Association of Poor Family Functioning From Pregnancy Onward With Preadolescent Behavior and Subcortical Brain Development.

Importance: The association of poor family functioning, a potent stressor, with child behavior is potentially long term and relevant for a person's well-being later in life. Whether changes in brain development underlie the associations with preadolescent behavior and help identify periods of vulnerability is unclear. Objective: To assess the associations of poor family functioning from pregnancy onward with cortical, white matter, and subcortical volumes, and to examine the extent to which, in particular, hippocampal volume mediates the association of prenatal parental environmental exposures with child problem behavior in preadolescence. Design, Setting, and Participants: This population-based cohort study, conducted from April 2002 to January 2006, was embedded in Generation R, a multiethnic population-based cohort from fetal life onward. All pregnant women living in Rotterdam, the Netherlands, with an expected delivery date between April 2002 and January 2006 were invited to participate. Of the 8879 pregnant women enrolled during pregnancy, 1266 mothers with no partner data and 490 with missing family functioning data were excluded, as well as 1 sibling of 32 twin pairs. After excluding an additional 657 children with poor imaging data quality or incidental findings, the final sample consisted of 2583 mother-child pairs. Data analysis was performed from March 1, 2019, to June 28, 2019. Exposures: Mother- and father-rated poor family functioning was repeatedly measured by the General Functioning subscale of the Family Assessment Device. Main Outcomes and Measures: Our primary hypothesis, formulated after data collection but before analysis, was that poor prenatal family functioning would be associated with smaller hippocampal and amygdala volumes in late childhood. High-resolution structural neuroimaging data of children aged 10 years were collected with a single 3-T magnetic resonance imaging system. Child emotional and behavioral problems were assessed with the Child Behavior Checklist. Results: Data were available for 2583 children (mean [SD] age, 10.1 [0.6] years; 1315 girls [50.9%]). Data for parents included 2583 mothers (mean [SD] age, 31.1 [4.7] years; 1617 Dutch race/ethnicity [62.6%]) and 1788 fathers (mean [SD] age, 33.5 [5.3] years; 1239 Dutch race/ethnicity [69.3%]). Children exposed to prenatal maternal-reported poor family functioning had smaller hippocampal (B = -0.08; 95% CI, -0.13 to -0.02) and occipital lobe (B = -0.70; 95% CI, -1.19 to -0.21) volumes in preadolescence. There was no evidence for an association of exposure to poor family functioning at mid- or late childhood with brain morphology. Hippocampal volumes partially mediated the association of prenatal maternal-reported poor family functioning with preadolescent problem behavior (B = 0.08; 95% CI, 0.03-0.13), even after adjusting for prior child problems at age 1.5 years. Analyses of combined maternal and paternal family functioning ratings showed similar results, but associations were largely driven by maternal family functioning reports. Conclusions and Relevance: In this population-based cohort study, prenatal maternal-reported poor family functioning was associated with a smaller hippocampus in preadolescents. This difference in brain structure may underlie behavioral problems and is a possible neurodevelopmental manifestation of the long-term consequences of poor family functioning for the child.

Psychotic symptoms are associated with lower cortical folding in youth at risk for mental illness

Background: Cortical folding is essential for healthy brain development. Previous studies have found regional reductions in cortical folding in adult patients with psychotic illness. It is unknown whether these neuroanatomical markers are present in youth with subclinical psychotic symptoms. Methods: We collected MRIs and examined the local gyrification index in a sample of 110 youth (mean age ± standard deviation 14.0 ± 3.7 yr; range 9­25 yr) with a family history of severe mental illness: 48 with psychotic symptoms and 62 without. Images were processed using the Human Connectome Pipeline and FreeSurfer. We tested for group differences in local gyrification index using mixed-effects generalized linear models controlling for age, sex and familial clustering. Sensitivity analysis further controlled for intracranial volume, IQ, and stimulant and cannabis use. Results: Youth with psychotic symptoms displayed an overall trend toward lower cortical folding across all brain regions. After adjusting for multiple comparisons and confounders, regional reductions were localized to the frontal and occipital lobes. Specifically, the medial (B = ­0.42, pFDR = 0.04) and lateral (B = ­0.39, pFDR = 0.04) orbitofrontal cortices as well as the cuneus (B = ­0.47, pFDR = 0.03) and the pericalcarine (B = ­0.45, pFDR = 0.03) and lingual (B = ­0.38, pFDR = 0.04) gyri. Limitations: Inference about developmental trajectories was limited by the cross-sectional data. Conclusion: Psychotic symptoms in youth are associated with cortical folding deficits, even in the absence of psychotic illness. The current study helps clarify the neurodevelopmental basis of psychosis at an early stage, before medication, drug use and other confounds have had a persistent effect on the brain.

