Working memory is an important cognitive process that develops throughout early life. During adolescence, there is marked improvement in this process that is associated with structural and functional brain changes. These changes have been linked to age; however, endogenous testosterone is thought to regulate structural and functional changes in the brain during puberty, with differential influences across adolescence into early adulthood. Thus, testosterone may have a direct impact on brain activity that is modulated by age. The current study aimed to examine this using a working memory functional magnetic resonance imaging (fMRI) task in adolescents and young adults. Saliva samples collected prior to scanning were assayed for endogenous testosterone levels. One hundred and forty-five typically developing participants (74 female), aged 12-25 yr, completed a working memory fMRI task. Results showed that, for the most difficult versus the 0back conditions, younger female participants (≤19) only had more deactivation in the anterior cingulate cortex with higher level of testosterone. In contrast, male participants showed increased activation in the precentral gyrus with higher testosterone, regardless of age. These findings indicate sex differences in how endogenous testosterone relates to the activity of different brain regions recruited during working memory. Furthermore, these associations vary across typical adolescent development.

Aging is accompanied by changes in brain architecture that alter the lateralization of functional networks. In this study, we examined how hemispheric specialization changes across the adult lifespan by analyzing resting-state fMRI and structural MRI data from 728 typical adults aged 18 to 88 years. Using the Language-and-Memory Network atlas, we quantified regional asymmetries in functional connectivity along the cortex's principal gradient, and normalized regional volumes across 37 bilateral regions. We identified two distinct age-related asymmetry trajectories: one pattern revealed a bilateralization of language-dominant regions, while the other showed increasing leftward specialization in multimodal regions associated with memory and language. These opposing patterns emerged around midlife and were linked to performance in language production tasks. By integrating connectivity gradients, structural asymmetries, and behavioral data, our findings provide new evidence for a dual mechanism reshaping functional brain lateralization with age and demonstrate the utility of resting-state metrics in tracking these shifts.

Developmental Language Disorder (DLD) is a common neurodevelopmental condition characterized by not only significant difficulty with language learning, comprehension, and expression but also with executive, procedural and/or motor functions. The understanding of the brain abnormalities in DLD remains largely unclear and functional MRI (fMRI) studies have largely focused on the language network. Using resting-state fMRI, we investigated whole-brain functional connectivity (FC) in 22 children with DLD and 23 with typical language development (TD), aged 7-to-13-years. Using a non-parametric network-based statistics approach, we found that children with DLD had an extensive network of lower FC across the whole brain, compared to the TD children. In particular, the sensorimotor (SM), cognitive control (CC) and default-mode (DM) networks included the largest amounts of altered FC. In detail, FC links within the DM network and between the SM and DM networks, and between the SM and CC networks were the most altered. No FC was found to be significantly higher in the children with DLD than in their peers with TD. To our knowledge, this is the first investigation of resting-state FC in children with DLD, showing widespread functional brain abnormalities that are not limited to the language network, but rather involve networks supporting other cognitive and motor functions. Such extensive functional abnormalities offer a potential explanation for the other cognitive and motor impairments characterizing DLD.

Rationale Cannabis is one of the most widely used psychoactive drugs in the United States, yet its long-term effects on brain function remain poorly understood. Prior resting-state functional connectivity (rsFC) studies have yielded inconsistent findings, likely due to variability in cannabis use thresholds, a predominant focus on younger populations, and region-of-interest (ROI)-based approaches limited to a small number of a priori brain regions. Objectives We aimed to address these limitations by examining rsFC across the entire brain using an atlas-based, whole-brain, ROI-to-ROI approach in a middle-aged sample (mean age = 41.64 years) of individuals with chronic cannabis use (CCU) and a demographically matched group of controls who did not use cannabis or other illicit substances. Based on the known neuroanatomical distribution of type 1 cannabinoid receptors (CB1Rs), we hypothesized that regions with high CB1R density would be the most affected. However, given our whole-brain approach, we were also sensitive to other regions that may exhibit altered connectivity. Methods Using the Automated Anatomical Labeling (AAL) atlas, we computed rsFC matrices across 116 brain regions in 22 adults with CCU and 23 demographically matched controls. Results The CCU group showed decreased rsFC (p(FDR)< .05) between the right cerebellar Crus II and the left pars triangularis, bilateral pars orbitalis, left superior frontal gyrus, left middle temporal gyrus, and left inferior temporal gyrus compared with the control group. The CCU group also had lower rsFC (p(FDR) < .05) between the right cerebellar Crus I and the left pars triangularis compared with controls. Conclusions Our findings revealed disrupted rsFC between cerebellar and prefrontal-temporal regions in the CCU group. This study advances the literature by using an atlas-based, whole-brain, ROI-to-ROI approach in a middle-aged sample with sustained cannabis use. Future studies should integrate neuropsychological assessments and task-based paradigms to understand how such alterations in rsFC affect behavioral outcomes.

