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Clinical Neurophysiology 120 (2009) 248256

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Clinical Neurophysiology
journal homepage: www.elsevier.com/locate/clinph

All-night EEG power spectral analysis of the cyclic alternating pattern


at different ages
Oliviero Bruni a,*, Luana Novelli a, Elena Finotti b, Anna Luchetti c, Giordana Uggeri a, Debora Aric d,
Raffaele Ferri d
a
Pediatric Sleep Center, Department of Developmental Neurology and Psychiatry, Sapienza University, Rome, Italy
b
Department of Pediatrics, University of Padua, Padua, Italy
c
Child Neuropsychiatry Division, 2nd School of Medicine, Sapienza University, Rome, Italy
d
Sleep Research Centre, Department of Neurology I.C., Oasi Institute (IRCCS), Troina, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Objective: To analyze in detail the frequency content of the different EEG components of the Cyclic Alter-
Accepted 3 November 2008 nating Pattern (CAP) in the whole sleep of pre-school and school age children compared to normal young
Available online 24 December 2008 adults.
Methods: Fourteen pre-school age and 18 school age children and 16 adults were included in this study.
Keywords: Each participant underwent a polysomnographic overnight recording, after an adaptation night; sleep
Sleep stages and CAP were scored following standard criteria. Average spectra were obtained for each CAP con-
Sleep stages
dition from the signal recorded from C3/A2 or C4/A1, separately in sleep stage 2 and slow-wave sleep
Cyclic alternating pattern
Fast Fourier transform
(SWS), for each subject.
EEG power spectra Results: The analysis of the relative power density in the three groups showed that in sleep stage 2 and in
Pre-school age SWS, CAP A1, A2, A3 subtypes had a signicantly higher power in all frequency ranges in pre-school chil-
School age dren than in adults, while school children differed mainly for the lower frequencies (<7 Hz). For non-CAP,
Adults pre-school and school children differed from adults at almost all frequencies analyzed. Generally, A1, A2
and A3 showed clear spectral differences in the three different groups of subjects with pre-school age
children showing slightly less evident differences.
Conclusions: CAP subtypes are characterized by clearly different spectra at different ages and also the
same subtype shows a different power spectrum, during sleep stage 2 or SWS. This study shows that
pre-school children have a different structure of sleep, especially from the microstructural (CAP) point
of view: the differences are evident for all the CAP components and for non-CAP in almost all the fre-
quency bands. This nding might be associated to the age-related delta decline in the 03 Hz frequency
reported in children of the same age.
Signicance: Our data seem to provide information not available before and useful for the understanding
of the impact of CAP on the sleep EEG neurophysiological dynamics at different ages. This type of infor-
mation is crucial for a more adequate interpretation of data provided by a growing number of studies
analyzing CAP in groups of pediatric patients.
2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights
reserved.

1. Introduction (Terzano et al., 1985, 1988; Halsz, 1998). CAP is therefore a peri-
odic EEG activity of non-REM sleep characterized by sequences of
Non-REM sleep is characterized by the recurring appearance of transient electro-cortical activations (phase A of the cycle) that
EEG transients that translate the sleep state stability or instability. are distinct from the background EEG activity (phase B of the
These EEG patterns are dened by phasic events, such as sleep cycle). Sequences of CAP are orderly distributed in NREM sleep,
spindles, K-complexes, vertex waves, and short-lasting arousals and the percentage of CAP time to NREM sleep time (CAP rate) is
and are coded phases A of the Cyclic Alternating Pattern or CAP considered to be a physiologic marker of NREM sleep instability.
CAP A phases have been subdivided into different subtypes: A1,
A2 and A3 based on the frequency content (Terzano et al., 2001;
* Corresponding author. Address: Center for Pediatric Sleep Disorders, Depart- Parrino et al., 2001). A1 subtypes show a power spectrum charac-
ment of Developmental Neurology and Psychiatry, University of Rome La Sapienza,
terized by a predominant peak in the frequency range of 0.25
Via dei Sabelli 108, 00185 Rome, Italy. Tel.: +39 0644712257; fax: +39 06 4957857.
E-mail address: oliviero.bruni@uniroma1.it (O. Bruni). 2.5 Hz (De Carli et al., 2004; Ferri et al., 2000, 2005a,b); these

