Everyday home radon exposure is associated with altered structural brain morphology in youths.

The refinement of brain morphology extends across childhood, and exposure to environmental toxins during this period may alter typical trends. Radon is a highly common radiologic toxin with a well-established role in cancer among adults. However, effects on developmental populations are understudied in comparison. This study investigated whether home radon exposure is associated with altered brain morphology in youths. Fifty-four participants (6-14yrs, M=10.52yrs, 48.15% male, 89% White) completed a T1-weighted MRI and home measures of radon. We observed a significant multivariate effect of home radon concentrations, which was driven by effects on GMV. Specifically, higher home radon was associated with smaller GMV (F=6.800, p=.012, ηp2=.13). Conversely, there was a trending radon-by-age interaction on WMV, which reached significance when accounting for the chronicity of radon exposure (F=4.12, p=.049, ηp2=.09). We found that youths with above-average radon exposure showed no change in WMV with age, whereas low radon was linked with normative, age-related WMV increases. These results suggest that everyday home radon exposure may alter sensitive structural brain development, impacting developmental trajectories in both gray and white matter.

Healthy aging alters the oscillatory dynamics and fronto-parietal connectivity serving fluid intelligence.

Fluid intelligence (Gf) involves logical reasoning and novel problem-solving abilities. Often, abstract reasoning tasks like Raven's progressive matrices are used to assess Gf. Prior work has shown an age-related decline in fluid intelligence capabilities, and although many studies have sought to identify the underlying mechanisms, our understanding of the critical brain regions and dynamics remains largely incomplete. In this study, we utilized magnetoencephalography (MEG) to investigate 78 individuals, ages 20-65 years, as they completed an abstract reasoning task. MEG data was co-registered with structural MRI data, transformed into the time-frequency domain, and the resulting neural oscillations were imaged using a beamformer. We found worsening behavioral performance with age, including prolonged reaction times and reduced accuracy. MEG analyses indicated robust oscillations in the theta, alpha/beta, and gamma range during the task. Whole brain correlation analyses with age revealed relationships in the theta and alpha/beta frequency bands, such that theta oscillations became stronger with increasing age in a right prefrontal region and alpha/beta oscillations became stronger with increasing age in parietal and right motor cortices. Follow-up connectivity analyses revealed increasing parieto-frontal connectivity with increasing age in the alpha/beta frequency range. Importantly, our findings are consistent with the parieto-frontal integration theory of intelligence (P-FIT). These results further suggest that as people age, there may be alterations in neural responses that are spectrally specific, such that older people exhibit stronger alpha/beta oscillations across the parieto-frontal network during abstract reasoning tasks.

Developmental changes in endogenous testosterone have sexually-dimorphic effects on spontaneous cortical dynamics.

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.

Aberrant age-related alterations in spontaneous cortical activity in participants with cerebral palsy.

Introduction: Cerebral Palsy (CP) is the most common neurodevelopmental motor disability, resulting in life-long sensory, perception and motor impairments. Moreover, these impairments appear to drastically worsen as the population with CP transitions from adolescents to adulthood, although the underlying neurophysiological mechanisms remain poorly understood. Methods: We began to address this knowledge gap by utilizing magnetoencephalographic (MEG) brain imaging to study how the amplitude of spontaneous cortical activity (i.e., resting state) is altered during this transition period in a cohort of 38 individuals with spastic diplegic CP (Age range = 9.80-47.50 years, 20 females) and 67 neurotypical controls (NT) (Age range = 9.08-49.40 years, Females = 27). MEG data from a five-minute eyes closed resting-state paradigm were source imaged, and the power within the delta (2-4 Hz), theta (5-7 Hz), alpha (8-12 Hz), beta (15-29 Hz), and gamma (30-59 Hz) frequency bands were computed. Results: For both groups, the delta and theta spontaneous power decreased in the bilateral temporoparietal and superior parietal regions with age, while alpha, beta, and gamma band spontaneous power increased in temporoparietal, frontoparietal and premotor regions with age. We also found a significant group x age interaction, such that participants with CP demonstrated significantly less age-related increases in the spontaneous beta activity in the bilateral sensorimotor cortices compared to NT controls. Discussion: Overall, these results demonstrate that the spontaneous neural activity in individuals with CP has an altered trajectory when transitioning from adolescents to adulthood. We suggest that these differences in spontaneous cortical activity may play a critical role in the aberrant motor actions seen in this patient group, and may provide a neurophysiological marker for assessing the effectiveness of current treatment strategies that are directed at improving the mobility and sensorimotor impairments seen in individuals with CP.

