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Abstract Pediatric obesity rates have quadrupled in the United States, and deficits in higher-order cognition have been linked to obesity, though it remains poorly understood how deviations from normal body mass are related to the neural dynamics serving cognition in youth. Herein, we determine how age- and sex-adjusted measures of body mass index (zBMI) scale with neural activity in brain regions underlying fluid intelligence. Seventy-two youth aged 9–16 years underwent high-density magnetoencephalography while performing an abstract reasoning task. The resulting data were transformed into the time-frequency domain and significant oscillatory responses were imaged using a beamformer. Whole-brain correlations with zBMI were subsequently conducted to quantify relationships between zBMI and neural activity serving abstract reasoning. Our results reveal that participants with higher zBMI exhibit attenuated theta (4–8 Hz) responses in both the left dorsolateral prefrontal cortex and left temporoparietal junction, and that weaker temporoparietal responses scale with slower reaction times. These findings suggest that higher zBMI values are associated with weaker theta oscillations in key brain regions and altered performance during an abstract reasoning task. Thus, future investigations should evaluate neurobehavioral function during abstract reasoning in youth with more severe obesity to identify the potential impact.

Working memory (WM) enables the temporary storage of limited information and is a central component of higher order cognitive function. Irrelevant and/or distracting information can have a negative impact on WM processing and suppressing such incoming stimuli is critical to maintaining adequate performance. However, the neural mechanisms and dynamics underlying such distractor inhibition remain poorly understood. In the current study, we enrolled 46 healthy adults (Mage: 27.92, Nfemale: 28) who completed a Sternberg type WM task with high- and low-distractor conditions during magnetoencephalography (MEG). MEG data were transformed into the time-frequency domain and significant task-related oscillatory responses were imaged to identify the underlying anatomical areas. Whole-brain paired t-tests, with cluster-based permutation testing for multiple comparisons correction, were performed to assess differences between the low- and high-distractor conditions for each oscillatory response. Across conditions, we found strong alpha and beta oscillations (i.e., decreases relative to baseline) and increases in theta power throughout the encoding and maintenance periods. Whole-brain contrasts revealed significantly stronger alpha and beta oscillations in bilateral prefrontal regions during maintenance in high- compared to low-distractor trials, with the stronger beta oscillations being centered on the left dorsolateral prefrontal cortex and right inferior frontal gyrus, while those for alpha being within the right anterior prefrontal cortices and the right middle frontal gyrus. These findings suggest that alpha and beta oscillations in the bilateral prefrontal cortices play a major role in the inhibition of distracting information during WM maintenance. Our results also contribute to prior research on cognitive control and functional inhibition, in which prefrontal regions have been widely implicated.

Despite effective antiretroviral therapy, cognitive impairment remains prevalent among people with HIV (PWH) and decrements in executive function are particularly prominent. One component of executive function is cognitive flexibility, which integrates a variety of executive functions to dynamically adapt one's behavior in response to changing contextual demands. Though substantial work has illuminated HIV-related aberrations in brain function, it remains unclear how the neural oscillatory dynamics serving cognitive flexibility are affected by HIV-related alterations in neural functioning. Herein, 149 participants (PWH: 74; seronegative controls: 75) between the ages of 29–76 years completed a perceptual feature matching task that probes cognitive flexibility during high-density magnetoencephalography (MEG). Neural responses were decomposed into the time-frequency domain and significant oscillatory responses in the theta (4–8 Hz), alpha (10–16 Hz), and gamma (74–98 Hz) spectral windows were imaged using a beamforming approach. Whole-brain voxel-wise comparisons were then conducted on these dynamic functional maps to identify HIV-related differences in the neural oscillatory dynamics supporting cognitive flexibility. Our findings indicated group differences in alpha oscillatory activity in the cingulo-opercular cortices, and differences in gamma activity were found in the cerebellum. Across all participants, alpha and gamma activity in these regions were associated with performance on the cognitive flexibility task. Further, PWH who had been treated with antiretroviral therapy for a longer duration and those with higher current CD4 counts had alpha responses that more closely resembled those of seronegative controls, suggesting that optimal clinical management of HIV infection is associated with preserved neural dynamics supporting cognitive flexibility.

Modeling dynamic interactions among network components is crucial to uncovering the evolution mechanisms of complex networks. Recently, spatio-temporal graph learning methods have achieved noteworthy results in characterizing the dynamic changes of inter-node relations (INRs). However, challenges remain: The spatial neighborhood of an INR is underexploited, and the spatio-temporal dependencies in INRs’ dynamic changes are overlooked, ignoring the influence of historical states and local information. In addition, the model’s explainability has been understudied. To address these issues, we propose an explainable spatio-temporal graph evolution learning (ESTGEL) model to model the dynamic evolution of INRs. Specifically, an edge attention module is proposed to utilize the spatial neighborhood of an INR at multi-level, i.e., a hierarchy of nested subgraphs derived from decomposing the initial node-relation graph. Subsequently, a dynamic relation learning module is proposed to capture the spatio-temporal dependencies of INRs. The INRs are then used as adjacent information to improve the node representation, resulting in comprehensive delineation of dynamic evolution of the network. Finally, the approach is validated with real data on brain development study. Experimental results on dynamic brain networks analysis reveal that brain functional networks transition from dispersed to more convergent and modular structures throughout development. Significant changes are observed in the dynamic functional connectivity (dFC) associated with functions including emotional control, decision-making, and language processing.

Abstract Prior research has shown that the sensorimotor cortical oscillations are uncharacteristic in persons with cerebral palsy (CP); however, it is unknown if these altered cortical oscillations have an impact on adaptive sensorimotor control. This investigation evaluated the cortical dynamics when the motor action needs to be changed “on-the-fly”. Adults with CP and neurotypical controls completed a sensorimotor task that required either proactive or reactive control while undergoing magnetoencephalography (MEG). When compared with the controls, the adults with CP had a weaker beta (18–24 Hz) event-related desynchronization (ERD), post-movement beta rebound (PMBR, 16–20 Hz) and theta (4–6 Hz) event-related synchronization (ERS) in the sensorimotor cortices. In agreement with normative work, the controls exhibited differences in the strength of the sensorimotor gamma (66–84 Hz) ERS during proactive compared to reactive trials, but similar condition-wise changes were not seen in adults with CP. Lastly, the adults with CP who had a stronger theta ERS tended to have better hand dexterity, as indicated by the Box and Blocks Test and Purdue Pegboard Test. These results may suggest that alterations in the theta and gamma cortical oscillations play a role in the altered hand dexterity and uncharacteristic adaptive sensorimotor control noted in adults with CP.

Introduction: The human cerebellum emerges as a posterior brain structure integrating neural networks for sensorimotor, cognitive, and emotional processing across the lifespan. Developmental studies of the cerebellar anatomy and function are scant. We examine age-dependent MRI morphometry of the anterior cerebellar vermis, lobules I-V and posterior neocortical lobules VI-VII and their relationship to sensorimotor and cognitive functions. Methods: Typically developing children (TDC; n=38; age 9–15) and healthy adults (HAC; n=31; 18–40) participated in high-resolution MRI. Rigorous anatomically informed morphometry of the vermis lobules I-V and VI-VII and total brain volume (TBV) employed manual segmentation computer-assisted FreeSurfer Image Analysis Program [http://surfer.nmr.mgh.harvard.edu]. The neuropsychological scores (WASI-II) were normalized and related to volumes of anterior, posterior vermis, and TBV. Results: TBVs were age independent. Volumes of I-V and VI-VII were significantly reduced in TDC. The ratio of VI-VII to I-V (∼60%) was stable across age-groups; I-V correlated with visual-spatial-motor skills; VI-VII with verbal, visual-abstract and FSIQ. Conclusions: In TDC neither anterior I-V nor posterior VI-VII vermis attained adult volumes. The ''inverted U'' developmental trajectory of gray matter peaking in adolescence does not explain this finding. The hypothesis of protracted development of oligodendrocyte/myelination is suggested as a contributor to TDC's lower cerebellar vermis volumes.

