A multi-scale cortical wiring space links cellular architecture and functional dynamics in the human brain.

The vast net of fibres within and underneath the cortex is optimised to support the convergence of different levels of brain organisation. Here, we propose a novel coordinate system of the human cortex based on an advanced model of its connectivity. Our approach is inspired by seminal, but so far largely neglected models of cortico-cortical wiring established by postmortem anatomical studies and capitalises on cutting-edge in vivo neuroimaging and machine learning. The new model expands the currently prevailing diffusion magnetic resonance imaging (MRI) tractography approach by incorporation of additional features of cortical microstructure and cortico-cortical proximity. Studying several datasets and different parcellation schemes, we could show that our coordinate system robustly recapitulates established sensory-limbic and anterior-posterior dimensions of brain organisation. A series of validation experiments showed that the new wiring space reflects cortical microcircuit features (including pyramidal neuron depth and glial expression) and allowed for competitive simulations of functional connectivity and dynamics based on resting-state functional magnetic resonance imaging (rs-fMRI) and human intracranial electroencephalography (EEG) coherence. Our results advance our understanding of how cell-specific neurobiological gradients produce a hierarchical cortical wiring scheme that is concordant with increasing functional sophistication of human brain organisation. Our evaluations demonstrate the cortical wiring space bridges across scales of neural organisation and can be easily translated to single individuals

The relationship between individual variation in macroscale functional gradients and distinct aspects of ongoing thought

Contemporary accounts of ongoing thought recognise it as a heterogeneous and multidimensional construct, varying in both form and content. An emerging body of evidence demonstrates that distinct types of experience are associated with unique neurocognitive profiles, that can be described at the whole-brain level as interactions between multiple large scale networks. The current study sought to explore the possibility that whole-brain functional connectivity patterns at rest may be meaningfully related to patterns of ongoing thought that occurred over this period. Participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) followed by a questionnaire retrospectively assessing the content and form of their ongoing thoughts during the scan. A non-linear dimension reduction algorithm was applied to the rs-fMRI data to identify components explaining the greatest variance in whole brain connectivity patterns, and ongoing thought patterns during the resting-state were measured retrospectively at the end of the scan. Multivariate analyses revealed that individuals for whom the connectivity of the sensorimotor system was maximally distinct from the visual system were most likely to report thoughts related to finding solutions to problems or goals and least likely to report thoughts related to the past. These results add to an emerging literature that suggests that unique patterns of experience are associated with distinct distributed neurocognitive profiles and highlight that unimodal systems may play an important role in this process

Differences in subcortico-cortical interactions identified from connectome and microcircuit models in autism.

The pathophysiology of autism has been suggested to involve a combination of both macroscale connectome miswiring and microcircuit anomalies. Here, we combine connectome-wide manifold learning with biophysical simulation models to understand associations between global network perturbations and microcircuit dysfunctions in autism. We studied neuroimaging and phenotypic data in 47 individuals with autism and 37 typically developing controls obtained from the Autism Brain Imaging Data Exchange initiative. Our analysis establishes significant differences in structural connectome organization in individuals with autism relative to controls, with strong between-group effects in low-level somatosensory regions and moderate effects in high-level association cortices. Computational models reveal that the degree of macroscale anomalies is related to atypical increases of recurrent excitation/inhibition, as well as subcortical inputs into cortical microcircuits, especially in sensory and motor areas. Transcriptomic association analysis based on postmortem datasets identifies genes expressed in cortical and thalamic areas from childhood to young adulthood. Finally, supervised machine learning finds that the macroscale perturbations are associated with symptom severity scores on the Autism Diagnostic Observation Schedule. Together, our analyses suggest that atypical subcortico-cortical interactions are associated with both microcircuit and macroscale connectome differences in autism

Multi-atlas segmentation and analysis of the fetal brain in ventriculomegaly

Nowadays, imaging of the human brain is vastly used in clinical settings and by the neuroscientific research community. There is an ever-increasing demand for novel biomedical image analysis approaches and tools to study the brain from its early intrauterine stage through adolescence to adulthood. The intrauterine period, in particular, is a crucial stage for the study of early neurodevelopmental processes. The idiosyncratic nature of the fetal brain poses numerous challenges and asks for the development of new techniques that take into consideration the peculiarities of in utero neurodevelopment. Although still in its infancy, medical image analysis techniques are progressively landing on the study of fetal brains. The purpose of this thesis is to develop automatic segmentation approaches that can be applied to brains at different life stages, including the gestational period, and investigate in utero brain development under ventriculomegaly.En la actualidad, las imagenes del cerebro humano son ampliamente utilizadas en entornos clıınicos y por la comunidad neurocientııfica. Existe una demanda, cada vez mayor, de herramientas y enfoques de analisis de imagenes biomédicas novedosos para estudiar el cerebro desde su temprana etapa intrauterina hasta la adolescencia y la edad adulta. El periodo intrauterino, en particular, es una etapa crucial para el estudio de los procesos iniciales del neurodesarrollo. La naturaleza idiosincrasica del cerebro fetal plantea numerosos desafııos y requiere el desarrollo de nuevas técnicas que contemplen las peculiaridades del neurodesarrollo fetal. Aunque todavııa esta en su infancia, las técnicas de analisis de imagenes médicas estan llegando progresivamente al estudio de los cerebros fetales. El objetivo de esta tesis es desarrollar métodos automaticos de segmentación que puedan aplicarse a cerebros en distintas etapas de la vida, incluyendo el periodo gestacional, e investigar el desarrollo del cerebro fetal con ventriculomegalia

