The Connectivity–Based Parcellation of The Angular Gyrus: Fiber Dissection And MR Tractography Study

The angular gyrus (AG) wraps the posterior end of the superior temporal sulcus (STS), so it is considered as a continuation of the superior/middle temporal gyrus and forms the inferior parietal lobule (IPL) with the supramarginal gyrus (SMG). The AG was functionally divided in the literature, but there is no fiber dissection study in this context. This study divided AG into superior (sAG) and inferior (iAG) parts by focusing on STS. Red blue silicone injected eight human cadaveric cerebrums were dissected via the Klingler method focusing on the AG. White matter (WM) tracts identified during dissection were then reconstructed on the Human Connectome Project 1065 individual template for validation. According to this study, superior longitudinal fasciculus (SLF) II and middle longitudinal fasciculus (MdLF) are associated with sAG; the anterior commissure (AC), optic radiation (OR) with iAG; the arcuate fasciculus (AF), inferior frontooccipital fasciculus (IFOF), and tapetum (Tp) with both parts. In cortical parcellation of AG based on STS, sAG and iAG were found to be associated with different fiber tracts. Although it has been shown in previous studies that there are functionally different subunits with AG parcellation, here, for the first time, different functions of the subunits have been revealed with cadaveric dissection and tractography images.

Fractal-Based Analysis of fMRI BOLD Signal During Naturalistic Viewing Conditions

Background: Temporal fractals are characterized by prominent scale-invariance and self-similarity across time scales. Monofractal analysis quantifies this scaling behavior in a single parameter, the Hurst exponent (H). Higher H reflects greater correlation in the signal structure, which is taken as being more fractal. Previous fMRI studies have observed lower H during conventional tasks relative to resting state conditions, and shown that H is negatively correlated with task difficulty and novelty. To date, no study has investigated the fractal dynamics of BOLD signal during naturalistic conditions.Methods: We performed fractal analysis on Human Connectome Project 7T fMRI data (n = 72, 41 females, mean age 29.46 ± 3.76 years) to compare H across movie-watching and rest.Results: In contrast to previous work using conventional tasks, we found higher H values for movie relative to rest (mean difference = 0.014; p = 5.279 × 10−7; 95% CI [0.009, 0.019]). H was significantly higher in movie than rest in the visual, somatomotor and dorsal attention networks, but was significantly lower during movie in the frontoparietal and default networks. We found no cross-condition differences in test-retest reliability of H. Finally, we found that H of movie-derived stimulus properties (e.g., luminance changes) were fractal whereas H of head motion estimates were non-fractal.Conclusions: Overall, our findings suggest that movie-watching induces fractal signal dynamics. In line with recent work characterizing connectivity-based brain state dynamics during movie-watching, we speculate that these fractal dynamics reflect the configuring and reconfiguring of brain states that occurs during naturalistic processing, and are markedly different than dynamics observed during conventional tasks.

Atlasing white matter and grey matter joint contributions to resting-state networks in the human brain

Over the past two decades, the study of resting-state functional magnetic resonance imaging (fMRI) has revealed the existence of multiple brain areas displaying synchronous functional blood oxygen level-dependent signals (BOLD) - resting-state networks (RSNs). The variation in functional connectivity between the different areas of a resting-state network or between multiple networks, have been extensively studied and linked to cognitive states and pathologies. However, the white matter connections supporting each network remain only partially described. In this work, we developed a data-driven method to systematically map the white and grey matter contributing to resting-state networks. Using the Human Connectome Project, we generated an atlas of 30 resting-state networks, each with two maps: white matter and grey matter. By integrating structural and functional neuroimaging data, this method builds an atlas that unlocks the joint anatomical exploration of white and grey matter to resting-state networks. The method also allows highlighting the overlap between networks, which revealed that most (89%) of the brain's white matter is shared amongst multiple networks, with 16% shared by at least 7 resting-state networks. These overlaps, especially the existence of regions shared by numerous networks, suggest that white matter lesions in these areas might strongly impact the correlations and the communication within resting-state networks. We provide an open-source software to explore the joint contribution of white and grey matter to RSNs and facilitate the study of the impact of white matter damage on RSNs.

Test–Retest Reliability of Synchrony and Metastability in Resting State fMRI

In recent years, interest has been growing in dynamic characteristic of brain signals from resting-state functional magnetic resonance imaging (rs-fMRI). Synchrony and metastability, as neurodynamic indexes, are considered as one of methods for analyzing dynamic characteristics. Although much research has studied the analysis of neurodynamic indices, few have investigated its reliability. In this paper, the datasets from the Human Connectome Project have been used to explore the test–retest reliabilities of synchrony and metastability from multiple angles through intra-class correlation (ICC). The results showed that both of these indexes had fair test–retest reliability, but they are strongly affected by the field strength, the spatial resolution, and scanning interval, less affected by the temporal resolution. Denoising processing can help improve their ICC values. In addition, the reliability of neurodynamic indexes was affected by the node definition strategy, but these effects were not apparent. In particular, by comparing the test–retest reliability of different resting-state networks, we found that synchrony of different networks was basically stable, but the metastability varied considerably. Among these, DMN and LIM had a relatively higher test–retest reliability of metastability than other networks. This paper provides a methodological reference for exploring the brain dynamic neural activity by using synchrony and metastability in fMRI signals.