Radon is a naturally occurring gas that contributes significantly to radiation in the environment and is the second leading cause of lung cancer globally. Previous studies have shown that other environmental toxins have deleterious effects on brain development, though radon has not been studied as thoroughly in this context. This study examined the impact of home radon exposure on the neural oscillatory activity serving attention reorientation in youths. Fifty-six participants (ages 6–14 years) completed a classic Posner cuing task during magnetoencephalography (MEG), and home radon levels were measured for each participant. Time-frequency spectrograms indicated stronger theta (3–7 Hz, 300–800 ms), alpha (9–13 Hz, 400–900 ms), and beta responses (14–24 Hz, 400–900 ms) during the task relative to baseline. Source reconstruction of each significant oscillatory response was performed, and validity maps were computed by subtracting the task conditions (invalidly cued – validly cued). These validity maps were examined for associations with radon exposure, age, and their interaction in a linear regression design. Children with greater radon exposure showed aberrant oscillatory activity across distributed regions critical for attentional processing and attention reorientation (e.g., dorsolateral prefrontal cortex, and anterior cingulate cortex). Generally, youths with greater radon exposure exhibited a reverse neural validity effect in almost all regions and showed greater overall power relative to peers with lesser radon exposure. We also detected an interactive effect between radon exposure and age where youths with greater radon exposure exhibited divergent developmental trajectories in neural substrates implicated in attentional processing (e.g., bilateral prefrontal cortices, superior temporal gyri, and inferior parietal lobules). These data suggest aberrant, but potentially compensatory neural processing as a function of increasing home radon exposure in areas critical for attention and higher order cognition.

Throughout childhood and adolescence, the brain undergoes significant structural and functional changes that contribute to the maturation of multiple cognitive domains, including selective attention. Selective attention is crucial for healthy executive functioning and while key brain regions serving selective attention have been identified, their age-related changes in neural oscillatory dynamics and connectivity remain largely unknown. We examined the developmental sensitivity of selective attention circuitry in 91 typically developing youth aged 6 – 13 years old. Participants completed a number-based Simon task while undergoing magnetoencephalography (MEG) and the resulting data were preprocessed and transformed into the time-frequency domain. Significant oscillatory brain responses were imaged using a beamforming approach, and task-related peak voxels in the occipital, parietal, and cerebellar cortices were used as seeds for subsequent whole-brain connectivity analyses in the alpha and gamma range. Our key findings revealed developmentally sensitive connectivity profiles in multiple regions crucial for selective attention, including the temporoparietal junction (alpha) and prefrontal cortex (gamma). Overall, these findings suggest that brain regions serving selective attention are highly sensitive to developmental changes during the pubertal transition period.

Numerous investigations have characterized the oscillatory dynamics serving working memory in adults, but few have probed its relationship with chronological age in developing youth. We recorded magnetoencephalography during a modified Sternberg verbal working memory task in 82 youth participants aged 6–14 years old. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting whole-brain maps were probed for developmental effects during the encoding and maintenance phases. Our results indicated robust oscillatory responses in the theta (4–7 Hz) and alpha (8–14 Hz) range, with older participants exhibiting stronger alpha oscillations in left-hemispheric language regions. Older participants also had greater occipital theta power during encoding. Interestingly, there were sex-by-age interaction effects in cerebellar cortices during encoding and in the right superior temporal region during maintenance. These results extend the existing literature on working memory development by showing strong associations between age and oscillatory dynamics across a distributed network. To our knowledge, these findings are the first to link chronological age to alpha and theta oscillatory responses serving working memory encoding and maintenance, both across and between male and female youth; they reveal robust developmental effects in crucial brain regions serving higher order functions.

Background: Psychosocial distress among youth is a major public health issue characterized by disruptions in cognitive control processing. Using the National Institute of Mental Health's Research Domain Criteria (RDoC) framework, we quantified multidimensional neural oscillatory markers of psychosocial distress serving cognitive control in youth. Methods: The sample consisted of 39 peri-adolescent participants who completed the NIH Toolbox Emotion Battery (NIHTB-EB) and the Eriksen flanker task during magnetoencephalography (MEG). A psychosocial distress index was computed with exploratory factor analysis using assessments from the NIHTB-EB. MEG data were analyzed in the time-frequency domain and peak voxels from oscillatory maps depicting the neural cognitive interference effect were extracted for voxel time series analyses to identify spontaneous and oscillatory aberrations in dynamics serving cognitive control as a function of psychosocial distress. Further, we quantified the relationship between psychosocial distress and dynamic functional connectivity between regions supporting cognitive control. Results: The continuous psychosocial distress index was strongly associated with validated measures of pediatric psychopathology. Theta-band neural cognitive interference was identified in the left dorsolateral prefrontal cortex (dlPFC) and middle cingulate cortex (MCC). Time series analyses of these regions indicated that greater psychosocial distress was associated with elevated spontaneous activity in both the dlPFC and MCC and blunted theta oscillations in the MCC. Finally, we found that stronger phase coherence between the dlPFC and MCC was associated with greater psychosocial distress. Conclusions: Greater psychosocial distress was marked by alterations in spontaneous and oscillatory theta activity serving cognitive control, along with hyperconnectivity between the dlPFC and MCC.

IntroductionIt is well-established that chronic exposure to environmental toxins can have adverse effects on neuropsychological health, particularly in developing youths. However, home radon, a ubiquitous radiotoxin, has been seldom studied in this context. In the present study, we investigated the degree to which chronic everyday home radon exposure was associated with alterations in transdiagnostic mental health outcomes.MethodsA total of 59 children and adolescents ages 6- to 14-years-old (M = 10.47 years, SD = 2.58; 28 males) completed the study. Parents completed questionnaires detailing aspects of attention and executive function. We used a principal components analysis to derive three domains of neuropsychological functioning: 1) task-based executive function skills, 2) self-and emotion-regulation abilities, and 3) inhibitory control. Additionally, parents completed a home radon test kit and provided information on how long their child had lived in the tested home. We computed a radon exposure index per person based on the duration of time that the child had lived in the home and their measured home radon concentration. Youths were divided into terciles based on their radon exposure index score. Using a MANCOVA design, we determined whether there were differences in neuropsychological domain scores across the three groups, controlling for age, sex, and socioeconomic status.ResultsThere was a significant multivariate effect of radon group on neuropsychological dysfunction (λ = 0.77, F = 2.32, p = 0.038, ηp2 = 0.12). Examination of univariate effects revealed specific increases in self-and emotion-regulation dysfunction among the youths with the greatest degree of chronic home radon exposure (F = 7.21, p = 0.002, ηp2 = 0.21). There were no significant differences by group in the other tested domains.DiscussionThe data suggest potential specificity in the neurotoxic effects of everyday home radon exposure in developing youths, with significant aberrations in self-and emotion-regulation faculties. These findings support the need for better public awareness and public health policy surrounding home radon safety and mitigation strategies.