1388-2457/$34.00 2008 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.clinph.2008.11.001
O. Bruni et al. / Clinical Neurophysiology 120 (2009) 248256 249

frequencies, during CAP events, are likely to be generated at the le- outer cantus and 1 cm below the left outer cantus and referred to
vel of the frontal areas of the brain and the scalp topographic map- A1), electromyogram (submental EMG), EMG of the right and left
ping and localization of their eventual scalp generators by means tibialis anterior muscle, and ECG (one derivation). Sleep signals
of the LORETA method (Pascual-Marqui et al., 1994, 1999) conrms were sampled at 200 or 256 Hz and stored on hard disk in Euro-
this idea (Ferri et al., 2005b). On the contrary, the high-frequency pean data format (EDF, see Kemp et al., 1992 for details) for further
components characterizing CAP A2 and A3 phases have been analysis. EEG signals, in particular, were rst acquired with a wide
shown to involve both midline and hemispheric areas within the band analog lter (0.00170 Hz) and then digitally band-pass l-
parietal and occipital areas (Ferri et al., 2005b). tered at 0.150 Hz.
Both visual and automatic detection of CAP are based mostly on
the frequency content of A phases and on that of the ongoing back- 2.3. Sleep stage scoring
ground activity, together with their amplitude. Ferri et al. (2005a)
analyzed in detail the spectral frequency content of the different Sleep stages were scored following standard criteria (Rechts-
CAP EEG components in normal young adults in order to obtain chaffen and Kales, 1968) on 30-s epochs, and the following conven-
information functional for their detection, showing that CAP sub- tional sleep parameters were evaluated:
types are characterized by different spectra and also the same sub-
type shows a different power spectrum, during sleep stage 2 or Time in bed (TIB).
slow-wave sleep (SWS). Sleep period time (SPT): time from sleep onset to sleep end.
However, all these studies are based on adult samples and no Total sleep time (TST): the time from sleep onset to the end
spectral EEG data are available in children, although the specic of the nal sleep epoch minus time awake.
features of CAP in this age range have been visually characterized Sleep latency (SOL): time from lights out to sleep onset,
and clearly shown to be somewhat different from adults (Bruni dened as the rst of two consecutive epochs of sleep stage
et al., 2002, 2005; Parrino et al., 1998). 1 or one epoch of any other stage, in minutes.
The aim of the present study was that of analyzing in detail the REM latency (FRL): time from sleep onset to the rst REM
frequency content of the different CAP EEG components, taking sleep epoch.
into account the ongoing EEG background and the non-CAP (NCAP) Number of stage shifts/hour (SS/h).
periods in polysomnographic (PSG) recordings of pre-school and Number of awakenings/hour (AWN/h).
school age children also in comparison to adults. Finally, we ana- Sleep efciency (SE%): the percentage ratio between total
lyzed the spectral differences between these components in order sleep time and time in bed (TST/TIB*100).
to obtain information useful for their detection and the quantica- Percentage of SPT spent in wakefulness after sleep onset
tion of their impact on the sleep EEG neurophysiological dynamics. (WASO%), i.e., the time spent awake between sleep onset
and end of sleep.
Percentage of SPT spent in sleep stages 1 (S1%), 2 (S2%),
2. Methods slow wave sleep (SWS%), and REM sleep (REM%).

