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A Robust Modular Automated Neuroimaging Pipeline for Model Inputs to TheVirtualBrain.

ABSTRACT: TheVirtualBrain, an open-source platform for large-scale network modeling, can be personalized to an individual using a wide range of neuroimaging modalities. With the growing number and scale of neuroimaging data sharing initiatives of both healthy and clinical populations comes an opportunity to create large and heterogeneous sets of dynamic network models to better understand individual differences in network dynamics and their impact on brain health. Here we present TheVirtualBrain-UK Biobank pipeline, a robust, automated and open-source brain image processing solution to address the expanding scope of TheVirtualBrain project. Our pipeline generates connectome-based modeling inputs compatible for use with TheVirtualBrain. We leverage the existing multimodal MRI processing pipeline from the UK Biobank made for use with a variety of brain imaging modalities. We add various features and changes to the original UK Biobank implementation specifically for informing large-scale network models, including user-defined parcellations for the construction of matching whole-brain functional and structural connectomes. Changes also include detailed reports for quality control of all modalities, a streamlined installation process, modular software packaging, updated software versions, and support for various publicly available datasets. The pipeline has been tested on various datasets from both healthy and clinical populations and is robust to the morphological changes observed in aging and dementia. In this paper, we describe these and other pipeline additions and modifications in detail, as well as how this pipeline fits into the TheVirtualBrain ecosystem.

SUBMITTER: Frazier-Logue N

PROVIDER: S-EPMC9239912 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:A commonly held assumption in cognitive neuroscience is that, because measures of human brain function are closer to underlying biology than distal indices of behavior/cognition, they hold more promise for uncovering genetic pathways. Supporting this view is an influential fMRI-based study of sentence reading/listening by Pinel et al. (2012), who reported that common DNA variants in specific candidate genes were associated with altered neural activation in language-related regions of healthy individuals that carried them. In particular, different single-nucleotide polymorphisms (SNPs) of FOXP2 correlated with variation in task-based activation in left inferior frontal and precentral gyri, whereas a SNP at the KIAA0319/TTRAP/THEM2 locus was associated with variable functional asymmetry of the superior temporal sulcus. Here, we directly test each claim using a closely matched neuroimaging genetics approach in independent cohorts comprising 427 participants, four times larger than the original study of 94 participants. Despite demonstrating power to detect associations with substantially smaller effect sizes than those of the original report, we do not replicate any of the reported associations. Moreover, formal Bayesian analyses reveal substantial to strong evidence in support of the null hypothesis (no effect). We highlight key aspects of the original investigation, common to functional neuroimaging genetics studies, which could have yielded elevated false-positive rates. Genetic accounts of individual differences in cognitive functional neuroimaging are likely to be as complex as behavioral/cognitive tests, involving many common genetic variants, each of tiny effect. Reliable identification of true biological signals requires large sample sizes, power calculations, and validation in independent cohorts with equivalent paradigms.SIGNIFICANCE STATEMENT A pervasive idea in neuroscience is that neuroimaging-based measures of brain function, being closer to underlying neurobiology, are more amenable for uncovering links to genetics. This is a core assumption of prominent studies that associate common DNA variants with altered activations in task-based fMRI, despite using samples (10-100 people) that lack power for detecting the tiny effect sizes typical of genetically complex traits. Here, we test central findings from one of the most influential prior studies. Using matching paradigms and substantially larger samples, coupled to power calculations and formal Bayesian statistics, our data strongly refute the original findings. We demonstrate that neuroimaging genetics with task-based fMRI should be subject to the same rigorous standards as studies of other complex traits.

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A Robust Modular Automated Neuroimaging Pipeline for Model Inputs to TheVirtualBrain.

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