Background: A fundamental grasp of the variability observed in healthy individuals holds paramount importance in the investigation of neuropsychiatric conditions characterized by sex-related phenotypic distinctions. Functional magnetic resonance imaging (fMRI) serves as a meaningful tool for discerning these differences. Among deep learning models, graph neural networks (GNNs) are particularly well-suited for analyzing brain networks derived from fMRI blood oxygen level-dependent (BOLD) signals, enabling the effective exploration of sex differences during adolescence. Method: In the present study, we introduce a multi-modal graph isomorphism network (MGIN) designed to elucidate sex-based disparities using fMRI task-related data. Our approach amalgamates brain networks obtained from multiple scans of the same individual, thereby enhancing predictive capabilities and feature identification. The MGIN model adeptly pinpoints crucial subnetworks both within and between multi-task fMRI datasets. Moreover, it offers interpretability through the utilization of GNNExplainer, which identifies pivotal sub-network graph structures contributing significantly to sex group classification. Results: Our findings indicate that the MGIN model outperforms competing models in terms of classification accuracy, underscoring the benefits of combining two fMRI paradigms. Additionally, our model discerns the most significant sex-related functional networks, encompassing the default mode network (DMN), visual (VIS) network, cognitive (CNG) network, frontal (FRNT) network, salience (SAL) network, subcortical (SUB) network, and sensorimotor (SM) network associated with hand and mouth movements. Remarkably, the MGIN model achieves superior sex classification accuracy when juxtaposed with other state-of-the-art algorithms, yielding a noteworthy 81.67% improvement in classification accuracy. Conclusion: Our model’s superiority emanates from its capacity to consolidate data from multiple scans of subjects within a proven interpretable framework. Beyond its classification prowess, our model guides our comprehension of neurodevelopment during adolescence by identifying critical subnetworks of functional connectivity.

IntroductionPeople with Alzheimer’s disease (AD) experience more rapid declines in their ability to form hippocampal-dependent memories than cognitively normal healthy adults. Degeneration of the whole hippocampal formation has previously been found to covary with declines in learning and memory, but the associations between subfield-specific hippocampal neurodegeneration and cognitive impairments are not well characterized in AD. To improve prognostic procedures, it is critical to establish in which hippocampal subfields atrophy relates to domain-specific cognitive declines among people along the AD spectrum. In this study, we examine high-resolution structural magnetic resonance imaging (MRI) of the medial temporal lobe and extensive neuropsychological data from 29 amyloid-positive people on the AD spectrum and 17 demographically-matched amyloid-negative healthy controls.MethodsParticipants completed a battery of neuropsychological exams including select tests of immediate recollection, delayed recollection, and general cognitive status (i.e., performance on the Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). Hippocampal subfield volumes (CA1, CA2, CA3, dentate gyrus, and subiculum) were measured using a dedicated MRI slab sequence targeting the medial temporal lobe and used to compute distance metrics to quantify AD spectrum-specific atrophic patterns and their impact on cognitive outcomes.ResultsOur results replicate prior studies showing that CA1, dentate gyrus, and subiculum hippocampal subfield volumes were significantly reduced in AD spectrum participants compared to amyloid-negative controls, whereas CA2 and CA3 did not exhibit such patterns of atrophy. Moreover, degeneration of the subiculum along the AD spectrum was linked to a significant decline in general cognitive status measured by the MMSE, while degeneration scores of the CA1 and dentate gyrus were more widely associated with declines on the MMSE and tests of learning and memory.DiscussionThese findings provide evidence that subfield-specific patterns of hippocampal degeneration, in combination with cognitive assessments, may constitute a sensitive prognostic approach and could be used to better track disease trajectories among individuals on the AD spectrum.

People with HIV (PWH) often develop HIV-related neurological impairments known as HIV-associated neurocognitive disorder (HAND), but cognitive dysfunction in older PWH may also be due to age-related disorders such as Alzheimer's disease (AD). Discerning these two conditions is challenging since the specific neural characteristics are not well understood and limited studies have probed HAND and AD spectrum (ADS) directly. We examined the neural dynamics underlying motor processing during cognitive interference using magnetoencephalography (MEG) in 22 biomarker-confirmed patients on the ADS, 22 older participants diagnosed with HAND, and 30 healthy aging controls. MEG data were transformed into the time-frequency domain to examine movement-related oscillatory activity and the impact of cognitive interference on distinct stages of motor programming. Both cognitively impaired groups (ADS/HAND) performed significantly worse on the task (e.g., less accurate and slower reaction time) and exhibited reductions in frontal and cerebellar beta and parietal gamma activity relative to controls. Disease-specific aberrations were also detected such that those with HAND exhibited weaker gamma interference effects than those on the ADS in frontoparietal and motor areas. Additionally, temporally distinct beta interference effects were identified, with ADS participants exhibiting stronger beta interference activity in the temporal cortex during motor planning, along with weaker beta interference oscillations dispersed across frontoparietal and cerebellar cortices during movement execution relative to those with HAND. These results indicate both overlapping and distinct neurophysiological aberrations in those with ADS disorders or HAND in key motor and top-down cognitive processing regions during cognitive interference and provide new evidence for distinct neuropathology.

The presence of conflicting stimuli adversely affects behavioral outcomes, which could either be at the level of stimulus (Flanker), response (Simon), or both (Multisource). Briefly, flanker interference involves conflicting stimuli requiring selective attention, Simon interference is caused by an incongruity between the spatial location of the task-relevant stimulus and prepotent motor mapping, and multisource is combination of both. Irrespective of the variant, interference resolution necessitates cognitive control to filter irrelevant information and allocate neural resources to task-related goals. Though previously studied in healthy young adults, the direct quantification of changes in oscillatory activity serving such cognitive control and associated inter-regional interactions in healthy aging are poorly understood. Herein, we used an adapted version of the multisource interference task and magnetoencephalography to investigate age-related alterations in the neural dynamics governing both divergent and convergent cognitive interference in 78 healthy participants (age range: 20-66 years). We identified weaker alpha connectivity between bilateral visual and right dorsolateral prefrontal cortices (DLPFC) and left dorsomedial prefrontal cortices (dmPFC), as well as weaker gamma connectivity between bilateral occipital regions and the right dmPFC during flanker interference with advancing age. Further, an age-related decrease in gamma power was observed in the left cerebellum and parietal region for Simon and differential interference effects (i.e., flanker-Simon), respectively. Moreover, the superadditivity model showed decreased gamma power in the right temporoparietal junction (TPJ) with increasing age. Overall, our findings suggest age-related declines in the engagement of top-down attentional control secondary to reduced alpha and gamma coupling between prefrontal and occipital cortices.

The neural and cognitive processes underlying the flexible allocation of attention undergo a protracted developmental course with changes occurring throughout adolescence. Despite documented age-related improvements in attentional reorienting throughout childhood and adolescence, the neural correlates underlying such changes in reorienting remain unclear. Herein, we used magnetoencephalography (MEG) to examine neural dynamics during a Posner attention-reorienting task in 80 healthy youth (6–14 years old). The MEG data were examined in the time-frequency domain and significant oscillatory responses were imaged in anatomical space. During the reorienting of attention, youth recruited a distributed network of regions in the fronto-parietal network, along with higher-order visual regions within the theta (3–7 Hz) and alpha-beta (10–24 Hz) spectral windows. Beyond the expected developmental improvements in behavioral performance, we found stronger theta oscillatory activity as a function of age across a network of prefrontal brain regions irrespective of condition, as well as more limited age- and validity-related effects for alpha-beta responses. Distinct brain-behavior associations between theta oscillations and attention-related symptomology were also uncovered across a network of brain regions. Taken together, these data are the first to demonstrate developmental effects in the spectrally-specific neural oscillations serving the flexible allocation of attention.

