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Pediatric neuroimaging studies1, 2, 3, 4, 5, up to now exclusively cross sectional, identify linear decreases in cortical gray matter and increases in white matter across ages 4 to 20. In this large-scale longitudinal pediatric neuroimaging study, we confirmed linear increases in white matter, but demonstrated nonlinear changes in cortical gray matter, with a preadolescent increase followed by a postadolescent decrease. These changes in cortical gray matter were regionally specific, with developmental curves for the frontal and parietal lobe peaking at about age 12 and for the temporal lobe at about age 16, whereas cortical gray matter continued to increase in the occipital lobe through age 20.
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nature neuroscience • volume 2 no 10 • october 1999 861
Brain development
during childhood and
adolescence: a
longitudinal MRI study
Jay N. Giedd
, Jonathan Blumenthal
, Neal O. Jeffries
F. X. Castellanos
, Hong Liu
, Alex Zijdenbos
To m á s˘ Paus
, Alan C. Evans
and Judith L. Rapoport
Child Psychiatry Branch, National Institute of Mental Health, Building 10,
Room 4C110, 10 Center Drive, MSC 1367, Bethesda, Maryland 20892, USA
Biometry Branch, National Institute of Neurological Disease and Stroke, Federal
Building, Room 7C06, 7550 Wisconsin Avenue, Bethesda, Maryland, 20892, USA
Montreal Neurological Institute, McGill University, 3801 University Street,
Montreal, Quebec H3A 2B4, Canada
Correspondence should be addressed to J.N.G. (
Pediatric neuroimaging studies
, up to now exclusively cross sec-
tional, identify linear decreases in cortical gray matter and increas-
es in white matter across ages 4 to 20. In this large-scale
longitudinal pediatric neuroimaging study, we confirmed linear
increases in white matter, but demonstrated nonlinear changes in
cortical gray matter, with a preadolescent increase followed by a
postadolescent decrease. These changes in cortical gray matter
were regionally specific, with developmental curves for the frontal
and parietal lobe peaking at about age 12 and for the temporal
lobe at about age 16, whereas cortical gray matter continued to
increase in the occipital lobe through age 20.
The subjects for this study were healthy boys and girls partici-
pating in an ongoing longitudinal pediatric brain-MRI project at
the Child Psychiatry Branch at the National Institute of Mental
Health. Subjects were recruited from the community as previous-
ly described, using phone screening, questionnaires mailed to par-
ents and teachers and face-to-face physical and psychological
testing; approximately one in six volunteers were accepted
. At least
1 scan was obtained from each of 145 healthy subjects (89 male). Of
these, 65 had at least 2 scans, 30 had at least 3 scans, 2 had at least
4 scans and 1 had 5 scans, acquired at approximately two-year
intervals. The age range was from 4.2 to 21.6 years. There were no
significant sex differences for age, Tanner stage, ethnicity, socioe-
conomic status, height, weight or handedness.
All subjects were scanned on the same GE 1.5 Tesla Signa scan-
ner using the same three-dimensional, spoiled-gradient, recalled
echo in the steady state (3D SPGR) imaging protocol, with an
axial-slice thickness of 1.5 mm, a time-to-echo of 5 ms, a repeti-
tion time of 24 ms, flip angle of 45°, a 192 ( 256 acquisition matrix,
1 excitation and a field of view of 24 cm. A clinical neuroradiolo-
gist evaluated all scans; no gross abnormalities were reported.
Volumes of white and cortical gray matter were quantitative-
ly analyzed by combining a technique using an artificial neural
network to classify tissues based on voxel intensity with non-lin-
ear registration to a template brain for which these tissue regions
had been manually defined
. This technique supplemented MRI
signal-intensity information with predetermined brain anatomy
and provides lobar (frontal, parietal, temporal and occipital) par-
cellation of cortical gray- and white-matter volumes.
We used previously described statistical analysis techniques
that combine cross-sectional and longitudinal data
. These lon-
gitudinal methods are more sensitive to detecting individual
growth patterns, even in the presence of large interindividual
. We assessed if there was significant change with age, if
developmental curves differed by sex and/or region and whether
the developmental curves were linear or quadratic.
