BioRxiv : the Preprint Server for Biology
S.-J. HongMichael Milham


Despite myriad demonstrations of feasibility, the high dimensionality of fMRI data remains a critical barrier to its utility for reproducible biomarker discovery. Recent studies applying dimensionality reduction techniques to resting-state fMRI (R-fMRI) have unveiled neurocognitively meaningful connectivity gradients that are present in both human and primate brains, and appear to differ meaningfully among individuals and clinical populations. Here, we provide a critical assessment of the suitability of connectivity gradients for biomarker discovery. Using the Human Connectome Project (discovery subsample=209; two replication subsamples= 209x2) and the Midnight scan club (n=9), we tested the following key biomarker traits, reliability, reproducibility, and predictive validity, of functional gradients. In doing so, we systematically assessed the effects of three analytical settings, including i) dimensionality reduction algorithms (i.e., linear vs. non-linear methods), ii) input data types (i.e., raw time series, [un-]thresholded functional connectivity), and iii) amount of the data (R-fMRI time-series lengths). We found that the reproducibility of functional gradients across algorithms and subsamples is generally higher for tho...Continue Reading

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