Introduction: Adolescence, a critical phase of human neurodevelopment, is marked by a tremendous reorganization of the brain and accompanied by improved cognitive performance. This development is driven in part by gene expression, which in turn is partly regulated by DNA methylation (DNAm).Methods: We collected brain imaging, cognitive assessments, and DNAm in a longitudinal cohort of approximately 200 typically developing participants, aged 9–14. This data, from three time points roughly 1 year apart, was used to explore the relationships between seven cytosine–phosphate–guanine (CpG) sites in genes highly expressed in brain tissues (GRIN2D, GABRB3, KCNC1, SLC12A9, CHD5, STXBP5, and NFASC), seven networks of grey matter (GM) volume change, and scores from seven cognitive tests.Results: The demethylation of the CpGs as well as the rates of change in DNAm were significantly related to improvements in total, crystalized, and fluid cognition scores, executive function, episodic memory, and processing speed, as well as several networks of GM volume increases and decreases that highlight typical patterns of brain maturation.Discussion: Our study provides a first look at the DNAm of genes involved in myelination, excitatory and inhibitory receptors, and connectivity, how they are related to the large-scale changes occurring in the brain structure as well as cognition during adolescence.

IntroductionCerebral 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.MethodsWe 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.ResultsFor 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.DiscussionOverall, 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.

Recent investigations have studied the development of motor-related oscillatory responses to delineate maturational changes from childhood to young adulthood. While these studies included youth during the pubertal transition period, none have probed the impact of testosterone levels on motor cortical dynamics and performance. We collected salivary testosterone samples and recorded magnetoencephalography during a complex motor sequencing task in 58 youth aged 9–15 years old. The relationships between testosterone, age, task behavior, and beta (15–23 Hz) oscillatory dynamics were examined using multiple mediation modeling. We found that testosterone mediated the effect of age on movement-related beta activity. We also found that the effect of age on movement duration was mediated by testosterone and reaction time. Interestingly, the relationships between testosterone and motor performance were not mediated by beta activity in the left primary motor cortex, which may indicate the importance of higher-order motor regions. Overall, our results suggest that testosterone has unique associations with neural and behavioral indices of complex motor performance, beyond those already characterized in the literature. These findings are the first to link developmental changes in testosterone levels to maturation of beta oscillatory dynamics serving complex motor planning and execution, and specific measures of motor performance.

Summary: Background: Alterations in resting-state neural activity have been reported in people with sleep disruptions and in patients with Alzheimer's disease, but the direct impact of sleep quality on Alzheimer's disease-related neurophysiological aberrations is unclear. Methods: We collected cross-sectional resting-state magnetoencephalography and extensive neuropsychological and clinical data from 38 biomarker-confirmed patients on the Alzheimer's disease spectrum and 20 cognitively normal older control participants. Sleep efficiency was quantified using the Pittsburgh Sleep Quality Index. Findings: Neural activity in the delta frequency range was differentially affected by poor sleep in patients on the Alzheimer's disease spectrum. Such neural changes were related to processing speed abilities and regional amyloid accumulation, and these associations were mediated and moderated, respectively, by sleep quality. Interpretation: Together, our results point to a mechanistic role for sleep disturbances in the widely reported neurophysiological aberrations seen in patients on the Alzheimer's disease spectrum, with implications for basic research and clinical intervention. Funding: National Institutes of Health, USA.

For decades, visual entrainment paradigms have been widely used to investigate basic visual processing in healthy individuals and those with neurological disorders. While healthy aging is known to be associated with alterations in visual processing, whether this extends to visual entrainment responses and the precise cortical regions involved is not fully understood. Such knowledge is imperative given the recent surge in interest surrounding the use of flicker stimulation and entrainment in the context of identifying and treating Alzheimer's disease (AD). In the current study, we examined visual entrainment in eighty healthy aging adults using magnetoencephalography (MEG) and a 15 Hz entrainment paradigm, while controlling for age-related cortical thinning. MEG data were imaged using a time-frequency resolved beamformer and peak voxel time series were extracted to quantify the oscillatory dynamics underlying the processing of the visual flicker stimuli. We found that, as age increased, the mean amplitude of entrainment responses decreased and the latency of these responses increased. However, there was no effect of age on the trial-to-trial consistency in phase (i.e., inter-trial phase locking) nor amplitude (i.e., coefficient of variation) of these visual responses. Importantly, we discovered that the relationship between age and response amplitude was fully mediated by the latency of visual processing. These results indicate that aging is associated with robust changes in the latency and amplitude of visual entrainment responses within regions surrounding the calcarine fissure, which should be considered in studies examining neurological disorders such as AD and other conditions associated with increased age.

The default mode network (DMN) plays a crucial role in internal self-processing, rumination, and social functions. Disruptions to DMN connectivity have been linked with early adversity and the emergence of psychopathology in adolescence and early adulthood. Herein, we investigate how subclinical psychiatric symptoms can impact DMN functional connectivity during the pubertal transition. Resting-state fMRI data were collected annually from 190 typically-developing youth (9–15 years-old) at three timepoints and within-network DMN connectivity was computed. We used latent growth curve modeling to determine how self-reported depressive and posttraumatic stress symptoms predicted rates of change in DMN connectivity over the three-year period. In the baseline model without predictors, we found no systematic changes in DMN connectivity over time. However, significant modulation emerged after adding psychopathology predictors; greater depressive symptomatology was associated with significant decreases in connectivity over time, whereas posttraumatic stress symptoms were associated with significant increases in connectivity over time. Follow-up analyses revealed that these effects were driven by connectivity changes involving the dorsal medial prefrontal cortex subnetwork. In conclusion, these data suggest that subclinical depressive and posttraumatic symptoms alter the trajectory of DMN connectivity, which may indicate that this network is a nexus of clinical significance in mental health disorders.

Abstract Objective Our prior magnetoencephalographic (MEG) investigations demonstrate that persons with cerebral palsy (CP) have weaker somatosensory cortical activity than neurotypical (NT) controls, which is associated with reduced muscular strength and mobility. Power training can improve lower extremity isokinetic strength, muscular power, and walking performance of youth with CP. Potentially, these clinically relevant improvements are partially driven by changes in somatosensory processing. The objective of this investigation was to determine if power training has complementary changes in muscular function and somatosensory cortical activity in youth with CP. Methods A cohort of youth with CP (N = 11; age = 15.90 ± 1.1 years) and NT controls (N = 10; Age = 15.93 ± 2.48 years) participated in this investigation. Youth with CP underwent 24 power training sessions. Pre‐post bilateral leg press 1‐repetition maximum (1RM), peak power production, 10‐m walking speed, and distance walked 1‐min were used as outcome measures. MEG neuroimaging assessed the changes in somatosensory cortical activity while at rest. NT controls only underwent a baseline MEG assessment. Results Youth with CP had a 56% increase in 1RM (p

Abstract Previous animal models have illustrated that reduced cortical activity in the developing brain has cascading activity-dependent effects on the microstructural organization of the spinal cord. A limited number of studies have attempted to translate these findings to humans with cerebral palsy (CP). Essentially, the aberrations in sensorimotor cortical activity in those with CP could have an adverse effect on the spinal cord microstructure. To investigate this knowledge gap, we utilized magnetoencephalographic (MEG) brain imaging to quantify motor-related oscillatory activity in fourteen adults with CP and sixteen neurotypical (NT) controls. A subset of these participants also underwent cervical-thoracic spinal cord MRI. Our results showed that the strength of the peri-movement beta desynchronization and the post-movement beta rebound were each weaker in the adults with CP relative to the controls, and these weakened responses were associated with poorer task performance. Additionally, our results showed that the strength of the peri-movement beta response was associated with the total cross-sectional area of the spinal cord and the white matter cross-sectional area. Altogether these results suggest that the altered sensorimotor cortical activity seen in CP may result in activity-dependent plastic changes within the spinal cord microstructure, which could ultimately contribute to the sensorimotor deficits seen in this population.