Embedding Functional Brain Networks in Low Dimensional Spaces Using Manifold Learning Techniques

Background: fMRI data is inherently high-dimensional and difficult to visualize. A recent trend has been to find spaces of lower dimensionality where functional brain networks can be projected onto manifolds as individual data points, leading to new ways to analyze and interpret the data. Here, we investigate the potential of two powerful non-linear manifold learning techniques for functional brain networks representation: (1) T-stochastic neighbor embedding (t-SNE) and (2) Uniform Manifold Approximation Projection (UMAP) a recent breakthrough in manifold learning.Methods: fMRI data from the Human Connectome Project (HCP) and an independent study of aging were used to generate functional brain networks. We used fMRI data collected during resting state data and during a working memory task. The relative performance of t-SNE and UMAP were investigated by projecting the networks from each study onto 2D manifolds. The levels of discrimination between different tasks and the preservation of the topology were evaluated using different metrics.Results: Both methods effectively discriminated the resting state from the memory task in the embedding space. UMAP discriminated with a higher classification accuracy. However, t-SNE appeared to better preserve the topology of the high-dimensional space. When networks from the HCP and aging studies were combined, the resting state and memory networks in general aligned correctly.Discussion: Our results suggest that UMAP, a more recent development in manifold learning, is an excellent tool to visualize functional brain networks. Despite dramatic differences in data collection and protocols, networks from different studies aligned correctly in the embedding space.

Multimodal lesion network mapping to predict sensorimotor behavior in stroke patients

Lesion network mapping (LNM) has proved to be a successful technique to map symptoms to brain networks after acquired brain injury. Beyond the characteristics of a lesion, such as its etiology, size or location, LNM has shown that common symptoms in patients after injury may reflect the effects of their lesions on the same circuits, thereby linking symptoms to specific brain networks. Here, we extend LNM to its multimodal form, using a combination of functional and structural connectivity maps drawn from data from 1000 healthy participants in the Human Connectome Project. We applied the multimodal LNM to a cohort of 54 stroke patients with the aim of predicting sensorimotor behavior, as assessed through a combination of motor and sensory tests. Test scores were predicted using a Canonical Correlation Analysis with multimodal brain maps as independent variables, and cross-validation strategies were employed to overcome overfitting. The results obtained led us to draw three conclusions. First, the multimodal analysis reveals how functional connectivity maps contribute more than structural connectivity maps in the optimal prediction of sensorimotor behavior. Second, the maximal association solution between the behavioral outcome and multimodal lesion connectivity maps suggests an equal contribution of sensory and motor coefficients, in contrast to the unimodal analyses where the sensory contribution dominates in both structural and functional maps. Finally, when looking at each modality individually, the performance of the structural connectivity maps strongly depends on whether sensorimotor performance was corrected for lesion size, thereby eliminating the effect of larger lesions that produce more severe sensorimotor dysfunction. By contrast, the maps of functional connectivity performed similarly irrespective of any correction for lesion size. Overall, these results support the extension of LNM to its multimodal form, highlighting the synergistic and additive nature of different types of imaging modalities, and the influence of their corresponding brain networks on behavioral performance after acquired brain injury.

Group-Level Ranking-Based Hubness Analysis of Human Brain Connectome Reveals Significant Interhemispheric Asymmetry and Intraparcel Heterogeneities

Objective: Graph theory applications are commonly used in connectomics research to better understand connectivity architecture and characterize its role in cognition, behavior and disease conditions. One of the numerous open questions in the field is how to represent inter-individual differences with graph theoretical methods to make inferences for the population. Here, we proposed and tested a simple intuitive method that is based on finding the correlation between the rank-ordering of nodes within each connectome with respect to a given metric to quantify the differences/similarities between different connectomes.Methods: We used the diffusion imaging data of the entire HCP-1065 dataset of the Human Connectome Project (HCP) (n = 1,065 subjects). A customized cortical subparcellation of HCP-MMP atlas (360 parcels) (yielding a total of 1,598 ROIs) was used to generate connectivity matrices. Six graph measures including degree, strength, coreness, betweenness, closeness, and an overall “hubness” measure combining all five were studied. Group-level ranking-based aggregation method (“measure-then-aggregate”) was used to investigate network properties on population level.Results: Measure-then-aggregate technique was shown to represent population better than commonly used aggregate-then-measure technique (overall rs: 0.7 vs 0.5). Hubness measure was shown to highly correlate with all five graph measures (rs: 0.88–0.99). Minimum sample size required for optimal representation of population was found to be 50 to 100 subjects. Network analysis revealed a widely distributed set of cortical hubs on both hemispheres. Although highly-connected hub clusters had similar distribution between two hemispheres, average ranking values of homologous parcels of two hemispheres were significantly different in 71% of all cortical parcels on group-level.Conclusion: In this study, we provided experimental evidence for the robustness, limits and applicability of a novel group-level ranking-based hubness analysis technique. Graph-based analysis of large HCP dataset using this new technique revealed striking hemispheric asymmetry and intraparcel heterogeneities in the structural connectivity of the human brain.

