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B. T. Thomas Yeo

Publications and source records attributed to B. T. Thomas Yeo.

7 recordsLinked to original sources

Excessive data censoring in fMRI undermines individual precision and weakens brain-behavior associations

Censoring high-motion volumes in fMRI is common practice to reduce effects of head motion on functional connectivity (FC). Although aggressive censoring removes more noise, it causes extensive data loss, creating a tradeoff that may ultimately improve or degrade FC accuracy. Here, we evaluate how censoring affects FC estimation and downstream brain-wide association studies (BWAS). Using extensively sampled participants from the Human Connectome Project (HCP) Retest dataset, we establish individual "ground truth" FC and assess the accuracy of FC estimated from 5-30 minute scans. We find that censoring degrades FC accuracy, with more aggressive censoring being more detrimental, particularly among participants exhibiting above-average motion. In these participants, aggressive censoring reduces FC accuracy by 30% for 30-minute scans denoised with ICA-FIX, an advanced denoising method, and by 3% for scans denoised with conventional confound regression. These effects reflect substantial data loss (34%) that outweighs comparatively modest noise reductions: 7% with ICA-FIX and 18% with confound regression. Compensating for this would require substantially longer scans (62% with confound regression; 76% with ICA-FIX), inflating data collection budgets. Introducing a repeated measures framework to separate motion trait from artifact, we find that standard QC metrics are dominated by motion trait and overstate motion bias, which is effectively mitigated with less aggressive censoring. Finally, using data from nearly 1,000 HCP participants, we demonstrate that unreliable FC substantially attenuates BWAS correlations: by ~30% under optimal conditions (longer ICA-FIX scans with no censoring) but exceeding 75% in short, aggressively censored scans. Our findings support the use of advanced denoising methods, limiting censoring, and collecting longer scans to maximize fidelity of FC and BWAS.

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Brain Harmony: A Multimodal Foundation Model Unifying Morphology and Function into 1D Tokens

We present Brain Harmony (BrainHarmonix), the first multimodal brain foundation model that unifies structural morphology and functional dynamics into compact 1D token representations. The model was pretrained on two of the largest neuroimaging datasets to date, encompassing 64,594 T1-weighted structural MRI 3D volumes (~ 14 million images) and 70,933 functional MRI (fMRI) time series. BrainHarmonix is grounded in two foundational neuroscience principles: structure complements function - structural and functional modalities offer distinct yet synergistic insights into brain organization; function follows structure - brain functional dynamics are shaped by cortical morphology. The modular pretraining process involves single-modality training with geometric pre-alignment followed by modality fusion through shared brain hub tokens. Notably, our dynamics encoder uniquely handles fMRI time series with heterogeneous repetition times (TRs), addressing a major limitation in existing models. BrainHarmonix is also the first to deeply compress high-dimensional neuroimaging signals into unified, continuous 1D tokens, forming a compact latent space of the human brain. BrainHarmonix achieves strong generalization across diverse downstream tasks, including neurodevelopmental and neurodegenerative disorder classification and cognition prediction - consistently outperforming previous approaches. Our models - pretrained on 8 H100 GPUs - aim to catalyze a new era of AI-driven neuroscience powered by large-scale multimodal neuroimaging.

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Gradients of brain organization: Smooth sailing from methods development to user community

Multimodal neuroimaging grants a powerful in vivo window into the structure and function of the human brain. Recent methodological and conceptual advances have enabled investigations of the interplay between large-scale spatial trends, or gradients, in brain structure and function, offering a framework to unify principles of brain organization across multiple scales. Strong community enthusiasm for these techniques has been instrumental in their widespread adoption and implementation to answer key questions in neuroscience. Following a brief review of current literature on this framework, this perspective paper will highlight how pragmatic steps aiming to make gradient methods more accessible to the community propelled these techniques to the forefront of neuroscientific inquiry. More specifically, we will emphasize how interest for gradient methods was catalyzed by data sharing, open-source software development, as well as the organization of dedicated workshops led by a diverse team of early career researchers. To this end, we argue that the growing excitement for brain gradients is the result of coordinated and consistent efforts to build an inclusive community and can serve as a case in point for future innovations and conceptual advances in neuroinformatics. We close this perspective paper by discussing challenges for the continuous refinement of neuroscientific theory, methodological innovation, and real-world translation to maintain our collective progress towards integrated models of brain organization.

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Control Theory Illustrates the Energy Efficiency in the Dynamic Reconfiguration of Functional Connectivity

The brain's functional connectivity fluctuates over time instead of remaining steady in a stationary mode even during the resting state. This fluctuation establishes the dynamical functional connectivity that transitions in a non-random order between multiple modes. Yet it remains unexplored how the transition facilitates the entire brain network as a dynamical system and what utility this mechanism for dynamic reconfiguration can bring over the widely used graph theoretical measurements. To address these questions, we propose to conduct an energetic analysis of functional brain networks using resting-state fMRI and behavioral measurements from the Human Connectome Project. Through comparing the state transition energy under distinct adjacent matrices, we justify that dynamic functional connectivity leads to 60% less energy cost to support the resting state dynamics than static connectivity when driving the transition through default mode network. Moreover, we demonstrate that combining graph theoretical measurements and our energy-based control measurements as the feature vector can provide complementary prediction power for the behavioral scores. Our approach integrates statistical inference and dynamical system inspection towards understanding brain networks.

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The Alzheimer's Disease Prediction Of Longitudinal Evolution (TADPOLE) Challenge: Results after 1 Year Follow-up

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

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Identification of brain states, transitions, and communities using functional MRI

Brain function relies on a precisely coordinated and dynamic balance between the functional integration and segregation of distinct neural systems. Characterizing the way in which neural systems reconfigure their interactions to give rise to distinct but hidden brain states remains an open challenge. In this paper, we propose a Bayesian model-based characterization of latent brain states and showcase a novel method based on posterior predictive discrepancy using the latent block model to detect transitions between latent brain states in blood oxygen level-dependent (BOLD) time series. The set of estimated parameters in the model includes a latent label vector that assigns network nodes to communities, and also block model parameters that reflect the weighted connectivity within and between communities. Besides extensive in-silico model evaluation, we also provide empirical validation (and replication) using the Human Connectome Project (HCP) dataset of 100 healthy adults. Our results obtained through an analysis of task-fMRI data during working memory performance show appropriate lags between external task demands and change-points between brain states, with distinctive community patterns distinguishing fixation, low-demand and high-demand task conditions.

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The Future of Data Analysis in the Neurosciences

Neuroscience is undergoing faster changes than ever before. Over 100 years our field qualitatively described and invasively manipulated single or few organisms to gain anatomical, physiological, and pharmacological insights. In the last 10 years neuroscience spawned quantitative big-sample datasets on microanatomy, synaptic connections, optogenetic brain-behavior assays, and high-level cognition. While growing data availability and information granularity have been amply discussed, we direct attention to a routinely neglected question: How will the unprecedented data richness shape data analysis practices? Statistical reasoning is becoming more central to distill neurobiological knowledge from healthy and pathological brain recordings. We believe that large-scale data analysis will use more models that are non-parametric, generative, mixing frequentist and Bayesian aspects, and grounded in different statistical inferences.

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