White matter functional gradients and their formation in adolescence.

It is well known that functional magnetic resonance imaging (fMRI) is a widely used tool for studying brain activity. Recent research has shown that fluctuations in fMRI data can reflect functionally meaningful patterns of brain activity within the white matter. We leveraged resting-state fMRI from an adolescent population to characterize large-scale white matter functional gradients and their formation during adolescence. The white matter showed gray-matter-like unimodal-to-transmodal and sensorimotor-to-visual gradients with specific cognitive associations and a unique superficial-to-deep gradient with nonspecific cognitive associations. We propose two mechanisms for their formation in adolescence. One is a "function-molded" mechanism that may mediate the maturation of the transmodal white matter via the transmodal gray matter. The other is a "structure-root" mechanism that may support the mutual mediation roles of the unimodal and transmodal white matter maturation during adolescence. Thus, the spatial layout of the white matter functional gradients is in concert with the gray matter functional organization. The formation of the white matter functional gradients may be driven by brain anatomical wiring and functional needs.

Examining the interaction between prenatal stress and polygenic risk for attention-deficit/hyperactivity disorder on brain growth in childhood: Findings from the DREAM BIG consortium.

This study explored the interactions among prenatal stress, child sex, and polygenic risk scores (PGS) for attention-deficit/hyperactivity disorder (ADHD) on structural developmental changes of brain regions implicated in ADHD. We used data from two population-based birth cohorts: Growing Up in Singapore Towards healthy Outcomes (GUSTO) from Singapore (n = 113) and Generation R from Rotterdam, the Netherlands (n = 433). Prenatal stress was assessed using questionnaires. We obtained latent constructs of prenatal adversity and prenatal mood problems using confirmatory factor analyses. The participants were genotyped using genome-wide single nucleotide polymorphism arrays, and ADHD PGSs were computed. Magnetic resonance imaging scans were acquired at 4.5 and 6 years (GUSTO), and at 10 and 14 years (Generation R). We estimated the age-related rate of change for brain outcomes related to ADHD and performed (1) prenatal stress by sex interaction models, (2) prenatal stress by ADHD PGS interaction models, and (3) 3-way interaction models, including prenatal stress, sex, and ADHD PGS. We observed an interaction between prenatal stress and ADHD PGS on mean cortical thickness annual rate of change in Generation R (i.e., in individuals with higher ADHD PGS, higher prenatal stress was associated with a lower rate of cortical thinning, whereas in individuals with lower ADHD PGS, higher prenatal stress was associated with a higher rate of cortical thinning). None of the other tested interactions were statistically significant. Higher prenatal stress may promote a slower brain developmental rate during adolescence in individuals with higher ADHD genetic vulnerability, whereas it may promote a faster brain developmental rate in individuals with lower ADHD genetic vulnerability.

Amyloid-ß accumulation in relation to functional connectivity in aging: A longitudinal study.

The brain undergoes many changes at pathological and functional levels in healthy aging. This study employed a longitudinal and multimodal imaging dataset from the OASIS-3 study (n = 300) and explored possible relationships between amyloid beta (Aß) accumulation and functional brain organization over time in healthy aging. We used positron emission tomography (PET) with Pittsburgh compound-B (PIB) to quantify the Aß accumulation in the brain and resting-state functional MRI (rs-fMRI) to measure functional connectivity (FC) among brain regions. Each participant had at least 2 to 3 follow-up visits. A linear mixed-effect model was used to examine longitudinal changes of Aß accumulation and FC throughout the whole brain. We found that the limbic and frontoparietal networks had a greater annual Aß accumulation and a slower decline in FC in aging. Additionally, the amount of the Aß deposition in the amygdala network at baseline slowed down the decline in its FC in aging. Furthermore, the functional connectivity of the limbic, default mode network (DMN), and frontoparietal networks accelerated the Aß propagation across their functionally highly connected regions. The functional connectivity of the somatomotor and visual networks accelerated the Aß propagation across the brain regions in the limbic, frontoparietal, and DMN networks. These findings suggested that the slower decline in the functional connectivity of the functional hubs may compensate for their greater Aß accumulation in aging. The Aß propagation from one brain region to the other may depend on their functional connectivity strength.

