Protracted neuronal recruitment in the temporal lobes of young children.

The temporal lobe of the human brain contains the entorhinal cortex (EC). This region of the brain is a highly interconnected integrative hub for sensory and spatial information; it also has a key role in episodic memory formation and is the main source of cortical hippocampal inputs1-4. The human EC continues to develop during childhood5, but neurogenesis and neuronal migration to the EC are widely considered to be complete by birth. Here we show that the human temporal lobe contains many young neurons migrating into the postnatal EC and adjacent regions, with a large tangential stream persisting until the age of around one year and radial dispersal continuing until around two to three years of age. By contrast, we found no equivalent postnatal migration in rhesus macaques (Macaca mulatta). Immunostaining and single-nucleus RNA sequencing of ganglionic eminence germinal zones, the EC stream and the postnatal EC revealed that most migrating cells in the EC stream are derived from the caudal ganglionic eminence and become LAMP5+RELN+ inhibitory interneurons. These late-arriving interneurons could continue to shape the processing of sensory and spatial information well into postnatal life, when children are actively interacting with their environment. The EC is one of the first regions of the brain to be affected in Alzheimer's disease, and previous work has linked cognitive decline to the loss of LAMP5+RELN+ cells6,7. Our investigation reveals that many of these cells arrive in the EC through a major postnatal migratory stream in early childhood.

Robust Hi-C Maps of Enhancer-Promoter Interactions Reveal the Function of Non-coding Genome in Neural Development and Diseases.

Genome-wide mapping of chromatin interactions at high resolution remains experimentally and computationally challenging. Here we used a low-input "easy Hi-C" protocol to map the 3D genome architecture in human neurogenesis and brain tissues and also demonstrated that a rigorous Hi-C bias-correction pipeline (HiCorr) can significantly improve the sensitivity and robustness of Hi-C loop identification at sub-TAD level, especially the enhancer-promoter (E-P) interactions. We used HiCorr to compare the high-resolution maps of chromatin interactions from 10 tissue or cell types with a focus on neurogenesis and brain tissues. We found that dynamic chromatin loops are better hallmarks for cellular differentiation than compartment switching. HiCorr allowed direct observation of cell-type- and differentiation-specific E-P aggregates spanning large neighborhoods, suggesting a mechanism that stabilizes enhancer contacts during development. Interestingly, we concluded that Hi-C loop outperforms eQTL in explaining neurological GWAS results, revealing a unique value of high-resolution 3D genome maps in elucidating the disease etiology.

The Prenatal Morphomechanic Impact of Agenesis of the Corpus Callosum on Human Brain Structure and Asymmetry.

Genetic, molecular, and physical forces together impact brain morphogenesis. The early impact of deficient midline crossing in agenesis of the Corpus Callosum (ACC) on prenatal human brain development and architecture is widely unknown. Here we analyze the changes of brain structure in 46 fetuses with ACC in vivo to identify their deviations from normal development. Cases of complete ACC show an increase in the thickness of the cerebral wall in the frontomedial regions and a reduction in the temporal, insular, medial occipital and lateral parietal regions, already present at midgestation. ACC is associated with a more symmetric configuration of the temporal lobes and increased frequency of atypical asymmetry patterns, indicating an early morphomechanic effect of callosal growth on human brain development affecting the thickness of the pallium along a ventro-dorsal gradient. Altered prenatal brain architecture in ACC emphasizes the importance of conformational forces introduced by emerging interhemispheric connectivity on the establishment of polygenically determined brain asymmetries.

Early Left-Planum Temporale Asymmetry in newborn monkeys (Papio anubis): A longitudinal structural MRI study at two stages of development.

The "language-ready" brain theory suggests that the infant brain is pre-wired for language acquisition prior to language exposure. As a potential brain marker of such a language readiness, a leftward structural brain asymmetry was found in human infants for the Planum Temporale (PT), which overlaps with Wernicke's area. In the present longitudinal in vivo MRI study conducted in 35 newborn monkeys (Papio anubis), we found a similar leftward PT surface asymmetry. Follow-up rescanning sessions on 29 juvenile baboons at 7-10 months showed that such an asymmetry increases across the two ages classes. These original findings in non-linguistic primate infants strongly question the idea that the early PT asymmetry constitutes a human infant-specific marker for language development. Such a shared early perisylvian organization provides additional support that PT asymmetry might be related to a lateralized system inherited from our last common ancestor with Old-World monkeys at least 25-35 million years ago.

