quantitative analysis of infant eeg development during quiet sleep

Electroencephalography and Clinical Neurophysiology, 1977, 43:371--385 371 © Elsevier/North-Holland Scientific Publishers, Ltd.

QUANTITATIVE ANALYSIS OF INFANT EEG DEVELOPMENT DURING QUIET SLEEP

M.B. STERMAN, R.M. HARPER, B. HAVENS, T. HOPPENBROUWERS, D.J. McGINTY and J.E. HODGMAN

Veterans Administration Hospital, Sepulveda; Departments of Anatomy, Psychiatry and Psychology, UCLA; LAC-USC Medical Center, Department of Pediatrics; USC School of Medicine, Los Angeles, Calif. (U.S.A.)

(Accepted for publication: February 14, 1977)

Changes in the EEG during the first several months of post-natal life exceed those seen at any other period in ontogeny. The objective description of these changes can provide evidence concerning functional correlates of neuronal maturat ion as well as a normative reference for the assessment of central nervous system disorders in infancy. An optimal description of this kind requires quantification and, unfor tunately , this has been diffi- cult to obtain with the EEG signal. The sub- stantial problem of providing a digital repre- sentation of this constant ly changing analog signal is complicated further by the significant pattern shifts associated with the states of sleep and wakefulness as well as substates within these.

Historically, the developmental characteriza- tion of the EEG was based upon a qualitative description with limited at tempts at quantitative analysis. The field advanced significantly after Aserinsky and Kleitman (1953) pointed out that sleep, which dominates behavior in the infant, contains two basic and recurrent physiological patterns. These are generally classified today as quiet sleep (QS), a pattern with EEG slow waves and spindles together with stable somatic and visceral activity, and active sleep (AS), which is defined by a low voltage, rapid EEG, marked phasic motor activity and autonomic irregularity and, in particular, rapid eye movements. The characteristics of these patterns, or states of sleep, in developing infants have been described in detail (see for example Dreyfus-Brisac et al.

1956; Kleitman 1963; Parmelee et al. 1964; Roffwarg et al. 1966; Sterman and Hoppen- brouwers 1971). A focus on EEG development as a function of state was provided by Dreyfus-Brisac (1964), Ellington (1964), Parmelee et al. (1968), Lenard (1970), Monod et al. (1972) and Hagne (1972) among others. Quantitative description, utilizing computer digital analysis, was a t tempted also by Prechtl et al. (1968, 1969), Parmelee (1969), Shulte and Bell (1973) and Havlicek et al. (1975). All of these efforts, however, have depended upon relatively limited data samples, and many have focused entirely upon the newborn period.

The developmental description of the infant EEG therefore remains fragmented and primarily qualitative. In pursuit of the goals specified at the outset of this discussion, we have collected longitudinal, bilateral central cortical EEG data at regular intervals between 1 and 24 weeks of age. Computer power-spectral analysis provided for quantification utilizing programs for a practical, numerical evaluation of multiple frequency bands within long samples of EEG activity, and for the comparison of these measures across time and between individuals. We have chosen the quiet sleep pattern for our initial focus because it is less disrupted by artifact and shows the most dramatic changes with development. The spectral density distribution of central cortical EEG activity during this state was evalu- ated as a function of time of night, hemisphere and age.

372

Me thods

Ten neuro log ica l ly n o r m a l infants o f pos t - c o n c e p t u a l ages b e t w e e n 39 - -41 weeks , and wi th one m i n u t e Apga r scores of 8 or 9, part i- c ipa ted in this s tudy . Six were females and fou r were males . Bir th weights ranged f r o m 3 ,040 to 4 ,550 g. Each in fan t was a d m i t t e d at 5 p .m . to the sleep l a b o r a t o r y fo r 12 h all-night m o n i t o r i n g sessions, once at 4 - -7 days o f age and again at 1, 2, 3, 4 and 6 m o n t h s o f age. The pa ren t s were i n f o r m e d o f the na tu re and object ives of the s t udy and wr i t t en pe rmiss ion ob t a ined f r o m each fo r use and release o f these data .

