hz) 100.8 (30.3) 118.0 (72.4) 124.2 (66.7) 144.9 (118.1) ns

REMS (min) 61.3 (22.6) 77.8 (21.4) 82.1 (25.3) 84.7 (28.9) 0.000;2.6;9.6 0.001 0.000 0.000 ns ns ns Lin>quad

REMS Density$ (/REMS) 12.6 (22.8) 10.0 (17.7) 11.3 (15.1) 10.6 (11.9) ns

Number of cycles (#) 3.8 (1.0) 4.1 (0.8) 4.2 (0.8) 4.2(0.9) (0.079;2.6;2.5)

RL_A (min) 117.9 (42.3) 99.7 (42.8) 88.1 (42.3) 77.0 (40.8) 0.001;2.8;6.7 ns 0.004 0.000 ns .021 ns Lin

RL_B (min) 123.6 (55.1) 110.8 (54.4) 86.3 (44.8) 96.1 (45.0) 0.048;2.4;3.0 ns 0.019 (0.071) ns ns ns Lin

RL2 (min) 123.0 (40.0) 116.4 (39.5) 97.8 (17.3) 112.4 (22.6) 0.027;1.8;4.2 ns 0.002 ns .026 .001 .014 Quad>lin

RL3 (min) 97.6 (24.2) 97.8 (19.5) 112.2 (25.2) 114.0 (38.2) 0.048;2.5;3.0 ns 0.013 (0.076) .021 (.090) ns Lin

RL4 (min) 90.2 (14.8) 91.1 (20.0) 94.0 (22.1) 90.8 (25.0) ns

RL5 (min) 66.5 (13.2) 79.0 (16.0) 84.6 (19.5) 68.2 (21,6) ns

REMS-US (mV2/Hz) 3282.6 (2207.3) 5747.7 (4161.5) 5268.4 (3118.3) 5699.6 (3542.4) 0.005;2.6;5.1 0.001 0.003 0.006 ns ns ns Lin

REMS-Delta (mV2/Hz) 1341.9 (802.9) 2169.5 (1219.7) 2091.4 (992.9) 2244.9 (1318.6) 0.002;2.3;6.7 0.000 0.003 0.004 ns ns ns Lin

REMS-Theta (mV2/Hz) 303.0 (224.6) 440.9 (320.4) 472.6 (281.7) 503.9 (323.6) 0.004;2.3;5.6 0.003 0.001 0.006 ns ns ns Lin

REMS-Alpha (mV2/Hz) 95.3 (56.7) 138.3 (105.8) 153.8 (101.4) 178.5 (150.6) 0.014;1.9;4.9 0.012 0.002 0.009 ns ns ns lin

REMS-Sigma (mV2/Hz) 32.2 (18.1) 49.7 (36.2) 58.4 (40.0) 70.6 (71.0) 0.024;1.7;4.4 0.009 0.003 0.011 ns ns ns Lin

REMS-Beta (mV2/Hz) 14.9 (7.3) 23.2 (16.5) 26.2 (15.6) 29.4 (20.9) 0.001;2.4;7.1 0.008 0.001 0.002 ns ns ns Lin

a N1, N2, N3, N4, nights 1–4; N1–N2, N1–N3, N1–N4, N2–N3, N2–N4, post-hoc contrasts;; slope as determined by polynomial contrasts : Lin, linear; Quad, quadratic, in decreasing order of

significance when more than one equation fitted the curveb Logtransformed for the comparisons; TIB, Time In Bed; SPT, Sleep Period Time; TST, Total Sleep Time; SEI, Sleep Efficiency Index; SOL, Sleep Onset Latency; WASO, Wake after sleep onset;

Microarousals, microarousal index; Mvt time, Movement time; SWS, Slow Wave Sleep ; NREMS, Non Rapid Eye Movement Sleep Time; REMS, Rapid Eye Movement Sleep Time; RL_A, REMS

latency, definition A ; RL_B, REMS latency, definition B; RL2-RL5, intervals between consecutive REMS episodes; NREMS-US, NREMS Ultra-Slow; REMS-US, REMS Ultra-Slow

168

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rch35(2001)165–172

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significant results were observed for SEI, WASO,Number of Awakenings, Movement Time, REMS,RL_A, RL_B, RL2, RL3, the spectral frequency bandsUltra-Slow and Delta corresponding to visually scoredNREMS and all frequency bands for visually scoredREMS. Trends were observed for TST, Stage 3 andNumber of Cycles. No age or gender interaction wasevidenced with the between-night comparison, and RM-ANOVA for bedtime was not significant (data notshown).

With the exception of the REMS latency measures,the variables that were significantly different in theRM-ANOVA were also significant for the contrastsbetween N1–N2, and these differences represent arather classic first-night effect. It is interesting to notethat Ultra-Slow in NREMS stages increased by 46%from N1 to N2, and Delta by 24%, which is insharp contrast with the absence of modifications inNREMS or Slow Wave Sleep (SWS) duration variables.Also, WASO and the Number of Awakenings on N1were almost doubled in comparison with consecutivenights.