Interindividual variability in functional connectivity discovers differential development of cognition and transdiagnostic dimensions of psychopathology in youth.

Cognitive and psychological development during adolescence is different from one another, which is rooted in individual differences in maturational changes in the adolescent brain. This study employed multi-modal MRI data and characterized interindividual variability in functional connectivity (IVFC) and its associations with cognition and psychopathology using the Philadelphia Neurodevelopmental Cohort (PNC) of 755 youth. We employed resting state functional MRI (rs-fMRI) and diffusion weighted images (DWIs) to estimate brain structural and functional networks. We computed the IVFC of individuals and examined its relation with structural and functional organizations. We further employed sparse partial least squares (sparse-PLS) and meta-analysis to examine the developmental associations of the IVFC with cognition and transdiagnostic dimensions of psychopathology in early, middle, and late adolescence. Our results revealed that the IVFC spatial topography reflects the brain functional integration and structure-function decoupling. Age effects on the IVFC of association networks were mediated by the FC among the triple networks, including frontoparietal, salience, and default mode networks (DMN), while those of primary and cerebellar networks were mediated by the cerebello-cortical FC. The IVFC of the triple and cerebellar networks explained the variance of executive functions and externalizing behaviors in early adolescence and then the variance of emotion and internalizing and psychosis in middle and late adolescence. We further evaluated this finding via meta-analysis on task-based studies on cognition and psychopathology. These findings implicate the emerging importance of the IVFC of the triple and cerebellar networks in cognitive, emotional, and psychopathological development during adolescence.

Maternal Adverse Childhood Experience and Depression in Relation with Brain Network Development and Behaviors in Children: A Longitudinal Study.

Maternal childhood maltreatment and depression increase risks for the psychopathology of the offspring. This study employed a longitudinal dataset of mother-child dyads to investigate the developmental trajectories of brain functional networks and behaviors of children in relation with maternal childhood adverse experience and depression. Maternal childhood trauma was retrospectively assessed via childhood trauma questionnaire, whereas maternal depressive symptoms were prospectively evaluated during pregnancy and after delivery (n = 518). Child brain scans were acquired at age of 4.5, 6, and 7.5 years (n = 163) and behavioral problems were measured at 7.5 years using the Child Behavior Checklist. We found the functional connectivity of the language network with the sensorimotor, frontal, and attentional networks as a function of maternal adverse experience that interacted with sex and age. Girls exposed to mothers with depressive symptoms or childhood abuse showed the increased development of the functional connectivity of the language network with the visual networks, which was associated with social problems. Girls exposed to mothers with depressive symptoms showed the slower growth of the functional connectivity of the language network with the sensorimotor networks. Our findings, in a community sample, suggest the language network organization as neuroendophenotypes for maternal childhood trauma and depression.

An initial investigation of neonatal neuroanatomy, caregiving, and levels of disorganized behavior.

Attachment disorganization is a risk factor for difficulties in attention, social relationships, and mental health. Conceptually, attachment disorganization may indicate a breakdown in fear regulation resulting from repeated exposure to frightening maternal care. In addition, past research has examined the influence of stress-inducing contextual factors and/or child factors upon the development of disorganization. However, no past work has assessed whether infant neuroanatomy, important to stress regulation, moderates the association between maternal care and levels of disorganized behavior. Here, utilizing data from a subsample of 82 dyads taking part in the "Growing Up in Singapore towards Healthy Outcomes" (GUSTO) cohort, we assessed the prediction from maternal sensitive caregiving at 6 mo and levels of attachment disorganization at 1.5 y, as moderated by hippocampal and amygdala volume determined within the first 2 weeks of life. Results indicate a significant interaction between neonatal left hippocampal volume and maternal sensitivity upon levels of disorganized behavior. Although these results require substantiation in further research, if replicated, they may enable new strategies for the identification of processes important to child mental health and points for intervention. This is because neonatal neuroanatomy, as opposed to genetic variation and sociodemographic risk, may be more directly linked to stress responses within individuals.