I n fan t s were fed dur ing p r e p a r a t i o n fo r m o n i t o r i n g and app l i ca t ion o f e lec t rodes . The skull was c leaned and mi ld ly ab raded fo r the p l a c e m e n t o f silver chlor ide cup e l ec t rodes a t sites a p p r o x i m a t i n g C3-T3 and C4-T4, accord- ing to the in t e rna t iona l 10-20 Sys t em. Grass EC-2 e lec t rode pas te was used for app l ica t ion , and c o t t o n balls p laced over each e l ec t rode p r io r to wrapp ing the head wi th elastic gauze. O t h e r e lec t rodes were a t t a c h e d for m o n i t o r - ing eye m o v e m e n t s , chin EMG, s o m a t i c activ- i ty, resp i ra t ion and ECG, as descr ibed else- where (Harpe r e t al. 1976) . E lec t rode impedance o f less t han 8K was requi red b e f o r e m o n - i tor ing was in i t ia ted. N e w b o r n in fan t s were swadd led and o lder infants p laced in e lb low res t ra in ts b e f o r e in i t ia t ion of record ing .

The EEG and o t h e r phys io logica l var iables were r eco rded s imu l t aneous l y on a Grass m o d e l 78-B p o l y g r a p h a n d on m agne t i c t ape (Honeywe l l , m o d e l 96). An I R I G E t i m e code signal was r eco rded on m agne t i c t ape and wr i t t en on p a p e r to cor re la te the t w o media . Moni to r ing was carr ied ou t in a d i m l y l ighted r o o m which was separa te f r o m the recording e q u i p m e n t . R o o m t e m p e r a t u r e s ranged f r o m 23 - -25°C . A d e m a n d feeding schedule was fo l lowed dur ing record ing and in several ins tances , in fan ts were b reas t fed by the m o t h e r .

Moni to r ing was c o n t i n u o u s over a 12 h per iod c o m m e n c i n g a t 7 p .m. Each m i n u t e o f the 12 h r eco rded was coded b y t ra ined per-

M.B. STERMAN ET AL.

TABLE I

Infant polygraphic state scoring criteria and decision making rules (1 min epochs)

State Criteria

Active sleep (AS) Absence of sustained EMG tonus

Quiet sleep (QS)

Awake (AW)

Transitions (TR)

together with three of the following criteria : 1. At least one eye movement,

independent of chin and gross body movements.

2. Within a given minute, breath- ing rate variation greater than 25 breaths/min as measured by respiratory tachometer.

3. Presence of twitches and brief head movements.

4. Absence of EEG spindles or trace alternant.

All of the following criteria must be fulfilled : 1. Within a given minute breath-

ing rate variation no greater than 25 breaths/min as measured by respiratory tachometer.

2. No more than one isolated eye movement. Eyes closed.

3. Sustained EMG tonus and/or EEG spindles or trace alternant.

Three of the following criteria must be fulfilled: 1. Sustained EMG tonus with

activity bursts. 2. Eyes open. 3. Within a given minute breath-

ing rate variation greater than 45 breaths/min as measured by respiratory tachometer.

4. Vocalization. 5. Sustained gross movements.

Minutes in which the criteria for AW, AS and QS are not fulfilled, or minutes in which these criteria are fulfilled for less than 30 consecutive sec.

sonnel in to qu ie t s leep (QS), act ive sleep (AS), wak ing (AW) or t rans i t iona l s ta te (TR) , using s ta te cr i ter ia and decis ion m a k i n g rules l isted in Tab le I. The first and last sus ta ined QS episodes were d e t e r m i n e d , and 10 min

https://www.researchgate.net/publication/22950130_Polygraphic_Studies_of_Normal_Infants_During_the_First_Six_Months_of_Life_Part_I_Heart_Rate_and_Variability_as_a_Function_of_State?el=1_x_8&enrichId=rgreq-00e7228a-ac40-4333-bcac-2ef9a3dfa117&enrichSource=Y292ZXJQYWdlOzIzMDY0OTMxO0FTOjk3MjAyNjAwOTM5NTM5QDE0MDAxODYzMTU2NDg=

EEG DEVELOPMENT DURING QUIET SLEEP IN INFANTS 373

EEG samples identified at the beginning of these epochs, with reference to the appropriate time codes. Additionally, a third sample was obtained from a sustained QS period at approximately 1 a.m. In no instances were these samples less than two complete sleep cycles apart (a sleep cycle being defined as a sustained period of QS followed by a period of AS).