There is a spike in reward sensitivity during adolescence. Delay discounting involves subjective valuation of a reward in context of when it is gained. This study sought to assess if dynamic functional connectivity between the cognitive control network and the amygdala could predict delay discounting in adolescents and young adults. 448 participants were separated into three age groups, including younger and older adolescents and young adults. A sliding-window approach was used to calculate dynamic functional connectivity between the left/right amygdala and the cognitive control network. Hierarchical models were run for each age group to determine if dynamic functional connectivity could predict delay discounting behavior in two delayed amount conditions above and beyond age and sex. Results showed that dynamic functional connectivity between the left, but not the right, amygdala and cognitive control network significantly predicted delay discounting in the larger amount condition for older adolescents. No significant results were found for the smaller amount condition in older adolescents or either condition in younger adolescents or adults. Stronger dynamic functional connectivity indicated a preference for immediate rewards during a larger amount condition in older adolescents only.

Developmental Language Disorder (DLD) is a common neurodevelopmental condition characterized by significant difficulty with language learning, comprehension, and expression. The neurocognitive bases of DLD are underspecified but are thought to be related, in part, to altered basal ganglia (BG). The BG are known to have a high level of brain iron, which contributes to myelination and dopaminergic pathways among other physiological mechanisms. In this study, we investigated whether a brain iron imbalance might contribute to the altered BG function that characterizes individuals with DLD. Using a T2*-weighted signal, we compared BG brain iron levels in 7-to-13-year olds with DLD and typical language development (TD). We found a significant age-by-group interaction in the caudate with children with DLD showing a positive association between brain iron and age, which was not the case in TD children. A sex-by-age-by-group interaction was also reported in the right putamen and right nucleus accumbens. Higher brain iron in the caudate was associated with poorer story recall; there was no relation between brain iron levels and recall of word lists. This first-ever investigation of brain iron levels in individuals with DLD provides preliminary evidence of an abnormal developmental trajectory of brain iron balance and offers a potential explanation for the altered BG function and verbal impairments that characterize DLD.

Childhood and adolescence are sensitive periods for the refinement of increasingly complex executive and social functions. A particularly important skill is the ability to navigate and interpret interpersonal relationships, which is reflected in part by the maturation of distributed resting networks. However, the relationships between negative social perceptions in youth and long-term alterations in between-network connectivity are limited. To partially address this gap, we utilized longitudinal resting-state functional magnetic resonance imaging (N = 93) with social pain measures from the NIH Toolbox Emotion Battery to determine the links between negative social perceptions on the trajectory of connectivity between the salience, frontoparietal, and default mode networks in the triple network model of psychopathology. Higher scores of perceived hostility, but not perceived rejection, tended to increase functional connectivity between the salience and both frontoparietal and default mode networks over time. These results suggest that more direct forms of threat (hostility) may be more impactful than rejection (limited desired social interactions), highlighting the importance of a dimensional approach to understanding developmental trajectories. While these connectivity changes align with several aberrant connectivity signatures observed across mental health disorders, these phenotypes are not pathognomonic of psychopathology and may reflect adaptive mechanisms in the context of social adversity.

