Youth Generalized Anxiety and Brain Activation States During Socioemotional Processing.

Importance: The brain enters distinct activation states to support differential cognitive and emotional processes, but little is known about how brain activation states differ in youths with clinical anxiety.

Objective: To characterize brain activation states during socioemotional processing (movie stimuli) and assess associations between state characteristics and movie features and anxiety symptoms.

Design, Setting, And Participants: The Healthy Brain Network is an ongoing cross-sectional study of individuals aged 5 to 21 years experiencing difficulties in school, of whom approximately 45% met criteria for a lifetime anxiety disorder diagnosis.

Prenatal social disadvantage is associated with alterations in functional networks at birth.

Childhood exposure to social disadvantage is a major risk factor for psychiatric disorders and poor developmental, educational, and occupational outcomes, presumably because adverse exposures alter the neurodevelopmental processes that contribute to risk trajectories. Yet, given the limited social mobility in the United States and other countries, childhood social disadvantage is frequently preceded by maternal social disadvantage during pregnancy, potentially altering fetal brain development during a period of high neuroplasticity through hormonal, microbiome, epigenetic, and immune factors that cross the placenta and fetal blood-brain barrier. The current study examines prenatal social disadvantage to determine whether these exposures in utero are associated with alterations in functional brain networks as early as birth.

Quantifying brain development in the HEALthy Brain and Child Development (HBCD) Study: The magnetic resonance imaging and spectroscopy protocol.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life.

Early Life Neuroimaging: The Generalizability of Cortical Area Parcellations Across Development.

The cerebral cortex comprises discrete cortical areas that form during development. Accurate area parcellation in neuroimaging studies enhances statistical power and comparability across studies. The formation of cortical areas is influenced by intrinsic embryonic patterning as well as extrinsic inputs, particularly through postnatal exposure.

Precision Functional Mapping to Advance Developmental Psychiatry Research.

Many psychiatric conditions have their roots in early development. Individual differences in prenatal brain function (which is influenced by a combination of genetic risk and the prenatal environment) likely interact with individual differences in postnatal experience, resulting in substantial variation in brain functional organization and development in infancy. Neuroimaging has been a powerful tool for understanding typical and atypical brain function and holds promise for uncovering the neurodevelopmental basis of psychiatric illness; however, its clinical utility has been relatively limited thus far.

Measuring neuroplasticity in human development: the potential to inform the type and timing of mental health interventions.

Neuroplasticity during sensitive periods, the molecular and cellular process of enduring neural change in response to external stimuli during windows of high environmental sensitivity, is crucial for adaptation to expected environments and has implications for psychiatry. Animal research has characterized the developmental sequence and neurobiological mechanisms that govern neuroplasticity, yet gaps in our ability to measure neuroplasticity in humans limit the clinical translation of these principles. Here, we present a roadmap for the development and validation of neuroimaging and electrophysiology measures that index neuroplasticity to begin to address these gaps.

Brexanolone Treatment in a Real-World Patient Population: A Case Series and Pilot Feasibility Study of Precision Neuroimaging.

Purpose/background: Brexanolone is approved for postpartum depression (PPD) by the United States Food and Drug Administration. Brexanolone has outperformed placebo in clinical trials, but less is known about the efficacy in real-world patients with complex social and medical histories. Furthermore, the impact of brexanolone on large-scale brain systems such as changes in functional connectivity (FC) is unknown.

Neighborhood Resource Deprivation as a Predictor of Bullying Perpetration and Resource-Driven Conduct Symptoms.

Objective: Resource deprivation is linked to systemic factors that disproportionately impact historically marginalized communities, and theoretical work suggests that resource deprivation may increase risk for bullying behaviors. Bullying perpetration is an intransigent social problem and an early risk factor that perpetuates the school-to-prison pipeline. This study explored how resource deprivation (family- and neighborhood-level metrics) was associated with early childhood bullying behaviors and clinician-rated symptoms of psychopathology, while accounting for other known risk factors (early life stressors, traumatic events, parental arrest, domestic violence).

Social anxiety moderates the association between adolescent irritability and bully perpetration.

Background: Preliminary work suggests anxiety moderates the relationship between irritability and bullying. As anxiety increases, the link between irritability and perpetration decreases. We hypothesize that any moderation effect of anxiety is driven by social anxiety symptoms.

Functional parcellation of the neonatal cortical surface.

The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that existing parcellations, including surface-based parcels derived from older samples as well as volume-based neonatal parcels, are a poor fit for neonatal surface data.

Higher Intersubject Variability in Neural Response to Narrative Social Stimuli Among Youth With Higher Social Anxiety.

Objective: Social anxiety is associated with alterations in socioemotional processing, but the pathophysiology remains poorly understood. Movies present an opportunity to examine more naturalistic socioemotional processing by providing narrative and sensory context to emotion cues. This study aimed to characterize associations between neural response to contextualized social cues and social anxiety symptoms in children.

