In vivo anatomical mapping of human locus coeruleus functional connectivity at 3 T MRI

Abstract

The locus coeruleus (LC) is involved in numerous crucial brain functions and several disorders like depression and Alzheimer's disease. Recently, the LC resting-state functional connectivity (rs-fc) has been investigated in functional MRI by calculating the blood oxygen level-dependent (BOLD) response extracted using Montreal Neurological Institute (MNI) space masks. To corroborate these results, we aimed to investigate the LC rs-fc at native space by improving the identification of the LC location using a neuromelanin sensitive sequence. Twenty-five healthy male participants (mean age 24.8 ± 4.2) were examined in a Siemens MAGNETOM Prisma 3 T MRT applying a neuromelanin sensitive T1TSE sequence and functional MRI. We compared the rs-fc of LC calculated by a MNIbased approach with extraction of the BOLD signal at the exact individual location of the LC after applying CompCor and field map correction. As a measure of advance, a marked increase of regional homogeneity (ReHo) of time series within LC could be achieved with the subject-specific approach. Furthermore, the methods differed in the rs-fc to the right temporoparietal junction, which showed stronger connectivity to the LC in the MNIbased method. Nevertheless, both methods comparably revealed LC rs-fc to multiple brain regions including ACC, bilateral thalamus, and cerebellum. Our results are relevant for further research assessing and interpreting LC function, especially in patient populations examined at 3 T MRI. K E Y W O R D S locus coeruleus, neuromelanin sensitive MRI, resting-state functional connectivity

What’s That (Blue) Spot on my MRI? Multimodal Neuroimaging of the Locus Coeruleus in Neurodegenerative Disease

“…Given these considerations, only recently have studies begun to investigate direct connectivity of the LC, and have treated it as a single nucleus, as opposed to segmenting it along the rostrocaudal axis. Although current results at 3 and 7T are largely congruent ( Zhang et al, 2016 ; Jacobs et al, 2018 ; Liebe et al, 2020 ), these preliminary experiments should be replicated and expanded using tasks known to evoke LC activity, at multiple points during disease states, and at higher resolution.…”

“…In healthy individuals at rest, the LC shows both negative and positive functional connectivity to a variety of brain regions such as the cingulate cortex, thalamus, cerebellum, and various frontal, parietal, and temporal regions ( Figure 2 ) ( Bär et al, 2016 ; Zhang et al, 2016 ; Jacobs et al, 2018 ; Liebe et al, 2020 ). These studies are highly consistent, but slight differences are apparent and are likely due to different imaging parameters, preprocessing protocols, and analyses.…”

“…Notably, PD is diagnosed by motor dysfunction that has largely been localized to the basal ganglia, with LC involvement mostly disregarded due to the sparse noradrenergic input to this region ( Berridge and Waterhouse, 2003 ). However, resting-state fMRI studies have provided evidence of noradrenergic contributions to the striatum ( Zhang et al, 2016 ; Lee et al, 2020 ; Liebe et al, 2020 ), and it was recently reported that the LC directly innervates the caudate and putamen in mice ( Zerbi et al, 2019 ). Stimulation of LC-striatal fibers in mice elicited NE release and increased overall functional connectivity.…”

Locus Coeruleus Malfunction Is Linked to Psychopathology in Prodromal Dementia With Lewy Bodies

“…As mentioned earlier, the LC's network is extremely important, and if degenerated, provides a link to its potential brain dysfunctions. The LC's widespread projections to the prefrontal cortex, limbic system containing structures such as the hippocampus, and amygdala and well as other cortical and subcortical regions such as the sensory cortex (Schwarz and Luo, 2015 ; Liebe et al, 2020 ) are crucial in generating psychiatric symptoms ( Figure 1 ). These pathways are being intensively investigated, and novel pathways have recently been identified.…”

A comparison of the effectiveness of functional MRI analysis methods for pain research: The new normal

“…In addition, the SC was divided into segments, with positions based on the anatomical study done by Lang and Bartram [57], and segments were divided into right/left and anterior/posterior quadrants. BS regions not included in the CONN15e region map were added based on examples and anatomical descriptions [1,[58][59][60][61][62], freely shared atlases as described by Pauli et al [63] (https://identifiers.org/neurovault.collection:3145), Keren et al [64], and Harvard atlases [65]. The resulting region maps are thus probabilistic, and indicate the likely location of anatomical regions of interest within each data set, after it has been spatially normalized.…”