2.1. Subjects
2.4. Cyclic alternating pattern (CAP) scoring
Forty-eight healthy subjects, 14 pre-school age children (seven
males, seven females, mean age 5.0, SD 1.19, range 2.96.5 years), CAP A phases were detected in each recording (on the C3/A2 or
18 school age children (11 males, seven females, mean age 7.8, SD C4/A1 derivation), during NREM sleep, and classied into three
1.20, range 6.610.3) and 16 adults (ve females and 11 males, subtypes (A1, A2, and A3), according to the rules dened by Terz-
mean age 30.7 years, SD 3.57, range 24.539 years), were included ano et al. (2001).
in this study. The group of adults was the same that was enrolled in CAP A phases have been subdivided into a 3-stage hierarchy of
the study by Ferri et al. (2005a). Children were recruited in the arousal strength:
community to participate to the study. Parents signed an informed
consent. Inclusion criteria were: normal healthy pre-pubertal chil- A1: A phase with synchronized EEG patterns (intermittent
dren attending local school, with normal sleep habits. These crite- alpha rhythm in stage 1; sequences of K-complexes or delta
ria were conrmed by parental and child interviews, sleep habits bursts in the other NREM stages), associated with mild or
and sleep disorders questionnaires, sleep diaries obtained for 15 trivial polygraphic variations.
days before the experiment and complete physical examination A2: A phase with desynchronized EEG patterns preceded by
that included determination of Tanner stage. None had any serious or mixed with slow high-voltage waves (K-complexes with
physical or neurological or psychiatric disorder nor history of ma- alpha and beta activities, k-alpha, arousals with slow wave
jor sleep problems and none was taking medication at the time of synchronization), linked with a moderate increase of mus-
the recording. cle tone.
and/or cardiorespiratory rate.
2.2. PSG recording A3: A phase with desynchronized EEG patterns alone (tran-
sient activation phases or arousals) or exceeding 2/3 of the
For this study each participant underwent a PSG overnight phase A length, and coupled with a remarkable enhance-
recording, after an adaptation night, in a standard sleep laboratory ment of muscle tone and/or cardiorespiratory rate (Terzano
with controlled sound (noise level to a maximum of 30 dB SPL). et al., 2001).
Subjects were not allowed to have drinks containing caffeine dur-
ing the afternoon preceding the recording and were allowed to These criteria were applied also with the subsequent modica-
sleep until their spontaneous awakening in the morning. tions proposed by Bruni et al. (2005) for pre-school age children.
The PSG montage included: EEG (at least three channels, F3 or CAP sequences are dened as three or more A phases separated
F4, C3 or C4, and O1 or O2, referenced to the contralateral mastoid; from each other by no more than 60 s. The percentage of NREM
electrodes placed following the 1020 International System); left occupied by CAP sequences denes the CAP rate. All the remaining
and right electrooculogram (electrodes placed 1 cm above the right NREM sleep, not occupied by CAP sequences is called NCAP.
250 O. Bruni et al. / Clinical Neurophysiology 120 (2009) 248256

