Generative modeling of brain maps with spatial autocorrelation

Studies of large-scale brain organization have revealed interesting relationships between spatial gradients in brain maps across multiple modalities. Evaluating the significance of these findings requires establishing statistical expectations under a null hypothesis of interest. Through generative modeling of synthetic data that instantiate a specific null hypothesis, quantitative benchmarks can be derived for arbitrarily complex statistical measures. Here, we present a generative null model, provided as an open-access software platform, that generates surrogate maps with spatial autocorrelation (SA) matched to SA of a target brain map. SA is a prominent and ubiquitous property of brain maps that violates assumptions of independence in conventional statistical tests. Our method can simulate surrogate brain maps, constrained by empirical data, that preserve the SA of cortical, subcortical, parcellated, and dense brain maps. We characterize how SA impacts p-values in pairwise brain map comparisons. Furthermore, we demonstrate how SA-preserving surrogate maps can be used in gene set enrichment analyses to test hypotheses of interest related to brain map topography. Our findings demonstrate the utility of SA-preserving surrogate maps for hypothesis testing in complex statistical analyses, and underscore the need to disambiguate meaningful relationships from chance associations in studies of large-scale brain organization.