Common functional brain networks between attention deficit and disruptive behaviors in youth.

Attention deficits (AD) and disruptive behavior (DB) are highly comorbid youth externalizing behaviors. This study aimed to study reliable functional brain networks shared by AD and DB in youth aged from 8 to 21 years from the Philadelphia Neurodevelopmental Cohort (PNC). The PNC study assessed AD and DB behaviors via Kiddie-Schedule for Affective Disorders and Schizophrenia (K-SADS). This study employed sparse canonical correlation analysis (SCCA) to examine the correlation of AD and DB behaviors with resting-state functional connectivity maps of the brain regions identified via activation likelihood estimation (ALE) meta-analyses on attention deficit/hyperactivity disorder (ADHD) and DB disorder (DBD). Our meta-analyses identified that the middle cingulate cortex, pre-supplementary motor area (pre-SMA), and striatum had a great consensus in existing ADHD studies and the amygdala and inferior parietal lobule were consistently found in existing DBD studies. Our SCCA analysis revealed that the AD and DB behavioral items relevant to inattention and delinquency were correlated with the functional connectivity of the pre-SMA with the ventral attentional and frontoparietal networks (FPN), and the striatum with the default mode (DMN) and dorsal attentional networks. The AD and DB behavioral items relevant to inattention and irritability were associated with the functional connectivity between the amygdala and the DMN and FPN. Our findings suggest that the functional organization of the ADHD- and DBD-related brain regions provides insights on the shared neural basis in AD and DB.

Spatio-temporal correlates of gene expression and cortical morphology across lifespan and aging.

Evidence from neuroimaging and genetic studies supports the concept that brain aging mirrors development. However, it is unclear whether mechanisms linking brain development and aging provide new insights to delay aging and potentially reverse it. This study determined biological mechanisms and phenotypic traits underpinning brain alterations across the lifespan and in aging by examining spatio-temporal correlations between gene expression and cortical volumes using datasets d with the age range from 2 to 82 years. We revealed that a large proportion of genes whose expression was associated with cortical volumes across the lifespan were in astrocytes. These genes, which showed up-regulation during development and down-regulation during aging, contributed to fundamental homeostatic functions of astrocytes. Included among these genes were those encoding components of cAMP, Ras, and retrograde endocannabinoid signaling pathways. Genes associated with cortical volumes in the same data aged above 55 years were also enriched for the sphingolipid, renin-angiotensin system (RAS), proteasome, and TGF-ß signaling pathway, which is linked to senescence-associated secretory phenotypes. Neuroticism, drinking, and smoking were the common phenotypic traits in the lifespan and aging, while memory was the unique phenotype associated with aging. These findings provide biological mechanisms mirroring development and aging as well as unique to aging.

Integrated structural and functional atlases of Asian children from infancy to childhood.

The developing brain grows exponentially in the first few years of life. There is a need to have age-appropriate brain atlases that coherently characterize the geometry of the cerebral cortex, white matter tracts, and functional organization. This study employed multi-modal brain images of an Asian cohort and constructed brain structural and functional atlases for 6-month-old infants, 4.5-, 6-, and 7.5-year-old children. We exploited large deformation diffeomorphic metric mapping and probabilistic atlas generation approaches to integrate structural MRI and diffusion weighted images (DWIs) and to create the atlas where white matter tracts well fit into the cortical folding pattern. Based on this structural atlas, we then employed spectral clustering to parcellate the brain into functional networks from resting-state fMRI (rs-fMRI). Our results provided the atlas that characterizes the cortical folding geometry, subcortical regions, deep white matter tracts, as well as functional networks in a stereotaxic coordinate space for the four different age groups. The functional networks consisting of the primary cortex were well established in infancy and remained stable to childhood, while specific higher-order functional networks showed specific patterns of hemispherical, subcortical-cerebellar, and cortical-cortical integration and segregation from infancy to childhood. Our multi-modal fusion analysis demonstrated the use of the integrated structural and functional atlas for understanding coherent patterns of brain anatomical and functional development during childhood. Hence, our atlases can be potentially used to study coherent patterns of brain anatomical and functional development.