Developmental differences in functional organization of multispectral networks.

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.

Spontaneous cortical dynamics from the first years to the golden years.

In the largest and most expansive lifespan magnetoencephalography (MEG) study to date (n = 434, 6 to 84 y), we provide critical data on the normative trajectory of resting-state spontaneous activity and its temporal dynamics. We perform cutting-edge analyses to examine age and sex effects on whole-brain, spatially-resolved relative and absolute power maps, and find significant age effects in all spectral bands in both types of maps. Specifically, lower frequencies showed a negative correlation with age, while higher frequencies positively correlated with age. These correlations were further probed with hierarchical regressions, which revealed significant nonlinear trajectories in key brain regions. Sex effects were found in absolute but not relative power maps, highlighting key differences between outcome indices that are generally used interchangeably. Our rigorous and innovative approach provides multispectral maps indicating the unique trajectory of spontaneous neural activity across the lifespan, and illuminates key methodological considerations with the widely used relative/absolute power maps of spontaneous cortical dynamics.

Impacts of adrenarcheal DHEA levels on spontaneous cortical activity during development.

Dehydroepiandrosterone (DHEA) production is closely associated with the first pubertal hormonal event, adrenarche. Few studies have documented the relationships between DHEA and functional brain development, with even fewer examining the associations between DHEA and spontaneous cortical activity during the resting-state. Thus, whether DHEA levels are associated with the known developmental shifts in the brain's idling cortical rhythms remains poorly understood. Herein, we examined spontaneous cortical activity in 71 typically-developing youth (9-16 years; 32 male) using magnetoencephalography (MEG). MEG data were source imaged and the power within five canonical frequency bands (delta, theta, alpha, beta, gamma) was computed to identify spatially- and spectrally-specific effects of salivary DHEA and DHEA-by-sex interactions using vertex-wise ANCOVAs. Our results indicated robust increases in power with increasing DHEA within parieto-occipital cortices in all frequency bands except alpha, which decreased with increasing DHEA. In the delta band, DHEA and sex interacted within frontal and temporal cortices such that with increasing DHEA, males exhibited increasing power while females showed decreasing power. These data suggest that spontaneous cortical activity changes with endogenous DHEA levels during the transition from childhood to adolescence, particularly in sensory and attentional processing regions. Sexually-divergent trajectories were only observed in later-developing frontal cortical areas.

Eyes-closed versus eyes-open differences in spontaneous neural dynamics during development.

BACKGROUND: Assessing brain activity during rest has become a widely used approach in developmental neuroscience. Extant literature has measured resting brain activity both during eyes-open and eyes-closed conditions, but the difference between these conditions has not yet been well characterized. Studies, limited to fMRI and EEG, have suggested that eyes-open versus -closed conditions may differentially impact neural activity, especially in visual cortices. METHODS: Spontaneous cortical activity was recorded using MEG from 108 typically developing youth (9-15 years-old; 55 female) during separate sessions of eyes-open and eyes-closed rest. MEG source images were computed, and the strength of spontaneous neural activity was estimated in the canonical delta, theta, alpha, beta, and gamma bands, respectively. Power spectral density maps for eyes-open were subtracted from eyes-closed rest, and then submitted to vertex-wise regression models to identify spatially specific differences between conditions and as a function of age and sex. RESULTS: Relative alpha power was weaker in the eyes-open compared to -closed condition, but otherwise eyes-open was stronger in all frequency bands, with differences concentrated in the occipital cortex. Relative theta power became stronger in the eyes-open compared to the eyes-closed condition with increasing age in frontal cortex. No differences were observed between males and females. CONCLUSIONS: The differences in relative power from eyes-closed to -open conditions are consistent with changes observed in task-based visual sensory responses. Age differences occurred in relatively late developing frontal regions, consistent with canonical attention regions, suggesting that these differences could be reflective of developmental changes in attention processes during puberty. Taken together, resting-state paradigms using eyes-open versus -closed produce distinct results and, in fact, can help pinpoint sensory related brain activity.

Altered spontaneous cortical activity predicts pain perception in individuals with cerebral palsy.