The volume of white matter increased linearly with age
(Fig. 1; Table 1), increasing less in females than in males. The net
increase across ages 4 to 22 was 12.4%. Curves for white-matter
development did not significantly differ among various lobes. In
contrast, changes in volume of cortical gray matter were non-
linear and regionally specific. Gray matter in the frontal lobe
increased during pre-adolescence with a maximum size occur-
ring at 12.1 years for males and 11.0 years for females, followed by
a decline during post-adolescence that resulted in a net decrease
in volume across this age span. Parietal-lobe gray matter followed
a similar pattern, increasing during pre-adolescence to a maxi-
mum size at age 11.8 years for males and 10.2 years for females,
followed by decline during postadolescence and a net decrease
scientific correspondence
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the frontal cortex
. Striatal structures are involved in cognitive
functions such as learning, which is linked to frontal system func-
and improves throughout adolescence
. This suggests tem-
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postadolescent reductions in gray-matter density in frontal and
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We thank the McConnell Brain Imaging Center at the Montreal Neurological
Institute and the SPM software developers at the Wellcome Department of Cognitive
Neurology. Finally, we thank David Kornsand for assistance in anatomical analyses
and John Bacheller for artwork. This study was supported by grants P50 NS22343,
and R01 HD 23854, and NIMH NRSA grant 5T32 MH16381, NSF DBI 9601356,
the NCRR (P41 RR13642), NINDS (NS38753) and the pediatric supplement of the
Human Brain Project, funded jointly by NIMH and NIDA (P20 MH/DA52176).
© 1999 Nature America Inc. •
© 1999 Nature America Inc. •
862 nature neuroscience • volume 2 no 10 • october 1999
in volume; however, pre- and post-adolescent slopes were steep-
er for parietal than for frontal lobes. Temporal-lobe gray matter
also followed a nonlinear developmental course, but maximum
size was not reached until 16.5 years for males and 16.7 years for
females, with a slight decline thereafter. Occipital-lobe gray mat-
ter increased linearly over the age range, without evidence of sig-
nificant decline or leveling. Developmental curves for the different
cortical regions significantly differed from each other; those for
frontal and parietal lobes were the most similar. The
absolute size of the cortical gray matter was approxi-
mately 10% larger in boys, and peaked slightly earlier
in girls, but the shapes of the curves were not signifi-
cantly different between boys and girls.
The regional specificity of findings in cortical gray
matter sheds light on the debate regarding synchro-
nous versus heterochronous development of the cere-
bral cortex. Nonhuman primate studies generally
reveal synchronous cortical development (that is, with
similar timing in diverse cortical regions)
. However,
in humans there are limited but compelling histologi-
cal data to suggest that synapse elimination is hete-
rochronous, with changes in primary visual and
auditory cortex occurring before those in frontal cor-
. The present data support heterochronic devel-
opment in human cerebral cortex. The pre-adolescent
increase and post-adolescent decrease in cortical gray
matter parallel developmental PET studies of cerebral
glucose metabolism
and EEG studies of slow-wave
sleep amplitude
This MRI study demonstrates a pre-adolescent
increase in cortical gray matter; this phenomenon was
previously obscured, probably by the lack of longitudi-
nal data, as even in an analysis of the 145 cross-section-
al data points in our sample, the largest to date, we could
not detect nonlinearity in these developmental curves.
Whether this gray-matter increase is related to changes
in neuropil, neuronal size or dendritic or axonal
arborization will be best addressed by methods other
scientific correspondence
Fig. 1. Predicted size with 95% confidence intervals for
cortical gray matter in frontal, parietal, temporal and occip-
ital lobes for 243 scans from 89 males and 56 females, ages
4 to 22 years. The arrows indicate peaks of the curves.
4 6 8 10121416182022
4 6 8 10121416182022
4 6 8 10121416182022
4 6 8 10121416182022
4 6 8 10121416182022
Male (Predicted) peak
Female (Predicted)
95% Confidence Intervals
4 6 8 10121416182022
Table 1. Developmental curves for different regions.