Left lateralization of neonatal caudate microstructure affects emerging language development at 24 months.

The complex interaction between brain and behaviour in language disorder is well established. Yet to date, the imaging literature in the language disorder field has continued to pursue heterogeneous and relatively small clinical cross-sectional samples, with emphasis on cortical structures and volumetric analyses of subcortical brain structures. In our current work, we aimed to go beyond this state of knowledge to focus on the microstructural features of subcortical brain structures (specifically the caudate nucleus) in a large cohort of neonates and study its association with emerging language skills at 24 months. Variations in neonatal brain microstructure could be interpreted as a proxy for in utero brain development. As language development is highly dependent on cognitive function and home literacy environment, we also examined their effect on the caudate-language function relationship utilizing a conditional process model. Our findings suggest that emerging language development at 24 months is influenced by the degree of left lateralization of neonatal caudate microstructure, indexed by diffusion tensor imaging (DTI)-derived fractional anisotropy (FA). FA is an indirect measure of neuronal and dendritic density within grey matter structures. We also found that the caudate-language function relationship is partially mediated by cognitive function. The conditional indirect effect of left caudate FA on language composite score through cognitive function was only statistically significant at low levels of home literacy score (-1 standard deviation [SD]). The authors proposed that this may be related to 'compensatory' development of cognitive skills in less favourable home literacy environments.

Spatial correlation maps of the hippocampus with cerebrospinal fluid biomarkers and cognition in Alzheimer's disease: A longitudinal study.

This study is an observational study that takes the existing longitudinal data from Alzheimer's disease Neuroimaging Initiative to examine the spatial correlation map of hippocampal subfield atrophy with CSF biomarkers and cognitive decline in the course of AD. This study included 421 healthy controls (HC), 557 patients of stable mild cognitive impairment (s-MCI), 304 Alzheimer's Disease (AD) patients, and 241 subjects who converted to be AD from MCI (c-MCI), and 6,525 MRI scans in a period from 2004 to 2019. Our findings revealed that all the hippocampal subfields showed their accelerated atrophy rate from cognitively normal aging to stable MCI and AD. The presubiculum, dentate gyrus, and fimbria showed greater atrophy beyond the whole hippocampus in the HC, s-MCI, and AD groups and corresponded to a greater decline of memory and attention in the s-MCI group. Moreover, the higher atrophy rates of the subiculum and CA2/3, CA4 were also associated with a greater decline in attention in the s-MCI group. Interestingly, patients with c-MCI showed that the presubiculum atrophy was associated with CSF tau levels and corresponded to the onset age of AD and a decline in attention in patients with c-MCI. These spatial correlation findings of the hippocampus suggested that the hippocampal subfields may not be equally impacted by normal aging, MCI, and AD, and their atrophy was selectively associated with declines in specific cognitive domains. The presubiculum atrophy was highlighted as a surrogate marker for the AD prognosis along with tau pathology and attention decline.

Association of increased abdominal adiposity at birth with altered ventral caudate microstructure.