EEG signals were subjected to electronic band-pass filtering to a t tenuate noise and arti- facts. These filters were 3 dB down at 0.5 and 20 c/sec. The resulting EEG data were digitized at 64 samples/sec onto industry- compatible magnetic tape. EEG data from the specified samples were drawn from the digitized tapes, cosine tapered, and subjected to the Fast Fourier transform (FFT), utilizing the algorithm of Jennrich (1970) in a program of Pacheco et al. (1974). Successive 16 sec samples (1024 data points) were analyzed,

with 64 coefficients summed to provide a resolution of 1 c/sec from 0--20 c/sec. To provide an indication of absolute changes in spectra over age, spectra of a 50 pv, 13 c/sec sine wave recorded at the beginning and end of the session were also calculated. The amplitude of the spectra was then scaled by reference to a ratio of the calibration spectral peak to an arbitrary amplitude, following a similar method described by Clusin et al. (1970). This adjustment corrected for errors of scaling in the data acquisition process. The spectra could then be plot ted isometrically to provide compressed spectral arrays depicting the entire 10 min data sample (Bickford et al., 1972). All spectral values were subjected to log transformation and sorted into five 4 c/sec bands between 0--19 c/sec (i.e., 0--3, 4--7, 8--11, 12--15, 16--19 c/sec), corresponding partially to the designation by Davis et al. (1938) of delta, theta, alpha, sigma and beta

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SOM ACT

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Fig. 1. An example of polygraphic data ut i l ized for state scoring and art i fact removal is shown here f rom a one- week-old infant. This sample i l lustrates a per iod o f quiet sleep interrupted by a br ief startle response. EEG 1 refers to le f t central cor tex (approx imate ly C3-T3)and EEG 2 indicates r ight central cor tex (C4-T4). The remaining traces show eye movements, chin EMG, gross somatic act iv i ty, respirat ion as indicated by expired air pCO2, t ime marker, respirat ion as indicated by pO 2 (shown here) or more of ten thoracic impedance, electrocardiogram, cardiac cycle interval and cardiac rate. EEG epochs (16 see) containing movement art ifact such as shown here were deleted from power-spectral analysis data.

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FR£O(Hz)

NEEK

ONE

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Fig. 2. Power -spec t ra l p lo t s a n d r e c o n s t r u c t e d (digi t ized) EEG f rom c o n ' e s p o n d i n g 16 see cen t ra l cor t ica l e p o c h s are s h o w n here f rom the f irst qu ie t s leep pe r iod o f t he n igh t in t he same i n f a n t at var ious ages. Samples at B were se lected on t he basis o f a high pe rcen tage o f power in the 12 - -15 c/sec b a n d wi th re fe rence to spec t ra l p r i n t o u t s , whi le samples a t A r ep re sen t ad j acen t e p o c h s in wh ich th is ac t iv i ty was min imal . No te d e t e c t i o n o f high fre- q u e n c y sleep spindles in 3 and 6 m o n t h samples.


EEG frequencies. Spectral density in each of these bands was computed by calculating the area under the spectral curve during each successive 16 sec epoch. Means and standard deviations were computed for the log power in each band over the 37 spectra which con- st i tuted each 10 min sample. These calcula- tions were ou tpu t ted through a Versatec line printer.

A sample polygraphic recording during quiet sleep in a one-week-old infant is shown in Fig. 1. The quality of EEG samples utilized in the power-spectral analysis was determined by visual inspection of polygraphic records such as these, and by sampled reconstruction of the analog record from digital tapes after transformation (Fig. 2). The latter tests also provided for a validation of the power-spectral analysis, since the numerical record and power-spectral plots could be compared directly with the reconstructed analog signal.

The power-spectral analysis generated log power for successive 16 sec epochs of EEG data in each of the five frequency bands. These values were printed in sequence together with the mean and standard deviation of the 37 spectra in each 10 min sample of QS. An additional check of data quality was achieved at this step in the analysis through visual inspection of these power-spectral values. Aberrant values were first checked by reference to the polygraphic recording. If artifact in the original recording could account for these values they were dropped from the analysis, and corrected statistics calculated for the sample. If the recording was artifact free at these points the digital tape records were inspected. When an error or defect in the tape was disclosed the data were corrected by redigitizing the entire sample and recalculating the power-spectral values. As a result of these adjustments data from two of the infants were sufficiently incomplete so as to require their deletion from the analysis. Less than 5% of the data from the remaining eight infants was lost by these quality control measures.

