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Main Authors: Boutet, Dominic, Baillet, Sylvain
Format: Preprint
Published: 2025
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Online Access:https://arxiv.org/abs/2509.16070
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author Boutet, Dominic
Baillet, Sylvain
author_facet Boutet, Dominic
Baillet, Sylvain
contents Turning rich neuroimaging data into mechanistic insight remains challenging. Statistical models capture associations but remain largely agnostic to underlying mechanisms. Biophysical models embody candidate mechanisms but remain difficult to deploy without specialized expertise. Here, we present a hypothesis-first framework recasting model specifications as testable mechanistic hypotheses and streamlines the procedure for rejecting inappropriate hypotheses before moving to typical analyses. The key innovation is an expectation of model behavior under feature generalization constraints: we compute the model's expected $Y$ output across the parameter space based on the likelihood for a broader/distinct feature $Z$. Mirror statistical models are derived from these expected outputs and compared to the empirical ones with standard statistics. In synthetic experiments, our framework rejected mis-specified hypotheses and penalized unnecessary degrees of freedom while retaining valid hypotheses. These results demonstrate a practical hypothesis-driven approach for using mechanistic models in neuroimaging without requiring advanced training, complementing traditional analyses.
format Preprint
id arxiv_https___arxiv_org_abs_2509_16070
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle A Hypothesis-First Framework for Mechanistic Modeling in Neuroimaging
Boutet, Dominic
Baillet, Sylvain
Neurons and Cognition
Quantitative Methods
Turning rich neuroimaging data into mechanistic insight remains challenging. Statistical models capture associations but remain largely agnostic to underlying mechanisms. Biophysical models embody candidate mechanisms but remain difficult to deploy without specialized expertise. Here, we present a hypothesis-first framework recasting model specifications as testable mechanistic hypotheses and streamlines the procedure for rejecting inappropriate hypotheses before moving to typical analyses. The key innovation is an expectation of model behavior under feature generalization constraints: we compute the model's expected $Y$ output across the parameter space based on the likelihood for a broader/distinct feature $Z$. Mirror statistical models are derived from these expected outputs and compared to the empirical ones with standard statistics. In synthetic experiments, our framework rejected mis-specified hypotheses and penalized unnecessary degrees of freedom while retaining valid hypotheses. These results demonstrate a practical hypothesis-driven approach for using mechanistic models in neuroimaging without requiring advanced training, complementing traditional analyses.
title A Hypothesis-First Framework for Mechanistic Modeling in Neuroimaging
topic Neurons and Cognition
Quantitative Methods
url https://arxiv.org/abs/2509.16070