BACKGROUND: Neonatal adiposity is associated with a higher risk of obesity and cardiometabolic risk factors in later life. It is however unknown if central food intake regulating networks in the ventral striatum are altered with in-utero abdominal growth, indexed by neonatal adiposity in our current study. We aim to examine the relationship between striatal microstructure and abdominal adipose tissue compartments (AATCs) in Asian neonates from the Growing Up in Singapore Toward healthy Outcomes mother-offspring cohort. STUDY DESIGN: About 109 neonates were included in this study. Magnetic resonance imaging (MRI) was performed for the brain and abdominal regions between 5 to 17 days of life. Diffusion-weighted imaging of the brain was performed for the derivation of caudate and putamen fractional anisotropy (FA). Abdominal imaging was performed to quantify AATCs namely superficial subcutaneous adipose tissue (sSAT), deep subcutaneous adipose tissue (dSAT), and internal adipose tissue (IAT). Absolute and percentage adipose tissue of total abdominal volume (TAV) were calculated. RESULTS: We showed that AATCs at birth were significantly associated with increased FA in bilateral ventral caudate heads which are part of the ventral striatum (sSAT: ßleft = 0.56, p < 0.001; ßright = 0.65, p < 0.001, dSAT: ßleft = 0.43, p < 0.001; ßright = 0.52, p < 0.001, IAT: ßleft = 0.30, p = 0.005; ßright = 0.32, p = 0.002) in neonates with low birth weights adjusted for gestational age. CONCLUSIONS: Our study provides preliminary evidence of a potential relationship between neonatal adiposity and in-utero programming of the ventral striatum, a brain structure that governs feeding behavior.

Cohort profile: Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO).

The Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth, metabolic and neural phenotypes in the offspring. Between February 2015 and October 2017, the S-PRESTO study recruited 1039 Chinese, Malay or Indian (or any combinations thereof) women aged 18-45 years and who intended to get pregnant and deliver in Singapore, resulting in 1032 unique participants and 373 children born in the cohort. The participants were followed up for 3 visits during the preconception phase and censored at 12 months of follow up if pregnancy was not achieved (N = 557 censored). Women who successfully conceived (N = 475) were characterised at gestational weeks 6-8, 11-13, 18-21, 24-26, 27-28 and 34-36. Follow up of their index offspring (N = 373 singletons) is on-going at birth, 1, 3 and 6 weeks, 3, 6, 12, 18, 24 and 36 months and beyond. Women are also being followed up post-delivery. Data is collected via interviewer-administered questionnaires, metabolic imaging (magnetic resonance imaging), standardized anthropometric measurements and collection of diverse specimens, i.e. blood, urine, buccal smear, stool, skin tapes, epithelial swabs at numerous timepoints. S-PRESTO has extensive repeated data collected which include genetic and epigenetic sampling from preconception which is unique in mother-offspring epidemiological cohorts. This enables prospective assessment of a wide array of potential determinants of future health outcomes in women from preconception to post-delivery and in their offspring across the earliest development from embryonic stages into early childhood. In addition, the S-PRESTO study draws from the three major Asian ethnic groups that represent 50% of the global population, increasing the relevance of its findings to global efforts to address non-communicable diseases.

Sex-Dependent Associations among Maternal Depressive Symptoms, Child Reward Network, and Behaviors in Early Childhood.

Maternal depression is associated with disrupted neurodevelopment in offspring. This study examined relationships among postnatal maternal depressive symptoms, the functional reward network and behavioral problems in 4.5-year-old boys (57) and girls (65). We employed canonical correlation analysis to evaluate whether the resting-state functional connectivity within a reward network, identified through an activation likelihood estimation (ALE) meta-analysis of fMRI studies, was associated with postnatal maternal depressive symptoms and child behaviors. The functional reward network consisted of three subnetworks, that is, the mesolimbic, mesocortical, and amygdala-hippocampus reward subnetworks. Postnatal maternal depressive symptoms were associated with the functional connectivity of the mesocortical subnetwork with the mesolimbic and amygdala-hippocampus complex subnetworks in girls and with the functional connectivity within the mesocortical subnetwork in boys. The functional connectivity of the amygdala-hippocampus subnetwork with the mesocortical and mesolimbic subnetworks was associated with both internalizing and externalizing problems in girls, while in boys, the functional connectivity of the mesocortical subnetwork with the amygdala-hippocampus complex and the mesolimbic subnetworks was associated with the internalizing and externalizing problems, respectively. Our findings suggest that the functional reward network might be a promising neural phenotype for effects of maternal depression and potential intervention to nurture child behavioral development.