A Lifespan fMRI Study of Neurodevelopment Associated with Reading Chinese.

We used functional magnetic resonance imaging (fMRI) to map the neural systems involved in reading Chinese in 125 participants 6-74 years old to examine two theoretical issues: how brain structure and function are related in the context of the lifetime neural development of human cognition and whether the neural network for reading is universal or different across languages. Our findings showed that a common network of left frontal and occipital regions typically involved in reading Chinese was recruited across all participants. Crucially, activation in left mid-inferior frontal regions, fusiform and striate-extrastriate sites, premotor cortex, right inferior frontal gyrus, bilateral insula, and supplementary motor area all showed linearly decreasing changes with age. These findings differ from previous findings on alphabetic reading development and suggest that early readers at age 6-7 are already using the same cortical network to process printed words as adults, though the connections among these regions are modulated by reading proficiency, and cortical regions for reading are tuned by experience toward reduced and more focused activation. This fMRI study has demonstrated, for the first time, the neurodevelopment of reading across the lifespan and suggests that learning experience, instead of pre-existing brain structures, determines reading acquisition.

The intimate relationship between coalescent generators in very premature human newborn brains: Quantifying the coupling of nested endogenous oscillations.

Temporal theta slow-wave activity (TTA-SW) in premature infants is a specific neurobiomarker of the early neurodevelopment of perisylvian networks observed as early as 24 weeks of gestational age (wGA). It is present at the turning point between non-sensory driven spontaneous networks and cortical network functioning. Despite its clinical importance, the underlying mechanisms responsible for this spontaneous nested activity and its functional role have not yet been determined. The coupling between neural oscillations at different timescales is a key feature of ongoing neural activity, the characteristics of which are determined by the network structure and dynamics. The underlying mechanisms of cross-frequency coupling (CFC) are associated with several putative functions in adults. In order to show that this generic mechanism is already in place early in the course of development, we analyzed electroencephalography recordings from sleeping preterm newborns (24-27 wGA). Employing cross-frequency phase-amplitude coupling analyses, we found that TTAs were orchestrated by the SWs defined by a precise temporal relationship. Notably, TTAs were synchronized to the SW trough, and were suppressed during the SW peak. Spontaneous endogenous TTA-SWs constitute one of the very early signatures of the developing temporal neural networks with key functions, such as language and communication. The presence of a fine-tuned relationship between the slow activity and the TTA in premature neonates emphasizes the complexity and relative maturity of the intimate mechanisms that shape the CFC, the disruption of which can have severe neurodevelopmental consequences.

Altered resting-state functional connectivity within the developing social brain after pediatric traumatic brain injury.

Traumatic brain injury (TBI) in childhood and adolescence can interrupt expected development, compromise the integrity of the social brain network (SBN) and impact social skills. Yet, no study has investigated functional alterations of the SBN following pediatric TBI. This study explored functional connectivity within the SBN following TBI in two independent adolescent samples. First, 14 adolescents with mild complex, moderate or severe TBI and 16 typically developing controls (TDC) underwent resting-state functional magnetic resonance imaging 12-24 months post-injury. Region of interest analyses were conducted to compare the groups' functional connectivity using selected SBN seeds. Then, replicative analysis was performed in an independent sample of adolescents with similar characteristics (9 TBI, 9 TDC). Results were adjusted for age, sex, socioeconomic status and total gray matter volume, and corrected for multiple comparisons. Significant between-group differences were detected for functional connectivity in the dorsomedial prefrontal cortex and left fusiform gyrus, and between the left fusiform gyrus and left superior frontal gyrus, indicating positive functional connectivity for the TBI group (negative for TDC). The replication study revealed group differences in the same direction between the left superior frontal gyrus and right fusiform gyrus. This study indicates that pediatric TBI may alter functional connectivity of the social brain. Frontal-fusiform connectivity has previously been shown to support affect recognition and changes in the function of this network could relate to more effortful processing and broad social impairments.

Left temporal plane growth predicts language development in newborns with congenital heart disease.

