Improved Reliability of Resting-State fMRI Connectivity Using Multi-Echo Acquisition: Implications for Personalized...

Multi-echo (ME) fMRI acquisition improves the separation of signal from noise relative to single-echo (SE). We tested whether this enhances the reliability of functional connectivity (FC), with a focus on personalizing transcranial magnetic stimulation (TMS) targets in the dorsolateral prefrontal cortex (DLPFC) in patients with depression.

Resting-state fMRI scans were acquired from adult patients with major depression (20 women, 15 men) presenting for clinical TMS using either SE (n=21) or ME (n=31). Each subject's fMRI time-series was split in half, and voxelwise seed-based FC was computed for 100 general ROIs and for 2 TMS-specific ROIs: subgenual cingulate cortex (SGC) and a previously published depression circuit (DEP). Reliability was assessed using 1) spatial correlation between split-half connectivity maps and 2) intraclass correlation coefficient (ICC) for each ROI's connectivity to the DLPFC.

In general ROI analysis, ME showed significantly higher whole-brain split-half correlations than SE (P = .006) and higher ICC (ΔICC = 0.16; P = .03). In TMS-specific ROI analysis, ME showed higher split-half correlations for both the SGC-DLPFC (P = .04) and DEP-DLPFC (P = .01). TMS-specific ICC values were numerically higher for ME (SGC-DLPFC: 0.47; DEP-DLPFC: 0.75) than for SE (0.02 and 0.40, respectively), although these differences were not statistically significant.

ME fMRI improves general FC reliability over SE, with suggested advantages for TMS-specific measures. Future work is needed to determine whether these gains meaningfully improve TMS targeting.