Structural and functional characterization of the locus coeruleus in young and late middle-aged individuals

Abstract

IntroductionThe brainstem locus coeruleus (LC) influences a broad range of brain processes, including cognition. The so-called LC contrast is an accepted marker of the integrity of the LC that consists of a local hyperintensity on specific Magnetic Resonance Imaging (MRI) structural images. The small size of the LC has, however, rendered its functional characterization difficult in humans, including in aging. A full characterization of the structural and functional characteristics of the LC in healthy young and late middle-aged individuals is needed to determine the potential roles of the LC in different medical conditions. Here, we wanted to determine whether the activation of the LC in a mismatch negativity task changes in aging and whether the LC functional response was associated to the LC contrast.MethodsWe used Ultra-High Field (UHF) 7-Tesla functional MRI (fMRI) to record brain response during an auditory oddball task in 53 healthy volunteers, including 34 younger (age: 22.15y ± 3.27; 29 women) and 19 late middle-aged (age: 61.05y ± 5.3; 14 women) individuals.ResultsWhole-brain analyses confirmed brain responses in the typical cortical and subcortical regions previously associated with mismatch negativity. When focusing on the brainstem, we found a significant response in the rostral part of the LC probability mask generated based on individual LC images. Although bilateral, the activation was more extensive in the left LC. Individual LC activity was not significantly different between young and late middle-aged individuals. Importantly, while the LC contrast was higher in older individuals, the functional response of the LC was not significantly associated with its contrast.DiscussionThese findings may suggest that the age-related alterations of the LC structural integrity may not be related to changes in its functional response. The results further suggest that LC responses may remain stable in healthy individuals aged 20 to 70.

Locus coeruleus activity while awake is associated with REM sleep quality in older individuals

“…As already reported in this sample ( 29 ), we found significant activations within the bilateral (though more left lateralized) rostral part of the LC for the detection of the target sound ( Figure 1C ; P < 0.05, family-wise error [FWE] corrected for multiple comparisons over the group-wise LC mask), supporting a robust LC activation during the oddball task. Individual estimates of LC activity were then extracted within the entire individual LC masks in the participant brain space, for higher accuracy, and contrasted against the sleep metrics of interest.…”

“…Both with the left and the right LC activity, post hoc tests yielded a significant correlation in the older ( t > 2, P ≤ 0.04) but not in the younger group (–0.9 < t < 0, P > 0.39). Furthermore, since we previously reported in our sample a significant age group difference in LC integrity — as indexed by its contrast ( 29 ) — we added LC contrast as a covariate in the GLMM, which yielded the same main effects of LC activity and LC-activity-by-age-group interaction ( Table 3 ). Interestingly, the GLMM yielded a significant main effect of LC contrast (F = 5.34; P = 0.025, R 2* = 0.1), with higher LC contrast associated to better sleep quality ( Figure 2B ) and no significant interaction between LC contrast and age group ( P > 0.9)…”

Locus coeruleus features are linked to vagus nerve stimulation response in drug-resistant epilepsy

“…Knowing that the auditory oddball task recruits the LC ( Murphy et al, 2014 ; Berger et al, 2023 ), this paradigm was chosen to extract the functional response of the LC in a VNS OFF condition in the current study. The task was administered during functional MRI acquisitions and consisted of rare target stimuli (1,000 Hz sinusoidal waves, 100 ms) appearing approximately 20% of the time and pseudorandomly interleaved in a stream of standard sounds (500 Hz sinusoidal waves, 100 ms).…”

Exploring the Role of Locus Coeruleus in Alzheimer’s Disease: a Comprehensive Update on MRI Studies and Implications

“…A lower LC signal was related to worse memory performances [ 39 , 40 , 49 ••], global cognition and behavioral status [ 41 ] and was also able to predict a further deterioration of memory overtime [ 49 ••]. These structural findings are supported by functional MRI (fMRI) studies, which disclosed a reduction of LC activation in elderlies with worse cognitive performances [ 53 , 54 ].…”