The Coronavirus Disease 2019 (COVID-19) pandemic has caused massive disruptions to daily life in the United States, closing schools and businesses and increasing physical and social isolation, leading to deteriorations in mental health and well-being in people of all ages. Many studies have linked chronic stress with long-term changes in cortisol secretion, which has been implicated in many stress-related physical and mental health problems that commonly emerge in adolescence. However, the physiological consequences of the pandemic in youth remain understudied. Using hair cortisol concentrations (HCC), we quantified average longitudinal changes in cortisol secretion across a four-month period capturing before, during, and after the transition to pandemic-lockdown conditions in a sample of healthy youth (n = 49). Longitudinal changes in HCC were analyzed using linear mixed-effects models. Perceived levels of pandemic-related stress were measured and compared to the physiological changes in HCC. In children and adolescents, cortisol levels significantly increased across the course of the pandemic. These youth reported a multitude of stressors during this time, although changes in HCC were not associated with self-reported levels of COVID-19-related distress. We provide evidence that youth are experiencing significant physiological changes in cortisol activity across the COVID-19 pandemic, yet these biological responses are not associated with perceived stress levels. Youth may be especially vulnerable to the deleterious impacts of chronic cortisol exposure due to their current status in the sensitive periods for development, and the incongruency between biological and psychological stress responses may further complicate these developmental problems.

Puberty is a period of substantial hormonal fluctuations, and pubertal hormones can modulate structural and functional changes in the developing brain. Many previous studies have characterized the neural oscillatory responses serving movement, which include a beta event-related desynchronization (ERD) preceding movement onset, gamma and theta responses coinciding with movement execution, and a post-movement beta-rebound (PMBR) response following movement offset. While a few studies have investigated the developmental trajectories of these neural oscillations serving motor control, the impact of pubertal hormone levels on the maturation of these dynamics has not yet been examined. Since the timing and tempo of puberty varies greatly between individuals, pubertal hormones may uniquely impact the maturation of motor cortical oscillations distinct from other developmental metrics, such as age. In the current study we quantified these oscillations using magnetoencephalography (MEG) and utilized chronological age and measures of endogenous testosterone as indices of development during the transition from childhood to adolescence in 69 youths. Mediation analyses revealed complex maturation patterns for the beta ERD, in which testosterone predicted both spontaneous baseline and ERD power through direct and indirect effects. Age, but not pubertal hormones, predicted motor-related theta, and no relationships between oscillatory responses and developmental metrics were found for gamma or PMBR responses. These findings provide novel insight into how pubertal hormones affect motor-related oscillations, and highlight the continued development of motor cortical dynamics throughout the pubertal period.

Abstract Alcohol and cannabis use disorder (AUD/CUD) are two of the most common addictive disorders. While studies are beginning to understand the neural changes related to acute and chronic use, few studies have examined the independent effects of AUD and CUD on neural oscillatory activity. We examined 45 adults who reported current use of both cannabis and alcohol. Participants underwent the SCID-V to determine whether they met criteria for AUD and/or CUD. Participants also completed a visual-spatial processing task while undergoing magnetoencephalography (MEG). ANCOVA with a 2 × 2 design was then used to identify the main effects of AUD and CUD on source-level oscillatory activity. Of the 45 adults, 17 met criteria for AUD, and 26 met criteria for CUD. All participants, including comparison groups, reported use of both cannabis and alcohol. Statistical analyses showed a main effect of AUD, such that participants with AUD displayed a blunted occipital alpha (8–16 Hz) response. Post-hoc testing showed this decreased alpha response was related to increased AUD symptoms, above and beyond amount of use. No effects of AUD or CUD were identified in visual theta or gamma activity. In conclusion, AUD was associated with reduced alpha responses and scaled with increasing severity, independent of CUD. These findings indicate that alpha oscillatory activity may play an integral part in networks affected by alcohol addiction.

Background: Spontaneous beta activity in the primary motor cortices has been shown to increase in amplitude with advancing age, and that such increases are tightly coupled to stronger motor-related beta oscillations during movement planning. However, the relationship between these age-related changes in spontaneous beta in the motor cortices, local cortical thickness, and overall motor function remains unclear. Methods: We collected resting-state magnetoencephalography (MEG), high-resolution structural MRI, and motor function scores using a neuropsychological battery from 126 healthy adults (56 female; age range = 22–72 years). MEG data were source-imaged and a whole-brain vertex-wise regression model was used to assess age-related differences in spontaneous beta power across the cortex. Cortical thickness was computed from the structural MRI data and local beta power and cortical thickness values were extracted from the sensorimotor cortices. To determine the unique contribution of age, spontaneous beta power, and cortical thickness to the prediction of motor function, a hierarchical regression approach was used. Results: There was an increase in spontaneous beta power with age across the cortex, with the strongest increase being centered on the sensorimotor cortices. Sensorimotor cortical thickness was not related to spontaneous beta power, above and beyond age. Interestingly, both cortical thickness and spontaneous beta power in sensorimotor regions each uniquely contributed to the prediction of motor function when controlling for age. Discussion: This multimodal study showed that cortical thickness and spontaneous beta activity in the sensorimotor cortices have dissociable contributions to motor function across the adult lifespan. These findings highlight the complexity of interactions between structure and function and the importance of understanding these interactions in order to advance our understanding of healthy aging and disease.

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.

Functional connectivity (FC) between brain region has been widely studied and linked with cognition and behavior of an individual. FC is usually defined as the correlation or partial correlation of fMRI blood oxygen level-dependent (BOLD) signals between two brain regions. Although FC has been effective to understand brain organization, it cannot reveal the direction of interactions. Many directed acyclic graph (DAG) based methods have been applied to study the directed interactions but their performance was limited by the small sample size while high dimensionality of the available data. By enforcing group regularization and utilizing samples from both case and control groups, we propose a joint DAG model to estimate the directed FC. We first demonstrate that the proposed model is efficient and accurate through a series of simulation studies. We then apply it to the case-control study of schizophrenia (SZ) with data collected from the MIND Clinical Imaging Consortium (MCIC). We have successfully identified decreased functional integration, disrupted hub structures and characteristic edges (CtEs) in SZ patients. Those findings have been confirmed by previous studies with some identified to be potential markers for SZ patients. A comparison of the results between the directed FC and undirected FC showed substantial differences in the selected features. In addition, we used the identified features based on directed FC for the classification of SZ patients and achieved better accuracy than using undirected FC or raw features, demonstrating the advantage of using directed FC for brain network analysis.

Background Trait dissociation has not been examined from a structural human brain mapping perspective in healthy adults or children. Non-pathological dissociation shares some features with daydreaming and mind-wandering, but also involves subtle disruptions in affect and autobiographical memory. Aims To identify neurostructural biomarkers of trait dissociation in healthy children. Method Typically developing 9- to 15-year-olds (n = 180) without psychological or behavioural disorders were enrolled in the Developmental Chronnecto-Genomics (DevCoG) study of healthy brain development and completed psychological assessments of trauma exposure and dissociation, along with a structural T1-weighted magnetic resonance imaging. We conducted univariate ANCOVA generalised linear models for each region of the default mode network examining the effects of trait dissociation, including scanner site, age, gender and trauma as covariates and correcting for multiple comparison. Results We found that the precuneus was significantly larger in children with higher levels of trait dissociation but this was not related to trauma exposure. The inferior parietal volume was smaller in children with higher levels of trauma but was not related to dissociation. No other regions of interest, including frontal and limbic structures, were significantly related to trait dissociation even before multiple comparison correction. Conclusions Trait dissociation reflects subtle cognitive disruptions worthy of study in healthy people and warrants study as a potential risk factor for psychopathology. This neurostructural study of trait dissociation in healthy children identified the precuneus as an essential brain region to consider in future dissociation research.