It is well accepted that the brain is functionally organized into multiple networks and extensive literature has demonstrated that the organization of these networks shows major changes during adolescence. Yet, there is limited option for a reference functional brain atlas derived from typically-developing adolescents, which is problematic as the reliable identification of functional brain networks crucially depends on the use of such reference functional atlases. In this context, we utilized resting-state functional MRI data from 1,391 typically-developing youth aged 8-17 years to create an adolescent-specific reference atlas of functional brain networks. We further investigated the impact of age and sex on these networks. Using a multiscale individual component clustering algorithm, we identified 24 reliable functional brain networks, classified within six domains: Default-Mode (5 networks), Control (4 networks), Salience (3 networks), Attention (4 networks), Somatomotor (5 networks), and Visual (3 networks). We identified reliable and large effects of age on the spatial topography of these majority of networks, as well as on the functional network connectivity. Sex effects were not as widespread. We created a novel brain atlas, named Dev-Atlas, focused on a typically-developing sample, with the hope that this atlas can be used in future developmental neuroscience studies.

Facial expressions convey important social information and can initiate behavioral change through the processing and understanding of emotions. However, while this ability is known to evolve throughout development, it remains unclear whether this ability differs between girls and boys or how other variables such as level of anxiety can modulate it. Furthermore, understanding the underlying neural mechanisms of facial expression processing and how they are linked by sex and anxiety during development is essential, as alterations in this processing have been associated with psychiatric disorders. Herein, 191 typically developing youth (6- to 15-years old) completed an implicit face processing task involving three facial expressions (angry, happy, and neutral) during functional magnetic resonance imaging. We conducted linear models on the fMRI data to investigate the impact sex and anxiety on brain responses to emotional faces, accounting for age. Our findings indicated a significant anxiety-by-sex interaction in a posterior network covering bilateral visual and medial temporal cortices during the happy > neutral contrast. Specifically, girls with higher anxiety showed weaker activation while boys showed the opposite pattern. These findings suggest that the inter-subject variability reported in typically developing individuals in response to facial emotions may be related to many factors, including sex and anxiety level.

Visual processing relies on the identification of both local and global features of visual stimuli. While well investigated at the behavioral level, the underlying brain mechanisms are less clear, especially in the context of aging. Using fMRI, we aimed to investigate the neural correlates underlying local and global processing in early and late adulthood. We recruited 77 healthy adults aged 19-77 who completed a visual search task based on 2-level hierarchical stimuli made of squares and/or circles. Participants were instructed to detect a target (a square) at either a local (small) or global (large) level of a hierarchical geometrical form, in the presence or absence of other hierarchical geometrical forms (distractors). At the behavioral level, we revealed high accuracy for all participants, but older participants were slower to detect local targets, specifically in presence of distractors. At the brain level, while both local and global processing were associated with occipital activation, local processing also recruited the anterior insula and dorsal anterior cingulate cortex, that are core regions of the salience network. However, while the presence of distractors in the local condition elicited specifically stronger activation within the right anterior insula for the young group, it was not observed for older participants. In addition, older participants showed less activation than younger participants in the occipital cortex, especially for the most complex conditions. Our findings suggest that the brain correlates underlying local and global processing change with aging, especially for complex visual patterns. These results are discussed in terms of top-down reduction effects from the salience network on primary visual areas, that may lead to specific difficulties to process local visual details in older adults.

Emotional intelligence includes an assortment of factors related to emotion function. Such factors involve emotion recognition (in this case via facial expression), emotion trait, reactivity, and regulation. We aimed to investigate how the subjective appraisals of emotional intelligence (i.e. trait, reactivity, and regulation) are associated with objective emotion recognition accuracy, and how these associations differ between young and older adults. Data were extracted from the CamCAN dataset (189 adults: 57 young/118 older) from assessments measuring these emotion constructs. Using linear regression models, we found that greater negative reactivity was associated with better emotion recognition accuracy among older adults, though the pattern was opposite for young adults with the greatest difference in disgust and surprise recognition. Positive reactivity and depression level predicted surprise recognition, with the associations significantly differing between the age groups. The present findings suggest the level to which older and young adults react to emotional stimuli differentially predicts their ability to correctly identify facial emotion expressions. Older adults with higher negative reactivity may be able to integrate their negative emotions effectively in order to recognize other’s negative emotions more accurately. Alternatively, young adults may experience interference from negative reactivity, lowering their ability to recognize other’s negative emotions.