The detection of CAP was carried out by means of the sleep 2.6. Statistical analysis
analysis software Hypnolab 1.2 (SWS Soft, Italy) which allows
computer-assisted detection of CAP A phase subtypes. With this For the statistical analysis, individual average spectra were
software, the automatic detection of CAP is performed by analyzing used, for each CAP and sleep stage condition, so that each subject
the power course of two frequency bands, one for the detection of contributed equally to the group average.
candidates for A1 CAP subtypes and one for candidates of A3 CAP The comparison between the different CAP subtypes and
subtypes. Periods in which both A1 and A3 candidates coexist are between them and NCAP periods during sleep stage 2 or SWS
assigned to the A2 CAP subtype. The automatic approach is super- was carried out by means of the Students t-test for paired data
vised by the scorer who can change all the detection parameters. sets which was computed for each frequency bin in the spectra.
The performances of this system have been evaluated and vali- For these comparisons, the Bonferroni correction for multiple
dated (Ferri et al., 2005c); additionally, for the present study, after statistical tests was applied and differences were considered as
the supervision of the detection, the scorer visually edited carefully statistically signicant at p < 0.025, because two simultaneous
the detections proposed by the automatic analysis, before the com- comparisons were carried out. This analysis was repeated for each
putation of the various CAP parameters, which were automatically of the three groups. Statistical estimators in the context of this
generated by the same software and were used for statistical study were used essentially as descriptors. The comparisons be-
analysis. tween sleep or CAP parameters obtained in each group (pre-school
The following CAP parameters were measured: age children, school age children, adults) was conducted using the
one-way ANOVA followed by post-hoc comparisons, when
CAP rate (percentage of total NREM sleep time occupied by appropriate.
CAP sequences). The commercially available Statistica software package (Stat-
Percentage and duration of each A phase subtype. Soft, Inc., 2001. STATISTICA data analysis software system, version
A1 index (number of phases A1 per hour of NREM sleep, 6. www.statsoft.com) was used for this statistical analysis.
and of S1, S2, and SWS sleep stage).
A2 index (number of phases A2 per hour of NREM sleep, 3. Results
and of S1, S2, and SWS sleep stage).
A3 index (number of phases A3 per hour of NREM sleep, Table 1 shows the statistical comparison between the sleep
and of S1, S2 and SWS sleep stage). architecture parameters obtained in the three groups. As expected,
Duration of B phases. adults showed a reduction of SPT and TST and a signicantly higher
Number and duration of CAP sequences. number of stage shifts per hour vs. school and pre-school age
children.
The evaluation of CAP parameters (Table 2) revealed several sig-
2.5. Selection of EEG mini-epochs and power spectra computation nicant differences with the pre-school age group showing the big-
gest differences vs. the other two groups: lower A1%, higher A2%
For this study, we utilized the same approach that was used in and A2 index and shorter A2 mean duration. School age children
the previous study on adults by Ferri et al. (2005a). The same chan- showed only few differences vs. adults: shorter mean A1 duration
nel used for the detection of CAP A phases (C3/A2 or C4/A1) was and a slight increase in number of CAP sequences.
subdivided into 2-s mini-epochs. Each mini-epoch was assigned Fig. 1 shows the comparison between the relative power den-
to a sleep stage, based on the sleep scoring previously performed sity of the three groups for each CAP phase. Each frequency bin
- only mini-epochs from sleep stage 2 and sleep stages 3 or 4 of pre-school and school age children for each CAP subtype is ex-
(SWS) were considered in this study - and to a CAP condition pressed as a percentage of the corresponding bin of the adult
(based on the CAP detection carried out previously); in particular, group. The dotted line indicates the baseline value of adults, while
the following CAP conditions were assigned: A1, A2, A3, and NCAP black bars at the bottom indicate frequency bins in which the rel-
(periods of absence of CAP). Additionally, also CAP B phases were ative power density of pre-school and school age children groups
indicated as B1 (B phase following A1), B2 (B phase following differ signicantly from adults.
A2), and B3 (B phase following A3). In order to be assigned one In NREM S2 sleep stage, CAP A1, A2, A3 and NCAP showed sta-
of the conditions listed above, mini-epochs needed to be occupied tistically signicant differences in all frequency ranges between
for more than half of their length (>1 s) by the same condition. All pre-school children and adults while school children differed
mini-epochs belonging to these different conditions were ana- mainly for low frequencies (<7 Hz).
lyzed; thus practically all NREM was included in this study, in each In SWS, statistically signicant differences were found in all fre-
subject. Epochs with artifacts and with a signicant amount of con- quency ranges for CAP A1, A2 and A3 between pre-school and
tamination by electromyographic activity were carefully detected adults. School aged children showed differences vs. adults for
and excluded from the analysis. CAP A1, A2 and A3 mainly in the low-frequency range (<7 Hz)
Power spectra were calculated for each mini-epoch using the and in the high frequency range (>20 Hz). For NCAP, pre-school
sleep analysis software Hypnolab 1.2 (SWS Soft, Italy), after Welch children differed from adults at all frequencies analyzed while
windowing, in order to minimize the truncation error and reduce school children differed for frequency 0.519 Hz and 2125 Hz.
spectral leakage by suppressing sidelobes (Press et al., 1989), by Fig. 2 shows the comparison between the different CAP sub-
means of the fast Fourier transform (Cooley and Tukey, 1965); in types (A1, A2, A3) in NREM S2 (left column) and in SWS (right col-
order to calculate the FFT on 2-s epochs of recordings sampled at umn), within the same group of subjects. The dotted line indicates
200 Hz, a zero-padding was performed in order to reach the re- A1 as the baseline value. As expected adults showed signicant dif-
quired samples for this calculation (i.e. 512 samples) followed by ferences in A2 and A3 for almost all the frequency bins except for
a linear interpolation of the spectral values in order to obtain 35 Hz for A2 and 58 Hz for A3, in NREM S2 while in SWS the dif-
power spectrum data for frequencies between 0.5 and 25 Hz with ferences were found only above 5 Hz for both A2 and A3.
a frequency step of 0.5 Hz. The linear interpolation was not needed School age children showed a different trend; in NREM S2 the
for recordings sampled at 256 Hz. Average spectra were obtained A2 differed from A1 in frequency bins 411 Hz and 14.525 Hz,
for each CAP condition, separately in sleep stage 2 and SWS, for while A3 phases in 0.54 Hz, 811 Hz and 1425 Hz; in SWS
each subject.
Table 1
Comparison between the different sleep scoring parameters obtained in the three groups of subjects.