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.

Background: The brain-derived neurotrophic factor (BDNF) protein plays a prominent role in the capacity for neuroplastic change. However, a single nucleotide polymorphism at codon 66 of the BDNF gene results in significant reductions in neuroplastic change. Potentially, this polymorphism also contributes to the weaker somatosensory cortical activity that has been extensively reported in the neuroimaging literature on cerebral palsy (CP). Aims: The primary objective of this study was to use magnetoencephalography (MEG) to probe if BDNF genotype affects the strength of the somatosensory-evoked cortical activity seen within individuals with CP. Methods and procedures: and Procedures: Twenty individuals with CP and eighteen neurotypical controls participated. Standardized low resolution brain electromagnetic tomography (sLORETA) was used to image the somatosensory cortical activity evoked by stimulation of the tibial nerve. BDNF genotypes were determined from saliva samples. Outcomes and results: The somatosensory cortical activity was weaker in individuals with CP compared to healthy controls (P = 0.04). The individuals with a Val66Met or Met66Met BDNF polymorphism also showed a reduced response compared to the individuals without the polymorphism (P = 0.03), had higher GMFCS levels (P = 0.04), and decreased walking velocity (P = 0.05). Conclusions and implications: These results convey that BDNF genotype influences the strength of the somatosensory activity and mobility in individuals with CP. What this paper adds: Previous literature has extensively documented altered sensorimotor cortical activity in individuals with CP, which ultimately contributes to the clinical deficits in sensorimotor processing documented in this population. While some individuals with CP see vast improvements in their sensorimotor functioning following therapeutic intervention, others are clear non-responders. The underlying basis for this discrepancy is not well understood. Our study is the first to identify that a polymorphism at the gene that codes for brain derived neurotrophic factor (BDNF), a protein well-known to be involved in the capacity for neuroplastic change, may influence the altered sensorimotor cortical activity within this population. Potentially, individuals with CP that have a polymorphism at the BDNF gene may reflect those that have difficulties in achieving beneficial outcomes following intervention. Thus, these individuals may require different therapeutic approaches in order to stimulate neuroplastic change and get similar benefits from therapy as their neurotypical peers.

Abstract Background Entrainment of neural oscillations in occipital cortices by external rhythmic visual stimuli has been proposed as a novel therapy for patients with Alzheimer’s disease (AD). Despite this increased interest in visual neural oscillations in AD, little is known regarding their role in AD-related cognitive impairment and in particular during visuospatial processing. Methods We used source-imaged magnetoencephalography (MEG) and an established visuospatial processing task to elicit multi-spectral neuronal responses in 35 biomarker-confirmed patients on the AD spectrum and 20 biomarker-negative older adults. Neuronal oscillatory responses were imaged to the level of the cortex, and group classifications and neurocognitive relationships were modeled using logistic and linear regression, respectively. Results Visuospatial neuronal oscillations in the theta, alpha, and gamma ranges significantly predicted the classification of patients on the AD spectrum. Importantly, the direction of these effects differed by response frequency, such that patients on the AD spectrum exhibited weaker alpha-frequency responses in lateral occipital regions, and stronger gamma-frequency responses in the primary visual cortex, as compared to biomarker-negative older adults. In addition, alpha and gamma, but not theta, oscillations robustly predicted cognitive status (i.e., MoCA and MMSE scores), such that patients with neural responses that deviated more from those of healthy older adults exhibited poorer cognitive performance. Conclusions We find that the multi-spectral neural dynamics supporting visuospatial processing differentiate patients on the AD spectrum from cognitively normal, biomarker-negative older adults. Oscillations in the alpha and gamma bands also relate to cognitive status in ways that are informative for emerging clinical interventions.

Fluid reasoning is the ability to problem solve in the absence of prior knowledge and is commonly conceptualized as “non-verbal” intelligence. Importantly, fluid reasoning abilities rapidly develop throughout childhood and adolescence. Although numerous studies have characterized the neural underpinnings of fluid reasoning in adults, there is a paucity of research detailing the developmental trajectory of this neural processing. Herein, we examine longitudinal changes in the neural oscillatory dynamics underlying fluid intelligence in a sample of typically developing youths. A total of 34 participants age 10 to 16 years-old completed an abstract reasoning task during magnetoencephalography (MEG) on two occasions set one year apart. We found robust longitudinal optimization in theta, beta, and gamma oscillatory activity across years of the study across a distributed network commonly implicated in fluid reasoning abilities. More specifically, activity tended to decrease longitudinally in additional, compensatory areas such as the right lateral prefrontal cortex and increase in areas commonly utilized in mature adult samples (e.g., left frontal and parietal cortices). Importantly, shifts in neural activity were associated with improvements in task performance from one year to the next. Overall, the data suggest a longitudinal shift in performance that is accompanied by a reconfiguration of the functional oscillatory dynamics serving fluid reasoning during this important period of development.

People with HIV (PWH) may be particularly vulnerable to the psychological impacts of COVID-19. To assess this, participants were recruited from two established cohorts of PWH and HIV− adults with the available pre-pandemic baseline data and completed the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), Alcohol Use Identification Test (AUDIT), National Institute on Drug Abuse Quick Screen (NIDA-QS), and Pittsburgh Sleep Quality Index (PSQI) at two distinct intra-pandemic time periods. All outcomes were evaluated using generalized linear mixed models. In total, 87 participants completed all the questionnaires; 45 were PWH and 42 were HIV−. The pre-pandemic mean BDI-II, BAI, AUDIT and PSQI scores were higher in the PWH cohort. After the onset of the pandemic, the mean BDI-II, AUDIT and PSQI scores increased within the sample as a whole (p < 0.001, p = 0.029 and p = 0.046, respectively). The intra-pandemic mean BDI-II scores fell slightly for both groups and the AUDIT scores increased slightly for the PWH group and fell slightly for the HIV− group, but not significantly. The intra-pandemic PSQI scores increased sharply for both groups. The percentage of PWH and HIV− participants who moved into a more severe category of depression was identical (18%), but more PWH met the criteria for clinical evaluation. The BAI and NIDA-QS scores did not increase significantly. In conclusion, the measures of mental health symptoms and alcohol use increased in both groups after the onset of the pandemic. Although there were no significant differences in the changes between the groups, the PWH had higher baseline scores and the changes in this group had more clinical impacts.

Abstract Adolescence is a critical period for the development and refinement of several higher-level cognitive functions, including visual selective attention. Clinically, it has been noted that adolescents with cerebral palsy (CP) may have deficits in selectively attending to objects within their visual field. This study aimed to evaluate the neural oscillatory activity in the ventral attention network while adolescents with CP performed a visual selective attention task. Adolescents with CP (N = 14; Age = 15.7 ± 4 years; MACS I–III; GMFCS I–IV) and neurotypical (NT) adolescents (N = 21; Age = 14.3 ± 2 years) performed the Eriksen flanker task while undergoing magnetoencephalographic (MEG) brain imaging. The participants reported the direction of a target arrow that was surrounded by congruent or incongruent flanking arrows. Compared with NT adolescents, adolescents with CP had slower responses and made more errors regarding the direction of the target arrow. The MEG results revealed that adolescents with CP had stronger alpha oscillations in the left insula when the flanking arrows were incongruent. Furthermore, participants that had more errors also tended to have stronger alpha oscillatory activity in this brain region. Altogether these results indicate that the aberrant activity seen in the left insula is associated with diminished visual selective attention function in adolescents with CP.