Statistical analysis of main effects was

achieved utilizing the Analysis o f Variance test (ANOVA) for repeated measurements. Multiple comparison tests were used to further evaluate significant parameters. Unless otherwise specified, the 0.05 level of significance was required for all indicated differences. These tests were focused upon three basic dimensions; t ime of night, hemisphere and age.

Results

Mean values of log power showing spectral density in each of five frequency bands for three 10 min QS samples at all ages measured are plot ted for bo th left and right central cortex in Fig. 3. It can be seen from these curves that the distribution of spectral densities was inversely related to frequency at all ages sampled, with maximum values at the lowest frequency (0--3 c/sec) being approximately five- times greater than those at the highest frequency (16--19 c/sec). Specific results discussed below refer primarily to these data.

Time of night At 1, 4 and 24 weeks of age there were no

significant differences be tween the three sample periods in the power distribution of the five frequency bands. However, the spectral density of lower frequencies (0--11 c/sec) during the first QS episode of the night was significantly greater than the other samples between 8 and 16 weeks of age. This finding is noted in Fig. 3 by asterisks placed adjacent to values showing a significant increase. It can be seen that differences were manifest first on the left side (0--3, 4--7 and 8--11 c/sec) at 8 weeks of age, became bilateral at 12 weeks, and were restricted to 4--7 c/sec on the left at 16 weeks. Inspection of the curves, however, indicated that the tendency was comparable in both hemispheres. Thus, while no difference in the distribution of spectral densities was found in various QS samples across the night prior to 8 weeks and after 16 weeks of age, during the intervening age period there

376 M.B. STERMAN ET AL.

LEFT (C3-T 3), N=8

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25 / ~ RIGHT (C4-T 4 )

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; " 4 " ' ~ ...... ~ = ~ " 1 2 ,6 . . . . . 2'o ~=--24 '~ . . . . 4 ~ 8' ','2 l'6 2'o ~T--2~ AGE IN WEEKS

Fig. 3. Mean log spectral power in each of five frequency bands is shown here for left and right central cortex in eight infants for the three 10 min QS periods sampled at each age between 1 and 24 weeks. The solid curve represents mean longitudinal data from the first QS period of the night, the dashed curve from the middle QS period and the dash-dot curve from the last QS period of the night. Asterisks indicate significant differences in power between QS samples at a given age and frequency, with one representing the 0.05 level of significance and two the 0.01 level of significance. Note that deviation among QS samples was essentially restricted to lower frequencies during the first QS sample at 8--16 weeks of age, with the middle and last samples of the night l~eing comparable at all ages and frequencies. Developmental patterns are discussed in the text.

was a significant increase in low frequency power with the initial onset of sleep.

Hemisphere A comparison of power-spectral values cal-

culated from left and right central cortex, combining all samples and ages, showed no significant difference between hemispheres. There was a significant interaction between

QS sample, age and hemisphere, with the first QS episode showing greater power in lower frequencies on the left at 8 and again at 16 weeks than on the right. This finding is in agreement with the time of night effect described above.

Inspection of individual spectra indicated that hemispheric asymmetries often did exist in a given sample (Fig. 4). While these differ-


ences were consistent throughout the night, they were variable both between infants and for the same infant at different ages.

Age The parameter of age proved to be a signifi-

cant variable for all frequency bands tested and for all QS samples. Since effects were different among frequency bands, they will be considered separately.

(a) 0--3 c/sec. Multiple comparisons of mean values for spectral density in this frequency band across age indicated a significant increase from 1 to 8 weeks of age in both hemispheres. There were no significant differences noted between 8 and 24 weeks. Values at 4 weeks were intermediate. As described above, spectral density in this band was spe- cifically enhanced during the first QS epoch of the night at 8 and 12 weeks. This effect may have contributed to the statistical increment at 8 weeks, but did not separate this period from older ages when all three QS samples were combined for longitudinal analysis.

(b) 4--7 c/sec. Developmental changes in spectral density for this frequency band showed a slightly different progression. Val- ues between 1 and 8 weeks of age were comparable and significantly lower than those at 16--24 weeks. Power at 12 weeks was intermediate. Thus, the developmental increment of power in this frequency band was delayed relative to that observed for the 0--3 c/sec band, achieving significance at 16 weeks rather than 8 weeks.

