Subcortical Maturation Research Articles

T2* Mapping of Placental Oxygenation to Estimate Fetal Cortical and Subcortical Maturation

This cohort study investigates the association between T2* mapping of placental oxygenation and cortical and subcortical fetal brain volumes in typically developing fetuses scanned longitudinally in the third trimester.

A unified model for reconstruction and [formula omitted] mapping of accelerated 7T data using the quantitative recurrent inference machine

Quantitative MRI (qMRI) acquired at the ultra-high field of 7 Tesla has been used in visualizing and analyzing subcortical structures. qMRI relies on the acquisition of multiple images with different scan settings, leading to extended scanning times. Data redundancy and prior information from the relaxometry model can be exploited by deep learning to accelerate the imaging process. We propose the quantitative Recurrent Inference Machine (qRIM), with a unified forward model for joint reconstruction and R2*-mapping from sparse data, embedded in a Recurrent Inference Machine (RIM), an iterative inverse problem-solving network. To study the dependency of the proposed extension of the unified forward model to network architecture, we implemented and compared a quantitative End-to-End Variational Network (qE2EVN). Experiments were performed with high-resolution multi-echo gradient echo data of the brain at 7T of a cohort study covering the entire adult life span. The error in reconstructed R2* from undersampled data relative to reference data significantly decreased for the unified model compared to sequential image reconstruction and parameter fitting using the RIM. With increasing acceleration factor, an increasing reduction in the reconstruction error was observed, pointing to a larger benefit for sparser data. Qualitatively, this was following an observed reduction of image blurriness in R2*-maps. In contrast, when using the U-Net as network architecture, a negative bias in R2* in selected regions of interest was observed. Compressed Sensing rendered accurate, but less precise estimates of R2*. The qE2EVN showed slightly inferior reconstruction quality compared to the qRIM but better quality than the U-Net and Compressed Sensing. Subcortical maturation over age measured by a linearly increasing interquartile range of R2* in the striatum was preserved up to an acceleration factor of 9. With the integrated prior of the unified forward model, the proposed qRIM can exploit the redundancy among repeated measurements and shared information between tasks, facilitating relaxometry in accelerated MRI.

Charting human subcortical maturation across the adult lifespan with in vivo 7 T MRI

The human subcortex comprises hundreds of unique structures. Subcortical functioning is crucial for behavior, and disrupted function is observed in common neurodegenerative diseases. Despite their importance, human subcortical structures continue to be difficult to study in vivo. Here we provide a detailed account of 17 prominent subcortical structures and ventricles, describing their approximate iron and myelin contents, morphometry, and their age-related changes across the normal adult lifespan. The results provide compelling insights into the heterogeneity and intricate age-related alterations of these structures. They also show that the locations of many structures shift across the lifespan, which is of direct relevance for the use of standard magnetic resonance imaging atlases. The results further our understanding of subcortical morphometry and neuroimaging properties, and of normal aging processes which ultimately can improve our understanding of neurodegeneration.

Attention-deficit/hyperactivity disorder is characterized by a delay in subcortical maturation

Although previous studies have found that ADHD is characterized by a delay in cortical maturation, it is not clear whether this phenomenon was secondary to developmental trajectories in subcortical regions (caudate, putamen, pallidum, thalamus, hippocampus and amygdala). Using the ADHD-200 dataset, we estimated subcortical volumes in 339 individuals with ADHD and 568 typically developing controls. We defined the growth trajectory of each subcortical structure, delineating a phase of childhood increase followed by an adolescent decrease in subcortical volumes using a quadratic growth model. From these trajectories, the age of attaining peak subcortical volumes was derived and used as an index of subcortical maturation. We found that subcortical structures (caudate, putamen, pallidum, thalamus, hippocampus and amygdala) followed curvilinear trajectories similar to those reported in previous studies. The volumes of these subcortical structures in ADHD were also delayed in the developmental trajectory, which suggested that ADHD may be characterized by a delay in subcortical maturation. This delay may lead to a shift in which individuals with ADHD go through the process of pruning the nerve connections that is part of the normal maturation process during adolescence. Further, we also found that the asymmetric development of subcortical structures was abnormal in ADHD, which resulted from the imbalance of the maturation delay of bilateral subcortical structures. The subcortical maturation delay may play an important role in the pathophysiology of ADHD. Our findings provide new potential targets to investigate the pathophysiology of ADHD.

