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

An evaluation of how connectopic mapping reveals visual field maps in V1

Functional gradients, in which response properties change gradually across the cortical surface, have been proposed as a key organising principle of the brain. However, the presence of these gradients remains undetermined in many brain regions. Resting-state neuroimaging studies have suggested these gradients can be reconstructed from patterns of functional connectivity. Here we investigate the accuracy of these reconstructions and establish whether it is connectivity or the functional properties within a region that determine these "connectopic maps". Different manifold learning techniques were used to recover visual field maps while participants were at rest or engaged in natural viewing. We benchmarked these reconstructions against maps measured by traditional visual field mapping. We report an initial exploratory experiment of a publicly available naturalistic imaging dataset, followed by a preregistered replication using larger resting-state and naturalistic imaging datasets from the Human Connectome Project. Connectopic mapping accurately predicted visual field maps in primary visual cortex, with better predictions for eccentricity than polar angle maps. Non-linear manifold learning methods outperformed simpler linear embeddings. We also found more accurate predictions during natural viewing compared to resting-state. Varying the source of the connectivity estimates had minimal impact on the connectopic maps, suggesting the key factor is the functional topography within a brain region. The application of these standardised methods for connectopic mapping will allow the discovery of functional gradients across the brain. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 19 April 2022. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.19771717

Latent Factor Analysis of High-Dimensional Brain Imaging Data

Recent advances in neuroimaging study, especially functional magnetic resonance imaging (fMRI), has become an important tool in understanding the human brain. Human cognitive functions can be mapped with the brain functional organization through the high-resolution fMRI scans. However, the high-dimensional data with the increasing number of scanning tasks and subjects pose a challenge to existing methods that wasn’t optimized for high-dimensional imaging data. In this thesis, I develop advanced data-driven methods to help utilize more available sources of information in order to reveal more robust brain-behavior relationship. In the first chapter, I provide an overview of the current related research in fMRI and my contributions to the field. In the second chapter, I propose two extensions to the connectome-based predictive modeling (CPM) method that is able to combine multiple connectomes when building predictive models. The two extensions are both able to generate higher prediction accuracy than using the single connectome or the average of multiple connectomes, suggesting the advantage of incorporating multiple sources of information in predictive modeling. In the third chapter, I improve CPM from the target behavioral measure’s perspective. I propose another two extensions for CPM that are able to combine multiple available behavioral measures into a composite measure for CPM to predict. The derived composite measures are shown to be predicted more accurately than any other single behavioral measure, suggesting a more robust brainbehavior relationship. In the fourth chapter, I propose a nonlinear dimensionality reduction framework to embed fMRI data from multiple tasks into a low-dimensional space. This framework helps reveal the common brain state in the multiple available tasks while also help discover the differences among these tasks. The results also provide valuable insights into the various prediction performance based on connectomes from different tasks. In the fifth chapter, I propose an another hyerbolic geometry-based brain graph edge embedding framework. The framework is based on Poincar´e embedding and is able to more accurately represent edges in the brain graph in a low-dimensional space than traditional Euclidean geometry-based embedding. Utilizing the embedding, we are able to cluster edges of the brain graph into disjoint clusters. The edge clusters can then be used to define overlapping brain networks and the derived metrics like network overlapping number can be used to investigate functional flexibility of each brain region. Overall, these work provide rich data-driven methods that help understand the brain-behavioral relationship through predictive modeling and low-dimensional data representation

Decoding Task-Based fMRI Data Using Graph Neural Networks, Considering Individual Differences