The vast majority of individuals experience trauma within their lifetime. Yet, most people do not go on to develop clinical levels of psychopathology. Recently, studies have highlighted the potential protective effects of having larger amygdala and hippocampal volumes, such that larger volumes may promote adaptive functioning following trauma. However, research has not yet elucidated whether certain subregions of these stress-sensitive structures have specific protective effects. Herein, we examined the mediating effects of amygdala and hippocampal subregions on the relationship between traumatic exposure and concurrent or longitudinal changes in psychiatric symptom levels in typically developing youth (9–15 years of age). Using high-resolution T1-and T2-weighted structural MRI scans, we found that the volume of the right basolateral complex of the amygdala mediated associations between trauma exposure and internalizing symptoms. Specifically, greater levels of childhood trauma related to larger volumes, and larger volumes were associated with fewer internalizing symptoms. The volume of the right CA4/dentate gyrus (DG) of the hippocampus yielded similar mediation results, such that greater trauma was related to larger volumes, which in turn were associated with decreases in internalizing symptoms across time. These findings provide initial support for potentially protective effects of larger right amygdala and hippocampal subregion volumes against internalizing symptomology concurrently and longitudinally during adolescence.

Objective: To utilize magnetoencephalographic (MEG) brain imaging to examine potential changes in sensorimotor cortical oscillations after therapeutic power training in individuals with cerebral palsy (CP). Design: Cohort. Setting: Academic medical center. Participants: Individuals with CP (N=11; age=15.9±1.1 years; Gross Motor Function Classification System I- III) and neurotypical controls (NTs; N=16; age=14.6±0.8 years). Interventions: Participants with CP underwent 24 (8 weeks; 3 days a week) sessions of high-velocity lower extremity power training on a leg press. The NTs underwent single baseline MEG assessments. Main Outcome Measures: Pre-post bilateral leg press 1-repetition maximum and peak power production were used to assess the muscular performance changes. The 10-m walk and 1-minute walk tests were used to assess mobility changes. During MEG recordings, participants used their right leg to complete a goal-directed isometric target-matching task. Advanced beamforming methods were subsequently used to image the strength of the sensorimotor beta oscillatory power. Results: Before the therapeutic power training, the participants with CP had stronger beta sensorimotor cortical oscillations compared with the NT controls. However, the beta sensorimotor cortical oscillations were weaker and approximated the controls after the participants with CP completed the therapeutic power training protocol. There also was a link between the amount of improvement in leg peak power production and the amount of reduction in sensorimotor cortical oscillations seen after therapy. Conclusions: Therapeutic power training appears to optimize the sensorimotor cortical oscillations of individuals with CP, and these neuroplastic changes partly contribute to improvements in the leg peak power production of individuals with CP. Therapeutic power training might provide the key ingredients for beneficial neuroplastic change.

Adolescence is a critical period of structural and functional neural maturation among regions serving the cognitive control of emotion. Evidence suggests that this process is guided by developmental changes in amygdala and striatum structure and shifts in functional connectivity between subcortical (SC) and cognitive control (CC) networks. Herein, we investigate the extent to which such developmental shifts in structure and function reciprocally predict one another over time. 179 youth (9-15 years-old) completed annual MRI scans for three years. Amygdala and striatum volumes and connectivity within and between SC and CC resting state networks were measured for each year. We tested for reciprocal predictability of within-person and between-person changes in structure and function using random-intercept cross-lagged panel models. Within-person shifts in amygdala volumes in a given year significantly and specifically predicted deviations in SC-CC connectivity in the following year, such that an increase in volume was associated with decreased SC-CC connectivity the following year. Deviations in connectivity did not predict changes in amygdala volumes over time. Conversely, broader group-level shifts in SC-CC connectivity were predictive of subsequent deviations in striatal volumes. We did not see any cross-predictability among amygdala or striatum volumes and within-network connectivity measures. Within-person shifts in amygdala structure year-to-year robustly predicted weaker SC-CC connectivity in subsequent years, whereas broader increases in SC-CC connectivity predicted smaller striatal volumes over time. These specific structure function relationships may contribute to the development of emotional control across adolescence.

While magnetoencephalography (MEG) has proven to be a valuable and reliable tool for presurgical functional mapping of eloquent cortices for at least two decades, widespread use of this technique by clinicians has remained elusive. This modest application may be attributable, at least in part, to misunderstandings regarding the success rate of such mapping procedures, as well as the primary sources contributing to mapping failures. To address this, we conducted a retrospective comparison of sensorimotor functional mapping success rates in 141 patients with epilepsy and 75 tumor patients from the Center for MEG in Omaha, NE. Neurosurgical candidates either completed motor mapping (i.e., finger tapping paradigm), somatosensory mapping (i.e., peripheral stimulation paradigm), or both motor and somatosensory protocols during MEG. All MEG data underwent subsequent time-domain averaging and source localization of left and right primary motor (M1) and somatosensory (S1) cortices was conducted using a single equivalent dipole model. Successful mapping was determined based on dipole goodness of fit metrics ∼ 95%, as well as an accurate and conceivable spatial correspondence to precentral and postcentral gyri for M1 and S1, respectively. Our results suggest that mapping M1 in epilepsy and tumor patients was on average 94.5% successful, when patients only completed motor mapping protocols. In contrast, mapping S1 was successful 45–100% of the time in these patient groups when they only completed somatosensory mapping paradigms. Importantly, Z-tests for independent proportions revealed that the percentage of successful S1 mappings significantly increased to ∼ 94% in epilepsy patients who completed both motor/somatosensory mapping protocols during MEG. Together, these data suggest that ordering more comprehensive mapping procedures (e.g., both motor and somatosensory protocols for a collective sensorimotor network) may substantially increase the accuracy of presurgical functional mapping by providing more extensive data from which to base interpretations. Moreover, clinicians and magnetoencephalographers should be considerate of the major contributors to mapping failures (i.e., low SNR, excessive motion and magnetic artifacts) in order to further increase the percentage of cases achieving successful mapping of eloquent cortices.

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.

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.

Background: Alzheimer's disease (AD) is generally thought to spare primary sensory function; however, such interpretations have drawn from a literature that has rarely taken into account the variable cognitive declines seen in patients with AD. As these cognitive domains are now known to modulate cortical somatosensory processing, it remains possible that abnormalities in somatosensory function in patients with AD have been suppressed by neuropsychological variability in previous research. Methods: In this study, we combine magnetoencephalographic (MEG) brain imaging during a paired-pulse somatosensory gating task with an extensive battery of neuropsychological tests to investigate the influence of cognitive variability on estimated differences in somatosensory function between biomarker-confirmed patients on the AD spectrum and cognitively-normal older adults. Findings: We show that patients on the AD spectrum exhibit largely non-significant differences in somatosensory function when cognitive variability is not considered (p-value range: .020–.842). However, once attention and processing speed abilities are considered, robust differences in gamma-frequency somatosensory response amplitude (p

Successful interaction with one’s visual environment is paramount to developing and performing many basic and complex mental functions. Although major aspects of visual development are completed at an early age, other structural and functional components of visual processing appear to be dynamically changing across a much more protracted period extending into late childhood and adolescence. However, the underlying neurophysiological changes and cortical oscillatory dynamics that support maturation of the visual system during this developmental period remain poorly understood. The present study utilized magnetoencephalography (MEG) to investigate maturational changes in the neural dynamics serving basic visual processing during childhood and adolescence (ages 9–15, n = 69). Our key results included robust sex differences in alpha oscillatory activity within the left posterior parietal cortex, and sex-by-age interactions in gamma activity in the right lingual gyrus and superior parietal lobule. Hierarchical regression revealed that the peak frequency of both the alpha and gamma responses predicted response power in parietal regions above and beyond the noted effects of age and sex. These findings affirm the view that neural oscillations supporting visual processing develop over a much more protracted period, and illustrate that these maturational trajectories are influenced by numerous elements, including age, sex, and individual variation.