A genome-wide association study identifies genetic loci associated with specific lobar brain volumes.

Brain lobar volumes are heritable but genetic studies are limited. We performed genome-wide association studies of frontal, occipital, parietal and temporal lobe volumes in 16,016 individuals, and replicated our findings in 8,789 individuals. We identified six genetic loci associated with specific lobar volumes independent of intracranial volume. Two loci, associated with occipital (6q22.32) and temporal lobe volume (12q14.3), were previously reported to associate with intracranial and hippocampal volume, respectively. We identified four loci previously unknown to affect brain volumes: 3q24 for parietal lobe volume, and 1q22, 4p16.3 and 14q23.1 for occipital lobe volume. The associated variants were located in regions enriched for histone modifications (DAAM1 and THBS3), or close to genes causing Mendelian brain-related diseases (ZIC4 and FGFRL1). No genetic overlap between lobar volumes and neurological or psychiatric diseases was observed. Our findings reveal part of the complex genetics underlying brain development and suggest a role for regulatory regions in determining brain volumes.

Emerging neural specialization of the ventral occipitotemporal cortex to characters through phonological association learning in preschool children.

The ventral occipitotemporal (vOT) cortex serves as a core region for visual processing, and specific areas of this region show preferential activation for various visual categories such as faces and print. The emergence of such functional specialization in the human cortex represents a pivotal developmental process, which provides a basis for targeted and efficient information processing. For example, functional specialization to print in the left vOT is an important prerequisite for fluent reading. However, it remains unclear, which processes initiate the preferential cortical activations to characters arising in the vOT during child development. Using a multimodal neuroimaging approach with preschool children at familial risk for developmental dyslexia, we demonstrate how varying levels of expertise modulate the neural response to single characters, which represent the building blocks of print units. The level of expertise to characters was manipulated firstly through brief training of false-font speech-sound associations and secondly by comparing characters for which children differed in their level of familiarity and expertise accumulated through abundant exposure in their everyday environment. Neural correlates of character processing were tracked with simultaneous high-density electroencephalography and functional magnetic resonance imaging in a target detection task. We found training performance and expertise-dependent modulation of the visual event-related potential around 220 ms (N1) and the corresponding vOT activation. Additionally, trained false-font characters revealed stronger functional connectivity between the left fusiform gyrus (FFG) seed and left superior parietal/lateral occipital cortex regions with higher training performance. In sum, our results demonstrate that learning artificial-character speech-sound associations enhances activation to trained characters in the vOT and that the magnitude of this activation and the functional connectivity of the left FFG to the parieto-occipital cortex depends on learning performance. This pattern of results suggests emerging development of the reading network after brief training that parallels network specialization during reading acquisition.

Developmental Reorganization of the Core and Extended Face Networks Revealed by Global Functional Connectivity.

Prior studies on development of functional specialization in human brain mainly focus on age-related increases in regional activation and connectivity among regions. However, a few recent studies on the face network demonstrate age-related decrease in face-specialized activation in the extended face network (EFN), in addition to increase in activation in the core face network (CFN). Here we used a voxel-based global brain connectivity approach to investigate whether development of the face network exhibited both increase and decrease in network connectivity. We found the voxel-wise resting-state functional connectivity (FC) within the CFN increased with age in bilateral posterior superior temporal sulcus, suggesting the integration of the CFN during development. Interestingly, the FC of the voxels in the EFN to the right fusiform face area and occipital face area decreased with age, suggesting that the CFN segregated from the EFN during development. Moreover, the age-related connectivity in the CFN was related to behavioral performance in face processing. Overall, our study demonstrated developmental reorganization of the face network achieved by both integration within the CFN and segregation of the CFN from the EFN, which may account for the simultaneous increases and decreases in neural activation during the development of the face network.

Biomechanical Analysis of Normal Brain Development during the First Year of Life Using Finite Strain Theory.

