Longitudinal four-dimensional mapping of subcortical anatomy in human development

Abstract

Growing access to large-scale longitudinal structural neuroimaging data has fundamentally altered our understanding of cortical development en route to human adulthood, with consequences for basic science, medicine, and public policy. In striking contrast, basic anatomical development of subcortical structures such as the striatum, pallidum, and thalamus has remained poorly describeddespite these evolutionarily ancient structures being both intimate working partners of the cortical sheet and critical to diverse developmentally emergent skills and disorders. Here, to begin addressing this disparity, we apply methods for the measurement of subcortical volume and shape to 1,171 longitudinally acquired structural magnetic resonance imaging brain scans from 618 typically developing males and females aged 5-25 y. We show that the striatum, pallidum, and thalamus each follow curvilinear trajectories of volume change, which, for the striatum and thalamus, peak after cortical volume has already begun to decline and show a relative delay in males. Four-dimensional mapping of subcortical shape reveals that (i) striatal, pallidal, and thalamic domains linked to specific fronto-parietal association cortices contract with age whereas other subcortical territories expand, and (ii) each structure harbors hotspots of sexually dimorphic change over adolescence-with relevance for sex-biased mental disorders emerging in youth. By establishing the developmental dynamism, spatial heterochonicity, and sexual dimorphism of human subcortical maturation, these data bring our spatiotemporal understanding of subcortical development closer to that of the cortex-allowing evolutionary, basic, and clinical neuroscience to be conducted within a more comprehensive developmental framework.O ur understanding of human brain maturation has been rapidly advanced over the past decade by increased availability of large longitudinal in vivo structural magnetic resonance imaging (sMRI) datasets of pediatric brain development (1). However, to date, large-scale longitudinal sMRI studies have focused on the cortical sheet at the expense of subcortical structures such as the striatum, pallidum, and thalamus. Through the analysis of such data, we now know that cortical volume does not undergo a spatially homogenous linear change with development, but rather follows a highly dynamic and regionally heterogenous "inverted-U" trajectory (2-5). These basic aspects of anatomical maturation-the timing of overall growth and regional differences in the tempo of structural maturation-have yet to be longitudinally resolved in the human subcortex (6-9).Access to spatiotemporally fine-grained maps of human cortical development has had major scientific and societal consequences. These maps have impacted the study of brain evolution (10), cognitive-behavioral variation in health (11), and mechanisms of neurodevelopmental disease (12, 13). However, evolution, function, and dysfunction of the cortical sheet occur in the context of its rich structural and functional connectedn...

Child Psychiatry Branch of the National Institute of Mental Health Longitudinal Structural Magnetic Resonance Imaging Study of Human Brain Development

“…In our sample, the striatum, pallidum, and thalamus, like cortical GM, follow an inverted U-shaped developmental trajectory (Raznahan et al, 2014). Striatum and thalamus volumes peak later than cortical volumes and show a relative delay in males.…”

Sensitive Periods in Affective Development: Nonlinear Maturation of Fear Learning

“…The prefrontal and subcortical circuitry implicated in adult fear learning undergoes substantial developmental change from childhood through adulthood (Gogtay et al, 2004;Lenroot and Giedd, 2006;Raznahan et al, 2014). Mirroring these pronounced changes in the brain, numerous studies to date suggest that fear learning and regulation exhibit qualitative changes across development (Figure 1).…”

“…In contrast to the development of sensory and motor systems, structural and functional changes within affective neural circuits continue well into young adulthood. The neurocircuitry supporting affective learning and regulation comprises a network of cortical and subcortical regions that exhibit extended maturational trajectories (Gogtay et al, 2004;Raznahan et al, 2014). Variation in early-life experience can persistently alter the development and function of these circuits (Lupien et al, 2009), highlighting the important role of experience-dependent plasticity in determining adult affective outcomes.…”

Studying neuroanatomy using MRI

“…Box 3: developmental structural neuroimaging Our first major longitudinal insight into the dynamics of in vivo human brain development came from a structural neuroimaging study 157 , which revealed that the maturational trajectory of human gray matter volume follows a curvilinear "inverted-U", rather than showing a linear progression to adult values. Since this seminal study there has been a steep climb in the number of large-scale longitudinal structural neuroimaging datasets 158 and associated research reports detailing the spatiotemporal heterogeneity of neuroanatomical maturation within the brain 16,159 , and charting how the dynamics of structural brain development can vary as a function of genetic 160 , environmental 19 , demographic (e.g. biological sex 159 ), cognitive 161 and clinical 162 factors.…”

“…It has become clear that these diverse metrics follow distinct developmental trajectories in health 163 , which reflect non-overlapping sets of genetic and environmental influences 18 , but can be inter-related in a spatiotemporally specific manner 164 . These normative observations carry major consequences for the optimal design of structural neuroimaging analysis in clinical populations, because conclusions regarding the presence and regional distribution of cortical abnormalities in a given genetic disorder can vary greatly across different morphometric features 159 .…”