p value for p value for
Age Age
p value for no only linear curves
Male Female coefficient coefficient change change having same
Structure intercept intercept β
0, β
0) (β
0) shape
Total 1382 1260 5.6 –0.72 p < 0.0001 p < 0.0001 p = 0.83
cerebrum (12.3) (19.3) (10.0) (0.15)
Total 758 686 –0.50 –0.39 p = 0.001 p = 0.001 p = 0.47
gray (7.3) (11.3) (0.80) (0.12)
Frontal 235 214 –0.38 –0.18 p < 0.0001 p < 0.0001 p = 0.84
gray (2.3) (3.8) (0.28) (0.04)
Temporal 191 175 0.81 –0.10 p < 0.0001 p = 0.002 p = 0.99
gray (1.7) (2.6) (0.22) (0.03)
Parietal 126 116 –0.31 –0.10 p < 0.0001 p < 0.0001 p = 0.51
gray (1.3) (20.0) (0.15) (0.02)
Occipital 70.1 61.5 0.41 0.009 p = 0.007 p = 0.69 p = 0.07
gray (1.2) (1.7) (0.14) (0.02)
The developmental curves are modeled by the equation: size = intercept + β
(age – mean age) + β
(age – mean age)
+ ε
where the intercept term is a random effect that varies by individual and intra-individual correlation of ε is taken into account. A Wald statistic assesses
whether the curve changes with age (that is, whether β
and β
are both 0). A z statistic of β
assesses whether the curve is best fit by a linear (β
= 0) or
quadratic curve (β
0). The curves were found to have similar shapes by sex (no significant differences for any structure), but because the height of the
curves did vary, separate terms were used for boys and girls. Multivariate analysis showed that shapes for the four regions of gray matter significantly differed
from one another (p < 0.0001), with parietal and frontal regions most similar and temporal the most distinct.
Total cerebral volume
White matter
Parietal gray matter
Temporal gray matter
Frontal gray matter
Age in years
Volume in cubic cm
Volume in cubic cm
Volume in cubic cm
Volume in cubic cm
Volume in cubic cm
Volume in cubic cm
Age in years
Age in years
Age in years
Age in years
Age in years
Occipital gray matter
© 1999 Nature America Inc. •
© 1999 Nature America Inc. •
nature neuroscience • volume 2 no 10 • october 1999 863
A contingent aftereffect
in the auditory system
C.-J. Dong, N. V. Swindale and M. S. Cynader
Department of Ophthalmology, University of British Columbia, 2550 Willow
Street, Vancouver, British Columbia V5Z 3N9, Canada
Correspondence should be addressed to C.-J.D. (
Pairs of stimulus attributes, such as color and orientation, that
are normally uncorrelated in the real world are generally per-
ceived independently; that is, the perception of color is usually
uninfluenced by orientation and vice versa. Yet this independence
can be altered by relatively brief exposure to artificially correlat-
ed stimuli, as has been shown for vision
. Here we report an anal-
ogous contingent aftereffect in the auditory system that can
persist for four hours after the initial adaptation.
After a few minutes of alternately viewing an orange-black
vertical grating and a blue-black horizontal grating, the white
stripes in a vertical black-and-white grating appear blue-green,
whereas the white stripes in a horizontal grating appear orange
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scientific correspondence
than MRI. If the increase is related to a second wave of overpro-
duction of synapses, it may herald a critical stage of development
when the environment or activities of the teenager may guide selec-
tive synapse elimination during adolescence. The relative promi-
nence of the role of the environment in shaping late synaptogenesis
is supported by rat studies
. That the frontal and parietal gray
matter peaks approximately one year earlier in females, corre-
sponding with the earlier age of onset of puberty, suggests a possi-
ble influence of gonadal hormones. Studies of healthy monozygotic
and dizygotic twins, chromosomal aneuploidies (XXY, XXYY, XYY),
congenital adrenal hyperplasia (producing high levels of testos-
terone in utero) and psychiatric illnesses are underway to address
the effects of genes, hormones and environment on this process.
UGUST 1999
1. Jernigan, T. L., Trauner, D. A., Hesselink, J. R. & Tallal, P. A. Brain 114,
2037–2049 (1991).
There are numerous demonstrations of other types of visual con-
tingent aftereffect, such as color-contingent orientation
aftereffects and spatial frequency
- and motion
tingent color aftereffects. These visual contingent aftereffects can
be extremely persistent. For example, the motion-contingent
color aftereffect and the color-contingent motion aftereffect can
persist for at least 24 hours
. The motion-contingent color after-
effect can last as long as six weeks in some cases
In contrast to the rich variety of reported visual contingent
aftereffects, there are no reports of contingent aftereffects for
Fig. 1. Stimulus protocols. (a) Time sequence of stimuli. Each run began
with 10 minutes of adaptation, followed by a series of brief test sounds
(1 s), with either a rising (0.7 octaves per s) or a falling (–0.7 octaves per
s) pitch presented by a loudspeaker moving at one of six different veloc-
ities (2°, 6° or 10° per s, either to the left or the right). For each test
presentation, the subject was asked to press one of two buttons to indi-
cate the direction (leftward or rightward) of spatial movement.