Congenital heart defects are the most common congenital anomalies, accounting for a third of all congenital anomaly cases. While surgical correction dramatically improved survival rates, the lag behind normal neurodevelopment appears to persist. Deficits in higher cognitive functions are particularly common, including developmental delay in communication and oral-motor apraxia. It remains unclear whether the varying degree of cognitive developmental delay is reflected in variability in brain growth patterns. To answer this question, we aimed to investigate whether the rate of regional brain growth is correlated with later life neurodevelopment. Forty-four newborns were included in our study, of whom 33 were diagnosed with dextro-transposition of the great arteries and 11 with other forms of severe congenital heart defects. During the first month of life, neonates underwent corrective or palliative cardiovascular bypass surgery, pre- and postoperative cerebral MRI were performed 18.7 ± 7.03 days apart. MRI was performed in natural sleep on a 3.0 T scanner using an 8-channel head coil, fast spin-echo T2-weighted anatomical sequences were acquired in three planes. Based on the principles of deformation-based morphometry, we calculated brain growth rate maps reflecting average daily growth occurring between pre- and postoperative brain images. An explorative, whole-brain, threshold-free cluster enhancement analysis revealed strong correlation between the growth rate of the Heschl's gyrus, anterior planum temporale and language score at 12 months of age, corrected for demographic variables (P = 0.018, t = 5.656). No significant correlation was found between brain growth rates and motor or cognitive scores. Post hoc analysis showed that the length of hospitalization interacted with this correlation, longer hospitalization resulted in faster enlargement of the internal CSF spaces. Our longitudinal cohort study provides evidence for the early importance of left-dominant perisylvian regions in auditory and language development before direct postnatal exposure to native language. In congenital heart disease patients, the perioperative period results in a critical variability of brain growth rate in this region, which is a reliable neural correlate of language development at 1 year of age.

Early Developmental Trajectories of Functional Connectivity Along the Visual Pathways in Rhesus Monkeys.

Early social interactions shape the development of social behavior, although the critical periods or the underlying neurodevelopmental processes are not completely understood. Here, we studied the developmental changes in neural pathways underlying visual social engagement in the translational rhesus monkey model. Changes in functional connectivity (FC) along the ventral object and motion pathways and the dorsal attention/visuo-spatial pathways were studied longitudinally using resting-state functional MRI in infant rhesus monkeys, from birth through early weaning (3 months), given the socioemotional changes experienced during this period. Our results revealed that (1) maturation along the visual pathways proceeds in a caudo-rostral progression with primary visual areas (V1-V3) showing strong FC as early as 2 weeks of age, whereas higher-order visual and attentional areas (e.g., MT-AST, LIP-FEF) show weak FC; (2) functional changes were pathway-specific (e.g., robust FC increases detected in the most anterior aspect of the object pathway (TE-AMY), but FC remained weak in the other pathways (e.g., AST-AMY)); (3) FC matures similarly in both right and left hemispheres. Our findings suggest that visual pathways in infant macaques undergo selective remodeling during the first 3 months of life, likely regulated by early social interactions and supporting the transition to independence from the mother.

The Longitudinal Trajectory of Default Mode Network Connectivity in Healthy Older Adults Varies As a Function of Age and Is Associated with Changes in Episodic Memory and Processing Speed.

The default mode network (DMN) supports memory functioning and may be sensitive to preclinical Alzheimer's pathology. Little is known, however, about the longitudinal trajectory of this network's intrinsic functional connectivity (FC). In this study, we evaluated longitudinal FC in 111 cognitively normal older human adults (ages 49-87, 46 women/65 men), 92 of whom had at least three task-free fMRI scans (n = 353 total scans). Whole-brain FC and three DMN subnetworks were assessed: (1) within-DMN, (2) between anterior and posterior DMN, and (3) between medial temporal lobe network and posterior DMN. Linear mixed-effects models demonstrated significant baseline age × time interactions, indicating a nonlinear trajectory. There was a trend toward increasing FC between ages 50-66 and significantly accelerating declines after age 74. A similar interaction was observed for whole-brain FC. APOE status did not predict baseline connectivity or change in connectivity. After adjusting for network volume, changes in within-DMN connectivity were specifically associated with changes in episodic memory and processing speed but not working memory or executive functions. The relationship with processing speed was attenuated after covarying for white matter hyperintensities (WMH) and whole-brain FC, whereas within-DMN connectivity remained associated with memory above and beyond WMH and whole-brain FC. Whole-brain and DMN FC exhibit a nonlinear trajectory, with more rapid declines in older age and possibly increases in connectivity early in the aging process. Within-DMN connectivity is a marker of episodic memory performance even among cognitively healthy older adults.SIGNIFICANCE STATEMENT Default mode network and whole-brain connectivity, measured using task-free fMRI, changed nonlinearly as a function of age, with some suggestion of early increases in connectivity. For the first time, longitudinal changes in DMN connectivity were shown to correlate with changes in episodic memory, whereas volume changes in relevant brain regions did not. This relationship was not accounted for by white matter hyperintensities or mean whole-brain connectivity. Functional connectivity may be an early biomarker of changes in aging but should be used with caution given its nonmonotonic nature, which could complicate interpretation. Future studies investigating longitudinal network changes should consider whole-brain changes in connectivity.