Subcortical structural variations associated with low socioeconomic status in adolescents

Low socioeconomic status (SES) is associated with a higher probability of multiple exposures (e.g., neighborhood violence, poor nutrition, housing instability, air pollution, and insensitive caregiving) known to affect structural development of subcortical brain regions that subserve threat and reward processing, however, few studies have examined the relationship between SES and such subcortical structures in adolescents. We examined SES variations in volume and surface morphometry of subcortical regions. The sample comprised 256 youth in eighth grade (mean age = 13.9 years), in whom high dimensional deformation mapping of structural 3T magnetic resonance imaging scans was performed. Vertex‐wise linear regression analyses examined associations between income to poverty ratio and surfaces of the hippocampus, amygdala, thalamus, caudate, putamen, nucleus accumbens and pallidum, with the covariates age, pubertal status, and intracranial volume. Given sex differences in pubertal development and subcortical maturation at this age, the analyses were stratified by sex. Among males, who at this age average an earlier pubertal stage than females, the relationship between SES and local shape variation in subcortical regions was almost entirely positive. For females, the relationship between SES and local shape variation was negative. Racial identity was associated with SES in our sample, however supplementary analyses indicated that most of the associations between SES and subcortical structure were independent of it. Although these cross‐sectional results are not definitive, they are consistent with a scenario where low SES delays structural maturation of subcortical regions involved with threat and reward processing. Future longitudinal studies are needed to test this hypothesis.

Neuroscience-Inspired, Behavioral Change Program for University Students.

It is clear that environmental influences impact the structure and function of the human brain, and thus, thoughts, actions, and behaviors. These in turn influence whether an individual engages in high-risk (drugs, alcohol, violence) or health-promoting (exercise, meditation, music) activities. The developmental mismatch between cortical and subcortical maturation of the transitional age brain places college students at risk for negative outcomes. This article argues that the prescription of incentive-based behavioral change and brain-building activities simply make good scientific, programmatic, and financial sense for colleges and universities. The authors present University of Vermont Wellness Environment as an example.

P.1.c.020 The neuro-functional impact of a childhood diagnosis of attention deficit/hyperactivity disorder upon decision making in adulthood

Although previous studies have found that ADHD is characterized by a delay in cortical maturation, it is not clear whether this phenomenon was secondary to developmental trajectories in subcortical regions (caudate, putamen, pallidum, thalamus, hippocampus and amygdala). Using the ADHD-200 dataset, we estimated subcortical volumes in 339 individuals with ADHD and 568 typically developing controls. We defined the growth trajectory of each subcortical structure, delineating a phase of childhood increase followed by an adolescent decrease in subcortical volumes using a quadratic growth model. From these trajectories, the age of attaining peak subcortical volumes was derived and used as an index of subcortical maturation. We found that subcortical structures (caudate, putamen, pallidum, thalamus, hippocampus and amygdala) followed curvilinear trajectories similar to those reported in previous studies. The volumes of these subcortical structures in ADHD were also delayed in the developmental trajectory, which suggested that ADHD may be characterized by a delay in subcortical maturation. This delay may lead to a shift in which individuals with ADHD go through the process of pruning the nerve connections that is part of the normal maturation process during adolescence. Further, we also found that the asymmetric development of subcortical structures was abnormal in ADHD, which resulted from the imbalance of the maturation delay of bilateral subcortical structures. The subcortical maturation delay may play an important role in the pathophysiology of ADHD. Our findings provide new potential targets to investigate the pathophysiology of ADHD.