1. Adults 2. School-age children 3. Pre-school-age children ANOVA Post-hoc


1 vs. 2 1 vs. 3 2 vs. 3
Mean Standard 95% Condence Mean Standard 95% Condence Mean Standard 95% Condence p< p< p< p<
deviation interval deviation interval deviation interval
TIB, min 419.4 32.93 401.9437.0 547.1 37.43 528.5565.7 559.3 46.91 532.2 586.4 0.000001
SPT, min 398.1 37.47 378.1418.1 499.3 45.06 476.8521.7 533.3 60.51 498.3 568.2 0.000001 0.000001 0.000001 NS
TST, min 378.9 34.87 360.3397.5 484 46.05 461.1506.9 521.9 69.38 481.8 561.9 0.000001 0.000001 0.000001 0.05
SOL, min 18.9 15.6 10.627.2 36.3 24.97 23.948.8 22.4 20.88 10.334.4 0.05 0.02 NS NS
FRL, min 65.5 28.85 50.280.9 122.9 53.52 96.3149.5 96.1 35.52 75.6116. 6 0.001 0.00025 NS NS
SS/hour 8.9 1.79 8.09.9 7 2.57 5.78.2 6.7 2.42 5.38.1 0.02 0.02 0.015 NS
AWN/hour 1.7 1.26 1.12.4 1 1.19 0.41.6 1 1.21 0.31.7 NS
MT/hour 1 0.59 0.71.3 1.8 1.6 1.02.6 2.3 1.13 1.73.0 0.02 NS 0.01 NS
SE% 90.5 6.28 87.193.8 88.6 7.17 85.092.1 93 5.94 89.696.4 NS
WASO, % 4.7 4.35 2.47.0 3.7 3.25 1.95.5 2.7 2.72 1.04.5 NS

O. Bruni et al. / Clinical Neurophysiology 120 (2009) 248256


S1, % 0.9 0.67 0.51.2 2.9 2.2 1.84.0 3.1 2.07 1.94.3 0.002 0.02 0.015 NS
S2, % 46.8 7.02 43.150.6 44.6 7.2 41.048.1 44.8 7.07 40.748.9 NS
SWS, % 23.8 6.54 20.327.3 27.6 4.88 25.230.0 26.7 6.42 23.030.4 NS
REM, % 23.8 4.89 21.226.4 21.9 5.23 19.324.5 23.1 4.92 20.325.9 NS

TIB, time in bed; SPT, sleep period time; TST, total sleep time; SOL, sleep onset latency; FRL, 1st REM latency; SS, stage shifts; AWN, awakenings; MT, movement time; SE%, sleep efciency; WASO, wakefulness after sleep onset; S1,
NREM sleep stage 1; S2, NREM sleep stage 2; SWS, slow-wave sleep; REM, rapid-eye-movement sleep.

Table 2
Comparison between the different CAP parameters obtained in the three groups of subjects.

