Heritability Estimation of Reliable Connectomic Features*

Brain imaging genetics is an emerging research field to explore the underlying genetic architecture of brain structure and function measured by different imaging modalities. However, not all the changes in the brain are a consequential result of genetic effect and it is usually unknown which imaging phenotypes are promising for genetic analyses. In this paper, we focus on identifying highly heritable measures of structural brain networks derived from diffusion weighted imaging data. Using the twin data from the Human Connectome Project (HCP), we evaluated the reliability of fractional anisotropy measure, fiber length and fiber number of each edge in the structural connectome and seven network level measures using intraclass correlation coefficients. We then estimated the heritability of those reliable network measures using SOLAR-Eclipse software. Across all 64,620 network edges between 360 brain regions in the Glasser parcellation, we observed ~5% of them with significantly high heritability in fractional anisotropy, fiber length or fiber number. All the tested network level measures, capturing the network integrality, segregation or resilience, are highly heritable, with variance explained by the additive genetic effect ranging from 59% to 77%

Predicting the Outcome of Cognitive Training in Parkinson’s Disease using Magnetic Resonance Imaging

Motivation: Cognitive impairment is an important symptom of Parkinson’s Disease (PD), usually having a substantial negative impact on the quality of life of patients, families, and caregivers. Cognitive Training (CT) have been proven effective in halting the process of cognitive decline in PD. However, the efficacy of CT is unpredictable from subject to subject. Objective: Investigate the possibility of predicting the outcome of CT in PD patients with Mild Cognitive Impairment using structural and functional Magnetic Resonance Imaging (MRI) data. Methods: Before CT, a sample of 42 PD patients underwent structural and functional MRI. Graph measures were then extracted from their structural and functional con nectomes and used as features for random forest (RFo) and decision tree (DT) machine learning (ML) regression algorithms with and without prior latent component analysis (LCA). CT response was evaluated by assessing the outcomes of the Tower of London task pre- and post-treatment. Finally, the 4 ML models were used to predict CT response and their performances were assessed. Post hoc analyses were conducted to investigate whether these algorithms could predict age using connectomic measures on a sample of 80 PD patients. Results: The performances of the aforementioned algorithms did not differ signifi cantly from the baseline performance predicting the subject-specific CT outcome. The performance of the RFo without LCA differed significantly from the baseline performance in the age prediction task for the sample of 80 patients. Conclusion: Notwithstanding the lack of statistical significance in predicting our xicognitive outcomes, the relative success of the age prediction task points towards the potential of this approach. We hypothesise that bigger sample sizes are needed in order to predict the outcome of CT using ML

Toward leveraging human connectomic data in large consortia: Generalizability of fmri-based brain graphs across sites, sessions, and paradigms

While graph theoretical modeling has dramatically advanced our understanding of complex brain systems, the feasibility of aggregating connectomic data in large imaging consortia remains unclear. Here, using a battery of cognitive, emotional and resting fMRI paradigms, we investigated the generalizability of functional connectomic measures across sites and sessions. Our results revealed overall fair to excellent reliability for a majority of measures during both rest and tasks, in particular for those quantifying connectivity strength, network segregation and network integration. Processing schemes such as node definition and global signal regression (GSR) significantly affected resulting reliability, with higher reliability detected for the Power atlas (vs. AAL atlas) and data without GSR. While network diagnostics for default-mode and sensori-motor systems were consistently reliable independently of paradigm, those for higher-order cognitive systems were reliable predominantly when challenged by task. In addition, based on our present sample and after accounting for observed reliability, satisfactory statistical power can be achieved in multisite research with sample size of approximately 250 when the effect size is moderate or larger. Our findings provide empirical evidence for the generalizability of brain functional graphs in large consortia, and encourage the aggregation of connectomic measures using multisite and multisession data

