Searching Reproducible Brain Features using NeuroMark: Templates for Different Age Populations and Imaging Modalities.

A primary challenge to the data-driven analysis is the balance between poor generalizability of population-based research and characterizing more subject-, study- and population-specific variability. We previously introduced a fully automated spatially constrained independent component analysis (ICA) framework called NeuroMark and its functional MRI (fMRI) template. NeuroMark has been successfully applied in numerous studies, identifying brain markers reproducible across datasets and disorders. The first NeuroMark template was constructed based on young adult cohorts. We recently expanded on this initiative by creating a standardized normative multi-spatial-scale functional template using over 100,000 subjects, aiming to improve generalizability and comparability across studies involving diverse cohorts. While a unified template across the lifespan is desirable, a comprehensive investigation of the similarities and differences between components from different age populations might help systematically transform our understanding of the human brain by revealing the most well-replicated and variable network features throughout the lifespan. In this work, we introduced two significant expansions of NeuroMark templates first by generating replicable fMRI templates for infants, adolescents, and aging cohorts, and second by incorporating structural MRI (sMRI) and diffusion MRI (dMRI) modalities. Specifically, we built spatiotemporal fMRI templates based on 6,000 resting-state scans from four datasets. This is the first attempt to create robust ICA templates covering dynamic brain development across the lifespan. For the sMRI and dMRI data, we used two large publicly available datasets including more than 30,000 scans to build reliable templates. We employed a spatial similarity analysis to identify replicable templates and investigate the degree to which unique and similar patterns are reflective in different age populations. Our results suggest remarkably high similarity of the resulting adapted components, even across extreme age differences. With the new templates, the NeuroMark framework allows us to perform age-specific adaptations and to capture features adaptable to each modality, therefore facilitating biomarker identification across brain disorders. In sum, the present work demonstrates the generalizability of NeuroMark templates and suggests the potential of new templates to boost accuracy in mental health research and advance our understanding of lifespan and cross-modal alterations.

Multi-study evaluation of neuroimaging-based prediction of medication class in mood disorders.

Clinicians often face a dilemma in diagnosing bipolar disorder patients with complex symptoms who spend more time in a depressive state than a manic state. The current gold standard for such diagnosis, the Diagnostic and Statistical Manual (DSM), is not objectively grounded in pathophysiology. In such complex cases, relying solely on the DSM may result in misdiagnosis as major depressive disorder (MDD). A biologically-based classification algorithm that can accurately predict treatment response may help patients suffering from mood disorders. Here we used an algorithm to do so using neuroimaging data. We used the neuromark framework to learn a kernel function for support vector machine (SVM) on multiple feature subspaces. The neuromark framework achieves up to 95.45% accuracy, 0.90 sensitivity, and 0.92 specificity in predicting antidepressant (AD) vs. mood stabilizer (MS) response in patients. We incorporated two additional datasets to evaluate the generalizability of our approach. The trained algorithm achieved up to 89% accuracy, 0.88 sensitivity, and 0.89 specificity in predicting the DSM-based diagnosis on these datasets. We also translated the model to distinguish responders to treatment from nonresponders with up to 70% accuracy. This approach reveals multiple salient biomarkers of medication-class of response within mood disorders.