(b) Detailed time sequence of adapting stimuli. While the central fre-
quency of an adapting sound (1-octave band-pass noise) was moving
upward (0.7 octave per s), the loudspeaker moved to the left (30° per s)
for 1 second (from –15° to 15° in azimuth). Following a silent interval of
1.4 seconds, the loudspeaker moved to the right (–30° per s) for 1 sec-
ond, while the central frequency of the sound moved downward (–0.7
octave per s). During adaptation, this sequence was repeated continu-
ously. In the control condition, the loudspeaker moved over the same
trajectory with the same time course, but the center frequency of the
adapting sound was kept constant at 1.5 kHz. Note that the vertical axis
in the top panel has a logarithmic scale.
Speaker position (deg)
Frequency (Hz)
Sound on
10 min 1 s
Initial adapt. Test Resp.
© 1999 Nature America Inc. •
© 1999 Nature America Inc. •
... Indeed, since the KAS score was close to the maximum possible score on a group level, the ability to form typical assumptions about others' world knowledge develops first, and then, interestingly, it takes a while before the ability to use these representations online emerges. This may be ascribed to the functional reorganizations and structural changes of brain regions important to perspective taking during online communication that take place in adolescence [7,34,65], and supports a processing model distinguishing between the mental representations of others' knowledge as such and the usage of these representations during online communication [35]. ...
... Why do children entering adolescence not routinely use information about the world knowledge of the interlocutor during online production, even when this information is accessible? From a neurobiological perspective, the functional reorganization and structural changes of brain regions important to communicative perspective taking that take place in adolescence [7,34,65] may be ascribed as a causal explanation. Co-development of these neural changes and functional changes are also likely. ...
The ability to adapt utterances to the world knowledge of one's addressee is undeniably ubiquitous in human social cognition, but its development and association with other cognitive mechanisms during adolescence have not been studied. In an online production task, we measured the ability of children entering adolescence (ages 11-12, M = 11.8, N = 29 , 17 girls ) and adolescents (ages 15-16, M = 15.9, N = 29 , 17 girls ) to tailor referential expressions in accordance with the inferred world knowledge of their addressee-an ability we refer to as world knowledge-based audience design (AD). A post-test survey showed that both age groups held similar assumptions about the addressees' knowledge of referents, but the younger age group did not consistently adapt their utterances in accordance with these assumptions during online production, resulting in a significantly improved AD behaviour across age groups. We also investigated the reliance of AD on executive functions (EF). Executive functioning (as reflected by performance on the Wisconsin card sorting task) increased significantly with age, but did not explain the age-related increase in AD performance. We thus provide evidence in support of an adolescent development of world knowledge-based AD over and above development of EF.
... Rapid development and reorganization of neural system lead to significant gain in cognitive and emotional functions, but also increase the risk of potential dysfunctions and disease in individuals [2,3]. During this period, different brain networks exhibit differing developmental trajectories [4,5] some of which are synchronized and thus covariant [6,7]. The mismatch among these maturational trajectories could result in long-lasting functional breakdown, exhibited as mental and behavioral problems, such as impulsive behaviors and emotional disorders [8]. ...
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Previous studies on late-night digital media use and adolescent sleep have not considered how chronotype, a natural tendency to be awake or asleep at certain time, is associated with this relationship. Therefore, the nature of the relationship between late-night digital media use and sleep in different chronotypes remains still unknown. The sample consisted of 15–20-year-old Finnish adolescents ( n = 1084, mean age = 16.9 years, SD = 0.93, 45.7% female). This study examined whether chronotype, measured as diurnal type and midpoint of sleep, was associated with the time of evening/night when digital media was used. Associations between the use of different forms of digital media and sleep quality, sleep duration and tiredness on school days were also investigated. Finally, the mediation effect of late-night digital media use to the relationship between chronotype and sleep was examined. Generalized linear models showed that evening chronotype, weekend midpoint of sleep, and the time of evening or night at which digital media was used were associated with more insufficient sleep and tiredness, lower sleep quality and shorter sleep duration on school days. The total use of all media forms, i.e., late-night digital media for music, movies/series, social media, and studying, were associated with shorter sleep duration and more insufficient sleep and daytime tiredness. Late-night social media use also mediated the association between diurnal type and sleep quality. Watching movies or listening to music late at night was the strongest mediator of the association between diurnal type and sleep and tiredness. The most prominent finding shows that of the all different media forms, watching movies or listening to music late at night were associated with increased daytime tiredness, whereas late social media use was associated with poor sleep quality. These interactions were pronounced especially for evening-types. The findings of the current study suggest that the negative effects of late-night media use are reflected especially in sleep quality and daytime tiredness among evening-types during adolescence.
Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly complex and heterogeneous disorder. Abnormal brain connectivity in ADHD might be influenced by developmental ages which might lead to the lacking of significant spatial convergence across studies. However, the developmental patterns and mechanisms of ADHD brain connectivity remain to be fully uncovered. Methods: In the present study, we searched PubMed, Scopus, Web of Science, and Embase for seed-based whole-brain resting-state functional connectivity studies of ADHD published through October 12th, 2020. The seeds meeting inclusion criteria were categorized into the cortex group and subcortex group, as previous studies suggested that the cortex and subcortex have different temporal patterns of development. Activation likelihood estimation meta-analysis was performed to investigate the abnormal connectivity in different age groups (all-age group, younger: <12 years, older: ≥12 years). Moreover, significant convergence of reported foci was used as seeds for validation with our independent dataset. Results: As with previous studies, scarce results were found in the all-age group. However, we found that the younger group consistently exhibited hyper-connectivity between different parts of the cortex and left middle frontal gyrus, and hypo-connectivity between different parts of the cortex and left putamen/pallidus/amygdala. Whereas, the older group (mainly for adults) showed hyper-connectivity between the cortex and right precuneus/sub-gyral/cingulate gyrus. Besides, the abnormal cortico-cortical and cortico-subcortical functional connectivity in children, and the abnormal cortico-cortical functional connectivity in adults were verified in our independent dataset. Conclusion: Our study emphasizes the importance of developmental age effects on the study of brain networks in ADHD. Further, we proposed that cortico-cortical and cortico-subcortical connectivity might play an important role in the pathophysiology of children with ADHD, while abnormal cortico-cortical connections were more important for adults with ADHD. This work provided a potential new insight to understand the neurodevelopmental mechanisms and possible clinical application of ADHD.
It is well established that the brain changes dramatically in appearance during gestation and even after birth. Due to the multi-channelled origins and the number of developmental options, the adult venous system is characterised by a higher incidence of anatomical variations than the arterial system. Limited information is available on imaging of the intracranial veins and sinuses. It is therefore important to understand the normal anatomy of the cerebral venous system and its variants in order to provide adequate and comprehensive training to medical students and researchers. We used a novel approach to trace the volumes of the dural venous sinuses. The approach included constructing three-dimensional (3D) models of the dural venous sinuses which could then be used for statistical and morphological analyses. This chapter will expand on current literature and visualisation techniques of the dural venous sinuses. The reader will be presented with a novel way of looking at the venous drainage of the brain and how to use this visualisation in understanding venous anatomy and its clinical implications.KeywordsCerebral sinusesVisualisationsVolume tracingVenous system
Adverse social experience during childhood and adolescence leads to developmental alterations in emotional and stress regulation and underlying neurocircuits. We examined the consequences of social subordination (low social rank) in juvenile female rhesus monkeys, as an ethologically valid model of chronic social stressor exposure, on brain structural and behavioral development through the pubertal transition. Adolescence is a developmental period of extensive brain remodeling and increased emotional and stress reactivity. Puberty-induced increases in gonadal hormones, particularly estradiol (E2), are likely involved due to its organizational effects on the brain and behavior. Thus, we also examined how experimentally delaying pubertal onset with Lupron (gonadotropin releasing hormone -GnRH- agonist used clinically to delay early puberty) interacted with social rank (dominant vs. subordinate) to affect brain and behavioral outcomes. Using a longitudinal experimental design, structural MRI (sMRI) scans were collected on socially housed juvenile female rhesus monkeys living in indoor-outdoor enclosures prior to the onset of puberty (18-25 months), defined as menarche or the initial occurrence of perineal swelling and coloration, and again at 29-36 months, when all control animals had reached puberty but none of the Lupron-treated had. We examined the effects of both social rank and pubertal delay on overall structural brain volume (i.e. intracranial, grey matter (GM) and white matter (WM) volumes), as well as on cortico-limbic regions involved in emotion and stress regulation: amygdala (AMYG), hippocampus (HC), and prefrontal cortex (PFC). Measures of stress physiology, social behavior, and emotional reactivity were collected to examine functional correlates of the brain structural effects. Apart from expected developmental effects, subordinates had bigger AMYG volumes than dominant animals, most notably in the right hemisphere, but pubertal delay with Lupron-treatment abolished those differences, suggesting a role of gonadal hormones potentiating the brain structural impact of social stress. Subordinates also had elevated baseline cortisol, indicating