The first year of life is the most critical time period for structural and functional development of the human brain. Combining longitudinal MR imaging and finite strain theory, this study aimed to provide new insights into normal brain development through a biomechanical framework. Thirty-three normal infants were longitudinally imaged using MRI from 2 weeks to 1 year of age. Voxel-wise Jacobian determinant was estimated to elucidate volumetric changes while Lagrange strains (both normal and shear strains) were measured to reveal directional growth information every 3 months during the first year of life. Directional normal strain maps revealed that, during the first 6 months, the growth pattern of gray matter is anisotropic and spatially inhomogeneous with higher left-right stretch around the temporal lobe and interhemispheric fissure, anterior-posterior stretch in the frontal and occipital lobes, and superior-inferior stretch in right inferior occipital and right inferior temporal gyri. In contrast, anterior lateral ventricles and insula showed an isotropic stretch pattern. Volumetric and directional growth rates were linearly decreased with age for most of the cortical regions. Our results revealed anisotropic and inhomogeneous brain growth patterns of the human brain during the first year of life using longitudinal MRI and a biomechanical framework.

Development of Neural Sensitivity to Face Identity Correlates with Perceptual Discriminability.

Face perception is subserved by a series of face-selective regions in the human ventral stream, which undergo prolonged development from childhood to adulthood. However, it is unknown how neural development of these regions relates to the development of face-perception abilities. Here, we used functional magnetic resonance imaging (fMRI) to measure brain responses of ventral occipitotemporal regions in children (ages, 5-12 years) and adults (ages, 19-34 years) when they viewed faces that parametrically varied in dissimilarity. Since similar faces generate lower responses than dissimilar faces due to fMRI adaptation, this design objectively evaluates neural sensitivity to face identity across development. Additionally, a subset of subjects participated in a behavioral experiment to assess perceptual discriminability of face identity. Our data reveal three main findings: (1) neural sensitivity to face identity increases with age in face-selective but not object-selective regions; (2) the amplitude of responses to faces increases with age in both face-selective and object-selective regions; and (3) perceptual discriminability of face identity is correlated with the neural sensitivity to face identity of face-selective regions. In contrast, perceptual discriminability is not correlated with the amplitude of response in face-selective regions or of responses of object-selective regions. These data suggest that developmental increases in neural sensitivity to face identity in face-selective regions improve perceptual discriminability of faces. Our findings significantly advance the understanding of the neural mechanisms of development of face perception and open new avenues for using fMRI adaptation to study the neural development of high-level visual and cognitive functions more broadly. SIGNIFICANCE STATEMENT: Face perception, which is critical for daily social interactions, develops from childhood to adulthood. However, it is unknown what developmental changes in the brain lead to improved performance. Using fMRI in children and adults, we find that from childhood to adulthood, neural sensitivity to changes in face identity increases in face-selective regions. Critically, subjects' perceptual discriminability among faces is linked to neural sensitivity: participants with higher neural sensitivity in face-selective regions demonstrate higher perceptual discriminability. Thus, our results suggest that developmental increases in face-selective regions' sensitivity to face identity improve perceptual discrimination of faces. These findings significantly advance understanding of the neural mechanisms underlying the development of face perception and have important implications for assessing both typical and atypical development.

Delayed Development of Brain Connectivity in Adolescents With Schizophrenia and Their Unaffected Siblings.

IMPORTANCE: Abnormalities in structural brain connectivity have been observed in patients with schizophrenia. Mapping these abnormalities longitudinally and understanding their genetic risk via sibship studies will provide crucial insight into progressive developmental changes associated with schizophrenia. OBJECTIVES: To identify corticocortical connections exhibiting an altered developmental trajectory in adolescents with childhood-onset schizophrenia (COS) and to determine whether similar alterations are found in patients' unaffected siblings. DESIGN, SETTING, AND PARTICIPANTS: Using prospective structural brain magnetic resonance imaging, large-scale corticocortical connectivity was mapped from ages 12 to 24 years in 109 patients with COS (272 images), 86 of their unaffected siblings (184 images), and 102 healthy controls (262 images) over a 20-year period beginning January 1, 1991, through April 30, 2011, as part of the ongoing COS study at the National Institute of Mental Health. MAIN OUTCOMES AND MEASURES: Structural connectivity between pairs of cortical regions was estimated using a validated technique based on across-subject covariation in magnetic resonance imaging-derived cortical thickness measurements. RESULTS: Compared with normally developing controls, significant left-hemisphere occipitotemporal deficits in cortical thickness correlations were found in patients with COS as well as their healthy siblings (P < .05). Deficits in siblings normalized by mid-adolescence, whereas patients with COS showed significantly longer maturational delays, with cortical thickness correlations between the left temporal lobe and left occipital cortex not showing evidence of development until early adulthood. The normalization of deficits with age in patients with COS correlated with improvement in symptoms. Compared with controls, left-hemisphere occipitotemporal thickness correlations in a subgroup of patients with high positive symptoms were significantly reduced from age 14 to 18 years (P < .05); however, other patients with low positive symptoms showed no significant deficits. CONCLUSIONS AND RELEVANCE: Delayed maturation of occipitotemporal connectivity appears to be a trait marker in patients with COS, with a milder endophenotype in unaffected siblings associated with resilience to developing schizophrenia. These findings indicate genetically influenced and connection-specific developmental abnormalities in the schizophrenia connectome, and lead to the hypothesis that visual hallucinations in patients with COS may be because of delayed development of the inferior longitudinal fasciculus, a prominent occipitotemporal fiber.