(c) The three higher frequency bands (8--11, 12--15 and 16--19 c/sec). These all showed a somewhat different developmental sequence than the lower frequencies. Minimal values were noted at 4 weeks instead of at 1 week, and maximal power was observed between 12 and 16 weeks of age.

8--11 c/sec. The lowest power for this band was registered at 4 weeks. However, mean values did not differ significantly between one and 8 weeks of age. Power at 12 weeks was significantly greater than at 4 weeks and power at 16--24 weeks was higher than all

values between 1--8 weeks. 12--15 c/sec. The development of this fre-

quency band showed the most significant shifts among the characteristic pattern of all higher frequency bands. Power at 4 weeks of age was clearly less than mean power at 1 and 8 weeks. No significant difference was found between 1 and 8 weeks, while power at 8 weeks was significantly greater than at 4 weeks, suggesting a real 'dip' at 4 weeks. A large increment in power was registered at 12 weeks and sustained to 24 weeks. The increase in 12--15 c/~ec power at 12 weeks of age was the single largest ontogenetic change observed in the EEG, and was comparable in both hemispheres.

16--19 c/sec. The lowest spectral densities found in this frequency band were registered also at 4 weeks of age. These values were not significantly different from those at 1 and 8 weeks, but were lower than the power at 12 weeks, whereas 1 and 8 week values were not. Power was comparable in this band between 12 and 24 weeks on the right, but was greater at 24 weeks than at 12 weeks on the left.

Inspection of Fig. 3 suggests that developmental changes in the 0--3 and 12--15 c/sec bands were primary, with other frequency bands showing patterns related to their prox- imity to these two bands. While 0--3 c/sec activity increased from 1 to 8 weeks, 12--15 c/sec activity was minimal at 4 weeks, increased at 8 weeks and again sharply at 12 weeks. Developmental changes in 8--11 and 16--19 c/sec activity paralleled the 12--15 c/sec pattern, but were at tenuated in comparison, while activity at 4--7 c/sec appeared to be intermediate between this pattern and the 0--3 c/sec curve.

While statistical analysis is essential for longitudinal comparisons, additional insight into developmental events was obtained. through the examination of data from individual infants. Figs. 4 and 5 show longitudinal isometric spectral plots from comparable QS samples in four infants. These plots were 'clipped' so that scaling the significantly higher power at the low frequency end of the

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Fig. 4. Isometric power-spectral plots are s h o w n here for 10 rain samples o f quiet sleep taken from the middle o f the night in t w o infants. Left and right central cortical plots are s h o w n from data sampled b e t w e e n 1 and 12 weeks o f age. Traces were derived from successive 16 sec epochs o f EEG data. The ampl i tude of l o w frequencies was l imited in these plots in order to scale for resolut ion o f higher frequencies. Data from these infants were selected to s h o w some of the individual deviat ions from group (statistical) characteristics. See text for details.

A B RIGHT ~ LEFT

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0 5 I0 15 20 0 5 I0 15 20 0 5 I0 15 20 0 5 I0 15 20

FREQ (Hz) FREQ (Hz) Fig. 5. I somet r i c power - spec t ra l plots , as in Fig. 4, are s h o w n here fo r da ta f rom two o t h e r in fan t s b e t w e e n 1 and 16 weeks of age. These in fan t s s h o w e d d e v e l o p m e n t a l p a t t e r n s indica t ive of the overall f indings. No te di f fuse bu t de f in i t e peaks at 1 week b e t w e e n 10- -15 c/sec, a t t e n u a t i o n o f th i s ac t iv i ty at 4 weeks, a s tabi l ized reappear- ance at 8 weeks and m a r k e d e n h a n c e m e n t a t 12 weeks. Power was sh i f t ed to h igher f requenc ies a f te r 8 weeks and mul t ip le peaks were c o m m o n .


spectrum would not a t tenuate resolution at higher frequencies. The data from infant A in Fig. 4 show a rather stationary peak at approximately 12 c/sec, particularly on the right, at 1 week of age. This peak was progres- sively at tenuated between 4 and 8 weeks, only to reappear strikingly at 12 weeks, at a somewhat higher frequency and with a bimodal character (again most marked on the right). Infant B in Fig. 4 showed a different pattern. At 1 week, activity above 10 c/sec was apparent but diffuse; it disappeared (relatively) on the right at 4 weeks, but increased and became stationary on the left. By 8 weeks a well-developed peak was obtained at 12--15 c/sec on the left, and at 12 weeks strong peaks were apparent bilaterally, but the largest was now on the right. Data from the two infants shown in Fig. 5 tend to corre- spond more to expectations gained from the statistical analysis, but also indicate more diffuse, lower frequency peaks above 10 c/sec at 1 week than at 8 weeks of age.