1. Adults 2. School-age children 3. Pre-school-age children ANOVA Post-hoc


1 vs. 2 1 vs. 3 2 vs. 3
Mean Standard 95% Condence Mean Standard 95% Condence Mean Standard 95% Condence p< p< p< p<
deviation interval deviation interval deviation interval
CAP rate, total 34.8 8.59 30.339.4 37.5 9.58 32.742.2 34 17.96 23.644.4 NS
CAP rate, S2 18.8 7.5 14.822.8 23.4 8.18 19.327.4 21.2 12.66 13.928.5 NS
CAP rate, SWS 66.1 17.92 56.575.7 60.4 19.78 50.670.3 55.3 25.95 40.370.3 NS
A1, % 79.2 8.1 74.983.5 81.4 5.18 78.884.0 65.9 10.74 59.772.1 0.000005 NS 0.00005 0.000002
A2, % 10 4.36 7.712.3 10.3 5.56 7.513.0 21 6.97 16.925.0 0.000002 NS 0.000003 0.000003
A3, % 10.8 5.33 8.013.6 8.4 3.38 6.710.0 13.2 6.38 9.516.8 0.04 NS NS 0.011
A1 duration, min 9.2 1.65 8.310.1 7.3 2.76 6.08.7 7.5 2.27 6.28.8 0.05 0.03 0.05 NS
A2 duration, min 11.5 1.78 10.612.5 10.5 1.87 9.611.4 8.9 1.87 7.810.0 0.0014 NS 0.00032 0.02
A3 duration, min 15.3 2.93 13.716.8 18.5 4.37 16.320.6 16.6 3.61 14.518.7 NS
A1 index 36.7 9.48 31.741.8 42.2 9.22 37.646.8 34 21.19 21.846.3 NS
A2 index 3.9 1.97 2.84.9 5.2 4.31 3.17.4 8.5 4.93 5.611.3 0.008 NS 0.0026 0.026
A3 index 3.8 2.54 2.45.1 3 1.47 2.33.7 4.4 1.99 3.25.5 NS
B duration, min 22.4 2.74 20.923.8 22 3.49 20.323.8 22.3 3.94 20.024.5 NS
Sequence 243.1 83.08 198.8287.3 276 114 219.3332.7 231.2 110.11 167.6294.8 NS
duration, min
Sequence number 25.8 7.2 21.929.6 32.7 7.01 29.236.2 34.6 8.18 29.839.3 0.005 0.01 0.0025 NS

251
252 O. Bruni et al. / Clinical Neurophysiology 120 (2009) 248256

Fig. 1. Comparison between the relative power density of the three groups for each CAP phase. Each frequency bin of pre-school and school age children for each CAP subtype
is expressed as a percentage of the corresponding bin of the adult group. The dotted line indicates the baseline value of adults, while black bars at the bottom indicate
frequency bins in which the relative power density of pre-school and school age children groups differ signicantly from adults.

differences were found in the frequency ranges 36 Hz and 15 was clearly different from NCAP in the frequency range below
24 Hz for A2 and 46 Hz, 8.511.5 Hz and 1225 Hz for A3. 15 Hz.
Pre-school age children showed more similarities between A1 Similarly to A1, A2 showed differences in all frequency bands in
and A2 with scattered differences in the whole frequency range all the three age groups considered vs. NCAP. The phase B following
in sleep stage 2 while A3 showed differences mainly in the higher A2 showed differences in frequencies below 10 Hz in pre-school
frequency range. In SWS the differences were more evident and A3 and school age children, while it could be considered similar to
differed in all frequency bins analyzed while A2 differed for fre- NCAP in adults.
quencies above 4 Hz. Again, A3 showed a difference from NCAP in all frequency
Fig. 3 shows the different CAP subtypes and NCAP periods dur- ranges and in the three age groups while the phase B after A3
ing NREM S2. Each frequency bin of CAP A subtypes and of their was virtually equivalent to NCAP.
following B phases is expressed as a percentage of the correspond- Fig. 4 shows the different CAP subtypes and NCAP periods dur-
ing bin of NCAP. The dotted line indicates the baseline value of ing NREM SWS. In SWS, CAP A1 showed very few differences from
NCAP, while black bars at the bottom of each panel indicate fre- NCAP (in frequencies below 7 Hz) and the phase B following A1 is
quency bins in which the relative power density of the CAP sub- practically no different from NCAP in all the three groups.
type or the B phase differs signicantly from NCAP. Phases A2 and A3, on the other hand, showed a clearly different
A1 showed a clear difference from NCAP in all frequency ranges spectrum from NCAP while the respective phases B were very sim-
and with a similar trend in all age groups; also the phase B after A1 ilar to NCAP.
O. Bruni et al. / Clinical Neurophysiology 120 (2009) 248256 253