Background: Despite effective combination antiretroviral therapy (cART), people living with HIV (PLWH) remain at risk for developing neurocognitive impairment primarily due to systemic inflammation that persists despite virologic suppression, albeit the mechanisms underlying such inflammation are poorly understood. Methods: Herein, we evaluate the predictive capacity of the mitochondrial redox environment on circulating neuro- and T-lymphocyte-related inflammation and concomitant cognitive function in 40 virally-suppressed PLWH and 40 demographically-matched controls using structural equation modeling. We used state-of-the-art systems biology approaches including Seahorse Analyzer of mitochondrial function, electron paramagnetic resonance (EPR) spectroscopy to measure superoxide levels, antioxidant activity assays, and Meso Scale multiplex technology to quantify inflammatory proteins in the periphery. Findings: We observed disturbances in mitochondrial function and the redox environment in PLWH compared to controls, which included reduced mitochondrial capacity (t(76) = −1.85, p = 0.034, 95% CI: −∞,−0.13), elevated levels of superoxide (t(75) = 1.70, p = 0.047, 95% CI: 8.01 E 3, ∞) and alterations in antioxidant defense mechanisms (t(74) = 1.76, p = 0.041, 95% CI: −710.92, ∞). Interestingly, alterations in both superoxide- and hydrogen peroxide-sensitive redox environments were differentially predictive of neuro-, but not T-lymphocyte-related inflammatory profiles in PLWH and controls, respectively (ps < 0.026). Finally, when accounting for superoxide-sensitive redox pathways, neuroinflammatory profiles significantly predicted domain-specific cognitive function across our sample (β = −0.24, p = 0.034, 95% CI: −0.09, −0.004 for attention; β = −0.26, p = 0.018, 95% CI: −0.10, −0.01 for premorbid function). Interpretation: Our results suggest that precursors to neuroinflammation apparent in PLWH (i.e., mitochondrial function and redox environments) predict overall functionality and cognitive dysfunction and importantly, may serve as a proxy for characterizing inflammation-related functional decline in the future.

The encoding, maintenance, and subsequent retrieval of memories over short time intervals is an essential cognitive function. Load effects on the neural dynamics supporting the maintenance of short-term memories have been well studied, but experimental design limitations have hindered the study of similar effects during the encoding of information into online memory stores. Theoretically, the active encoding of complex visual stimuli into memory must also recruit neural resources in a manner that scales with memory load. Understanding the neural systems supporting this encoding load effect is of particular importance, as some patient populations exhibit difficulties specifically with the encoding, and not the maintenance, of short-term memories. Using magnetoencephalography, a visual sequence memory paradigm, and a novel encoding slope analysis, we provide evidence for a left-lateralized network of regions, oscillating in the alpha frequency range, that exhibit a progressive loading effect of complex visual stimulus information during memory encoding. This progressive encoding load effect significantly tracked the eventual retrieval of item-order memories at the single trial level, and neural activity in these regions was functionally dissociated from that of earlier visual networks. These findings suggest that the active encoding of stimulus information into short-term stores recruits a left-lateralized network of frontal, parietal, and temporal regions, and might be susceptible to modulation (e.g., using non-invasive stimulation) in the alpha band.

Working parents in are struggling to balance the demands of their occupation with those of childcare and homeschooling during the COVID-19 pandemic. Moreover, studies show that women are shouldering more of the burden and reporting greater levels of psychological distress, anxiety, and depression relative to men. However, research has yet to show that increases in psychological symptoms are linked to changes in stress during the pandemic. Herein, we conduct a small-N study to explore the associations between stress and psychological symptoms during the pandemic among mothers using structural equation modeling, namely latent change score models. Thirty-three mothers completed questionnaires reporting current anxious and depressive symptoms (Beck Anxiety and Depression Index, respectively), as well as stressful life experiences prior to-versus during the pandemic (Social Readjustment Rating Scale). Women endorsed significantly more stressful events during the pandemic, relative to the pre-pandemic period. Additionally, 58% of mothers scored as moderate-to-high risk for developing a stress-related physical illness in the near future because of their pandemic-level stress. Depressive symptoms were associated with the degree of change in life stress, whereas anxiety symptoms were more related to pre-pandemic levels of stress. The present study preliminarily sheds light on the nuanced antecedents to mothers’ experiences of anxious and depressive symptoms during the COVID-19 pandemic. Although further work is needed in larger, more diverse samples of mothers, this study highlights the potential need for appropriate policies, and prevention and intervention programs to ameliorate the effects of pandemics on mothers’ mental health.

Selective attention processes are critical to everyday functioning and are known to develop through at least young adulthood. Although numerous investigations have studied the maturation of attention systems in the brain, these studies have largely focused on the spatial configuration of these systems; there is a paucity of research on the neural oscillatory dynamics serving selective attention, particularly among youth. Herein, we examined the developmental trajectory of neural oscillatory activity serving selective attention in 53 typically developing youth age 9-to-16 years-old. Participants completed the classic arrow-based flanker task during magnetoencephalography, and the resulting data were imaged in the time-frequency domain. Flanker interference significantly modulated theta and alpha/beta oscillations within prefrontal, mid-cingulate, cuneus, and occipital regions. Interference-related neural activity also increased with age in the temporoparietal junction and the rostral anterior cingulate. Sex-specific effects indicated that females had greater theta interference activity in the anterior insula, whereas males showed differential effects in theta and alpha/beta oscillations across frontoparietal regions. Finally, males showed age-related changes in alpha/beta interference in the cuneus and middle frontal gyrus, which predicted improved behavioral performance. Taken together, these data suggest sexually-divergent developmental trajectories underlying selective attention in youth.

Even when movement outputs are identical, the neural responses supporting them might differ substantially in order to adapt to changing environmental contexts. Despite the essential nature of this adaptive capacity of the human motor system, little is known regarding the effects of contextual response (un)certainty on the neural dynamics known to serve motor processing. In this study, we use a novel bimanual motor task and neuroimaging with magnetoencephalography (MEG) to examine the effects of contextual response certainty on the dynamic neural responses that are important for proper movement. Significant neural responses were identified in the time-frequency domain at the sensor-level and imaged to the cortex using a spectrally resolved beamformer. Combined frequentist and Bayesian statistical testing between neural motor responses under certain and uncertain conditions indicated evidence for no conditional effect on the peri-movement beta desynchronization (18 – 28 Hz; -100 to 300 ms). In contrast, the movement-related gamma synchronization (MRGS; 66 – 86 Hz; -50 to 150 ms) exhibited a robust effect of motor certainty, such that increased contextual response certainty reduced the amplitude of this response. Interestingly, the peak frequency of the MRGS was unaffected by response certainty. These findings both advance our understanding of the neural processes required to adapt our movements under altered environmental contexts, and support the growing conceptualization of the MRGS as being reflective of ongoing higher cognitive processes during movement execution.