Functional Organization of the Temporal-Parietal Junction for Theory of Mind in Preverbal Infants: A Near-Infrared Spectroscopy Study.

Successful human social life requires imagining what others believe or think to understand and predict behavior. This ability, often referred to as theory of mind (ToM), reliably engages a specialized network of temporal and prefrontal brain regions in older children and adults, including selective recruitment of the temporal-parietal junction (TPJ). To date, how and when this specialized brain organization for ToM arises is unknown due to limitations in functional neuroimaging at younger ages. Here, we used the emerging technique of functional near-infrared spectroscopy to measure the functional brain response across parietal, temporal, and prefrontal regions in 7-month-old male and female infants as they viewed different video scenarios of a person searching for a hidden object. Over different conditions, we manipulated whether the person held an accurate (true) or inaccurate (false) belief about the location of the hidden object in the videos. In two separate experiments, we observed that activity from the TPJ, but not other temporal and prefrontal regions, spontaneously tracked with the beliefs of the other person, responding more during scenarios when the other person's belief regarding the location of the object was false compared with scenarios when her belief was true. These results mirror those obtained with adults to show that the TPJ already shows some functional organization relevant to high-level social cognition by around 7 months of age. Furthermore, these results suggest that infants may draw on similar core mechanisms to implicitly track beliefs, as adults do when reasoning explicitly about them.SIGNIFICANCE STATEMENT Humans selectively engage a network of brain regions, including the temporal-parietal junction (TPJ), to track what others think, an ability referred to as theory of mind. How and when this specialized brain organization for high-level social cognition arises is unknown. Using the emerging technique of near-infrared spectroscopy with 7-month-old infants, we observed that activity of the TPJ, but not other temporal and frontal regions, distinguished between scenarios when another person's belief about the location of the object was false compared with scenarios when the belief was true. These results suggest that a basic neural architecture to understand and predict the actions of others based on their beliefs may be present from the first year of life.

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.

Interregional causal influences of brain metabolic activity reveal the spread of aging effects during normal aging.

During healthy brain aging, different brain regions show anatomical or functional declines at different rates, and some regions may show compensatory increases in functional activity. However, few studies have explored interregional influences of brain activity during the aging process. We proposed a causality analysis framework combining high dimensionality independent component analysis (ICA), Granger causality, and least absolute shrinkage and selection operator regression on longitudinal brain metabolic activity data measured by Fludeoxyglucose positron emission tomography (FDG-PET). We analyzed FDG-PET images from healthy old subjects, who were scanned for at least five sessions with an averaged intersession interval of 1 year. The longitudinal data were concatenated across subjects to form a time series, and the first-order autoregressive model was used to measure interregional causality among the independent sources of metabolic activity identified using ICA. Several independent sources with reduced metabolic activity in aging, including the anterior temporal lobe and orbital frontal cortex, demonstrated causal influences over many widespread brain regions. On the other hand, the influenced regions were more distributed, and had smaller age-related declines or even relatively increased metabolic activity. The current data demonstrated interregional spreads of aging on metabolic activity at the scale of a year, and have identified key brain regions in the aging process that have strong influences over other regions.

Atypical Structural Asymmetry of the Planum Temporale is Related to Family History of Dyslexia.

Research on the neural correlates of developmental dyslexia indicates atypical anatomical lateralization of the planum temporale, a higher-order cortical auditory region. Yet whether this atypical lateralization precedes reading acquisition and is related to a familial risk for dyslexia is not currently known. In this study, we address these questions in 2 separate cohorts of young children and adolescents with and without a familial risk for dyslexia. Planum temporale surface area was manually labeled bilaterally, on the T1-weighted MR brain images of 54 pre-readers (mean age: 6.2 years, SD: 3.2 months; 33 males) and 28 adolescents (mean age: 14.7 years, SD: 3.3 months; 11 males). Half of the pre-readers and adolescents had a familial risk for dyslexia. In both pre-readers and adolescents, group comparisons of left and right planum temporale surface area showed a significant interaction between hemisphere and family history of dyslexia, with participants who had no family risk for dyslexia showing greater leftward asymmetry of the planum temporale. This effect was confirmed when analyses were restricted to normal reading participants. Altered planum temporale asymmetry thus seems to be related to family history of dyslexia.