Functional magnetic resonance imaging (fMRI) is a non-invasive technology that provides high spatial resolution in determining the human brain\u27s responses and measures regional brain activity through metabolic changes in blood oxygen consumption associated with neural activity. Task fMRI provides an opportunity to analyze the working mechanisms of the human brain during specific task performance. Over the past several years, a variety of computational methods have been proposed to decode task fMRI data that can identify brain regions associated with different task stimulations. Despite the advances made by these methods, several limitations exist due to graph representations and graph embeddings transferred from task fMRI signals. In the present study, we proposed an end-to-end graph convolutional network by combining the convolutional neural network with graph representation, with three convolutional layers to classify task fMRI data from the Human Connectome Project (302 participants, 22–35 years of age). One goal of this dissertation was to improve classification performance. We applied four of the most widely used node embedding algorithms—NetMF, RandNE, Node2Vec, and Walklets—to automatically extract the structural properties of the nodes in the brain functional graph, then evaluated the performance of the classification model. The empirical results indicated that the proposed GCN framework accurately identified the brain\u27s state in task fMRI data and achieved comparable macro F1 scores of 0.978 and 0.976 with the NetMF and RandNE embedding methods, respectively. Another goal of the dissertation was to assess the effects of individual differences (i.e., gender and fluid intelligence) on classification performance. We tested the proposed GCN framework on sub-datasets divided according to gender and fluid intelligence. Experimental results indicated significant differences in the classification predictions of gender, but not high/low fluid intelligence fMRI data. Our experiments yielded promising results and demonstrated the superior ability of our GCN in modeling task fMRI data

Quantification of cortical folding using MR image data

The cerebral cortex is a thin layer of tissue lining the brain where neural circuits perform important high level functions including sensory perception, motor control and language processing. In the third trimester the fetal cortex folds rapidly from a smooth sheet into a highly convoluted arrangement of gyri and sulci. Premature birth is a high risk factor for poor neurodevelopmental outcome and has been associated with abnormal cortical development, however the nature of the disruption to developmental processes is not fully understood. Recent developments in magnetic resonance imaging have allowed the acquisition of high quality brain images of preterms and also fetuses in-utero. The aim of this thesis is to develop techniques which quantify folding from these images in order to better understand cortical development in these two populations. A framework is presented that quantifies global and regional folding using curvature-based measures. This methodology was applied to fetuses over a wide gestational age range (21.7 to 38.9 weeks) for a large number of subjects (N = 80) extending our understanding of how the cortex folds through this critical developmental period. The changing relationship between the folding measures and gestational age was modelled with a Gompertz function which allowed an accurate prediction of physiological age. A spectral-based method is outlined for constructing a spatio-temporal surface atlas (a sequence of mean cortical surface meshes for weekly intervals). A key advantage of this method is the ability to do group-wise atlasing without bias to the anatomy of an initial reference subject. Mean surface templates were constructed for both fetuses and preterms allowing a preliminary comparison of mean cortical shape over the postmenstrual age range 28-36 weeks. Displacement patterns were revealed which intensified with increasing prematurity, however more work is needed to evaluate the reliability of these findings.Open Acces

Data-Based And Theory-Based Network Models Of Perturbations To Neural Dynamics

Much of neuroscience is centered on uncovering simple principles that constrain the behavior of the brain. When considering the formation of neural architectures, similar structures can be recreated following the principles of minimizing wiring and maximizing topological complexity. However, a similar understanding of neural dynamics on top of these structural connections has not yet been achieved. One promising strategy for identifying underlying principles of neural dynamics is quantifying and modeling the response of neural systems to perturbation. Here, we use a spectrum of data- and theory-based network models to characterize the response of neural systems to different types of perturbations. We report how functional networks change in the context of pathological epileptic activity and brain-computer interface control. We also specifically test one possible principle: that activity is constrained to spread along connections in both the context of brain-computer interfaces and direct electrical stimulation. In the first study, we demonstrate across a wide variety of functional connectivity metrics and frequency bands that epileptic activity increases amplitude-based functional interactions, an observation that can now be incorporated into future theory-based models. In a second study, we determine that modeling activity that is constrained to spread along connections suggests why certain connections are important for brain-computer interface learning; specifically, these connections support sustained activity in attention regions. In our third study, we demonstrate that modeling activity changes from direct electrical stimulation using white matter connectivity explains more variance than models with rewired connections. This model generates testable predictions about which individuals, regions, and time points would lead to successful applications of direct electrical stimulation. Overall, this work demonstrates the potential uses of a range of data- and theory-based models for uncovering simple guiding principles that determine the behavior of a system. It also uses one specific principle - that activity is constrained to spread along connections - to understand the role of specific connections that may support learning, and provide a method to optimize individually tailored stimulation therapies for a specific outcome