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. We sought to explicate the moderating effect of anxiety, while clarifying relations to other aggressive behaviors. METHODS: A sample of adolescents (n = 169, mean = 12.42 years of age) were assessed using clinician rated assessments of anxiety, parent reports of irritability and bullying behaviors (perpetration, generalized aggression, and victimization). Correlations assessed zero-order relations between variables, and regression-based moderation analyses were used to test interactions. Johnson-Neyman methods were used to represent significant interactions. RESULTS: Irritability was significantly related to bullying (r = .403, p < .001). Social, but not generalized, anxiety symptoms significantly moderated the effect of irritability on bully perpetration (t(160) = -2.94, b = -.01, p = .0038, ΔR2 = .0229, F(1, 160) = 8.635). As social anxiety symptoms increase, the link between irritability and perpetration decreases. CONCLUSIONS: Understanding how psychopathology interacts with social behaviors is of great importance. Higher social anxiety is linked to reduced relations between irritability and bullying; however, the link between irritability and other aggression remains positive. Comprehensively assessing how treatment of psychopathology impacts social behaviors may improve future intervention.

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). METHOD: Participants (306 children, mean age = 4.45 years) were enrolled in a longitudinal study (Preschool Depression Study) where demographics, clinician-rated assessments of psychopathology, and parent reports of social functioning were collected. Measures of bullying behaviors (bullying perpetration, generalized aggression, and victimization) were constructed. A cross-sectional approach was employed, and analyses examined the interrelations between race, bullying-related behaviors, resource deprivation, and psychopathology, while accounting for confounding variables, at the baseline assessment time point. RESULTS: The bullying measure showed acceptable model fit (comparative fit index = 0.956, Tucker-Lewis index = 0.945, root mean square error of approximation = 0.061, standardized root mean residual = 0.052, normed χ2 ratio = 2). Neighborhood resource deprivation was more strongly associated with bullying perpetration (r = 0.324, p < .001) than generalized aggression (r = 0.236, Williams t303 = 2.11, p = .036) and remained significant when controlling for other known risk factors (parental arrests, domestic violence, stressors, traumas) and demographic factors. Bullying perpetration was linked with racial category, but the relation was fully mediated by neighborhood resource deprivation. Linear regression including bullying behaviors and symptoms of clinical psychopathology suggested that resource deprivation specifically led to increases in bullying perpetration (t = 2.831, p = .005) and clinician-rated symptoms of conduct disorder (t = 2.827, p = .005), which were attributable to increased rates of resource-driven conduct symptoms (bullies, lies to obtain goods, stolen without confrontation). CONCLUSION: Resource deprivation is strongly and specifically associated with increases in bullying perpetration. Children growing up in impoverished neighborhoods show significant increases in resource-driven conduct behaviors, yet interventions often target individual-level factors. These results highlight the need to target social inequity to reduce bullying perpetration and suggest that interventions targeting neighborhoods should be tested to reduce bullying in early childhood. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. One or more of the authors of this paper received support from a program designed to increase minority representation in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. We actively worked to promote sex and gender balance in our author group. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list.

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. METHODS/PROCEDURES: We tracked changes in depressive symptoms across a diverse group of patients who received brexanolone at a large medical center. Edinburgh Postnatal Depression Scale (EPDS) scores were collected through chart review for 17 patients immediately prior to infusion through approximately 1 year postinfusion. In 2 participants, we performed precision functional neuroimaging (pfMRI), including before and after treatment in 1 patient. pfMRI collects many hours of data in individuals for precision medicine applications and was performed to assess the feasibility of investigating changes in FC with brexanolone. FINDINGS/RESULTS: The mean EPDS score immediately postinfusion was significantly lower than the mean preinfusion score (mean change [95% CI]: 10.76 [7.11-14.40], t (15) = 6.29, P < 0.0001). The mean EPDS score stayed significantly lower at 1 week (mean difference [95% CI]: 9.50 [5.23-13.76], t (11) = 4.90, P = 0.0005) and 3 months (mean difference [95% CI]: 9.99 [4.71-15.27], t (6) = 4.63, P = 0.0036) postinfusion. Widespread changes in FC followed infusion, which correlated with EPDS scores. IMPLICATIONS/CONCLUSIONS: Brexanolone is a successful treatment for PPD in the clinical setting. In conjunction with routine clinical care, brexanolone was linked to a reduction in symptoms lasting at least 3 months. pfMRI is feasible in postpartum patients receiving brexanolone and has the potential to elucidate individual-specific mechanisms of action.