Fig. 2. Comparison between the different CAP subtypes (A1, A2, A3) in NREM S2 (left column) and in SWS (right column), within the same group of subjects. The dotted line
indicates A1 as the baseline value. Black bars indicate frequency bins in which absolute power density of CAP subtypes A2 or A3 differed signicantly from A1.

4. Discussion frequencies but involves all frequency bands between 0.3 and
30 Hz, although it is most evident in the theta and delta bands.
Relatively recent previous studies on CAP in pre-school and Recently, signicant differences in the EEG spectra have been
school age children have shown clear developmental changes reported in adults related to the presence or absence of CAP, even
characterized mainly by the distribution and percentage of A in the same sleep stage (Ferri et al., 2005a). Starting from this pio-
phases (Bruni et al., 2002, 2005; Lopes et al., 2005). These changes neering study we extended the same analysis to other two younger
seem to reect the maturational course of the sleep EEG in the age groups. Therefore, the present study compared three different
rst years of life and are also strictly related to the modication age groups and is the rst which included in its analysis the com-
of the sleep structure and to the redistribution of NREM sleep. plete NREM sleep EEG and computed separate power spectra for
EEG frequencies are overall somewhat slower in children and the different CAP phases and NCAP. As expected, the evaluation
gradually get faster until they reach adult values, while the of CAP parameters revealed several signicant differences with
amplitude of waveforms at all frequencies increases gradually the pre-school age group showing the biggest differences vs. the
reaching a peak in the school age period and then declines. These other two groups, while school age children showed only few dif-
developmental changes occur also in several PSG measures, par- ferences vs. adults:
ticularly during transition from pre-school to early school age Our analysis demonstrated that pre-school children have a dif-
(Montgomery-Downs et al., 2006); in fact the process of sleep ferent structure of sleep, especially from the microstructural (CAP)
maturation determines a change in proportion of NREM stages point of view. The differences are evident for all the CAP compo-
during pre-school years, related to napping (Kahn et al., 1973; nents and for NCAP in almost all the frequency bands. These data
Smith et al., 1977; Sheldon, 1996; Curzi Dascalova and Challamel, are in agreement with a recent report that showed that develop-
2000). Also during the transition from preadolescence to adoles- mental changes occur in several PSG measures particularly during
cence, this process determines a steep decline in NREM sleep transition from pre-school to early school age (Montgomery-
and in the slow-wave (delta) activity (Coble et al., 1987; Feinberg Downs et al., 2006).
et al., 1990a) related to the waning synaptic connectivity that de- CAP A1, A2 and A3 phases in pre-school and school aged chil-
creases the intensity of waking brain activity (Feinberg et al., dren showed differences vs. adults in all frequencies with the big-
1990a,b). Moreover, a recent longitudinal study reported a dra- gest divergence in the delta range, in both stage 2 and SWS. This
matic change in power density from preadolescence to adoles- nding might be associated to the age-related delta decline in
cence beginning at age 915 year (Campbell et al., 2007) and the 03 Hz frequency reported by Feinberg et al. (1990) and Coble
showed that the power density decline is not limited to the delta et al. (1987) in children of the same ages. Also NCAP was
254 O. Bruni et al. / Clinical Neurophysiology 120 (2009) 248256

Fig. 3. Different CAP subtypes and NCAP periods during NREM S2. Each frequency bin of CAP A subtypes and of their following B phases is expressed as a percentage of the
corresponding bin of NCAP. The dotted line indicates the baseline value of NCAP, while black bars at the bottom of each panel indicate frequency bins in which the relative
power density of the CAP subtype or the B phase differs signicantly from NCAP.