Insights from the IronTract challenge: optimal methods for mapping brain pathways from multi-shell diffusion MRI

Limitations in the accuracy of brain pathways reconstructed by diffusion MRI (dMRI) tractography have received considerable attention. While the technical advances spearheaded by the Human Connectome Project (HCP) led to significant improvements in dMRI data quality, it remains unclear how these data should be analyzed to maximize tractography accuracy. Over a period of two years, we have engaged the dMRI community in the IronTract Challenge, which aims to answer this question by leveraging a unique dataset. Macaque brains that have received both tracer injections and ex vivo dMRI at high spatial and angular resolution allow a comprehensive, quantitative assessment of tractography accuracy on state-of-the-art dMRI acquisition schemes. We find that, when analysis methods are carefully optimized, the HCP scheme can achieve similar accuracy as a more time-consuming, Cartesian-grid scheme. Importantly, we show that simple pre- and post-processing strategies can improve the accuracy and robustness of many tractography methods. Finally, we find that fiber configurations that go beyond crossing (e.g., fanning, branching) are the most challenging for tractography. The IronTract Challenge remains open and we hope that it can serve as a valuable validation tool for both users and developers of dMRI analysis methods.

Novel Age-Dependent Cortico-Subcortical Morphologic Interactions Predict Fluid Intelligence: A Multi-Cohort Geometric Deep Learning Study

The relationship of human brain structure to cognitive function is complex, and how this relationship differs between childhood and adulthood is poorly understood. One strong hypothesis suggests the cognitive function of Fluid Intelligence (Gf) is dependent on prefrontal cortex and parietal cortex. In this work, we developed a novel graph convolutional neural networks (gCNNs) for the analysis of localized anatomic shape and prediction of Gf. Morphologic information of the cortical ribbons and subcortical structures was extracted from T1-weighted MRIs within two independent cohorts, the Adolescent Brain Cognitive Development Study (ABCD; age: 9.93 ± 0.62 years) of children and the Human Connectome Project (HCP; age: 28.81 ± 3.70 years). Prediction combining cortical and subcortical surfaces together yielded the highest accuracy of Gf for both ABCD (R = 0.314) and HCP datasets (R = 0.454), outperforming the state-of-the-art prediction of Gf from any other brain measures in the literature. Across both datasets, the morphology of the amygdala, hippocampus, and nucleus accumbens, along with temporal, parietal and cingulate cortex consistently drove the prediction of Gf, suggesting a significant reframing of the relationship between brain morphology and Gf to include systems involved with reward/aversion processing, judgment and decision-making, motivation, and emotion.

The intrinsic spatiotemporal organization of the human brain - A multi-dimensional functional network atlas

The human brain is a complex, integrative and segregative network that exhibits dynamic fluctuations in activity across space and time. A canonical set of large-scale networks has been historically identified from resting-state fMRI (rs-fMRI), including the default mode, visual, somatomotor, salience, attention, and executive control. However, the methods used in identification of these networks have relied on assumptions that may inadvertently constrain their properties and consequently our understanding of the human connectome. Here we define a brain "network" as a functional component that jointly describes its spatial distribution and temporal dynamics, where neither domain suffers from unrealistic constraints. Using our recently developed BrainSync algorithm and the Nadam-Accelerated SCAlable and Robust (NASCAR) tensor decomposition, we identified twenty-three brain networks using rs-fMRI data from a large group of healthy subjects acquired by the Human Connectome Project. These networks are spatially overlapped, temporally correlated, and highly reproducible across two independent groups and sessions. We show that these networks can be clustered into six distinct functional categories and naturally form a representative functional network atlas for a healthy population. Using this atlas, we demonstrate that individuals with attention-deficit/hyperactivity disorder display disproportionate brain activity increases, relative to neurotypical subjects, in visual, auditory, and somatomotor networks concurrent with decreases in the default mode and higher-order cognitive networks. Thus, this work not only yields a highly reproducible set of spatiotemporally overlapped functional brain networks, but also provides convergent evidence that individual differences in these networks can be used to explain individual differences in neurocognitive functioning.