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.

Prefrontal and temporal cortical thickness in adolescents with traumatic brain injury.

AIM: To investigate the impact of traumatic injury on the developing prefrontal-temporal adolescent cortex, and correlated brain structural measures with neurocognitive functioning. METHOD: Nineteen adolescents (12 males, 7 females, age range: 11-17y, mean 15y 8mo, standard deviation 1y 7mo, median 15y 11mo) with traumatic brain injury (TBI) were included. Cortical thickness of frontal and temporal lobes was assessed using magnetic resonance imaging. We correlated cortical thickness of prefrontal-temporal regions with age, time since injury, and neurocognitive functioning, and compared these results with a matched control cohort without TBI. RESULTS: We found thinner prefrontal (p=0.039) and temporal cortices (p=0.002) in adolescents with TBI compared to typically developing children. Furthermore, significant age effect was observed on the prefrontal (r=-0.75, p=0.003) and temporal (r=-0.66, p=0.013) cortical thickness in typically developing adolescents, but not in adolescents with TBI. Executive function (measured using the Behaviour Rating Inventory of Executive Function questionnaire, with lower scores meaning higher functioning) was correlated with prefrontal cortical thickness in typically developing adolescents (r=0.72, p=0.009). Opposite trends were found for correlations between cortical thickness and executive function in the TBI and control cohort. INTERPRETATION: Structural maturation in typically developing adolescents correlates with functional development: the older the adolescent, the thinner the prefrontal cortex, the better executive function. In adolescents with TBI we observed an opposite trend, that appeared significantly different from the control group: the thinner the prefrontal and temporal cortex, the worse executive functioning. WHAT THIS PAPER ADDS: Cortical thickness is negatively correlated with age in typically developing adolescents. Prefrontal cortex thickness correlates negatively with executive function in typically developing adolescents. Correlations between cortical thickness and executive functioning rise for adolescents without traumatic brain injury (TBI). Correlations between cortical thickness and executive functioning fall for adolescents with TBI. Adolescents with TBI have a long-term impairment of adaptive functioning in daily living.

ESPESOR CORTICAL PREFRONTAL Y TEMPORAL EN ADOLESCENTES CON LESIÓN CEREBRAL TRAUMÁTICA: OBJETIVO: Investigar el impacto de la lesión traumática en el desarrollo de la corteza prefrontal-temporal en adolescentes y las medidas estructurales cerebrales correlacionadas con el funcionamiento neurocognitivo. MÉTODO: Diecinueve adolescentes (12 varones, siete mujeres, rango de edad: 11-17 años, media: 15 años 8 meses, desviación estándar: 1 años 7 meses, mediana: 15 años 11 meses) con lesión cerebral traumática (LCT). El grosor cortical de los lóbulos frontal y temporal se evaluó mediante imágenes de resonancia magnética. Se correlacionó el grosor cortical de las regiones prefrontal-temporales con la edad, el tiempo transcurrido desde la lesión y el funcionamiento neurocognitivo, y se compararon estos resultados con una cohorte de control emparejada sin TCE. RESULTADOS: Encontramos cortezas prefrontales (p = 0.039) y corticales temporales delgadas (p = 0.002) en adolescentes con LCT en comparación con niños con desarrollo típico. Además, se observó un efecto significativo de la edad en el grosor cortical prefrontal (r = -0.75, p = 0.003) y temporal (r = -0.66, p = 0.013) en adolescentes de desarrollo típico, pero no en adolescentes con LCT. La función ejecutiva (medida con el cuestionario Inventario de clasificación de la conducta de la función ejecutiva, con puntuaciones más bajas que significan un funcionamiento más alto) se correlacionó con el grosor cortical prefrontal en adolescentes con desarrollo típico (r = 0.72, p = 0.009). Se encontraron tendencias opuestas para las correlaciones entre el grosor cortical y la función ejecutiva en el LCT y la cohorte de control. INTERPRETACIÓN: La maduración estructural en adolescentes con desarrollo típico se correlaciona con el desarrollo funcional: cuanto mayor es el adolescente, más delgada es la corteza prefrontal, y mejor la función ejecutiva. En adolescentes con LCT observamos una tendencia opuesta, que parecía significativamente diferente del grupo de control: cuanto más delgada era la corteza prefrontal y temporal, peor el funcionamiento ejecutivo.

