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Assessing brain connectivity during rest has become a widely used approach to identify changes in functional brain organization during development. Generally, previous works have demonstrated that brain activity shifts from more local to more distributed processing from childhood into adolescence. However, the majority of those works have been based on functional magnetic resonance imaging measures, whereas multispectral functional connectivity, as measured using magnetoencephalography (MEG), has been far less characterized. In our study, we examined spontaneous cortical activity during eyes-closed rest using MEG in 101 typically developing youth (9–15 years old; 51 females, 50 males). Multispectral MEG images were computed, and connectivity was estimated in the canonical delta, theta, alpha, beta, and gamma bands using the imaginary part of the phase coherence, which was computed between 200 brain regions defined by the Schaefer cortical atlas. Delta and alpha connectivity matrices formed more communities as a function of increasing age. Connectivity weights predominantly decreased with age in both frequency bands; delta-band differences largely implicated limbic cortical regions and alpha band differences in attention and cognitive networks. These results are consistent with previous work, indicating the functional organization of the brain becomes more segregated across development, and highlight spectral specificity across different canonical networks.

 

Neural oscillations may be sensitive to aspects of brain maturation such as myelination and synaptic density changes. Better characterization of developmental trajectories and reliability is necessary for understanding typical and atypical neurodevelopment. Here, we examined reliability in 110 typically developing children and adolescents (aged 9–17 years) across 2.25 years. From 10 min of magnetoencephalography resting-state data, normalized source spectral power and intraclass correlation coefficients were calculated. We found sex-specific differences in global normalized power, with males showing age-related decreases in delta and theta, along with age-related increases in beta and gamma. Females had fewer significant age-related changes. Structural magnetic resonance imaging revealed that males had more total gray, subcortical gray, and cortical white matter volume. There were significant age-related changes in total gray matter volume with sex-specific and frequency-specific correlations to normalized power. In males, increased total gray matter volume correlated with increased theta and alpha, along with decreased gamma. Split-half reliability was excellent in all frequency bands and source regions. Test–retest reliability ranged from good (alpha) to fair (theta) to poor (remaining bands). While resting-state neural oscillations can have fingerprint-like quality in adults, we show here that neural oscillations continue to evolve in children and adolescents due to brain maturation and neurodevelopmental change.

 

Abstract Working memory, the ability to hold items in memory stores for further manipulation, is a higher order cognitive process that supports many aspects of daily life. Childhood trauma has been associated with altered cognitive development including particular deficits in verbal working memory (VWM), but the neural underpinnings remain poorly understood. Magnetoencephalography (MEG) studies of VWM have reliably shown decreased alpha activity in left-lateralized language regions during encoding, and increased alpha activity in parieto-occipital cortices during the maintenance phase. In this study, we examined whether childhood trauma affects behavioral performance and the oscillatory dynamics serving VWM using MEG in a cohort of 9- to 15-year-old youth. All participants completed a modified version of the UCLA Trauma History Profile and then performed a VWM task during MEG. Our findings indicated a sex-by-age-by-trauma three-way interaction, whereby younger females experiencing higher levels of trauma had the lowest d’ accuracy scores and the strongest positive correlations with age (i.e. older performed better). Likewise, females with higher levels of childhood trauma exhibited altered age-related alpha changes during the maintenance phase within the right temporal and parietal cortices. These findings suggest that trauma exposure may alter the developmental trajectory of neural oscillations serving VWM processing in a sex-specific way. 

The anterior pituitary gland (PG) is a potential locus of hypothalamic–pituitary–adrenal (HPA) axis responsivity to early life stress, with documented associations between dehydroepiandrosterone (DHEA) levels and anterior PG volumes. In adults, elevated anxiety/depressive symptoms are related to diminished DHEA levels, and studies have shown a positive relationship between DHEA and anterior pituitary volumes. However, specific links between responses to stress, DHEA levels, and anterior pituitary volume have not been established in developmental samples.

High‐resolution T1‐weighted MRI scans were collected from 137 healthy youth (9–17 years;M_age = 12.99 (SD = 1.87); 49% female; 85% White, 4% Indigenous, 1% Asian, 4% Black, 4% multiracial, 2% not reported). The anterior and posterior PGs were manually traced by trained raters. We examined the mediating effects of salivary DHEA on trauma‐related symptoms (i.e., anxiety, depression, and posttraumatic) and PG volumes as well as an alternative model examining mediating effects of PG volume on DHEA and trauma‐related symptoms.

DHEA mediated the association between anxiety symptoms and anterior PG volume. Specifically, higher anxiety symptoms related to lower DHEA levels, which in turn were related to smaller anterior PG.

