Human brain development over the early years

Recent studies of the structural and functional development of the human brain over the early years have highlighted the rapid development of brain structures and their interconnectivity. Some regional functional specializations emerge within the first months after birth, while others have a more protracted course of development spanning over the first decade or longer. While some anatomical changes enable the emergence of new functions, evidence also points to the importance of resting state oscillations in sculpting neural architecture during development. In atypical development differences in brain structure, function and task-related activity in infancy often precede the emergence of later diagnostic behavioural symptoms

Economic, Neurobiological and Behavioral Perspectives on Building America's Future Workforce

A growing proportion of the U.S. workforce will have been raised in disadvantaged environments that are associated with relatively high proportions of individuals with diminished cognitive and social skills. A cross-disciplinary examination of research in economics, developmental psychology, and neurobiology reveals a striking convergence on a set of common principles that account for the potent effects of early environment on the capacity for human skill development. Central to these principles are the findings that early experiences have a uniquely powerful influence on the development of cognitive and social skills, as well as on brain architecture and neurochemistry; that both skill development and brain maturation are hierarchical processes in which higher level functions depend on, and build on, lower level functions; and that the capacity for change in the foundations of human skill development and neural circuitry is highest earlier in life and decreases over time. These findings lead to the conclusion that the most efficient strategy for strengthening the future workforce, both economically and neurobiologically, and for improving its quality of life is to invest in the environments of disadvantaged children during the early childhood years.

Economic, neurobiological, and behavioral perspectives on building America’s future workforce.

A growing proportion of the U.S. workforce will have been raised in disadvantaged environments that are associated with relatively high proportions of individuals with diminished cognitive and social skills. A cross-disciplinary examination of research in economics, developmental psychology, and neurobiology reveals a striking convergence on a set of common principles that account for the potent effects of early environment on the capacity for human skill development. Central to these principles are the findings that early experiences have a uniquely powerful influence on the development of cognitive and social skills and on brain architecture and neurochemistry, that both skill development and brain maturation are hierarchical processes in which higher level functions depend on, and build on, lower level functions, and that the capacity for change in the foundations of human skill development and neural circuitry is highest earlier in life and decreases over time. These findings lead to the conclusion that the most efficient strategy for strengthening the future workforce, both economically and neurobiologically, and improving its quality of life is to invest in the environments of disadvantaged children during the early childhood years. child development ͉ early experience ͉ economic productivity ͉ critical and sensitive periods ͉ brain developmen

Economic, neurobiological, and behavioral perspectives on building America’s future workforce.

A growing proportion of the U.S. workforce will have been raised in disadvantaged environments that are associated with relatively high proportions of individuals with diminished cognitive and social skills. A cross-disciplinary examination of research in economics, developmental psychology, and neurobiology reveals a striking convergence on a set of common principles that account for the potent effects of early environment on the capacity for human skill development. Central to these principles are the findings that early experiences have a uniquely powerful influence on the development of cognitive and social skills and on brain architecture and neurochemistry, that both skill development and brain maturation are hierarchical processes in which higher level functions depend on, and build on, lower level functions, and that the capacity for change in the foundations of human skill development and neural circuitry is highest earlier in life and decreases over time. These findings lead to the conclusion that the most efficient strategy for strengthening the future workforce, both economically and neurobiologically, and improving its quality of life is to invest in the environments of disadvantaged children during the early childhood years. child development ͉ early experience ͉ economic productivity ͉ critical and sensitive periods ͉ brain developmen

Autism as an adaptive common variant pathway for human brain development

While research on focal perinatal lesions has provided evidence for recovery of function, much less is known about processes of brain adaptation resulting from mild but widespread disturbances to neural processing over the early years (such as alterations in synaptic efficiency). Rather than being viewed as a direct behavioral consequence of life-long neural dysfunction, I propose that autism is best viewed as the end result of engaging adaptive processes during a sensitive period. From this perspective, autism is not appropriately described as a disorder of neurodevelopment, but rather as an adaptive common variant pathway of human functional brain development

Estrogen receptor β in Alzheimer's disease: from mechanisms to therapeutics

Alzheimer's disease (AD) disproportionally affects women and men. The female susceptibility for AD has been largely associated with the loss of ovarian sex hormones during menopause. This review examines current understanding of the role of estrogen receptor β (ERβ) in the regulation of neurological health and its implication in the development and intervention of AD. Since its discovery in 1996, research conducted over the last 15-20 years has documented a great deal of evidence indicating that ERβ plays a pivotal role in a broad spectrum of brain activities from development to aging. ERβ genetic polymorphisms have been associated with cognitive impairment and increased risk for AD predominantly in women. The role of ERβ in the intervention of AD has been demonstrated by the alteration of AD pathology in response to treatment with ERβ-selective modulators in transgenic models that display pronounced plaque and tangle histopathological presentations as well as learning and memory deficits. Future studies that explore the potential interactions between ERβ signaling and the genetic isoforms of human apolipoprotein E (APOE) in brain aging and development of AD-risk phenotype are critically needed. The current trend of lost-in-translation in AD drug development that has primarily been based on early-onset familial AD (FAD) models underscores the urgent need for novel models that recapitulate the etiology of late-onset sporadic AD (SAD), the most common form of AD representing more than 95% of the current human AD population. Combining the use of FAD-related models that generally have excellent face validity with SAD-related models that hold more reliable construct validity would together increase the predictive validity of preclinical findings for successful translation into humans