Morphometricity as a measure of the neuroanatomical signature of a trait

Complex physiological and behavioral traits, including neurological and psychiatric disorders, often associate with distributed anatomical variation. This paper introduces a global metric, called morphometricity, as a measure of the anatomical signature of different traits. Morphometricity is defined as the proportion of phenotypic variation that can be explained by macroscopic brain morphology. We estimate morphometricity via a linear mixed-effects model that uses an anatomical similarity matrix computed based on measurements derived from structural brain MRI scans. We examined over 3,800 unique MRI scans from nine large-scale studies to estimate the morphometricity of a range of phenotypes, including clinical diagnoses such as Alzheimer’s disease, and nonclinical traits such as measures of cognition. Our results demonstrate that morphometricity can provide novel insights about the neuroanatomical correlates of a diverse set of traits, revealing associations that might not be detectable through traditional statistical techniques.National Institute for Biomedical Imaging and Bioengineering (U.S.) (R01EB006758)National Institute for Biomedical Imaging and Bioengineering (U.S.) (P41EB015896)National Institute for Biomedical Imaging and Bioengineering (U.S.) (R21EB018907)National Institute for Biomedical Imaging and Bioengineering (U.S.) (R01EB019956)National Institute on Aging (5R01AG008122)National Institute on Aging (R01AG016495)National Institute of Neurological Diseases and Stroke (U.S.) (R01NS0525851)National Institute of Neurological Diseases and Stroke (U.S.) (R21NS072652)National Institute of Neurological Diseases and Stroke (U.S.) (R01NS070963)National Institute of Neurological Diseases and Stroke (U.S.) (R01NS083534)National Institute of Neurological Diseases and Stroke (U.S.) (5U01NS086625)United States. National Institutes of Health (5U01-MH093765)United States. National Institutes of Health (R01NS083534)United States. National Institutes of Health (R01NS070963)United States. National Institutes of Health (R41AG052246)United States. National Institutes of Health (1K25EB013649-01

Disentangling cortical functional connectivity strength and topography reveals divergent roles of genes and environment

The human brain varies across individuals in its morphology, function, and cognitive capacities. Variability is particularly high in phylogenetically modern regions associated with higher order cognitive abilities, but its relationship to the layout and strength of functional networks is poorly understood. In this study we disentangled the variability of two key aspects of functional connectivity: strength and topography. We then compared the genetic and environmental influences on these two features. Genetic contribution is heterogeneously distributed across the cortex and differs for strength and topography. In heteromodal areas genes predominantly affect the topography of networks, while their connectivity strength is shaped primarily by random environmental influence such as learning. We identified peak areas of genetic control of topography overlapping with parts of the processing stream from primary areas to network hubs in the default mode network, suggesting the coordination of spatial configurations across those processing pathways. These findings provide a detailed map of the diverse contribution of heritability and individual experience to the strength and topography of functional brain architecture.Nanyang Technological UniversityPublished versionThis work was supported by the Medical University of Vienna, the Austrian Research Fund (FWF) [grants P 35189, P 34198, and I 3925-B27] in collaboration with the French National Research Agency (ANR), the Vienna Science and Technology Fund (WWTF) [LS20-065], the European Research Council Grant [866533-CORTIGRAD], the National Natural Science Foundation of China [Grant No. 81790652, No.81790650] and the NAM Advanced Biomedical Imaging Program [FY2016] between Nanyang Technological University, Singapore and Medical University of Vienna, Austria

Frontoinsular cortical microstructure is linked to life satisfaction in young adulthood

Life satisfaction is a component of subjective wellbeing that reflects a global judgement of the quality of life according to an individual’s own needs and expectations. As a psychological construct, it has attracted attention due to its relationship to mental health, resilience to stress, and other factors. Neuroimaging studies have identified neurobiological correlates of life satisfaction; however, they are limited to functional connectivity and gray matter morphometry. We explored features of gray matter microstructure obtained through compartmental modeling of multi-shell diffusion MRI data, and we examined cortical microstructure in frontoinsular cortex in a cohort of 807 typical young adults scanned as part of the Human Connectome Project. Our experiments identified the orientation dispersion index (ODI), and analogously fractional anisotropy (FA), of frontoinsular cortex as a robust set of anatomically-specific lateralized diffusion MRI microstructure features that are linked to life satisfaction, independent of other demographic, socioeconomic, and behavioral factors. We further validated our findings in a secondary test-retest dataset and found high reliability of our imaging metrics and reproducibility of outcomes. In our analysis of twin and non-twin siblings, we found basic microstructure in frontoinsular cortex to be strongly genetically determined. We also found a more moderate but still very significant genetic role in determining microstructure as it relates to life satisfaction in frontoinsular cortex. Our findings suggest a potential linkage between well-being and microscopic features of frontoinsular cortex, which may reflect cellular morphology and architecture and may more broadly implicate the integrity of the homeostatic processing performed by frontoinsular cortex as an important component of an individual’s judgements of life satisfaction