Characterization of mitochondrial bioenergetics in neonatal anoxic model of rats.

Neonatal anoxia at the time of birth can lead to mitochondrial dysfunction and further neurodevelopmental abnormalities. The present study investigated the mitochondrial bioenergetics and associated sensorimotor changes in the anoxic neonatal rats. Rat pups after 30h to birth (2days) were subjected to anoxia of two episodes (10min in each) at a time interval of 24h by passing 100%N2 into an enclosed chamber. Brain mitochondrial respiration was measured using clark type oxygen electrode. A significant decrease in brain respiratory control ratio (RCR; State III/IV respiration) at all-time points, complex I (24h) and complex II (30min, 6 and 24h) enzyme activities indicated loss of mitochondrial integrity and function A significant increase in levels of nitric oxide was observed after second anoxic episode at all-time points. A significant change in sensorimotor activity in terms of increased reflex latency was observed 24h after second episode in this model, which is an indication of loss of subcortical maturation. All the above changes were observed after second but not after the first anoxic exposure. Therefore, this anoxic model shows significant changes in mitochondrial bioenergetics, nitric oxide levels and sensorimotor effects after second episode of anoxia. This model may be helpful to evaluate mitochondrial targeted pharmacological intervention for the treatment of anoxia.

Maturation of Cortico-Subcortical Structural Networks--Segregation and Overlap of Medial Temporal and Fronto-Striatal Systems in Development

The brain consists of partly segregated neural circuits within which structural convergence and functional integration occurs during development. The relationship of structural cortical and subcortical maturation is largely unknown. We aimed to study volumetric development of the hippocampus and basal ganglia (caudate, putamen, pallidum, accumbens) in relation to volume changes throughout the cortex. Longitudinal MRI data were obtained across a mean interval of 2.6 years in 85 participants with an age range of 8-19 years at study start. Left and right subcortical changes were related to cortical change vertex-wise in the ipsilateral hemisphere with general linear models with age, sex, interval between scans, and mean cortical volume change as covariates. Hippocampal-cortical change relationships centered on parts of the Papez circuit, including entorhinal, parahippocampal, and isthmus cingulate areas, and lateral temporal, insular, and orbitofrontal cortices in the left hemisphere. Basal ganglia-cortical change relationships were observed in mostly nonoverlapping and more anterior cortical areas, all including the anterior cingulate. Other patterns were unique to specific basal ganglia structures, including pre-, post-, and paracentral patterns relating to putamen change. In conclusion, patterns of cortico-subcortical development as assessed by morphometric analyses in part map out segregated neural circuits at the macrostructural level.

Longitudinal four-dimensional mapping of subcortical anatomy in human development

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 described--despite 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.

P300 Importance of auditory evoked potentials (AEP) in assessment of brain stem function in patients with axial tumors of posterior fossa

BAEP has been found to be useful for assessment of subcortical maturation. However, the precise maturational changes of the peripheral and central transmission in normal human subjects are still open to controversy. We obtained a total of 200 BAEPs from 165 normal human subjects ranging from infants to young adults. Electrodes were placed at both mastoids and the reference at the vertex. 85 dB SL click stimuli were presented binaurally at a rate of 13/sec and 2,048 responses were summated on line with an averager. Investigation of the maturation of the transmission time indicated that the peripheral auditory apparatus attains functional maturity during the first 2 months of life, whereas the central transmission time shortens up to the age of 5 to 8 years. III-II and V-IV interpeak latencies (IPLs) showed maturational changes similar to those of V-I IPLs, in contrast II-I and IV-III showed little changes. A clear increase of the amplitude of peak V up to 4 years of age and a subsequent decreasing tendency was observed. The V-I IPLs of males were longer than those of females in each age group. Females also displayed larger BAEPs for wave V than males after 2 years of age. These data indicate that it is worthwhile to have separate latency and amplitude norms for males and females from infants to adults for attaching diagnostic significance to BAEP measures.