Neural Transcription Correlates of Multimodal Cortical Phenotypes during Development.

During development, cellular events such as cell proliferation, migration, and synaptogenesis determine the structural organization of the brain. These processes are driven in part by spatiotemporally regulated gene expression. We investigated how the genetic signatures of specific neural cell types shape cortical organization of the human brain throughout infancy and childhood. Using a transcriptional atlas and in vivo magnetic resonance imaging (MRI) data, we demonstrated time-dependent associations between the expression levels of neuronal and glial genes and cortical macro- and microstructure. Neonatal cortical phenotypes were associated with prenatal glial but not neuronal gene expression. These associations reflect cell migration and proliferation during fetal development. Childhood cortical phenotypes were associated with neuronal and astrocyte gene expression related to synaptic signaling processes, reflecting the refinement of cortical connections. These findings indicate that sequential developmental stages contribute to distinct MRI measures at different time points. This helps to bridge the gap between the genetic mechanisms driving cellular changes and widely used neuroimaging techniques.

Do intrinsic brain functional networks predict working memory from childhood to adulthood?

Working memory (WM) is defined as the ability to maintain a representation online to guide goal-directed behavior. Its capacity in early childhood predicts academic achievements in late childhood and its deficits are found in various neurodevelopmental disorders. We employed resting-state fMRI (rs-fMRI) of 468 participants aged from 4 to 55 years and connectome-based predictive modeling (CPM) to explore the potential predictive power of intrinsic functional networks to WM in preschoolers, early and late school-age children, adolescents, and adults. We defined intrinsic functional networks among brain regions identified by activation likelihood estimation (ALE) meta-analysis on existing WM functional studies (ALE-based intrinsic functional networks) and intrinsic functional networks generated based on the whole brain (whole-brain intrinsic functional networks). We employed the CPM on these networks to predict WM in each age group. The CPM using the ALE-based and whole-brain intrinsic functional networks predicted WM of individual adults, while the prediction power of the ALE-based intrinsic functional networks was superior to that of the whole-brain intrinsic functional networks. Nevertheless, the CPM using the whole-brain but not the ALE-based intrinsic functional networks predicted WM in adolescents. And, the CPM using neither the ALE-based nor whole-brain networks predicted WM in any of the children groups. Our findings showed the trend of the prediction power of the intrinsic functional networks to cognition in individuals from early childhood to adulthood.

Quantification of regional myocardial mean intracellular water lifetime: A nonhuman primate study in myocardial stress.

Heart failure with preserved ejection fraction (HFpEF) is typically associated with early metabolic remodeling. Noninvasive imaging biomarkers that reflect these changes will be crucial in determining responses to early drug interventions in these patients. Mean intracellular water lifetime (τi ) has been shown to be partially inversely related to Na, K-ATPase transporter activity and may thus provide insight into the metabolic status in HFpEF patients. Here, we aim to perform regional quantification of τi using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in the nonhuman primate (NHP) heart and evaluate its region-specific variations under conditions of myocardial stress in the context of perturbed myocardial function. Cardiac stress was induced in seven naïve cynomolgus macaques using a dobutamine stepwise infusion protocol. All animals underwent 3 T cardiac dual-bolus DCE and tagging MRI experiments. The shutter-speed model was employed to quantify regional τi from the DCE-MR images. Additionally, τi values were correlated with myocardial strains. During cardiac stress, there was a significant decrease in global τi (192.9 ± 76.3 ms vs 321.6 ± 70 ms at rest, P < 0.05) in the left ventricle, together with an increase in global peak circumferential strain (-15.4% ± 2.7% vs -10.1% ± 2.9% at rest, P < 0.05). Specifically, slice-level analysis further revealed that a greater significant decrease in mean τi was observed in the apical region (ΔτI = 182.4 ms) compared with the basal (Δτi = 113.2 ms) and midventricular regions (Δτi = 108.4 ms). Regional analysis revealed that there was a greater significant decrease in mean τi in the anterior (Δτi = 243.9 ms) and antero-lateral (Δτi = 177.2 ms) regions. In the inferior and infero-septal regions, although a decrease in τi was observed, it was not significant. Whole heart regional quantification of τi is feasible using DCE-MRI. τi is sensitive to regional changes in metabolic state during cardiac stress, and its value correlates with strain.

