<p dir="ltr">Functional connectomes (FCs) contain all pairwise estimations of functional couplings between brain regions. Neural activity of brain regions is estimated for subjects, sessions and tasks based on fMRI BOLD data. FCs are commonly represented as correlation matrices that are symmetric positive definite (SPD) matrices lying on or inside the SPD manifold. Since the geometry on the SPD manifold is non-Euclidean, the inter-related entries of FCs undermine the use of Euclidean-based distances and its stability when using them as features in machine learning algorithms. By projecting FCs into a tangent space, we can obtain tangent functional connectomes (tangent-FCs), whose entries would not be inter-related, and thus, allow the use of Euclidean-based methods. Tangent-FCs have shown a higher predictive power of behavior and cognition, but no studies have evaluated the effect of such projections with respect to fingerprinting.</p><p dir="ltr">To some extent, FCs possess a recurrent and reproducible individual fingerprint that can identify if two FCs belong to the same participant. This process is referred to as fingerprinting or subject-identification. As research objects, FCs are expected to be reliable, which means FCs of the same person doing the same thing are expected to be more similar to each other compared to FCs of other individuals/conditions. The level of fingerprint, usually estimated by identification rate, tries to capture this expectation of reliability. When focusing on the dynamic functional connectivity (dFC) of a single fMRI scan, we proposed the concept of cognitive fingerprinting where the timing of functional reconfiguration is identified. This suggests that the changes of cognitive states can be reflected by the similarities/dissimilarities among dFCs.</p><p dir="ltr">In this dissertation, we hypothesize that comparing FCs in tangent space by using Euclidean algebra should result in higher subject fingerprinting for static FCs and higher cognitive fingerprinting for dynamic FCs. This hypothesis is evaluated by addressing three research questions. The first question investigates the impact of tangent space projection on subject identification rates for static FCs. The second and third questions focus on dFCs, examining their performance in uncovering cognitive fingerprinting on the manifold and in tangent space, respectively. The timing of functional reconfiguration is identified by performing recurrence quantification analysis on dFCs on the manifold. And then, dFCs are projected onto tangent space to assess the influence of this projection on cognitive fingerprinting. Results reveal that identification rates improve systematically with tangent-FCs. Additionally, critical timepoints of functional reconfigurations align closely with ground truth for both manifold-based and tangent-space dFCs.</p><p dir="ltr">Lastly, we tested those research questions together with data-driven mapping methods, connectome-based predictive modeling (CPM) and partial least squares (PLS), on a dataset of FCs that includes healthy controls and HIV patients as a case study. </p><p dir="ltr">In conclusion, our findings support the proposed hypothesis, demonstrating that tangent space projection enhances comparisons and offers strong advantages as a transformation for FCs before their use in other analysis/applications.</p>

<div>The innovations in Magnetic Resonance Imaging (MRI) in the recent decades have given rise to large open-source datasets. MRI affords researchers the ability to look at both structure and function of the human brain. This dissertation will make use of one of these large open-source datasets, the Human Connectome Project (HCP), to study the structural and functional connectivity in the brain.</div><div>Communication processes within the human brain at different cognitive states are neither well understood nor completely characterized. We assess communication processes in the human connectome using ant colony-inspired cooperative learning algorithm, starting from a source with no <i>a priori</i> information about the network topology, and cooperatively searching for the target through a pheromone-inspired model. This framework relies on two parameters, namely <i>pheromone</i> and <i>edge perception</i>, to define the cognizance and subsequent behaviour of the ants on the network and the communication processes happening between source and target. Simulations with different configurations allow the identification of path-ensembles that are involved in the communication between node pairs. In order to assess the different communication regimes displayed on the simulations and their associations with functional connectivity, we introduce two network measurements, effective path-length and arrival rate. These measurements are tested as individual and combined descriptors of functional connectivity during different tasks. Finally, different communication regimes are found in different specialized functional networks. This framework may be used as a test-bed for different communication regimes on top of an underlying topology.</div><div>The assessment of brain <i>fingerprints</i> has emerged in the recent years as an important tool to study individual differences. Studies so far have mainly focused on connectivity fingerprints between different brain scans of the same individual. We extend the concept of brain connectivity fingerprints beyond test/retest and assess <i>fingerprint gradients</i> in young adults by developing an extension of the differential identifiability framework. To do so, we look at the similarity between not only the multiple scans of an individual (<i>subject fingerprint</i>), but also between the scans of monozygotic and dizygotic twins (<i>twin fingerprint</i>). We have carried out this analysis on the 8 fMRI conditions present in the Human Connectome Project -- Young Adult dataset, which we processed into functional connectomes (FCs) and time series parcellated according to the Schaefer Atlas scheme, which has multiple levels of resolution. Our differential identifiability results show that the fingerprint gradients based on genetic and environmental similarities are indeed present when comparing FCs for all parcellations and fMRI conditions. Importantly, only when assessing optimally reconstructed FCs, we fully uncover fingerprints present in higher resolution atlases. We also study the effect of scanning length on subject fingerprint of resting-state FCs to analyze the effect of scanning length and parcellation. In the pursuit of open science, we have also made available the processed and parcellated FCs and time series for all conditions for ~1200 subjects part of the HCP-YA dataset to the scientific community.</div><div>Lastly, we have estimated the effect of genetics and environment on the original and optimally reconstructed FC with an ACE model.</div>