Adolescent brain maturation and cortical folding: evidence for reductions in gyrification

Evidence from anatomical and functional imaging studies have highlighted major modifications of cortical circuits during adolescence. These include reductions of gray matter (GM), increases in the myelination of cortico-cortical connections and changes in the architecture of large-scale cortical networks. It is currently unclear, however, how the ongoing developmental processes impact upon the folding of the cerebral cortex and how changes in gyrification relate to maturation of GM/WM-volume, thickness and surface area. In the current study, we acquired high-resolution (3 Tesla) magnetic resonance imaging (MRI) data from 79 healthy subjects (34 males and 45 females) between the ages of 12 and 23 years and performed whole brain analysis of cortical folding patterns with the gyrification index (GI). In addition to GI-values, we obtained estimates of cortical thickness, surface area, GM and white matter (WM) volume which permitted correlations with changes in gyrification. Our data show pronounced and widespread reductions in GI-values during adolescence in several cortical regions which include precentral, temporal and frontal areas. Decreases in gyrification overlap only partially with changes in the thickness, volume and surface of GM and were characterized overall by a linear developmental trajectory. Our data suggest that the observed reductions in GI-values represent an additional, important modification of the cerebral cortex during late brain maturation which may be related to cognitive development

Multimodality evaluation of the pediatric brain: DTI and its competitors

The development of the human brain, from the fetal period until childhood, happens in a series of intertwined neurogenetical and histogenetical events that are influenced by environment. Neuronal proliferation and migration, cell aggregation, axonal ingrowth and outgrowth, dendritic arborisation, synaptic pruning and myelinisation contribute to the ‘plasticity of the developing brain'. These events taken together contribute to the establishment of adult-like neuroarchitecture required for normal brain function. With the advances in technology today, mostly due to the development of non-invasive neuroimaging tools, it is possible to analyze these structural events not only in anatomical space but also longitudinally in time. In this review we have highlighted current ‘state of the art' neuroimaging tools. Development of the new MRI acquisition sequences (DTI, CHARMED and phase imaging) provides valuable insight into the changes of the microstructural environment of the cortex and white matter. Development of MRI imaging tools dedicated for analysis of the acquired images (i) TBSS and ROI fiber tractography, (ii) new tissue segmentation techniques and (iii) morphometric analysis of the cortical mantle (cortical thickness and convolutions) allows the researchers to map the longitudinal changes in the macrostructure of the developing brain that go hand-in-hand with the acquisition of cognitive skills during childhood. Finally, the latest and the newest technologies, like connectom analysis and resting state fMRI connectivity analysis, today, for the first time provide the opportunity to study the developing brain through the prism of maturation of the systems and networks beyond individual anatomical areas. Combining these methods in the future and modeling the hierarchical organization of the brain might ultimately help to understand the mechanisms underlying complex brain structure function relationships of normal development and of developmental disorder

Mother-child similarity in brain morphology: A comparison of structural characteristics of the brain\u27s reading network

Background: Substantial evidence acknowledges the complex gene-environment interplay impacting brain development and learning. Intergenerational neuroimaging allows the assessment of familial transfer effects on brain structure, function and behavior by investigating neural similarity in caregiver-child dyads. Methods: Neural similarity in the human reading network was assessed through well-used measures of brain structure (i.e., surface area (SA), gyrification (lG), sulcal morphology, gray matter volume (GMV) and cortical thickness (CT)) in 69 mother-child dyads (children\u27s age~11 y). Regions of interest for the reading network included left-hemispheric inferior frontal gyrus, inferior parietal lobe and fusiform gyrus. Mother-child similarity was quantified by correlation coefficients and familial specificity was tested by comparison to random adult-child dyads. Sulcal morphology analyses focused on occipitotemporal sulcus interruptions and similarity was assessed by chi-square goodness of fit. Results: Significant structural brain similarity was observed for mother-child dyads in the reading network for lG, SA and GMV (r = 0.349/0.534/0.542, respectively), but not CT. Sulcal morphology associations were non-significant. Structural brain similarity in lG, SA and GMV were specific to mother-child pairs. Furthermore, structural brain similarity for SA and GMV was higher compared to CT. Conclusion: Intergenerational neuroimaging techniques promise to enhance our knowledge of familial transfer effects on brain development and disorders