ESPESSURA PRÉ-FRONTAL E TEMPORAL EM ADOLESCENTES COM LESÃO CEREBRAL TRAUMÁTICA: OBJETIVO: Investigar o impacto da lesão cerebral traumática no córtex pré-frontal -temporal em desenvolvimento de adolescentes, e medidas cerebrais estruturais correlacionadas com o funcionamento cognitivo. MÉTODO: Dezenove adolescentes (12 do sexo masculino, sete do sexo feminino, variação de idade: 11-17a, média: 15a 8m, desvio padrão: 1a 7m, mediana: 15a 11m) com lesão cerebral traumática (LCT) foram incluídos. A espessura cortical dos lobos frontais e temporais foi avaliada usando ressonância magnética funcional. Correlacionamos a espessura cortical de regiões pré-frontais-temporais com a idade, tempo após a lesão, e funcionamento neurocognitivo, e comparamos estes resultados com uma coorte controle pareada, sem LCT. RESULTADOS: Encontramos córtex pré-frontal (p=0,039) e temporal (p=0,002) mais finos em adolescentes com LCT. Além disso, efeito significativo da idade foi observado na espessura pré-frontal (r=-0,75, p=0,003) e temporal (r=-0,66, p=0,013) em adolescentes com desenvolvimento típico, mas não nos com LCT. A função executiva (mensurada com o questionário Inventário de pontuação do comportamento da Função Executiva, com menor pontuação indicando maior funcionamento) foi correlacionada com a espessura cortical pré-frontal em adolescentes com desenvolvimento típico (r=0,72, p=0,009). Tendências opostas para as correlações entre espessura cortical e função executiva foram encontradas nas coortes com LCT e controle. INTERPRETAÇÃO: A maturação estrutural em adolescentes com desenvolvimento típico se correlaciona com o desenvolvimento functional: quanto mais velho o adolescente, mais fino o córtex e melhor a função executiva. Em adolescents com LCT observamos a tendência oposta, que foi significantemente diferente do grupo controle: quanto mais fino o córtex pré-frontal e temporal, pior a função cognitiva.

Altered brain cortical maturation is found in adolescents with a family history of alcoholism.

Substance-naïve offspring from high-density alcohol use disorder (AUD) families exhibit altered subcortical brain volumes structurally and altered executive-functioning and emotion-processing functionally, compared with their peers. However, there is a dearth of literature exploring alterations of cortical thickness (CTh) in this population. T1-weighted structural brain MRI was acquired in 75 substance-naïve male offspring of treatment-seeking early onset (<25 years) AUD patients with high familial loading of AUDs (≥2 affected relatives) (FHP) and 65 age-matched substance-naïve male controls with negative family history from the community. Surface-based CTh reconstruction was done using FreeSurfer. Univariate general linear models were implemented at each vertex using SurfStat, controlling for age (linear and quadratic effects), and head size, to examine the main effect of familial AUD risk on CTh and its relationship with externalizing symptom score (ESS). A Johnson-Neyman procedure revealed that the main effect of familial AUD risk on CTh was seen during adolescence, where the FHP group had thicker cortices involving bilateral precentral gyri, left caudal middle frontal gyrus (MFG), bilateral temporo-parietal junction, left inferior-frontal gyrus and right inferior-temporal gyrus. Thicker cortices in left MFG and inferior-parietal lobule were also associated with greater ESS within both groups. More importantly, these group differences diminished with age by young adulthood. Familial AUD risk is associated with age-related differences in maturation of several higher order association cortices that are critical to ongoing development in executive function, emotion regulation and social cognition during adolescence. Early supportive intervention for a delay in alcohol initiation during this critical phase may be crucial for this at-risk population.

Nestin-expressing cell types in the temporal lobe and hippocampus: Morphology, differentiation, and proliferative capacity.