completely different in the three age groups showing that NREM we could observe again a similar trend of the slope of power den-
sleep undergoes profound modication in its structure during sity in the pre-school, school and adult subjects. This results is in
development. part conrmed by the stability of the time structure of CAP at dif-
Analyzing the different power spectrum of the CAP A phases, we ferent ages as we demonstrated in previous studies (Bruni et al.,
found a similar trend in the three age groups: CAP A2 and A3 2005).
phases are clearly different from A1 mostly with respect to the Regarding the B phase, we can state that this component of
higher frequencies. This is clearly evident in adults and the differ- CAP seems not to be a simple return to the ongoing baseline
ence tends to be smaller in school and pre-school children. Fur- activity but shows a small and signicant increase in power in
thermore, CAP A phases are characterized by clearly different the delta-theta frequencies and a decrease in power in the sigma
spectra also during sleep stage 2 or SWS, in all groups and this nd- frequency range. The difference is more marked in stage 2 than
ing underlines a probable different functional meaning of the same in SWS, reecting the difculty of scoring CAP visually in some
CAP subtype during different sleep stages, independently from age. epochs of SWS.
Compared to NCAP, CAP A phases are characterized by clearly As stated in the previous paper (Ferri et al., 2005b), the A
different spectral patterns: the A1 subtype is characterized by a components of CAP might correspond to periods in which the
prominent peak in the delta range evident in stage 2 but not so very-slow delta activity of sleep groups a range of different EEG
clear in SWS; the power spectrum of A1 is signicantly higher than activities, including slow waves, and the sigma and beta bands,
that of NCAP over the whole frequency range studied during sleep while the B phase of CAP might correspond to a period in which
stage 2, but only up to 7.5 Hz during SWS, in all age groups. this activity is quiescent or inhibited.
Also A2 and A3 subtypes show a signicant increase in power, While some results were expected because the denition of
with respect to NCAP, over the whole frequency range studied; CAP, even if developed for visual detection, is also based on the
they show an prominent increase in the high-frequency part of EEG spectral content, our analysis was able to disclose additional
the spectrum, during both sleep stage 2 and SWS. This increase ne aspects which were not only the effect of the initial denition
in the high frequencies has been already reported (De Carli et al., of the CAP components and were only detected because of the de-
2004; Ferri et al., 2005a) and was more evident in adults than in tailed quantitative analysis performed.
the younger groups. Our analysis clearly conrmed that age is a potent modulator of
Analyzing Figs. 3 and 4, we can observe that the trend of the the power spectra of sleep EEG. There are clear differences be-
spectral differences between CAP phases and NCAP in stage 2 tween adults and children in the EEG spectra that are strictly re-
was similar in the three age groups indicating that the structural lated to age. This nding has been conrmed by previous studies
component of CAP is very stable over time and is not greatly inu- on the spectral components of sleep in children. Feinberg et al.
enced by age. In SWS, although the dissimilarities are less marked, (1990) in a group of subjects aged 4.223.7 years showed that
O. Bruni et al. / Clinical Neurophysiology 120 (2009) 248256 255

Fig. 4. Different CAP subtypes and NCAP periods during NREM SWS. Each frequency bin of CAP A subtypes and of their following B phases is expressed as a percentage of the
corresponding bin of NCAP. The dotted line indicates the baseline value of NCAP, while black bars at the bottom of each panel indicate frequency bins in which the relative
power density of the CAP subtype or the B phase differs signicantly from NCAP.

amplitude and incidence of delta waves decline at roughly the of information is crucial for a more adequate interpretation of data
same rate from the middle of the rst decade through the second provided by a growing number of studies analyzing CAP in groups
decade of life, in agreement with the previous report by Coble of pediatric patients (Bruni et al., 2002, 2005, 2007, 2008; Lopes
et al. (1987). et al., 2005; Guilleminault et al., 2005; Kheirandish-Gozal et al.,
However, we should also consider that the homeostatic mecha- 2007).
nism of sleep is active since the early period of life and remains sta-
ble until elderly, considering NREM sleep and mainly SWS. In the
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