Occipital cortical thickness in very low birth weight born adolescents predicts altered neural specialization of visual semantic category related neural networks.

Very low birth weight (VLBW) premature born infants have a high risk to develop visual perceptual and learning deficits as well as widespread functional and structural brain abnormalities during infancy and childhood. Whether and how prematurity alters neural specialization within visual neural networks is still unknown. We used functional and structural brain imaging to examine the visual semantic system of VLBW born (<1250 g, gestational age 25-32 weeks) adolescents (13-15 years, n = 11, 3 males) and matched term born control participants (13-15 years, n = 11, 3 males). Neurocognitive assessment revealed no group differences except for lower scores on an adaptive visuomotor integration test. All adolescents were scanned while viewing pictures of animals and tools and scrambled versions of these pictures. Both groups demonstrated animal and tool category related neural networks. Term born adolescents showed tool category related neural activity, i.e. tool pictures elicited more activity than animal pictures, in temporal and parietal brain areas. Animal category related activity was found in the occipital, temporal and frontal cortex. VLBW born adolescents showed reduced tool category related activity in the dorsal visual stream compared with controls, specifically the left anterior intraparietal sulcus, and enhanced animal category related activity in the left middle occipital gyrus and right lingual gyrus. Lower birth weight of VLBW adolescents correlated with larger thickness of the pericalcarine gyrus in the occipital cortex and smaller surface area of the superior temporal gyrus in the lateral temporal cortex. Moreover, larger thickness of the pericalcarine gyrus and smaller surface area of the superior temporal gyrus correlated with reduced tool category related activity in the parietal cortex. Together, our data suggest that very low birth weight predicts alterations of higher order visual semantic networks, particularly in the dorsal stream. The differences in neural specialization may be associated with aberrant cortical development of areas in the visual system that develop early in childhood.

Multisensory convergence of visual and haptic object preference across development.

Visuohaptic inputs offer redundant and complementary information regarding an object׳s geometrical structure. The integration of these inputs facilitates object recognition in adults. While the ability to recognize objects in the environment both visually and haptically develops early on, the development of the neural mechanisms for integrating visual and haptic object shape information remains unknown. In the present study, we used functional Magnetic Resonance Imaging (fMRI) in three groups of participants, 4 to 5.5 year olds, 7 to 8.5 year olds, and adults. Participants were tested in a block design involving visual exploration of two-dimensional images of common objects and real textures, and haptic exploration of their three-dimensional counterparts. As in previous studies, object preference was defined as a greater BOLD response for objects than textures. The analyses specifically target two sites of known visuohaptic convergence in adults: the lateral occipital tactile-visual region (LOtv) and intraparietal sulcus (IPS). Results indicated that the LOtv is involved in visuohaptic object recognition early on. More importantly, object preference in the LOtv became increasingly visually dominant with development. Despite previous reports that the lateral occipital complex (LOC) is adult-like by 8 years, these findings indicate that at least part of the LOC is not. Whole-brain maps showed overlap between adults and both groups of children in the LOC. However, the overlap did not build incrementally from the younger to the older group, suggesting that visuohaptic object preference does not develop in an additive manner. Taken together, the results show that the development of neural substrates for visuohaptic recognition is protracted compared to substrates that are primarily visual or haptic.