Discussion

The comparison of spectral data derived from selected samples of quiet sleep across the night was an initial objective in our data analysis, since the absence of any differences would allow for the combining of sample data for other analyses. However, significant differences were observed. Between 8 and 16 weeks of age the initial quiet sleep episode of the night was characterized by significantly greater spectral density in frequencies below 11 c/sec. No significant differences among QS samples were found at other ages. This effect was noted bilaterally, but significant changes were registered earlier on the left hemisphere than on the right.

The observed increase in slow-wave activity during the first sleep epoch of the night in 2--4 month old infants could have important functional implications. The protocol used in this s tudy required the parents to bring the child to the laboratory at approximately 5

p.m. In the Los Angeles area this often involved a drive of over an hour, particularly at that t ime of day. Subsequently the infant was manipulated for 2 h while electrodes were at tached and recording channels tested. The official recording was initiated at approximately 7 p.m. These manipulations consti tute a 2--4 h disruption of the infant 's normal behavioral routine. We speculate that this disruption produced significant sleep deprivation effects in the 2--4 month old infant. Sleep deprivation in adults is followed by a rebound enhancement of the so-called 'deeper ' stages of sleep (non-REM stages 3 and 4), which are characterized by high voltage slow-wave activity (Dement and Kleitman 1957; Berger and Oswald 1962; Johnson et al. 1965). Since our QS samples were obtained from the early seg- ment of the sleep epoch, a more rapid progression to such deeper stages would explain the increase observed in low frequency power.

Why would such an effect be limited to the 8--12 week-old infant? Prior to this age, sleep and waking show a more primitive level of organization. Waking periods are relatively brief and functionally specific (Parmelee et al. 1964), and the quiet state in early infancy is lacking in many of the characteristic features of sleep in later life (Sterman 1972). Several studies indicate a relative insensitivity to stimuli and stress at this age (Bridget 1961; Sostek et al. 1976). In particular, Sostek and Anders (1975) found that the application of electrodes for polygraphic recording in normal infants at 8 weeks of age produced increased quiet sleep and a shorter latency to sleep when compared to the effects of these same procedures at 2 weeks of age. Thus, the neural and social substrates of sleep organization which produce a responsive sleep pattern by 8 weeks of life are apparently incomplete in the younger infant, a fact which may pre- clude significant sleep deprivation prior to this age. By 6 months of life, characteristic physiological patterns of sleep m:e well developed (see review by Sterman and Hoppen- brouwers 1971), the circadian sleep-waking distribution is established (Kleitman and


Engelmann 1953; HeUbrugge 1960) and prolonged periods of wakefulness during the day are common (Parmelee et al. 1964). Participa- tion in the present s tudy would no t consti tute a significant disruption of normal sleep patterns.

These considerations point to the period between 2--4 months as a uniquely vulnerable age during which relatively mild stress or disruption of normal routine could result in sleep deprivation effects. It is interesting to note that the Sudden Infant Death Syndrome, a respiratory failure which appears to be trig- gered during sleep in presumably normal infants, has its peak incidence during this same age period (Bergman 1970; Froggatt et al. 1971), and is of ten preceded by a disruption of normal routine (Sterman 1975). More- over, Baker and McGinty (1974) found that sleep deprivation in developing kittens produced a significant increase in apneic episodes during sleep. It is possible to speculate, therefore, that an age-specific disturbance in normal sleep routine could increase risk for this disorder, an hypothesis which we are cur- rently exploring in our program.