These results shed light on the neurobiological sequelae of elevated anxiety in youth and are consistent with adult findings showing suppressed levels of DHEA in those with greater comorbid anxiety and depression. Specifically, adolescents with greater subclinical anxiety may exhibit diminished levels of DHEA during the pubertal window, which may be associated with disruptions in anterior PG growth.

 

The transition from childhood to adolescence is associated with an influx of sex hormones, which not only facilitates physical and behavioral changes, but also dramatic changes in neural circuitry. While previous work has shown that pubertal hormones modulate structural and functional brain development, few of these studies have focused on the impact that such hormones have on spontaneous cortical activity, and whether these effects are modulated by sex during this critical developmental window. Herein, we examined the effect of endogenous testosterone on spontaneous cortical activity in 71 typically‐developing youth (ages 10–17 years; 32 male). Participants completed a resting‐state magnetoencephalographic (MEG) recording, structural MRI, and provided a saliva sample for hormone analysis. MEG data were source‐reconstructed and the power within five canonical frequency bands (delta, theta, alpha, beta, and gamma) was computed. The resulting power spectral density maps were analyzed via vertex‐wise ANCOVAs to identify spatially specific effects of testosterone and sex by testosterone interactions, while covarying out age. We found robust sex differences in the modulatory effects of testosterone on spontaneous delta, beta, and gamma activity. These interactions were largely confined to frontal cortices and exhibited a stark switch in the directionality of the correlation from the low (delta) to high frequencies (beta/gamma). For example, in the delta band, greater testosterone related to lower relative power in prefrontal cortices in boys, while the reverse pattern was found for girls. These data suggest testosterone levels are uniquely related to the development of spontaneous cortical dynamics during adolescence, and such levels are associated with different developmental patterns in males and females within regions implicated in executive functioning.

 

The brain's functional architecture and organization undergo continual development and modification throughout adolescence. While it is well known that multiple factors govern brain maturation, the constantly evolving patterns of time‐resolved functional connectivity are still unclear and understudied. We systematically evaluated over 47,000 youth and adult brains to bridge this gap, highlighting replicable time‐resolved developmental and aging functional brain patterns. The largest difference between the two life stages was captured in a brain state that indicated coherent strengthening and modularization of functional coupling within the auditory, visual, and motor subdomains, supplemented by anticorrelation with other subdomains in adults. This distinctive pattern, which we replicated in independent data, was consistently less modular or absent in children and presented a negative association with age in adults, thus indicating an overall inverted U‐shaped trajectory. This indicates greater synchrony, strengthening, modularization, and integration of the brain's functional connections beyond adolescence, and gradual decline of this pattern during the healthy aging process. We also found evidence that the developmental changes may also bring along a departure from the canonical static functional connectivity pattern in favor of more efficient and modularized utilization of the vast brain interconnections. State‐based statistical summary measures presented robust and significant group differences that also showed significant age‐related associations. The findings reported in this article support the idea of gradual developmental and aging brain state adaptation processes in different phases of life and warrant future research via lifespan studies to further authenticate the projected time‐resolved brain state trajectories.

 

Consumption of alcohol during pregnancy impacts fetal development and may lead to a variety of physical, cognitive, and behavioral abnormalities in childhood collectively known as fetal alcohol spectrum disorder (FASD). The FASD spectrum includes children with fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), and alcohol‐related neurodevelopmental disorder (ARND). Children with a FASD or prenatal alcohol exposure (PAE) have impaired white matter, reduced structural volumes, impaired resting‐state functional connectivity when measured with fMRI, and spectral hypersynchrony as infants. Magnetoencephalography (MEG) provides high temporal resolution and good spatial precision for examining spectral power and connectivity patterns unique from fMRI. The impact of PAE on MEG resting‐state spectral power in children remains unknown.

We collected 2 minutes of eyes‐open and eyes‐closed resting‐state data in 51 children (8 to 12 years of age) with 3 subgroups included: 10 ARND/PAE, 15 FAS/pFAS, and 26 controls (TDC). MEG data were collected on the Elekta Neuromag system. The following spectral metrics were compared between subgroups: power, normalized power, half power, 95% power, and Shannon spectral entropy (SSE). MEG spectral data were correlated with behavioral measures.

Our results indicate children with FAS/pFAS had reduced spectral power and normalized power, particularly within the alpha frequency band in sensor parietal and source superior parietal and lateral occipital regions, along with elevated half power, 95% power, and SSE. We also found select hemisphere specific effects further indicating reduced corpus callosum connectivity in children with a FASD. Interestingly, while the ARND/PAE subgroup had significant differences from the FAS/pFAS subgroup, in many cases spectral data were not significantly different from TDC.

Our results were consistent with previous studies and provide new insight into resting‐state oscillatory differences both between children with FAS and TDC, and within FASD subgroups. Further understanding of these resting‐state variations and their impact on cognitive function may help provide early targets for intervention and enhance outcomes for individuals with a FASD.