The effort to close the gap: tracking the development of illusory contour processing from childhood to adulthood with high-density electrical mapping.

The adult human visual system can efficiently fill-in missing object boundaries when low-level information from the retina is incomplete, but little is known about how these processes develop across childhood. A decade of visual-evoked potential (VEP) studies has produced a theoretical model identifying distinct phases of contour completion in adults. The first, termed a perceptual phase, occurs from approximately 100-200 ms and is associated with automatic boundary completion. The second is termed a conceptual phase occurring between 230 and 400 ms. The latter has been associated with the analysis of ambiguous objects which seem to require more effort to complete. The electrophysiological markers of these phases have both been localized to the lateral occipital complex, a cluster of ventral visual stream brain regions associated with object-processing. We presented Kanizsa-type illusory contour stimuli, often used for exploring contour completion processes, to neurotypical persons ages 6-31 (N=63), while parametrically varying the spatial extent of these induced contours, in order to better understand how filling-in processes develop across childhood and adolescence. Our results suggest that, while adults complete contour boundaries in a single discrete period during the automatic perceptual phase, children display an immature response pattern-engaging in more protracted processing across both timeframes and appearing to recruit more widely distributed regions which resemble those evoked during adult processing of higher-order ambiguous figures. However, children older than 5years of age were remarkably like adults in that the effects of contour processing were invariant to manipulation of contour extent.

Family poverty affects the rate of human infant brain growth.

Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems.

Reduced occipital fractional anisotropy on cerebral diffusion tensor imaging in preterm infants with postnatally acquired cytomegalovirus infection.

BACKGROUND: Detection of white matter (WM) abnormalities on MRI is important regarding the neurodevelopmental outcome in preterm infants. The long-term neurodevelopmental outcome of preterm infants with postnatal cytomegalovirus (CMV) infection has not been studied extensively. OBJECTIVES: We aimed to assess WM microstructure in preterm infants with postnatal CMV infection using diffusion tensor imaging. METHODS: Infants <32 weeks' gestational age (GA) admitted to our hospital between 2007 and 2010, who had cerebral diffusion tensor imaging at term-equivalent age (40 weeks' GA) were included. CMV PCR in urine collected at term-equivalent age was performed to diagnose postnatal CMV infection. Congenital infection was excluded. In the frontal, parietal and occipital WM mean diffusivity, fractional anisotropy (FA), radial and axial diffusivity were calculated. Neurodevelopmental outcome was assessed at 16 months' corrected age using Griffiths' Mental Developmental Scales. RESULTS: Twenty-one postnatally infected and 61 noninfected infants were eligible. Both groups were comparable regarding GA, birth weight and age at MRI. There was a significant difference in median FA of the occipital WM between infected and noninfected infants (0.13 [IQR 0.11-0.16] versus 0.16 [IQR 0.14-0.18], p = 0.002). There were no differences in short-term neurodevelopmental outcome between infected and noninfected infants. CONCLUSIONS: A significantly reduced FA suggests microstructural changes in the occipital WM of postnatally infected infants. These microstructural changes do not appear to result in impaired neurodevelopmental outcome at 16 months' corrected age.

Increased regional homogeneity of blood oxygen level-dependent signals in occipital cortex of early blind individuals.

Although resting-state functional magnetic resonance imaging has shown altered functional connectivity between visual and other brain areas in the early blind individuals, it cannot answer which brain area's local activities are changed. In this study, regional homogeneity, a measure of the homogeneity of the local blood oxygen level-dependent signals, was used for the first time to investigate the changes in the resting-state brain activity in the early blind individuals. Compared with age-matched and sex-matched sighted individuals, the early blind individuals showed increased regional homogeneity only in the occipital areas, which might be explained by the abnormal cortical development and/or experience-dependent plasticity, resulted from an early visual deprivation.

Gene expression in the rat brain: high similarity but unique differences between frontomedial-, temporal- and occipital cortex.

