TE-dependent spatial and spectral specificity of functional connectivity

Previous studies suggest that spontaneous fluctuations in the resting-state fMRI (RS-fMRI) signal may reflect fluctuations in transverse relaxation time (T(2)(*)) rather than spin density (S(0)). However, such S(0) and T(2)(*) features have not been well characterized. In this study, spatial and spectral characteristics of functional connectivity on sensorimotor, default-mode, dorsal attention, and primary visual systems were examined using a multiple gradient-echo sequence at 3T. In the spatial domain, we found broad, local correlations at short echo times (TE ≤ 14 ms) due to dominant S(0) contribution, whereas long-range connections mediated by T(2)(*) became explicit at TEs longer than 22 ms. In the frequency domain, compared with the flat spectrum of S(0), spectral power of the T(2)(*)-weighted signal elevated significantly with increasing TE, particularly in the frequency ranges of 0.008-0.023 Hz and 0.037-0.043 Hz. Using the S(0) spectrum as a reference, we propose two indices to measure spectral signal change (SSC) and spectral contrast-to-noise ratio (SCNR), respectively, for quantifying the RS-fMRI signal. These indices demonstrated TE dependency of connectivity-related fluctuation strength, resembling functional contrasts in activation-based fMRI. These findings further confirm that large-scale functional circuit connectivity based on BOLD contrast may be constrained within specific frequency ranges in every brain network, and the spectral features of S(0) and T(2)(*) could be valuable for interpreting and quantifying RS-fMRI data.