P296 Source localization of middle- and long-latency auditory evoked potentials using realistic head models

BAEP has been found to be useful for assessment of subcortical maturation. However, the precise maturational changes of the peripheral and central transmission in normal human subjects are still open to controversy. We obtained a total of 200 BAEPs from 165 normal human subjects ranging from infants to young adults. Electrodes were placed at both mastoids and the reference at the vertex. 85 dB SL click stimuli were presented binaurally at a rate of 13/sec and 2,048 responses were summated on line with an averager. Investigation of the maturation of the transmission time indicated that the peripheral auditory apparatus attains functional maturity during the first 2 months of life, whereas the central transmission time shortens up to the age of 5 to 8 years. III-II and V-IV interpeak latencies (IPLs) showed maturational changes similar to those of V-I IPLs, in contrast II-I and IV-III showed little changes. A clear increase of the amplitude of peak V up to 4 years of age and a subsequent decreasing tendency was observed. The V-I IPLs of males were longer than those of females in each age group. Females also displayed larger BAEPs for wave V than males after 2 years of age. These data indicate that it is worthwhile to have separate latency and amplitude norms for males and females from infants to adults for attaching diagnostic significance to BAEP measures.

PS-42-6 Prognostic evaluation of patients with severe head injury by motor evoked potentials induced by transcranial magnetic stimulation

BAEP has been found to be useful for assessment of subcortical maturation. However, the precise maturational changes of the peripheral and central transmission in normal human subjects are still open to controversy. We obtained a total of 200 BAEPs from 165 normal human subjects ranging from infants to young adults. Electrodes were placed at both mastoids and the reference at the vertex. 85 dB SL click stimuli were presented binaurally at a rate of 13/sec and 2,048 responses were summated on line with an averager. Investigation of the maturation of the transmission time indicated that the peripheral auditory apparatus attains functional maturity during the first 2 months of life, whereas the central transmission time shortens up to the age of 5 to 8 years. III-II and V-IV interpeak latencies (IPLs) showed maturational changes similar to those of V-I IPLs, in contrast II-I and IV-III showed little changes. A clear increase of the amplitude of peak V up to 4 years of age and a subsequent decreasing tendency was observed. The V-I IPLs of males were longer than those of females in each age group. Females also displayed larger BAEPs for wave V than males after 2 years of age. These data indicate that it is worthwhile to have separate latency and amplitude norms for males and females from infants to adults for attaching diagnostic significance to BAEP measures.

Developmental changes of brainstem auditory evoked potentials (BAEPs) in normal human subjects from infants to young adults

BAEP has been found to be useful for assessment of subcortical maturation. However, the precise maturational changes of the peripheral and central transmission in normal human subjects are still open to controversy. We obtained a total of 200 BAEPs from 165 normal human subjects ranging from infants to young adults. Electrodes were placed at both mastoids and the reference at the vertex. 85 dB SL click stimuli were presented binaurally at a rate of 13/sec and 2,048 responses were summated on line with an averager. Investigation of the maturation of the transmission time indicated that the peripheral auditory apparatus attains functional maturity during the first 2 months of life, whereas the central transmission time shortens up to the age of 5 to 8 years. III-II and V-IV interpeak latencies (IPLs) showed maturational changes similar to those of V-I IPLs, in contrast II-I and IV-III showed little changes. A clear increase of the amplitude of peak V up to 4 years of age and a subsequent decreasing tendency was observed. The V-I IPLs of males were longer than those of females in each age group. Females also displayed larger BAEPs for wave V than males after 2 years of age. These data indicate that it is worthwhile to have separate latency and amplitude norms for males and females from infants to adults for attaching diagnostic significance to BAEP measures.