Statistical properties of functional connectivity MRI enrichment analysis in school-age autism research
Mass univariate testing on functional connectivity MRI (fcMRI) data is limited by difficulties achieving experiment-wide significance. Recent work addressing this problem has used enrichment analysis, which aggregates univariate screening statistics for a set of variables into a single enrichment statistic. There have been promising results using this method to explore fcMRI-behavior associations. However, there has not yet been a rigorous examination of the statistical properties of enrichment analysis when applied to fcMRI data. Establishing power for fcMRI enrichment analysis will be important for future neuropsychiatric and cognitive neuroscience study designs that plan to include this method. Here, we use realistic simulation methods, which mimic the covariance structure of fcMRI data, to examine the false positive rate and statistical power of one technique for enrichment analysis, over-representation analysis. We find it can attain high power even for moderate effects and sample sizes, and it strongly outperforms univariate analysis. The false positive rate associated with permutation testing is robust.
Authors
- Guido Gerig (ORCID: https://orcid.org/0000-0002-9547-6233)
- Alan C. Evans (ORCID: https://orcid.org/0000-0003-3841-6098)
- Jessica B. Girault (ORCID: https://orcid.org/0000-0002-9271-0354)
- Natasha Marrus (ORCID: https://orcid.org/0000-0001-6521-0373)
- Juhi Pandey
- Santiago Torres-Gomez
- Stephen R. Dager (ORCID: https://orcid.org/0000-0002-4034-6087)
- Lonnie Zwaigenbaum (ORCID: https://orcid.org/0000-0001-9607-0799)
- Alishia Ferguson
- Tomoyuki Nishino (ORCID: https://orcid.org/0000-0001-7540-6476)
- Robert T. Schultz
- Joseph Piven (ORCID: https://orcid.org/0000-0003-0255-9003)
- Tanya St. John (ORCID: https://orcid.org/0000-0003-2448-5797)
- Heather C. Hazlett (ORCID: https://orcid.org/0000-0001-9166-1434)
- Martin Andreas Styner (ORCID: https://orcid.org/0000-0002-8747-5118)
- Annette Estes (ORCID: https://orcid.org/0000-0003-2687-4155)
- John R. Pruett (ORCID: https://orcid.org/0000-0003-0000-7889)
- Alexandre A. Todorov
Institutions
- University of North Carolina at Chapel Hill (US)
- Children's Hospital of Philadelphia (US)
- University of Alberta (CA)
- University of Washington (US)
- Washington University in St. Louis (US)
- McGill University Health Centre (CA)
- University of Alberta Hospital (CA)
- Piedmont International University (US)
- McGill University (CA)
- New York University (US)
Publication Details
- Journal
- Developmental Cognitive Neuroscience
- Published
- 2025-02-22
- DOI
- https://doi.org/10.1016/j.dcn.2025.101534
- Citations
- 2
- Primary Topic
- Functional Brain Connectivity Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.86