The N1–N3 comparisons provided a few importantdivergences compared to the N1-N2 pairs. The lowerfrequency spectral power bands in NREMS (Ultra-Slowand Delta) were not significantly different, whereasassociations were found for RL_A, RL_B, RL2 andRL3. The comparisons between N1 and N4 provided analmost identical profile as in the N1–N3 comparisons,except for the absence of significance for RL2 andtrends observed in RL_B and RL3. The comparisonsbetween N2 and N4 were positive only for RL_A andRL2 (the contrast for NREMS Ultra-Slow was close tosignificance: P=0.052). The N3–N4 comparisonshowed a significant contrast only for RL2.

Examination of the means for several NREMS vari-ables, especially for the lower frequencies power bands(Ultra-Slow and Delta), showed peaks in N2, althoughno contrast proved significant between N2–N3 or N2–N4 for these values. The best-fit equation for theNREMS variables significant in the ANOVA (lowerfrequencies power bands) was quadratic. In contrast,evolution of the means of REMS variables significant inthe ANOVA (REMS, measures of REMS latencies,REMS spectral power) revealed gradual incrementsuntil N3 in all cases, except in lower frequencies powerbands. The comparisons of the various measures ofREMS latencies were not significant in N1–N2, yetproved significant in N1–N3 (RL_A, RL_B, RL2,RL3), and in some cases in N1–N4 (RL_A), N2–N3(RL2, RL3) and N2–N4 (RL_A, RL2). The slopes werelinear or predominantly linear except in all REMS rela-ted variables, except for RL2.

As an illustration of the gradual progression ofREMS related data, Fig. 1 presents a scattergram of thefour sequential RL_A.

Movement Time showed a progression globally simi-lar to that of REMS related variables.

4. Discussion

In this study of the dynamics of the habituation pro-cess to polysomnography, divergent patterns appearedaccording to the variables studied. Whereas NREMSduration parameters were not significantly influenced bythe habituation phenomenon, the intensity of NREMS(Slow Wave Activity, SWA), measured by spectral ana-lysis in the Ultra-Slow and Delta frequency bands,showed marked differences between N1 and N2, yet nosignificant differences between N1 and N3. This sig-nificant difference was due to a deficit in SWA in thefirst night compared to N2. Interpretation of theseresults is difficult as the mean power on N3 cannot benot different from two significantly different values, thatis, mean power on N1 and N2. Examination of themeans showed a peak of SWA on N2. From the trendobserved between N2 and N4 for NREMS Ultra-Slowpower band and the quadratic equation that best fittedthe curves across the 4 nights for NREMS Ultra-Slowand Delta power bands, we infer that a rebound inSWA was present on N2 with respect to the directlyconsecutive nights.

In contrast, the habituation process appeared to bedifferent for paradoxical sleep: REMS, RL, RL2, RL3and the spectral power bands in REMS showed a con-tinuous progression across sequential nights, at leastuntil N3. The differences became significant only incomparisons between the first and the third night for thevarious measures of REMS latency. The pattern ofevolution until the fourth night was more complex,showing a further increase in the differences for RL_A(N2-N4 pair). The slopes of the best-fit equations werelinear or predominantly linear in all cases except inREMS-related lower frequencies power bands.

Fig. 1. Bivariate scattergram of the RL_A in function of the con-

secutive nights (RL_A in minutes).

O. Le Bon et al. / Journal of Psychiatric Research 35 (2001) 165–172 169

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These data can be compared with outcomes fromsleep suppression and recovery studies and we canspeculate that the same type of mechanism is operatingin the habituation process. On one hand, the increaseobserved in SWA on N2 is consistent with the data onSWA recovery after sleep suppression (Borbely et al.,1981; Brunner et al., 1993) and could be compatiblewith the Two-Process Model proposed by Borbely(1982). On the other hand, the longer delay before theachievement of steady-state for REMS is in agreementwith studies on REMS homeostasis, showing a moreprotracted and progressive habituation process com-pared to NREMS (Endo et al., 1998). Furthermore, thetwo first REMS episodes were shown to be displacedtoward the end of the night (longer RL and RL2 on N1)starting from N1 and to recover subsequently in linearincrements, whereas the opposite was true of the thirdREMS episode (shorter RL3 on N1). This pattern ofstabilization is more in favor of an internal homeostasisfor REMS and a slower regulation than of an antag-onistic influence by SWA, which would probably haveaffected the second night more specifically.

Thus, a two-part sequence is suggested: an increasedstate of vigilance or arousal is observed on the firstnight, as demonstrated by an almost two-fold increasein the number of awakenings and the WASO in com-parison with further nights, resulting in lower SEI,SWA and REMS. We speculate that this first night,marked by a poor efficiency in relationship with a globalarousal effect due to the novelty of the situation, has aneffect on consecutive nights which is similar to that of apartial sleep deprivation. The second night shows animportant increase of SWA that is not paralleled byincreased NREMS duration, and a more limitedincrease of REMS. We speculate that it correspondsmainly to a recovery night after a partial sleep depriva-tion on N1. The N3 may correspond to a steady-statefor SWA (see first paragraph for this topic), whereassteady-state would be reached in N3 or even N4 forREMS, according to the variables and the definitionsused.