The functional neuroanatomy of bipolar disorder:a consensus model

OBJECTIVES: Functional neuroimaging methods have proliferated in recent years, such that functional magnetic resonance imaging, in particular, is now widely used to study bipolar disorder. However, discrepant findings are common. A workgroup was organized by the Department of Psychiatry, University of Cincinnati (Cincinnati, OH, USA) to develop a consensus functional neuroanatomic model of bipolar I disorder based upon the participants' work as well as that of others. METHODS: Representatives from several leading bipolar disorder neuroimaging groups were organized to present an overview of their areas of expertise as well as focused reviews of existing data. The workgroup then developed a consensus model of the functional neuroanatomy of bipolar disorder based upon these data. RESULTS: Among the participants, a general consensus emerged that bipolar I disorder arises from abnormalities in the structure and function of key emotional control networks in the human brain. Namely, disruption in early development (e.g., white matter connectivity and prefrontal pruning) within brain networks that modulate emotional behavior leads to decreased connectivity among ventral prefrontal networks and limbic brain regions, especially the amygdala. This developmental failure to establish healthy ventral prefrontal-limbic modulation underlies the onset of mania and ultimately, with progressive changes throughout these networks over time and with affective episodes, a bipolar course of illness. CONCLUSIONS: This model provides a potential substrate to guide future investigations and areas needing additional focus are identified

Theory-based Explorations of Associations between Human Brain Structure and Intelligence from Childhood to Early Adulthood

Intelligence is often defined as the ability of an agent to learn, adapt to its environment, and solve novel challenges. However, despite over 100 years of theoretical development (e.g., general intelligence), widespread explanatory power (up to 50% of variance in cognitive scores), and the ability of intelligence measures to predict important life outcomes such as educational achievement and mortality, the exact configuration and neural correlates of cognitive ability remain poorly understood. This dissertation aims to make progress in this pursuit by exploring how human brain structure and intelligence correlate and co-develop with each other from childhood to early adulthood (ages 5 – 22 years). This endeavour is undertaken in three large cohorts (N range: 337 – 2072), guided by theory (e.g., crystallised and fluid intelligence), and implemented using rigorous, cutting-edge quantitative methods (i.e., structural equation modelling and network science). The results of this research provide robust evidence that the brain-behaviour relationships in intelligence are complex (i.e., consists of many independent yet interacting parts) and change nonlinearly during development. The first study sought to elucidate the factorial structure and white matter substrates of child and adolescent intelligence using two cross-sectional, developmental samples (CALM: N = 551 (N = 165 neuroimaging), age range: 5 – 18 years; NKI-Rockland: N = 337 (N = 65 neuroimaging), age range: 6 – 18 years). In both samples, it was found (using structural equation modelling (SEM)) that cognitive ability is best modelled as two separable yet related constructs, crystallised and fluid intelligence, which became more distinct (i.e., less correlated) across development, in line with the age differentiation hypothesis. Further analyses revealed that white matter microstructure, most prominently of the superior longitudinal fasciculus, was strongly associated with crystallised (gc) and fluid (gf) abilities. Finally, SEM trees, which combines traditional SEM with decision trees, provided evidence for developmental reorganisation of gc and gf and their white matter substrates such that the relationships among these factors dropped between ages 7 – 8 years before increasing around age 10. Together, these results suggested that shortly before puberty marks a pivotal phase of change in the neurocognitive architecture of intelligence. The second study builds upon the first by again examining the neurocognitive structure of intelligence, this time from a network perspective. The network or mutualism theory of intelligence presupposes direct (statistical) interactions among cognitive abilities (e.g., maths, memory, and vocabulary) throughout development. Therefore, this project used network analytic methods (specifically graphical LASSO) to simultaneously model brain-behaviour relationships essential for general intelligence in a large (behavioural, N = 805; cortical volume, N = 246; fractional anisotropy, N = 165), developmental (ages 5 – 18 years) cohort of struggling learners (CALM). Results indicated that both the single-layer (cognitive or neural nodes) and multilayer (combined cognitive and neural variables) networks consisted of mostly positive, small partial correlations, providing further support for the mutualism/network theory of cognitive ability. Moreover, using community detection (i.e., the Walktrap algorithm) and calculating node centrality (absolute strength and bridge strength), convergent evidence suggested that subsets of both cognitive and neural nodes play an intermediary role ‘between’ brain and behaviour. Overall, these findings suggest specific behavioural and neural variables that may have greater influence among (or might be more influenced by) other nodes within general intelligence. The final study investigated the longitudinal relationships between human cortical grey matter structure and measures of decision-making, risk-related behaviours, and spatial working memory from adolescence to early adulthood (ages 14 – 22 years). In the IMAGEN study (maximum N across time points/waves = 2072), latent growth curve models were used to estimate the baseline and longitudinal associations between behavioural measures and cortical surface area, thickness, and volume. Univariate models (only behavioural or neural measures) revealed that performance in decision-making, risk-related behaviours, and spatial working memory, as well as brain structure changed nonlinearly from mid-adolescence (age 14) to early adulthood (age 22). Furthermore, bivariate models (combined behavioural and neural measures) provided evidence for adaptive reorganisation (behaviour intercept predicts changes in brain structure) but not structural scaffolding (brain structure intercept predicts changes in behaviour). Furthermore, findings suggested that there were no correlated changes between behavioural and brain structure slopes (rates of change from mid-adolescence to early adulthood). This dissertation concludes by summarising the core results, addressing key limitations, and discussing avenues for future research. Taken together, this thesis hopes to convince cognitive neuroscientists that to understand cognitive ability and its neural determinants, they (we) must work more diligently toward building coherent, rigorous, and testable neurocognitive theories of intelligence—particularly under the conceptual and analytic paradigm of complex systems.The Cambridge Commonwealth, European & International Trus