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. We next derive a set of 283 cortical surface parcels from a sample of n = 261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies.

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. We review cognitive training, which involves the lowest risk and may be applicable for problems with mild to moderate impact; psychotherapy, which includes a higher level of clinical involvement and may be sufficient for problems with moderate impact; and brain stimulation, which has the highest potential risks and is therefore most appropriate for problems with high impact. For each treatment, we review the specific underlying cognitive, emotional, and brain circuit mechanisms that are being targeted, whether treatments modify those underlying mechanisms, and efficacy in reducing symptoms. We conclude by highlighting future directions, including the importance of work that leverages developmental windows of high brain plasticity to time interventions to the specific epochs in childhood that have the largest and most enduring life-long impact.

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. METHOD: Data from the Healthy Brain Network (final N = 740; age range 5-15 years) were split into discovery and replication samples to maximize generalizability of findings. Associations of parent- and self-reported social anxiety (Screen for Child Anxiety-related Emotional Disorders) with mean differences and person-to-person variability in functional magnetic resonance imaging-measured activation to 2 emotionally dynamic movies were characterized. RESULTS: Though no evidence was found to indicate social anxiety symptoms were associated with mean differences in neural activity to emotional content (fit Spearman rs < 0.09), children with high social anxiety symptoms had higher intersubject activation variability in the posterior cingulate, supramarginal gyrus, and inferior frontal gyrus (Bonferroni familywise error-corrected ps < .05)-regions associated with attention, alertness, and emotion cue processing. Identified regions varied by age group and informant. Across ages, these effects were enhanced for scenes containing greater sensory intensity (brighter, louder, more motion, more vibrance). CONCLUSION: These results provide evidence that children with high social anxiety symptoms show high person-to-person variability in the neural processing of sensory aspects of emotional content. These data indicate that children with high social anxiety may require personalized interventions for sensory and emotional difficulties, as the underlying neurology differs from child to child. DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list.

Multi-echo Acquisition and Thermal Denoising Advances Infant 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, but precise characterization of systems organization during periods of high plasticity might be most influential towards discoveries promoting lifelong health. Collecting and analyzing precision fMRI data during early development has unique challenges and emphasizes the importance of novel methods to improve data acquisition, processing, and analysis strategies in infant samples. Here, we investigate the applicability of two such methods from adult MRI research, multi-echo (ME) data acquisition and thermal noise removal with Noise reduction with distribution corrected principal component analysis (NORDIC), in precision fMRI data from three newborn infants. Compared to an adult example subject, T2* relaxation times calculated from ME data in infants were longer and more variable across the brain, pointing towards ME acquisition being a promising tool for optimizing developmental fMRI. The application of thermal denoising via NORDIC increased tSNR and the overall strength of functional connections as well as the split-half reliability of functional connectivity matrices in infant ME data. While our findings related to NORDIC denoising are coherent with the adult literature and ME data acquisition showed high promise, its application in developmental samples needs further investigation. The present work reveals gaps in our understanding of the best techniques for developmental brain imaging and highlights the need for further developmentally-specific methodological advances and optimizations, towards precision functional imaging in infants.

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. We next derive a set of 283 cortical surface parcels from a sample of n=261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies.

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 N = 45 full-term, sleeping neonates during an adapted auditory oddball paradigm and measured BI from n = 27 of these children 1 year later using an observational assessment. Whole-brain analyses corrected for multiple comparisons identified 46 neonatal brain regions producing novelty-evoked BOLD responses associated with children's BI scores at 1 year of age. More than half of these regions (n = 24, 52%) were in prefrontal cortex, falling primarily within regions of the default mode or frontoparietal networks or in ventromedial/orbitofrontal regions without network assignments. Hierarchical clustering of the regions based on their patterns of association with BI resulted in two groups with distinct anatomical, network, and response-timing profiles. The first group, located primarily in subcortical and temporal regions, tended to produce larger early oddball responses among infants with lower subsequent BI. The second group, located primarily in prefrontal cortex, produced larger early oddball responses among infants with higher subsequent BI. These results provide preliminary insights into brain regions engaged by novelty in infants that may relate to later BI. The findings may inform understanding of anxiety disorders and guide future research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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