activation of stress systems. In general, Lupron-treated subjects had smaller AMYG and HC volume than controls, but larger total PFC (driven by bigger GM volumes), and different, region-specific, developmental patterns dependent on age and social rank. These findings highlight a region-specific effect of E2 on structural development during female adolescence, independent of those due to chronological age. Pubertal delay and AMYG volume, in turn, predicted differences in emotional reactivity and social behavior. These findings suggest that exposure to developmental increases in E2 modifies the consequences of adverse social experience on the volume of cortico-limbic regions involved in emotional and stress regulation during maturation. But, even more importantly, they indicate different brain structural effects of chronological age and pubertal developmental stage in females, which are very difficult to disentangle in human studies. These findings have additional relevance for young girls who experience prolonged pubertal delays or for those whose puberty is clinically arrested by pharmacological administration of Lupron.
Some children and adolescents have persistent concussion symptoms that extend beyond the typical 3–4 week recovery window. Our understanding about what to expect when recovery is atypical, particularly in elementary-age children, is incomplete because there are very few targeted studies of this age group in the published literature. Aims were to identify lingering symptoms that present at three months post-concussion and to determine what factors are associated with prolonged recovery in an elementary-age group. Participants were 123 children aged 5–10 years who were seen at specialized concussion clinics, divided into expected and late recovery groups. Parents rated concussion symptoms on a scale from the Sideline Concussion Assessment Tool-5 (SCAT-5). The most frequent symptoms were headache, irritability, feeling more emotional, and sensitivity to noise. Stepwise logistic regression determined that female sex and total symptom burden at initial visit, but not any specific symptom, predicted prolonged recovery. Clinicians are advised to carefully monitor children who report numerous symptoms after concussion, particularly when the concussed children are girls.
Adolescence is a key developmental period for developing and strengthening brain circuits that underlie effective decision‐making skills, which profoundly impact lifelong health and academic, professional, and economic achievement. But decision‐making skills are learned rather than inherent. School presents an ideal environment for the direct instruction and frequent practice of decision‐making skills, however, finding time in the school day is a challenge for contemporary educators. We have developed a learning curriculum that involves active student participation to strengthen decision‐making skills that is sufficiently flexible and adaptable to be utilized in a wide variety of content‐specific classwork. Using this curriculum, students show evidence of improved decision‐making skills, including increased consideration of the number of factors that are relevant to their decision, the resources needed to make a particular decision, and both the short‐term and long‐term consequences of decisions. We present a curriculum to strengthen decision‐making skills that involves mapping of the decision‐making process and is sufficiently universal to provide educators flexibility and adaptability to be utilized in a wide variety of content‐specific classwork. Using this curriculum, students show evidence of improved decision‐making skills, including consideration of an increased number of factors relevant to their decision, the resources needed to make a particular decision, and both the short‐term and long‐term consequences of decisions.
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An analysis of data by sleep cycle was carried out for the main variables concerning sleep with EEG slow waves (SSW), sleep with rapid eye movements, and awakenings. Data were presented for six age groups with mean ages of 7·4, 13·8, 21·6, 31·5, 55·3, 77·3 yr. While these data represent the first detailed statistical description of cycle changes with age, the results obtained are consistent with earlier observations. For SSW pronounced age changes occured in the first cycle; durations and rates of change across cycles 2–5 were highly similar for all six age groups. The changes with age in cycle 1 were attributed to the changing level of stage 4 EEG with age.Except for the oldest group, SREMP durations increased from cycle 1 to cycle 3, after which there was little change. In elderly subjects, the first SREMP was equal in length to succeeding periods. The trends across the night for eye movement activity were similar to those for SREMP duration; i.e., these trends showed increases from the first to third cycle for all groups except the oldest.It was suggested that the trends in sleep pattern across the night have significant implications for the brain processes which underlie the electrophysiological manifestations of sleep. A speculative hypothesis was advanced to account for the cyclical nature of sleep, the trends in cycles across the night, and the effects of age on these variables. This hypothesis proposes that the function of sleep with rapid eye movements is to provide a substrate or co-factor required to promote maximal occurrence of sleep with slow waves. Many data in the literature may be viewed as consistent with this hypothesis.
