4.8 Article

An uncertainty-aware, shareable, and transparent neural network architecture for brain-age modeling

Journal

SCIENCE ADVANCES
Volume 8, Issue 1, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abg9471

Keywords

-

Funding

  1. German Research Foundation (DFG) [HA7070/2-2, HA7070/3, HA7070/4]
  2. Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Munster [Dan3/012/17, MzH 3/020/20]
  3. Federal Ministry of Education and Research (BMBF) [01ER1301A/B/C, 01ER1511D, 01ER0816, 01ER1506]
  4. Helmholtz Association
  5. Leibniz Association
  6. German Research Foundation (Deutsche Forschungsgemeinschaft DFG
  7. Forschungsgruppe/Research Unit FOR2107)
  8. DFG [KI 588/14-1, KI 588/14-2]
  9. National Natural Science Foundation of China [30770594]
  10. National High Technology Program of China (863) [2008AA02Z405]
  11. University of Marburg [AZ: 07/14]
  12. University of Munster [AZ: 2014-422-b-S]
  13. [DA 1151/5-1]
  14. [DA 1151/5-2]
  15. [KR 3822/5-1]
  16. [KR 3822/7-2]
  17. [NE 2254/1-2]
  18. [KO 4291/3-1]
  19. [WO 1732/4-1]
  20. [WO 1732/4-2]
  21. [SCHW 559/14-1]
  22. [SCHW 559/14-2]
  23. [SCHR 1136/3-1]
  24. [1136/3-2]
  25. [AL 1145/5-2]
  26. [CU 43/9-1]
  27. [CU 43/9-2]
  28. [GA 545/5-1]
  29. [GA 545/7-2]
  30. [RI 908/11-1]
  31. [RI 908/11-2]
  32. [NO 246/10-1]
  33. [NO 246/10-2]
  34. [WI 3439/3-1]
  35. [WI 3439/3-2]
  36. [JA 1890/7-1]
  37. [JA 1890/7-2]
  38. [MU1315/8-2]
  39. [DE 1614/3-1]
  40. [DE 1614/3-2]
  41. [PF 784/1-1]
  42. [PF 784/1-2]
  43. [RE 737/20-1]
  44. [737/20-2]
  45. [KI 588/15-1]
  46. [KI 588/17-1]
  47. [DA 1151/6-1]
  48. [KO 4291/4-1]

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In order to address the issues with machine learning models in biological age research, researchers have developed an uncertainty-aware, shareable, and transparent neural network model. This model provides robust uncertainty quantification in neuroimaging data, allowing for more accurate detection of deviant brain aging compared to existing models.
The deviation between chronological age and age predicted from neuroimaging data has been identified as a sensitive risk marker of cross-disorder brain changes, growing into a cornerstone of biological age research. However, machine learning models underlying the field do not consider uncertainty, thereby confounding results with training data density and variability. Also, existing models are commonly based on homogeneous training sets, often not independently validated, and cannot be shared because of data protection issues. Here, we introduce an uncertainty-aware, shareable, and transparent Monte Carlo dropout composite quantile regression (MCCQR) Neural Network trained on N = 10,691 datasets from the German National Cohort. The MCCQR model provides robust, distribution-free uncertainty quantification in high-dimensional neuroimaging data, achieving lower error rates compared with existing models. In two examples, we demonstrate that it prevents spurious associations and increases power to detect deviant brain aging. We make the pretrained model and code publicly available.

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