Importance Maternal tobacco use during pregnancy (MTDP) remains a major public health challenge. However, the complete spectrum of effects of MTDP is not fully understood. Objectives To examine the longitudinal associations of MTDP and children's brain morphometric subcortical volume and gray-white matter contrast (GWC) development. Design, Setting, and Participants Cohort study of children aged 9 to 10 years at wave 1 (October 2016 to October 2018) and at a 2-year follow-up (wave 2; August 2018 to January 2021; aged 11-12 years) across 21 US sites in the Adolescent Brain Cognitive Development (ABCD) Study. Data were analyzed from October 2023 to October 2024. Exposure MTDP. Main outcomes and measures Morphometric brain measures of subcortical volume and GWC. Results Among the 11 448 children (51.5% male; 13.1% Black; 24.0% Hispanic; and 52.9% White) at wave 1, 1607 (16.6%; 95% CI, 13.0%-20.2%) were identified with MTDP exposure. At wave 1, children with MTDP exposure (vs no exposure) exhibited lower GWC in widespread brain regions primarily located in the frontal (eg, superior frontal; regression coefficient [B] = -0.0019; SE, 0.0006; P = .004), parietal (eg, supramarginal; B = -0.0021; SE, 0.0007; P = .002) and temporal lobes (eg, middle temporal; B = -0.0024; SE, 0.0007; P < .001). These differences in GWC continued to be significant at wave 2. In regard to subcortical volume, children with MTDP exposure demonstrated smaller volume of the lateral ventricle (B = -257.5; SE, 78.6; P = .001) and caudate (B = -37.7; SE, 14.0; P = .01) in the left hemisphere at wave 1, and lower volume of the caudate in both left (B = -48.7; SE, 15.9; P = .002) and right hemisphere (B = -45.5; SE, 16.1; P = .01) at wave 2. Conclusions and Relevance This cohort study found that MTDP exposure was associated with lower GWC across the whole cortex and smaller caudate nuclei volume compared with no exposure, signifying the importance of preventing MTDP and necessitating further research on this topic.

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.

Creativity, or divergent thinking, is essential to and supported by cognitive functions necessary for everyday tasks. The current study investigates divergent thinking and its neural mechanisms from adolescence to late adulthood. To do this, 180 healthy participants completed a creativity task called the egg task including 86 adolescents (mean age (SD) = 13.62 (1.98)), 52 young adults (24.92 (3.60), and 42 older adults (62.84 (7.02)). Additionally, a subsample of 111 participants completed a resting-state fMRI scan. After investigating the impact of age on different divergent thinking metrics, we investigated the impact of age on the association between divergent thinking and resting-state functional connectivity within and between major resting-state brain networks associated with creative thinking: the DMN, ECN, and SN. Adolescents tended to be less creative than both young and older adults in divergent thinking scores related to expansion creativity, and not in persistent creativity, while young and older adults performed relatively similar. We found that adolescents' functional integrity of the executive control network (ECN) was positively associated with expansion creativity, which was significantly different from the negative association in both the young and older adults. These results suggest that creative performance and supporting brain networks change throughout the lifespan.

The increasing incidence of age-related comorbidities in people with HIV (PWH) has led to accelerated aging theories. Functional neuroimaging research, including functional connectivity (FC) using resting-state functional magnetic resonance imaging (rs-fMRI), has identified neural aberrations related to HIV infection. Yet little is known about the relationship between aging and resting-state FC in PWH. This study included 86 virally suppressed PWH and 99 demographically matched controls spanning 22-72 years old who underwent rs-fMRI. The independent and interactive effects of HIV and aging on FC were investigated both within- and between-network using a 7-network atlas. The relationship between HIV-related cognitive deficits and FC was also examined. We also conducted network-based statistical analyses using a brain anatomical atlas (n = 512 regions) to ensure similar results across independent approaches. We found independent effects of age and HIV in between-network FC. The age-related increases in FC were widespread, while PWH displayed further increases above and beyond aging, particularly between-network FC of the default-mode and executive control networks. The results were overall similar using the regional approach. Since both HIV infection and aging are associated with independent increases in between-network FC, HIV infection may be associated with a reorganization of the major brain networks and their functional interactions in a manner similar to aging.

