Reproducibility of Single-Subject Functional Connectivity Measurements

TLDR

Resting‑state functional connectivity is increasingly used to characterize neuropathologic and neurodevelopmental populations. This study aimed to determine the imaging time required to obtain reproducible quantitative functional connectivity measurements for a reliable single‑subject diagnostic test. The authors acquired 100 five‑minute BOLD scans from a single subject across 10 sessions, alternating rest and cartoon viewing, and compared the resulting 64‑ROI correlation matrices to those from 36 healthy controls. Reliability of connectivity estimates scaled as 1/√n, with stable values reached within 25 minutes; this duration also allowed individual‑vs‑group discrimination, while 15 minutes sufficed for 95–100% accurate classification of rest versus cartoon states.

Abstract

<h3>BACKGROUND AND PURPOSE:</h3> Measurements of resting-state functional connectivity have increasingly been used for characterization of neuropathologic and neurodevelopmental populations. We collected data to characterize how much imaging time is necessary to obtain reproducible quantitative functional connectivity measurements needed for a reliable single-subject diagnostic test. <h3>MATERIALS AND METHODS:</h3> We obtained 100 five-minute BOLD scans on a single subject, divided into 10 sessions of 10 scans each, with the subject at rest or while watching video clips of cartoons. These data were compared with resting-state BOLD scans from 36 healthy control subjects by evaluating the correlation between each pair of 64 small spheric regions of interest obtained from a published functional brain parcellation. <h3>RESULTS:</h3> Single-subject and group data converged to reliable estimates of individual and population connectivity values proportional to 1 / <i>sqrt(n)</i>. Dramatic improvements in reliability were seen by using ≤25 minutes of imaging time, with smaller improvements for additional time. Functional connectivity “fingerprints” for the individual and population began diverging at approximately 15 minutes of imaging time, with increasing reliability even at 4 hours of imaging time. Twenty-five minutes of BOLD imaging time was required before any individual connections could reliably discriminate an individual from a group of healthy control subjects. A classifier discriminating scans during which our subject was resting or watching cartoons was 95% accurate at 10 minutes and 100% accurate at 15 minutes of imaging time. <h3>CONCLUSIONS:</h3> An individual subject and control population converged to reliable different functional connectivity profiles that were task-modulated and could be discriminated with sufficient imaging time.