Other findings presented here suggest that central cortical EEG patterns during quiet sleep develop symmetrically in both hemispheres, at least to 6 months of age. Marked individual difference in laterality were, in fact, sometimes noted in the 12--15 c/sec activity peaks related to sleep spindles. This asymmetry , while stable throughout a given night, was variable from month- to-month in the same infant, and among infants, thereby resulting in no significant group differences. Individual differences could reflect a moder- ate hemispheric variability enhanced by the sampling procedure, or a real but unstable laterality componen t characteristic of the early age period studied here. In light of cur- rent interest in the relationship of EEG pattern laterality to higher nervous functions (Galin and Ornstein 1972), it would be useful to extend this method of analysis in an effort to determine the age of onset of specific asymmetries or to evaluate the manifestations

of laterality in the sleep EEG of adults. The analysis of spectral density changes

with age was the primary objective of the present study. This analysis disclosed different developmental patterns for the various frequency bands studies. Activity ill the 0--3 c/sec band increased significantly by 8 weeks of age, while power in the 4--7 c/sec band showed no significant increase until 16 weeks of age. It is likely that these increases with development represent a stepwise continua- tion of a maturational process begun prena- tally, since Havlicek et al. (1975) found a significant increase in the power of these bands between preterm and fullterm infants.

In contrast, group data for the higher frequency bands indicated minimal power at 4 weeks instead of one week of age, intermediate values at 1 and 8 weeks, and maximal values by 12--16 weeks. The decrease in spectral density at 4 weeks was statistically significant for the12--15 c/sec band only. Moreover, this band showed the most abrupt increase in power at 12 weeks. The 12--15 c/sec band constitutes the primary frequency of the sleep spindle (see for example Fig. 2). The developmental EEG literature suggests that promi- nent sleep spindles first appear at 8--12 weeks of age (Pond 1963; Katsurada 1965; Metcalf 1969, 1970; Lenard 1970b). However, several investigators have suggested that rudimentary sleep spindles axe present also in the newborn period (Kellaway 1957; Petre-Quadens 1964; Ellingson 1967). In evaluating the developmental sequence noted here for the 12--15 c/sec band, it is important to determine whether these ' rudimentary ' spindles represent a developmental precursor to mature sleep spindles or are, in fact, manifestations of a separate process in early CNS development. Examination of individual spectral plots of ten showed relatively stable peaks at 11--13 c/sec in the one-week-old infant. These peaks were usually at tenuated or absent at 4 weeks, but reappeared at 8--12 weeks, shifted to the 12--15 c/see range. Spectral peaks at these older ages were of ten bimodal, with some power in the 11--13 c/sec range, but primary


density between 12--14, 12--15 and 13--16 c/sec. These observations suggest a maturational sequence involving several independent or partially independent substrates.

There is abundant neurophysiological evidence suggesting that EEG spindles are generated in lateral thalamus through thalamocortical circuits (see review by Creutzfeldt, 1974). Studies in kittens indicate that thala- mocorticai connections are available in the newborn period (eurpura 1971), but are altered significantly by the profound morpho- logic changes which occur during the first 3 weeks of life (Scheibel and Scheibel 1971). We may speculate that the development of intracortical connections at I month of age takes functional precedence over the maturation of thaiamocortical circuits. Thus, an increase in non-rhythmic low frequency activity (0--3 c/sec) was observed to parallel the attenuation of higher frequency rhythmic patterns at this age. The subsequent maturation of thalamocortical connections could, combined with an expanded cortical mileau, add new and dominant elements to the previous structure. Alternately, the functional maturation at 2--3 months of basal forebrain EEG synchronizing elements (Sterman and Cle- mente 1974), which are known to project to appropriate thalamic structures (Clemente and Sterman 1963; Mizuno et al. 1969), could provide the addition of a unique new element in the development of thalamocortical substrates for sleep, as suggested by Parmelee and Stern {1972). These considerations provide intriguing clues for the developmental study of rhythmic patterns in the EEG.

Finally it should be pointed out that the power-spectral method was developed by mathematics and engineering for the evaluation of stationary systems with linear oscilla- tion characteristic (Blackman and Tukey 1958). As such, its application to the study of a non-stationary parameter such as the EEG can be questioned. An optional analysis of the EEG would provide for the separate evaluation of amplitude, frequency and waveform configuration. Power-spectral analysis cannot

accomplish this, since the Fast Fourier transform, upon which it is based, obscures these separate dimensions. It should be remem- bered, however, that the EEG signal itself is an epiphenomenon reflecting physiological field and capacitive effects, and the amplification and filtering characteristics of EEG recording systems. Nevertheless, the measurement obtained by this method has proven very useful in the study of the central nervous system. Similarly, the use of power-spectral analysis, which clearly provides a reliable and responsive parameter of measurement, and the further advantage of quantification, can make a meaningful contribution to this study.