This slower adaptation of REMS and RL to sleeprecording has important implications for psychiatry.Shortened RL remains a frequent and puzzling phe-nomenon in a broad spectrum of affective and anxietydisorders, and several theories compete to explain theirorigin (see Le Bon et al., 1997b for a discussion). Thepresent observation revealed that the RL_A observedon N4 was more than 40 min shorter than in the usuallydiscarded N1, but also significantly more than 22 minshorter than in N2, which is the night that is often usedfor comparison with patient groups. Now, if the habi-tuation process is comparable between subjects andpatients, comparisons could be rightfully performedusing the corresponding night in both groups. However,various studies have shown that different populations

exhibit different habituation processes. FNE has beenreported to be present to a lesser degree in inpatientswith depression (Mendels and Hawkins, 1967; Kupfer etal, 1974; Toussaint et al, 1995; Rotenberg, 1997),insomnia (Coates et al., 1981; Edinger et al., 1997) andPTSD (Saletu et al., 1996; Woodward et al., 1996). Ininpatients suffering from sleep respiratory disorders,one night of recording alone is generally accepted fordiagnostic purposes (Lord et al., 1991; Mendelson,1994), although a recent study in a large group ofapneic-hypopneic patients (Le Bon et al., 2000) showedtypical FNE, as well as a substantial under-diagnosis ofrespiratory events when only the first night is con-sidered. In the use of plethysmographies for the detec-tion of male impotence, the FNE is considered to bemarginal (Kader and Griffin, 1983).

Comparison of the velocity of habituation in differentsubject groups has never been performed, to ourknowledge. If patients have already reached their steadystate on the second night while control subjects are stillaffected by a habituation process, false positive differ-ences in REMS latencies will be observed, leading tosystematic bias. Consequently, until the habituationpatterns for these parameters over more than 3 nightsare better known in patients and healthy controlsgroups, it is not safe to assume that the second night isan adequate basis for comparison. The wisest option inthe meantime may be to discard a minimum of two andperhaps three consecutive habituation nights in place ofone as is usually performed, and use the next night(s) asa basis for comparison. This is especially true for studieson REMS and REMS latency, which show a prolongedhabituation process, and perhaps also for spectral ana-lyses. At the very least, the cut-offs for the determina-tion of REMS latencies should be adapted in functionof the habituation process. It is also interesting to notethat REM density, which has also been associated withdepression (Foster et al., 1976), was not shown to beinfluenced by the habituation process in our study.

Another interesting result from this study is the pre-sence of a habituation process in a home setting. It isgenerally considered that no habituation is needed insuch cases and that the change in environment is moresignificant than the procedure of sleep recording itself.Previous studies performed at home in young healthysubjects have not demonstrated FNE (Coates et al.,1981; Sharpley et al., 1988). Conflicting results havebeen found in older age groups, however, with someevidence of FNE in one study (Wauquier et al., 1991)that was not replicated subsequently in a cross-overstudy (Edinger et al., 1997). Two studies also tended tofavor environmental changes (sleep unit versus homesetting (Coble et al., 1974; Browman and Cartwright,1980)) as being a more important factor than poly-somnography per se to explain FNE. These studiesadvocated the use of better accommodations for

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patients in sleep units or for the generalization of homestudies. The differences between the first 2 nights in ourstudy appear to be of the same magnitude as what isusually described in hospital sleep units. A larger num-ber of subjects and perhaps the rigorous definition ofhealthy controls in the present sample may explain thediscrepancy with previous reports on home recordings.Hence, home recordings, which are impractical in mostpsychiatric studies anyway, may still have to demon-strate advantages over hospital polysomnography. Onlymore double-blind cross-over studies will be able todemonstrate this without ambiguity. The difference ofsetting also precludes the present conclusions frombeing extended without caution to sleep laboratoriesstudies.

Even though a rather large group of 26 subjects wasanalyzed here, the logical issue of a discrepancy betweensome comparisons in lower frequencies spectral powerbands (see earlier) could not be resolved. This may bedue to the presence of large inter- and intra-subjectvariability that is commonly observed in sleep studiesand even larger samples should be examined in thefuture.

A limitation of this study was that no data onwomen’s menstrual cycle was available. However, nointeraction with gender or age was observed and sub-jects served as their own controls. Also, no data onbedtime on weekends preceding the study were avail-able, which could potentially affect the first recordingnight. However, bedtime means were very similar fromnight to night and RM-ANOVA did not reveal sig-nificant differences. These variables are hence not likelyto have influenced results in a significant manner.

In conclusion, the habituation to polysomnographyaffected differently NREMS, SWA and REMS. To beon the safe side, at least two and perhaps even threehabituation nights should be discarded before compar-ing nights, at least for studies on REMS and REMSlatencies. The longer delay before the achievement ofsteady state for REMS bears important consequences inpsychiatric research.

Acknowledgements

The authors wish to thank Philippe Dupont, AnitaBessemans and Marleen Bocken, for their meticulos-ness, constant help and availability. This work wassupported by SOMALCPE (Brussels), a private organi-zation dedicated exclusively to research in psychiatry.

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