Eating disorders (EDs) are psychiatric disorders with a neurobiological basis. ED-specific neuropsychological and brain characteristics have been identified, but often in individuals in the acute phase or recovered from EDs, precluding an understanding of whether they are correlates and scars of EDs vs. predisposing factors. Although familial high-risk (FHR) studies are available across other disorders, this study design has not been used in EDs. We carried out the first FMH study in EDs, investigating healthy offspring of women with EDs and controls. We preliminarily aimed to investigate ED-related neurocognitive and brain markers that could point to predisposing factors for ED. Sixteen girls at FHR for EDs and twenty control girls (age range: 8–15), completed neuropsychological tests assessing executive functions. Girls also underwent a resting-state fMRI scan to quantify functional connectivity (FC) within resting-state networks. Girls at FHR for EDs performed worse on a cognitive flexibility task compared with controls (F = 5.53, p = 0.02). Moreover, they showed different FC compared with controls in several resting-state networks (p < 0.05 FDR-corrected). Differences identified in cognitive flexibility and in FC are in line with those identified in individuals with EDs, strongly pointing to a role as potential endophenotypes of EDs.

Aging engenders neuroadaptations, generally reducing specificity and selectivity in functional brain responses. Our investigation delves into the functional specialization of brain hemispheres within language-related networks across adulthood. In a cohort of 728 healthy adults spanning ages 18 to 88, we modeled the trajectories of inter-hemispheric asymmetry concerning the principal functional gradient across 37 homotopic regions of interest (hROIs) of an extensive language network, known as the Language-and-Memory Network. Our findings reveal that over two-thirds of Language-and-Memory Network hROIs undergo asymmetry changes with age, falling into two main clusters. The first cluster evolves from left-sided specialization to right-sided tendencies, while the second cluster transitions from right-sided asymmetry to left-hemisphere dominance. These reversed asymmetry shifts manifest around midlife, occurring after age 50, and are associated with poorer language production performance. Our results provide valuable insights into the influence of functional brain asymmetries on language proficiency and present a dynamic perspective on brain plasticity during the typical aging process.

Optimism bias is the tendency to believe desirable events are more likely to happen than undesirable ones. People often display optimistic biases for themselves (personal optimism), but also for members of groups they like or identify with (social optimism). However, the neural bases of and connections between these two concepts are poorly understood. The present study hence used both questionnaires and a social optimism task performed during magnetic resonance imaging to investigate how network connectivity associates with personal and social optimism biases. Using sparse canonical correlation analysis, we found that a behavioral dimension that included both in-group optimism bias and personal optimism bias was positively associated with a dimension of network connectivity. This dimension comprised two networks with positive weights (dorsal precuneus-related default mode network and dorsal sensorimotor network), and three with negative weights (including parts of the salience and central executive networks). Our findings indicate that connectivity in networks adjacent to the temporoparietal junction favors propagation of both personal and social optimism biases. Meanwhile, low connectivity in more frontal networks associated with more complex cognition may also further such propagation.

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.

Introduction Healthy aging is typically associated with cognitive decline and lower negative affect. Previous studies have reported a significant and opposite role of the amygdala in relation to cognitive and affective processing in early adulthood. However, it remains unclear how aging impacts such relationships. Methods Seventy-seven healthy participants including 40 young (mean age = 26.1 years) and 37 older (mean age = 61.8 years) adults completed a functional MRI Affective Stroop (AS) paradigm, a cognitive battery, and the state-trait anxiety inventory. The AS fMRI paradigm included “task trials,” where participants saw a positively, negatively or neutrally valenced distractor image, followed by a numerical display, followed by another distractor image. We extracted signal in both amygdalas during the AS Task and compared it across all conditions and age group. We further conducted moderation analyses to investigate the impact of aging on the relationship between amygdala activation and anxiety or cognitive variables, respectively. Results At the behavioral level, older participants showed lower trait anxiety than the younger adults (p = 0.002). While overall slower during the AS task, older adults achieved comparable accuracy during the AS task, relative to the younger adults. At the brain level, we revealed a significant interaction between age group and trial types in amygdala activation (F = 4.9, p = 0.03), with the older group showing stronger activation during the most complex trials compared to the passive view trials. We further found that age significantly modulated the relationship between anxiety and the left amygdala activation during negative stimuli, where the younger adults showed a positive association while the older adults showed a negative association. Age also significantly modulated the relationship between verbal fluency and left amygdala activation during incongruent versus view trials, with the younger adults showing a negative association and the older adults showing a positive association. Discussion The current study suggests that the role of the amygdala on both emotional processing and cognitive traits changes between early and late adulthood.