BACKGROUND: The six-layered neocortex of the mammalian brain may appear largely homologous, but is in reality a modular structure of anatomically and functionally distinct areas. However, global gene expression seems to be almost identical across the cerebral cortex and only a few genes have so far been reported to show regional enrichment in specific cortical areas. RESULTS: In the present study on adult rat brain, we have corroborated the strikingly similar gene expression among cortical areas. However, differential expression analysis has allowed for the identification of 30, 24 and 11 genes enriched in frontomedial -, temporal- or occipital cortex, respectively. A large proportion of these 65 genes appear to be involved in signal transduction, including the ion channel Fxyd6, the neuropeptide Grp and the nuclear receptor Rorb. We also find that the majority of these genes display increased expression levels around birth and show distinct preferences for certain cortical layers and cell types in rodents. CONCLUSIONS: Since specific patterns of expression often are linked to equally specialised biological functions, we propose that these cortex sub-region enriched genes are important for proper functioning of the cortical regions in question.

Correlation between gray matter density-adjusted brain perfusion and age using brain MR images of 202 healthy children.

We examined the correlation between brain perfusion and age using pulsed arterial spin-labeling (ASL) magnetic resonance images (MRI) in a large number of healthy children. We collected data on brain structural and ASL perfusion MRI in 202 healthy children aged 5-18 years. Structural MRI data were segmented and normalized, applying a voxel-based morphometric analysis. Perfusion MRI was normalized using the normalization parameter of the corresponding structural MRI. We calculated brain perfusion with an adjustment for gray matter density (BP-GMD) by dividing normalized ASL MRI by normalized gray matter segments in 22 regions. Next, we analyzed the correlation between BP-GMD and age in each region by estimating linear, quadratic, and cubic polynomial functions, using the Akaike information criterion. The correlation between BP-GMD and age showed an inverted U shape followed by a U-shaped trajectory in most regions. In addition, age at which BP-GMD was highest was different among the lobes and gray matter regions, and the BP-GMD association with age increased from the occipital to the frontal lobe via the temporal and parietal lobes. Our results indicate that higher order association cortices mature after the lower order cortices, and may help clarify the mechanisms of normal brain maturation from the viewpoint of brain perfusion.

Prediction of individual brain maturity using fMRI.

Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals' brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain's major functional networks.

The role of early life stress in development of the anterior limb of the internal capsule in nonhuman primates.

Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) may be effective in treating depression. Parental verbal abuse has been linked to decreased fractional anisotropy (FA) of white matter and reduced FA correlated with depression and anxiety scores. Utilizing a nonhuman primate model of mood and anxiety disorders following disrupted mother-infant attachment, we examined whether adverse rearing conditions lead to white matter impairment of the ALIC. We examined white matter integrity using Diffusion Tensor Imaging (DTI) on a 3T-MRI. Twenty-one adult male Bonnet macaques participated in this study: 12 were reared under adverse [variable foraging demand (VFD)] conditions whereas 9 were reared under normative conditions. We examined ALIC, posterior limb of the internal capsule (PLIC) and occipital white matter. VFD rearing was associated with significant reductions in FA in the ALIC with no changes evident in the PLIC or occipital cortex white matter. Adverse rearing in monkeys persistently impaired frontal white matter tract integrity, a novel substrate for understanding affective susceptibility.

Developmental appearance and disappearance of cortical events and oscillations in infant rats.

Until recently, organized and state-dependent neocortical activity in infant rats was thought to commence with the emergence of delta waves at postnatal day (P)11. This view is changing with the discovery of several forms of cortical activity that are detectable soon after birth, including spindle bursts (SBs) and slow activity transients (SATs). Here we provide further evidence of surprisingly rich cortical activity patterns during early development and document, in P5-P13 rats, the appearance, disappearance, and transient expression of three cortical events and oscillations. EEG activity in frontal, parietal, and occipital cortices was recorded in unanesthetized, head-fixed subjects using 16-channel laminar silicon electrodes and Ag-AgCl electrodes. In addition to SATs, we identified two novel forms of activity: cortical sharp potentials (CSPs) and gamma bursts (GBs). SBs were not observed in these areas. CSPs, defined as discrete, biphasic events with a duration of 250 ms, exhibited an inverted-U developmental trajectory with peak prevalence at P9. In contrast, GBs, defined as brief bursts of 40-Hz activity, increased steadily in prevalence and duration from P5 through P13. The prevalence of SATs decreased steadily across the ages tested here. Furthermore, both CSPs and GBs were more likely to occur during sleep than during wakefulness. Because SATs, CSPs, and GBs exhibit different developmental trajectories and rates of occurrence, and can occur independently of each other, they appear to be distinct patterns of neuronal activity. We hypothesize that these diverse patterns of neurophysiological activity reflect the instantaneous local structure and connectivity of the developing neocortex.