Stage-dependent loss of cortical gyrification as Parkinson disease “unfolds”

Nigrostriatal terminal losses are known to progress most rapidly in early-stage Parkinson disease (PD) and then plateau, whereas cortical pathology continues and may provide a better marker of PD progression in later stages. We investigated cortical gyrification indices in patients with different durations of PD, since cortical folding may capture complex processes involving transverse forces of neuronal sheets or underlying axonal connectivity. Longitudinal cohort structural MRI were obtained at baseline, 18 months, and 36 months from 70 patients with PD without dementia and 70 control participants. Cortical local gyrification index (LGI) was compared between controls and PD subgroups based upon duration of illness (DOI, 5 years [PDL, n = 24]) and adjusted using false discovery rate. Associations between LGI and clinical measurements were assessed using multiple linear regression. Areas having significantly reduced LGI also were analyzed using baseline data from a newly established cohort (PD n = 87, control n = 66) to validate our findings. In the longitudinal cohort, PDL had significantly reduced overall gyrification, and bilaterally in the inferior parietal, postcentral, precentral, superior frontal, and supramarginal areas, compared to controls (p < 0.05). Longitudinally, loss of gyrification was accelerated in PDM participants, compared to controls. LGI showed robust correlations with DOI and also was correlated with PD-related clinical measurements. Similar results were obtained in the validation sample. Loss of cortical gyrification may be accelerated within the first few years after PD diagnosis, and become particularly prominent in later stages. Thus, it may provide a metric for monitoring progression in vivo

Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes.

We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE /presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. We now show that in an independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse model of Aβ amyloidosis, an ABX-perturbed gut microbiome is associated with a reduction in Aβ pathology and alterations in microglial morphology, thus establishing the generality of the phenomenon. Most importantly, these latter alterations occur only in brains of male mice, not in the brains of female mice. Furthermore, ABX treatment lead to alterations in levels of selected microglial expressed transcripts indicative of the "M0" homeostatic state in male but not in female mice. Finally, we found that transplants of fecal microbiota from age-matched APPPS1-21 male mice into ABX-treated APPPS1-21 male restores the gut microbiome and partially restores Aβ pathology and microglial morphology, thus demonstrating a causal role of the microbiome in the modulation of Aβ amyloidosis and microglial physiology in mouse models of Aβ amyloidosis

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Developmental trajectories of cortical thickness by functional brain network: The roles of pubertal timing and socioeconomic status

The human cerebral cortex undergoes considerable changes during development, with cortical maturation patterns reflecting regional heterogeneity that generally progresses in a posterior-to-anterior fashion. However, the organizing principles that govern cortical development remain unclear. In the current study, we characterized age-related differences in cortical thickness (CT) as a function of sex, pubertal timing, and two dissociable indices of socioeconomic status (i.e., income-to-needs and maternal education) in the context of functional brain network organization, using a cross-sectional sample (n = 789) diverse in race, ethnicity, and socioeconomic status from the Lifespan Human Connectome Project in Development (HCP-D). We found that CT generally followed a linear decline from 5 to 21 years of age, except for three functional networks that displayed nonlinear trajectories. We found no main effect of sex or age by sex interaction for any network. Earlier pubertal timing was associated with reduced mean CT and CT in seven networks. We also found a significant age by maternal education interaction for mean CT across cortex and CT in the dorsal attention network, where higher levels of maternal education were associated with steeper age-related decreases in CT. Taken together, our results suggest that these biological and environmental variations may impact the emerging functional connectome