Objective: 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. Methods: Children ages 8-12 with anxiety disorders (n = 18) participated in eight sessions of attention training over a 4-week period. At baseline and after completing training, participants completed clinical anxiety measures and a battery of cognitive tasks designed to measure three different aspects of attention: SDA, goal-oriented attention, and threat bias. A subset of participants (n = 12) underwent baseline and post-training neuroimaging while engaged in an SDA task. Brain analyses focused on activity within the rVLPFC. Results: Parent (p < 0.001)-, child (p < 0.002)-, and clinician-rated (p < 0.02) anxiety improved significantly over the course of training. Training significantly altered SDA [F(1,92) = 8.88, corrected p-value (pcor) < 0.012, uncorrected p-value (puncor) < 0.004]. Anxiety improvement correlated with improvements in goal-directed attention [r(10) = 0.60, pcor < 0.12 puncor < 0.04]. Within an area of the rVLPFC corresponding to the cingulo-opercular network (CON), there was a main effect of training [F(1,20) = 6.75, pcor < 0.16, puncor < 0.02], with decreasing signal across training. There was a significant interaction between training and anxiety on this region's activity [F(1,20) = 9.48, pcor < 0.048, puncor < 0.006]. Post hoc testing revealed that post-training activity within this CON area correlated with residual anxiety [r(10) = 0.68, p < 0.02]. Conclusions: SDA and rVLPFC neural activity may be novel therapeutic targets in pediatric anxiety. After undergoing a training paradigm aimed at modifying this aspect of attention and its underlying neural circuitry, patients showed lower anxiety, changes in SDA and goal-oriented attention, and decreased activity in the CON portion of the rVLPFC.

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. Here, in a sample of 5-15-year-old children (n = 823), we show that the brain represents different emotion concepts distinctly throughout the cortex, cerebellum and caudate. Patterns of activation to each emotion changed little across development. Using a model-free approach, we show that activation patterns were more similar between older children than between younger children. Moreover, scenes that required inferring negative emotional states elicited higher default mode network activation similarity in older children than younger children. These results suggest that representations of emotion concepts are relatively stable by mid to late childhood and synchronize between individuals during adolescence.

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 representations1,2, despite evidence for concentric functional zones3 and maps of complex actions4. 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 action5 and physiological control6, arousal7, errors8 and pain9. This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions4 and connectivity to internal organs10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate-isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement.

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. Task-fMRI measures evoked brain activity in response to specific stimuli through changes in the blood oxygen level-dependent signal. First, we review extant studies using task fMRI from birth through the first few years of life and synthesize current evidence for when, where, and how different neural computations are performed across the infant brain. Neural circuits for sensory perception, the perception of abstract categories, and the detection of statistical regularities have been characterized with task fMRI in infants, providing developmental context for identifying and interpreting variation in the functioning of neural circuits related to psychiatric risk. Next, we discuss studies that specifically examine variation in the functioning of these neural circuits during infancy in relation to risk for psychiatric disorders. These studies reveal when maturation of specific neural circuits diverges, the influence of environmental risk factors, and the potential utility for task fMRI to facilitate early treatment or prevention of later psychiatric problems. Finally, we provide considerations for future infant task-fMRI studies with the potential to advance understanding of both functioning of neural circuits during infancy and subsequent risk for psychiatric 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. first weeks of life) marked by heightened neuroplasticity remains uncharted. Using multivariate pattern classification techniques and functional connectivity magnetic resonance imaging, we detected robust differences in brain systems related to age in newborns (n = 262; R2 = 0.51). Development over the first month of life occurred brain-wide, but differed and was more pronounced in brain systems previously characterized as developing early (i.e. sensorimotor networks) than in those characterized as developing late (i.e. association networks). The cingulo-opercular network was the only exception to this organizing principle, illuminating its early role in brain development. This study represents a step towards a normative brain "growth curve" that could be used to identify atypical brain maturation in infancy.