Functional parcellation of the neonatal brain.

The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that adult- and older infant-derived parcels are a poor fit with neonatal data, emphasizing the need for neonatal-specific parcels.

Neonatal neural responses to novelty related to behavioral inhibition at 1 year.

Behavioral inhibition (BI), an early-life temperament characterized by vigilant responses to novelty, is a risk factor for anxiety disorders. In this study, we investigated whether differences in neonatal brain responses to infrequent auditory stimuli relate to children's BI at 1 year of age. Using functional magnetic resonance imaging (fMRI), we collected blood-oxygen-level-dependent (BOLD) data from = 45 full-term, sleeping neonates during an adapted auditory oddball paradigm and measured BI from = 27 of these children 1 year later using an observational assessment.

Multi-echo Acquisition and Thermal Denoising Advances Precision Functional Imaging.

The characterization of individual functional brain organization with Precision Functional Mapping has provided important insights in recent years in adults. However, little is known about the ontogeny of inter-individual differences in brain functional organization during human development. Precise characterization of systems organization during periods of high plasticity is likely to be essential for discoveries promoting lifelong health.

A Novel Cognitive Training Program Targets Stimulus-Driven Attention to Alter Symptoms, Behavior, and Neural Circuitry in Pediatric Anxiety Disorders: Pilot Clinical Trial.

Pediatric anxiety disorders are associated with increased stimulus-driven attention (SDA), the involuntary capture of attention by salient stimuli. Increased SDA is linked to increased activity in the right ventrolateral prefrontal cortex (rVLPFC), especially in the portion corresponding to the ventral attention network (VAN). In this study, we present a small clinical trial using a novel attention training program designed to treat pediatric anxiety by decreasing SDA and activity in the rVLPFC.

Novel mechanism-based treatments for pediatric anxiety and depressive disorders.

Pediatric anxiety and depressive disorders are common, can be highly impairing, and can persist despite the best available treatments. Here, we review research into novel treatments for childhood anxiety and depressive disorders designed to target underlying cognitive, emotional, and neural circuit mechanisms. We highlight three novel treatments lying along a continuum relating to clinical impact of the disorder and the intensity of clinical management required.

Large-scale encoding of emotion concepts becomes increasingly similar between individuals from childhood to adolescence.

Humans require a shared conceptualization of others' emotions for adaptive social functioning. A concept is a mental blueprint that gives our brains parameters for predicting what will happen next. Emotion concepts undergo refinement with development, but it is not known whether their neural representations change in parallel.

A somato-cognitive action network alternates with effector regions in motor cortex.

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations, despite evidence for concentric functional zones and maps of complex actions. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action and physiological control, arousal, errors and pain.

Baby Brains at Work: How Task-Based Functional Magnetic Resonance Imaging Can Illuminate the Early Emergence of Psychiatric Risk.

Psychiatric disorders are complex, often emerging from multiple atypical processes within specified domains over the course of development. Characterizing the development of the neural circuits supporting these domains may help break down the components of complex disorders and reveal variations in functioning associated with psychiatric risk. This review highlights the current and potential role of infant task-based functional magnetic resonance imaging (fMRI) in elucidating the developmental neurobiology of psychiatric disorders.

Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group.

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls.

Whole-Brain Resting-State Functional Connectivity Patterns Associated With Pediatric Anxiety and Involuntary Attention Capture.

Background: Pediatric anxiety disorders are linked to dysfunction in multiple functional brain networks, as well as to alterations in the allocation of spatial attention. We used network-level analyses to characterize resting-state functional connectivity (rs-fc) alterations associated with 1) symptoms of anxiety and 2) alterations in stimulus-driven attention associated with pediatric anxiety disorders. We hypothesized that anxiety was related to altered connectivity of the frontoparietal, default mode, cingulo-opercular, and ventral attention networks and that anxiety-related connectivity alterations that include the ventral attention network would simultaneously be related to deviations in stimulus-driven attention.

Neurocircuitry of treatment in anxiety disorders.

Background: Understanding how treatments change neurobiology is critical to developing predictors of treatment response. This is especially true for anxiety disorders-the most common psychiatric disorders across the lifespan. With this in mind, we examined neurofunctional predictors of treatment response and neurofunctional changes associated with treatment across anxiety disorders.

Maturation of large-scale brain systems over the first month of life.

The period immediately after birth is a critical developmental window, capturing rapid maturation of brain structure and a child's earliest experiences. Large-scale brain systems are present at delivery, but how these brain systems mature during this narrow window (i.e.

Network-specific selectivity of functional connections in the neonatal brain.

The adult human brain is organized into functional brain networks, groups of functionally connected segregated brain regions. A key feature of adult functional networks is long-range selectivity, the property that spatially distant regions from the same network have higher functional connectivity than spatially distant regions from different networks. Although it is critical to establish the status of functional networks and long-range selectivity during the neonatal period as a foundation for typical and atypical brain development, prior work in this area has been mixed.