Segmentation of the intracranial cavity in medical images is valuable in several research areas such as the quantitative analysis of normal and abnormal brain tissues, the registration of different imaging modalities (MRI, PET, CT) based on surface models of the brain, and the rendering of volume data. Because the manual delineation of the brain contour in the images can be demanding and error prone, an automatic procedure to perform this task is desirable. We have developed and tested a robust method that permits the automatic detection of the intracranial contour in transverse MR images. The method is described and its performance evaluated.
In the present study using magnetic resonance imaging (MRI), age changes in the morphology of the cerebral cortex, greatest in the frontal and parietal convexities, were observed during adolescence. Results suggest that increases in cerebrospinal fluid (CSF) within the sulci of these cortical regions accompany grey matter decreases. Smaller reductions in volume are also observed in subcortical grey matter nuclei. These apparent grey matter volume reductions presumably reflect processes of late brain maturation. The changes may be related to decreasing neural plasticity.
We used quantitative electron microscopy to determine the effect of precocious visual experience on the time course, magnitude, and pattern of perinatal synaptic overproduction in the primary visual cortex of the rhesus monkey. Fetuses were delivered by caesarean section 3 weeks before term, exposed to normal light intensity and day/night cycles, and killed within the first postnatal month, together with age-matched controls that were delivered at term. We found that premature visual stimulation does not affect the rate of synaptic accretion and overproduction. Both of these processes proceed in relation to the time of conception rather than to the time of delivery. In contrast, the size, type, and laminar distribution of synapses were significantly different between preterm and control infants. The changes and differences in these parameters correlate with the duration of visual stimulation and become less pronounced with age. If visual experience in infancy influences the maturation of the visual cortex, it must do so predominantly by strengthening, modifying, and/or eliminating synapses that have already been formed, rather than by regulating the rate of synapse production.
From over 100 children studied with 2-deoxy-2[18F]fluoro-D-glucose and positron emission tomography we selected 29 children (aged 5 days to 15.1 years) who had suffered transient neurological events not significantly affecting normal neurodevelopment. These 29 children were reasonably representative of normal children and provided an otherwise unobtainable population in which to study developmental changes in local cerebral metabolic rates for glucose (lCMRGlc). In infants less than 5 weeks old lCMRGlc was highest in sensorimotor cortex, thalamus, brainstem, and cerebellar vermis. By 3 months, lCMRGlc had increased in parietal, temporal, and occipital cortices; basal ganglia; and cerebellar cortex. Frontal and dorsolateral occipital cortical regions displayed a maturational rise in lCMRGlc by approximately 6 to 8 months. Absolute values of lCMRGlc for various grey matter regions were low at birth (13 to 25 mumol/min/100 gm), and rapidly rose to reach adult values (19 to 33 mumol/min/100 gm) by 2 years. lCMRGlc continued to rise until, by 3 to 4 years, it reached values of 49 to 65 mumol/min/100 gm in most regions. These high rates were maintained until approximately 9 years, when they began to decline, and reached adult rates again by the latter part of the second decade. The highest increases of lCMRGlc over adult values occurred in cerebral cortical structures; lesser increases were seen in subcortical structures and in the cerebellum. This time course of lCMRGlc changes matches that describing the process of initial overproduction and subsequent elimination of excessive neurons, synapses, and dendritic spines known to occur in the developing brain. The determination of changing metabolic patterns accompanying normal brain development is a necessary prelude to the study of abnormal brain development with positron emission tomography.
Synapses develop concurrently and at identical rates in different layers of the visual, somatosensory, motor, and prefrontal areas of the primate cerebral cortex. This isochronic course of synaptogenesis in anatomically and functionally diverse regions indicates that the entire cerebral cortex develops as a whole and that the establishment of cell-to-cell communication in this structure may be orchestrated by a single genetic or humoral signal. This is in contrast to the traditional view of hierarchical development of the cortical regions and provides new insight into the maturation of cortical functions.