Test–retest reliability and predictive utility of a macroscale principal functional connectivity gradient

• Published in: Human Brain Mapping Vol. 44; no. 18; pp. 6399 - 6417
• Main Authors: Knodt, Annchen R., Elliott, Maxwell L., Whitman, Ethan T., Winn, Alex, Addae, Angela, Ireland, David, Poulton, Richie, Ramrakha, Sandhya, Caspi, Avshalom, Moffitt, Terrie E., Hariri, Ahmad R.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA Wiley 15.12.2023; John Wiley & Sons, Inc
• Subjects: Aging; Behavior; Brain; Brain - diagnostic imaging; Brain mapping; Circuits; Cognition; Cognition & reasoning; Cognitive ability; cognitive function; connectivity gradient; Connectome; Connectome - methods; cortical hierarchy; Datasets; functional MRI; Humans; Hypotheses; Magnetic Resonance Imaging; Magnetic Resonance Imaging - methods; Neural networks; Reliability; Reproducibility of Results; test–retest reliability; Young Adult; Young adults; cognitive function; connectivity gradient; functional MRI; cortical hierarchy; aging; test-retest reliability
• ISSN: 1065-9471; 1097-0193; 1097-0193
• DOI: 10.1002/hbm.26517

Mapping individual differences in brain function has been hampered by poor reliability as well as limited interpretability. Leveraging patterns of brain‐wide functional connectivity (FC) offers some promise in this endeavor. In particular, a macroscale principal FC gradient that recapitulates a hierarchical organization spanning molecular, cellular, and circuit level features along a sensory‐to‐association cortical axis has emerged as both a parsimonious and interpretable measure of individual differences in behavior. However, the measurement reliabilities of this FC gradient have not been fully evaluated. Here, we assess the reliabilities of both global and regional principal FC gradient measures using test–retest data from the young adult Human Connectome Project (HCP‐YA) and the Dunedin Study. Analyses revealed that the reliabilities of principal FC gradient measures were (1) consistently higher than those for traditional edge‐wise FC measures, (2) higher for FC measures derived from general FC (GFC) in comparison with resting‐state FC, and (3) higher for longer scan lengths. We additionally examined the relative utility of these principal FC gradient measures in predicting cognition and aging in both datasets as well as the HCP‐aging dataset. These analyses revealed that regional FC gradient measures and global gradient range were significantly associated with aging in all three datasets, and moderately associated with cognition in the HCP‐YA and Dunedin Study datasets, reflecting contractions and expansions of the cortical hierarchy, respectively. Collectively, these results demonstrate that measures of the principal FC gradient, especially derived using GFC, effectively capture a reliable feature of the human brain subject to interpretable and biologically meaningful individual variation, offering some advantages over traditional edge‐wise FC measures in the search for brain–behavior associations. We demonstrate that a macroscale hierarchical functional connectivity gradient that recapitulates fundamental biological features of the human cortex has higher test–retest reliability than traditional edge‐wise measures, especially when derived from combined resting‐state and task‐based data. Further, gradient measures capture individual differences in aging and cognition.