Maternal antenatal anxiety and electrophysiological functioning amongst a sub-set of preschoolers participating in the GUSTO cohort.

BACKGROUND: Antenatal maternal anxiety is a risk for offspring psychological and cognitive difficulties. The preschool years represent an important time for brain development, and so may be a window for intervention. However, electrophysiological investigations of maternal anxiety and preschoolers' brain functioning are lacking. We ask whether anxiety symptoms predict neurophysiology, and consider timing specificity (26-weeks antenatal or 24-months postnatal), form of insult (anxiety symptoms, per se, or also depression symptoms), and offspring gender. METHODS: The sample consisted of a subset of 71 mothers and their 3 year old children taking part in the prospective birth cohort, GUSTO. Mothers provided antenatal (26 weeks) and postnatal (2 years) anxiety and depressive symptomatology data, respectively via the "State Trait Anxiety Questionnaire" and the "Edinburgh Postpartum Depression Scale." Offspring provided electrophysiological data, obtained while they indicated the emotional expression of actors whose facial expressions remained consistent throughout a pre-switch block, but were reversed at "post-switch." RESULTS: Three electrophysiological components linked to different information processing stages were identified. The two earliest occurring components (i.e., the N1 and P2) differed across blocks. During post-switch, both were significantly predicted by maternal anxiety, after controlling for pre-switch neurophysiology. Similar results were observed with depression. Antenatal mental health remained a significant predictor after controlling for postnatal mental health. CONCLUSION: In combination with past work, these findings suggest the importance of reducing symptoms in women prior to and during pregnancy, and offering support to offspring early in development.

Maternal sensitivity during infancy and the regulation of startle in preschoolers.

Caregiving insensitivity and fear dysregulation predict anxiety symptoms in children. It is unclear, however, whether sensitive parental care during infancy predicts fear regulation later in childhood. To address this question, we asked whether observed maternal sensitivity, measured at 6 months, predicts 42-month-old children's laboratory-induced fear responses (n=213) during a fear-eliciting episode. We predicted that higher levels of maternal sensitivity would be associated with greater fear regulation. We operationalized fear regulation as decreases in fear over repeated trials of a novel, potentially frightening, stimulus. Two aspects of fear responses were considered: expressed fear and startle. Expressed fear scores did not decrease over time but children exhibited less startle behavior in the second half of the task. Maternal sensitivity predicted this startle attenuation across trials. These findings highlight the contribution of maternal sensitivity during infancy to the development of fear regulation in early childhood, further suggesting its influence on offspring anxiety problems.

A review on neuroimaging studies of genetic and environmental influences on early brain development.

The past decades witnessed a surge of interest in neuroimaging study of normal and abnormal early brain development. Structural and functional studies of normal early brain development revealed massive structural maturation as well as sequential, coordinated, and hierarchical emergence of functional networks during the infancy period, providing a great foundation for the investigation of abnormal early brain development mechanisms. Indeed, studies of altered brain development associated with either genetic or environmental risks emerged and thrived. In this paper, we will review selected studies of genetic and environmental risks that have been relatively more extensively investigated-familial risks, candidate risk genes, and genome-wide association studies (GWAS) on the genetic side; maternal mood disorders and prenatal drug exposures on the environmental side. Emerging studies on environment-gene interactions will also be reviewed. Our goal was not to perform an exhaustive review of all studies in the field but to leverage some representative ones to summarize the current state, point out potential limitations, and elicit discussions on important future directions.