Nestin is expressed in immature neuroepithelial and progenitor cell types and transiently upregulated in proliferative neuroglial cells responding to acute brain injury, including following seizures. In 36 temporal lobe (TLobe) specimens from patients with TLobe epilepsy (age range 8-60 years) we studied the number, distribution and morphology of nestin-expressing cells (NEC) in the pes, hippocampus body, parahippocampal gyrus, amygdala, temporal cortex and pole compared with post mortem control tissues from 26 cases (age range 12 gestational weeks to 76 years). The proliferative fraction of NEC was evaluated in selected regions, including recognized niches, using MCM2. Their differentiation was explored with neuronal (DCX, mushashi, ßIII tubulin, NeuN) and glial (GFAP, GFAPdelta, glutamine synthetase, aquaporin4, EAAT1) markers, both in sections or following culture. Findings were correlated with clinical parameters. A stereotypical pattern in the distribution and morphologies of NEC was observed, reminiscent of patterns in the developing brain, with increased densities in epilepsy than adult controls (p < .001). Findings included MCM2-positive radial glial-like cells in the periventricular white matter and rows of NEC in the hippocampal fimbria and sulcus. Nestin cells represented 29% of the hippocampal proliferative fraction in epilepsy cases; 20% co-expressed ßIII tubulin in culture compared with 28% with GFAP. Significant correlations were noted between age at surgery, memory deficits and nestin populations. TLobe NEC with ongoing proliferative capacity likely represent vestiges of developmental migratory streams and resident reactive cell populations of potential relevance to hippocampal epileptogenesis, TLobe pathology, and co-morbidities, including memory decline.

Postnatal Development of Intrinsic Horizontal Axons in Macaque Inferior Temporal and Primary Visual Cortices.

Two distinct areas along the ventral visual stream of monkeys, the primary visual (V1) and inferior temporal (TE) cortices, exhibit different projection patterns of intrinsic horizontal axons with patchy terminal fields in adult animals. The differences between the patches in these 2 areas may reflect differences in cortical representation and processing of visual information. We studied the postnatal development of patches by injecting an anterograde tracer into TE and V1 in monkeys of various ages. At 1 week of age, labeled patches with distribution patterns reminiscent of those in adults were already present in both areas. The labeling intensity of patches decayed exponentially with projection distance in monkeys of all ages in both areas, but this trend was far less evident in TE. The number and extent of patches gradually decreased with age in V1, but not in TE. In V1, axonal and bouton densities increased postnatally only in patches with short projection distances, whereas in TE this density change occurred in patches with various projection distances. Thus, patches with area-specific distribution patterns are formed early in life, and area-specific postnatal developmental processes shape the connectivity of patches into adulthood.

Robust Resilience of the Frontotemporal Syntax System to Aging.

UNLABELLED: Brain function is thought to become less specialized with age. However, this view is largely based on findings of increased activation during tasks that fail to separate task-related processes (e.g., attention, decision making) from the cognitive process under examination. Here we take a systems-level approach to separate processes specific to language comprehension from those related to general task demands and to examine age differences in functional connectivity both within and between those systems. A large population-based sample (N = 111; 22-87 years) from the Cambridge Centre for Aging and Neuroscience (Cam-CAN) was scanned using functional MRI during two versions of an experiment: a natural listening version in which participants simply listened to spoken sentences and an explicit task version in which they rated the acceptability of the same sentences. Independent components analysis across the combined data from both versions showed that although task-free language comprehension activates only the auditory and frontotemporal (FTN) syntax networks, performing a simple task with the same sentences recruits several additional networks. Remarkably, functionality of the critical FTN is maintained across age groups, showing no difference in within-network connectivity or responsivity to syntactic processing demands despite gray matter loss and reduced connectivity to task-related networks. We found no evidence for reduced specialization or compensation with age. Overt task performance was maintained across the lifespan and performance in older, but not younger, adults related to crystallized knowledge, suggesting that decreased between-network connectivity may be compensated for by older adults' richer knowledge base. SIGNIFICANCE STATEMENT: Understanding spoken language requires the rapid integration of information at many different levels of analysis. Given the complexity and speed of this process, it is remarkably well preserved with age. Although previous work claims that this preserved functionality is due to compensatory activation of regions outside the frontotemporal language network, we use a novel systems-level approach to show that these "compensatory" activations simply reflect age differences in response to experimental task demands. Natural, task-free language comprehension solely recruits auditory and frontotemporal networks, the latter of which is similarly responsive to language-processing demands across the lifespan. These findings challenge the conventional approach to neurocognitive aging by showing that the neural underpinnings of a given cognitive function depend on how you test it.