Summary

A quantitative evaluation of central cortical EEG activity during quiet sleep was under- taken in normal infants followed from I to 24 weeks of age. Bilateral (C3-T3, C4-T4) EEG activity was recorded continuously on magnetic tape during 12-h polygraphic monitoring sessions at 1, 4, 8, 12, 16 and 24 weeks of age. Power-spectral densities were calculated from three independent 10 min quiet sleep samples from the first, middle and last epochs of the night. Data were calibrated, log trans- formed and sorted into five sequential 4 c/sec frequency bands between 0--19 c/sec. Anal- ysis focused upon the distribution of power in these bands as a function of time of night, hemisphere and age.

A time of night effect was found only between 8 and 16 weeks of age. During this period the initial sleep epoch showed a significant increase in low frequency power. This was interpreted as an age-specific sleep deprivation effect related to experimental manipu- lation of the infant. No significant developmental difference in power distribution was found between hemispheres, although specific asymmetries were noted. All frequency bands changed significantly with age. Lower frequencies (0--3 and 4--7 c/sec) increased in power with age, 0--3 c/sec increasing abruptly


from 1 to 8 weeks and 4--7 c/sec showing a more delayed increment after 12 weeks of age. Power in the higher frequency bands (8--11, 12--:[5 and 16--19 c/sec decreased between 1 and 4 weeks and then increased significantly at 12 weeks and older. The decrease at 4 weeks and increase at 12 weeks was most marked for the 12--15 c/sec band, and was interpreted in terms of the development of thalamocortical mechanisms related to the generation of EEG sleep spindles.

R~sum~

Analyse quantitative du ddveloppernent de l'EEG du nouveau-ne au cours du sornmeil calme

Une ~valuation quantitative de l'activ~ EEG corticale des r~gions centrales au cours du sommeil calme a ~t~ entreprise chez des nourrissons normaux suivis ~ l'~ge de I ~ 24 semaines. L'activit~ EEG bilat~rale (C3--T3, C4--T4) a ~t~ enregistr~e en continu sur bande magn~tique pendant des sessions d'enregistre- ments polygraphiques de 12 h aux ~ges de 1, 4, 8, 12, 16 et 24 semaines. Les densit~s spec- trales ont ~t~ calcul~es sur 3 ~chantillons ind~pendants de 10 min de sommeil calme, lors du d~but, du milieu et de la fin de la nuit. Les donn~es ont ~t~ calibr~es, mises en ~chelle logarithmique et sorties en 5 bandes de fr& quence s~quentielle de 4 c/sec entre 0 et 19 c/sec. L'analyse est centr~e sur la distribution de puissance dans ces bandes de fr~quence en fonct ion du moment de la nuit, de l'h~mi- sphere et de l'~ge.

L 'effe t du moment de la nuit s 'observe seulement entre 8 et 16 semaines. Au cours de cette p~riode, la premiere ~poque de sommeil montre une augmentation significative de puissance dans les basses fr~quences. Ceci est interpr~t~ comme un effet de privation de sommeil sp~cifique h l'~ge, et lib ~ la mani- pulation exp~rimentale du nourrisson. Aucune difference significative de distribution de puissance like ~ l'~ge n'a ~t~ observ~e entre les deux h~misph~res, bien que des

asym~tries sp~cifiques aient ~t~ not~es. Les bandes de fr~quence changent significative- ment avec l'~ge. Les fr~quences les plus basses (0--3 et 4--7 c/sec) augmentent en puissance avec l'~ge, les fr~quences de 0 ~ 3 c/sec aug- mentant de faqon abrupte entre 1 et 8 semaines et celle de 4 h 7 c/sec montrant une augmentat ion plus tardive apr~s la 12~me semaine. La puissance d 'ondes de fr~quence plus ~lev~es (8--11, 12--15 et 16--19 c/sec) diminue entre 1 et 4 semaines puis augmente de faqon significative fi la 12bme semaine et plus tard. La diminution de puissance ~ 4 semaines et son augmentation ~ 12 semaines sont maximales pour la bande de 12--15 c/sec et interpr~t~es en termes de d~veloppement des m~canismes thalamo-corticaux li~s ~ la product ion des spindles EEG de sommeil.

This research was supported by the Veterans Administration, the Los Angeles County Hospital system and by the National Institute of Child Health and Human Development Contracts Nos. NO1-HD-2-2777 and HD4-2810. We also wish to thank Mrs. Kazuko Arakawa for her important contribution to the statistical analysis of the data presented here.

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