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. Although some studies report distributed adult-like networks, other studies suggest that neonatal networks are immature and consist primarily of spatially isolated regions. Using a large sample of neonates (n = 262), we demonstrate that neonates have long-range selective functional connections for the default mode, fronto-parietal, and dorsal attention networks. An adult-like pattern of functional brain networks is evident in neonates when network-detection algorithms are tuned to these long-range connections, when using surface-based registration (versus volume-based registration), and as per-subject data quantity increases. These results help clarify factors that have led to prior mixed results, establish that key adult-like functional network features are evident in neonates, and provide a foundation for studies of typical and atypical brain development.

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. Methods: PubMed/Medline was searched for prospective treatment studies that included parallel examinations of functional activation or connectivity (both task-based and resting state) in adults and youth with panic disorder and generalized, separation, and/or social anxiety disorders published before April 30, 2021. All studies examining baseline predictors or changes related to pharmacologic and psychotherapeutic treatment of DSM-TV and DSM-5 anxiety disorders were included. Demographic, clinical, and treatment data as well as neurofunctional outcomes were extracted and summarized. Results: Twenty-nine studies examined changes in functional activation and/or connectivity (56 treatment arms) related to treatment and twenty-three examined neurofunctional predictors of treatment response. Predictors of treatment response and treatment-related neurofunctional changes were frequently observed within amygdala-prefrontal circuits. However, immense heterogeneity and few replication studies preclude a cohesive neurofunctional treatment response model across anxiety disorders. Conclusions: The extant literature describing neurofunctional aspects of treatment response in anxiety disorders is best viewed as a partially constructed scaffold on which to build a clinically translatable set of robust neuroimaging biomarkers that can be used to guide treatment and to select from available treatment. The construction of this understanding will require harmonization of analytic and task approaches, larger samples, and replication of component studies.

Parallel hippocampal-parietal circuits for self- and goal-oriented processing.

The hippocampus is critically important for a diverse range of cognitive processes, such as episodic memory, prospective memory, affective processing, and spatial navigation. Using individual-specific precision functional mapping of resting-state functional MRI data, we found the anterior hippocampus (head and body) to be preferentially functionally connected to the default mode network (DMN), as expected. The hippocampal tail, however, was strongly preferentially functionally connected to the parietal memory network (PMN), which supports goal-oriented cognition and stimulus recognition. This anterior-posterior dichotomy of resting-state functional connectivity was well-matched by differences in task deactivations and anatomical segmentations of the hippocampus. Task deactivations were localized to the hippocampal head and body (DMN), relatively sparing the tail (PMN). The functional dichotomization of the hippocampus into anterior DMN-connected and posterior PMN-connected parcels suggests parallel but distinct circuits between the hippocampus and medial parietal cortex for self- versus goal-oriented processing.

Neonatal Brain Response to Deviant Auditory Stimuli and Relation to Maternal Trait Anxiety.

OBJECTIVE: Excessive response to unexpected or "deviant" stimuli during infancy and early childhood represents an early risk marker for anxiety disorders. However, research has yet to delineate the specific brain regions underlying the neonatal response to deviant stimuli near birth and the relation to risk for anxiety disorders. The authors used task-based functional MRI (fMRI) to delineate the neonatal response to deviant stimuli and its relationship to maternal trait anxiety. METHODS: The authors used fMRI to measure brain activity evoked by deviant auditory stimuli in 45 sleeping neonates (mean age, 27.8 days; 60% female; 64% African American). In 41 of the infants, neural response to deviant stimuli was examined in relation to maternal trait anxiety on the State-Trait Anxiety Inventory, a familial risk factor for offspring anxiety. RESULTS: Neonates manifested a robust and widespread neural response to deviant stimuli that resembles patterns found previously in adults. Higher maternal trait anxiety was related to higher responses within multiple brain regions, including the left and right anterior insula, the ventrolateral prefrontal cortex, and multiple areas within the anterior cingulate cortex. These areas overlap with brain regions previously linked to anxiety disorders and other psychiatric illnesses in adults. CONCLUSIONS: The neural architecture sensitive to deviant stimuli robustly functions in newborns. Excessive responsiveness of some circuitry components at birth may signal risk for anxiety and other psychiatric disorders.