Topological Learning for Brain Networks

This paper proposes a novel topological learning framework that can integrate networks of different sizes and topology through persistent homology. This is possible through the introduction of a new topological loss function that enables such challenging task. The use of the proposed loss function bypasses the intrinsic computational bottleneck associated with matching networks. We validate the method in extensive statistical simulations with ground truth to assess the effectiveness of the topological loss in discriminating networks with different topology. The method is further applied to a twin brain imaging study in determining if the brain network is genetically heritable. The challenge is in overlaying the topologically different functional brain networks obtained from the resting-state functional MRI (fMRI) onto the template structural brain network obtained through the diffusion MRI (dMRI)

The individuality of shape asymmetries of the human cerebral cortex

Asymmetries of the cerebral cortex are found across diverse phyla and are particularly pronounced in humans, with important implications for brain function and disease. However, many prior studies have confounded asymmetries due to size with those due to shape. Here, we introduce a novel approach to characterize asymmetries of the whole cortical shape, independent of size, across different spatial frequencies using magnetic resonance imaging data in three independent datasets. We find that cortical shape asymmetry is highly individualized and robust, akin to a cortical fingerprint, and identifies individuals more accurately than size-based descriptors, such as cortical thickness and surface area, or measures of inter-regional functional coupling of brain activity. Individual identifiability is optimal at coarse spatial scales (~37 mm wavelength), and shape asymmetries show scale-specific associations with sex and cognition, but not handedness. While unihemispheric cortical shape shows significant heritability at coarse scales (~65 mm wavelength), shape asymmetries are determined primarily by subject-specific environmental effects. Thus, coarse-scale shape asymmetries are highly personalized, sexually dimorphic, linked to individual differences in cognition, and are primarily driven by stochastic environmental influences

Dysconnection and cognition in schizophrenia: A spectral dynamic causal modeling study

Schizophrenia (SZ) is a severe mental disorder characterized by failure of functional integration (aka dysconnection) across the brain. Recent functional connectivity (FC) studies have adopted functional parcellations to define subnetworks of large-scale networks, and to characterize the (dys)connection between them, in normal and clinical populations. While FC examines statistical dependencies between observations, model-based effective connectivity (EC) can disclose the causal influences that underwrite the observed dependencies. In this study, we investigated resting state EC within seven large-scale networks, in 66 SZ and 74 healthy subjects from a public dataset. The results showed that a remarkable 33% of the effective connections (among subnetworks) of the cognitive control network had been pathologically modulated in SZ. Further dysconnection was identified within the visual, default mode and sensorimotor networks of SZ subjects, with 24%, 20%, and 11% aberrant couplings. Overall, the proportion of discriminative connections was remarkably larger in EC (24%) than FC (1%) analysis. Subsequently, to study the neural correlates of impaired cognition in SZ, we conducted a canonical correlation analysis between the EC parameters and the cognitive scores of the patients. As such, the self-inhibitions of supplementary motor area and paracentral lobule (in the sensorimotor network) and the excitatory connection from parahippocampal gyrus to inferior temporal gyrus (in the cognitive control network) were significantly correlated with the social cognition, reasoning/problem solving and working memory capabilities of the patients. Future research can investigate the potential of whole-brain EC as a biomarker for diagnosis of brain disorders and for neuroimaging-based cognitive assessment