Cortical folding alterations in fetuses with isolated non-severe ventriculomegaly

Neuroimaging of brain diseases plays a crucial role in understanding brain abnormalities and early diagnosis. Of great importance is the study of brain abnormalities in utero and the assessment of deviations in case of mal-development. In this work, brain magnetic resonance images from 23 isolated non-severe ventriculomegaly (INSVM) fetuses and 25 healthy controls between 26 and 29 gestational weeks were used to identify INSVM-related cortical folding deviations from normative development. Since these alterations may reflect abnormal neurodevelopment, our working hypothesis is that markers of cortical folding can provide cues to improve theprediction of later neurodevelopmental problems in INSVM subjects. We analyzed the relationship of ventricular enlargement with cortical folding alterations in a regional basis using several curvature-based measures de-scribing the folding of each cortical region. Statistical analysis (global and hemispheric) and sparse linear regression approaches were then used to find the cortical regions whose folding is associated with ventricular dilation. Results from both approaches were in great accordance, showing a significant cortical folding decrease in the insula, posterior part of the temporal lobe and occipital lobe. Moreover, compared to the global analysis, stronger ipsilateral associations of ventricular enlargement with reduced cortical folding were encountered by the hemispheric analysis. Our findings confirm and extend previous studies by identifying various cortical regions and emphasizing ipsilateral effects of ventricular enlargement in altered folding. This suggests that INSVM is an indicator of altered cortical development, and moreover, cortical regions with reduced folding constitute potential prognostic biomarkers to be used in follow-up studies to decipher the outcome of INSVM fetuses.This work was co-financed by the Marie Curie FP7-PEOPLE-2012-COFUND Action, Grant agreement no: 600387. This study was partly supported by Instituto de Salud Carlos III (PI16/00861) integrados en el Plan Nacional de I+D+I y cofinanciados por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) “ Una manera de hacer Europa"

Adolescent development of multiscale structural wiring and functional interactions in the human connectome

Copyright © 2022 the Author(s).Adolescence is a time of profound changes in the physical wiring and function of the brain. Here, we analyzed structural and functional brain network development in an accelerated longitudinal cohort spanning 14 to 25 y (n = 199). Core to our work was an advanced in vivo model of cortical wiring incorporating MRI features of corticocortical proximity, microstructural similarity, and white matter tractography. Longitudinal analyses assessing age-related changes in cortical wiring identified a continued differentiation of multiple corticocortical structural networks in youth. We then assessed structure–function coupling using resting-state functional MRI measures in the same participants both via cross-sectional analysis at baseline and by studying longitudinal change between baseline and follow-up scans. At baseline, regions with more similar structural wiring were more likely to be functionally coupled. Moreover, correlating longitudinal structural wiring changes with longitudinal functional connectivity reconfigurations, we found that increased structural differentiation, particularly between sensory/unimodal and default mode networks, was reflected by reduced functional interactions. These findings provide insights into adolescent development of human brain structure and function, illustrating how structural wiring interacts with the maturation of macroscale functional hierarchies.11Nsciescopu

Learning to combine complementary segmentation methods for fetal and 6-month infant brain MRI segmentation

Segmentation of brain structures during the pre-natal and early post-natal periods is the first step for subsequent analysis of brain development. Segmentation techniques can be roughly divided into two families. The first, which we denote as registration-based techniques, rely on initial estimates derived by registration to one (or several) templates. The second family, denoted as learning-based techniques, relate imaging (and spatial) features to their corresponding anatomical labels. Each approach has its own qualities and both are complementary to each other. In this paper, we explore two ensembling strategies, namely, stacking and cascading to combine the strengths of both families. We present experiments on segmentation of 6-month infant brains and a cohort of fetuses with isolated non-severe ventriculomegaly (INSVM). INSVM is diagnosed when ventricles are midly enlarged and no other anomalies are apparent. Prognosis is difficult based solely on the degree of ventricular enlargement. In order to find markers for a more reliable prognosis, we use the resulting segmentations to find abnor-malities in the cortical folding of INSVM fetuses. Segmentation results show that either combination strategy outperform all of the individual methods, thus demonstrating the capability of learning systematic combinations that lead to an overall improvement. In particular, the cascading strategy outperforms the ensembling one, the former one obtaining top 5, 7 and 13 results (out of 21 teams) in the segmentation of white matter, gray matter and cerebro-spinal fluid in the iSeg2017 MICCAI Segmentation Challenge. The resulting segmentations reveal that INSVM fetuses have a less convoluted cortex. This points to cortical folding abnormalities as potential markers of later neurodevelopmental outcomes.The first author is co-financed by the Marie Curie FP7-PEOPLE-2012- COFUND Action, Grant agreement no: 600387. This study was partly sup345 ported by Instituto de Salud Carlos III (PI16/00861) integrados en el Plan Nacional de I+D+I y cofinanciados por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) "Una manera de hacer Europa"; additionally the research leading to these results has received funding from "la Caixa" Foundation. This work is partly supported by the 350 Spanish Ministry of Economy and Competitiveness under the Maria de Maeztu Units of Excellence Programme (MDM-2015-0502)