Estimates of locus coeruleus function with functional magnetic resonance imaging are influenced by localization approaches and the use of multi-echo data

The locus coeruleus (LC) plays a central role in regulating human cognition, arousal, and autonomic states. Efforts to characterize the LC’s function in humans using functional magnetic resonance imaging have been hampered by its small size and location near a large source of noise, the fourth ventricle. We tested whether the ability to characterize LC function is improved by employing neuromelanin-T1 weighted images (nmT1) for LC localization and multi-echo functional magnetic resonance imaging (ME-fMRI) for estimating intrinsic functional connectivity (iFC). Analyses indicated that, relative to a probabilistic atlas, utilizing nmT1 images to individually localize the LC increases the specificity of seed time series and clusters in the iFC maps. When combined with independent components analysis (ME-ICA), ME-fMRI data provided significant gains in the temporal signal to noise ratio relative to denoised single-echo (1E) data. The effects of acquiring nmT1 images and ME-fMRI data did not appear to only reflect increases in power: iFC maps for each approach only moderately overlapped. This is consistent with findings that ME-fMRI offers substantial advantages over 1E data acquisition and denoising. It also suggests that individually identifying LC with nmT1 scans is likely to reduce the influence of other nearby brainstem regions on estimates of LC function. Highlights * LC : locus coeruleus 4thV : 4th ventricle NE : norepinephrine nmT1 : neuromelanin-weighted T1 iFC : intrinsic functional connectivity 1E-fMRI : single-echo fMRI ME-fMRI : multi-echo fMRI K1, K2 : binary atlas from [Keren, Lozar, Harris, Morgan, & Eckert (2009)][1], 1SD and 2SD [1]: #ref-44