Cerebral palsy is the most common paediatric neurological disorder and results in extensive impairment to the sensorimotor system. However, these individuals also experience increased pain perception, resulting in decreased quality of life. In the present study, we utilized magnetoencephalographic brain imaging to examine whether alterations in spontaneous neural activity predict the level of pain experienced in a cohort of 38 individuals with spastic diplegic cerebral palsy and 67 neurotypical controls. Participants completed 5 min of an eyes closed resting-state paradigm while undergoing a magnetoencephalography recording. The magnetoencephalographic data were then source imaged, and the power within the delta (2-4 Hz), theta (5-7 Hz), alpha (8-12 Hz), beta (15-29 Hz), low gamma (30-59 Hz) and high gamma (60-90 Hz) frequency bands were computed. The resulting power spectral density maps were analysed vertex-wise to identify differences in spontaneous activity between groups. Our findings indicated that spontaneous cortical activity was altered in the participants with cerebral palsy in the delta, alpha, beta, low gamma and high gamma bands across the occipital, frontal and secondary somatosensory cortical areas (all p FWE < 0.05). Furthermore, we also found that the altered beta band spontaneous activity in the secondary somatosensory cortices predicted heightened pain perception in the individuals with cerebral palsy (P = 0.039). Overall, these results demonstrate that spontaneous cortical activity within individuals with cerebral palsy is altered in comparison to their neurotypical peers and may predict increased pain perception in this patient population. Potentially, changes in spontaneous resting-state activity may be utilized to measure the effectiveness of current treatment approaches that are directed at reducing the pain experienced by individuals with cerebral palsy.

Spontaneous cortical MEG activity undergoes unique age- and sex-related changes during the transition to adolescence.

BACKGROUND: While numerous studies have examined the developmental trajectory of task-based neural oscillations during childhood and adolescence, far less is known about the evolution of spontaneous cortical activity during this time period. Likewise, many studies have shown robust sex differences in task-based oscillations during this developmental period, but whether such sex differences extend to spontaneous activity is not understood. METHODS: Herein, we examined spontaneous cortical activity in 111 typically-developing youth (ages 9-15 years; 55 male). Participants completed a resting state magnetoencephalographic (MEG) recording and a structural MRI. MEG data were source imaged and the power within five canonical frequency bands (delta, theta, alpha, beta, gamma) was computed. The resulting power spectral density maps were analyzed via vertex-wise ANCOVAs to identify spatially-specific effects of age, sex, and their interaction. RESULTS: We found robust increases in power with age in all frequencies except delta, which decreased over time, with findings largely confined to frontal cortices. Sex effects were distributed across frontal and temporal regions; females tended to have greater delta and beta power, whereas males had greater alpha. Importantly, there was a significant age-by-sex interaction in theta power, such that males exhibited decreasing power with age while females showed increasing power with age in the bilateral superior temporal cortices. DISCUSSION: These data suggest that the strength of spontaneous activity undergoes robust change during the transition from childhood to adolescence (i.e., puberty onset), with intriguing sex differences in some cortical areas. Future developmental studies should probe task-related oscillations and spontaneous activity in parallel.

Three-year reliability of MEG resting-state oscillatory power.

INTRODUCTION: Resting-state oscillatory activity has been extensively studied across a wide array of disorders. Establishing which spectrally- and spatially-specific oscillatory components exhibit test-retest reliability is essential to move the field forward. While studies have shown short-term reliability of MEG resting-state activity, no studies have examined test-retest reliability across an extended period of time to establish the stability of these signals, which is critical for reproducibility. METHODS: We examined 18 healthy adults age 23 - 61 who completed three visits across three years. For each visit, participants completed both a resting state MEG and structural MRI scan. MEG data were source imaged, and the cortical power in canonical frequency bands (delta, theta, alpha, beta, low gamma, high gamma) was computed. Intra-class correlation coefficients (ICC) were then calculated across the cortex for each frequency band. RESULTS: Over three years, power in the alpha and beta bands displayed the highest reliability estimates, while gamma showed the lowest estimates of three-year reliability. Spatially, delta, alpha, and beta all showed the highest degrees of reliability in the parietal cortex. Interestingly, the peak signal for each of these frequency bands was located outside of the parietal cortex, suggesting that reliability estimates were not solely dependent on the signal-to-noise ratio. CONCLUSION: Oscillatory resting-state power in parietal delta, posterior beta, and alpha across most of the cortex are reliable across three years and future MEEG studies may focus on these measures for the development of specific markers.