Higher locus coeruleus MRI contrast is associated with lower parasympathetic influence over heart rate variability

Abstract

The locus coeruleus (LC) is a key node of the sympathetic nervous system and suppresses parasympathetic activity that would otherwise increase heart rate variability. In the current study, we examined whether LC-MRI contrast reflecting neuromelanin accumulation in the LC was associated with high-frequency heart rate variability (HF-HRV), a measure reflecting parasympathetic influences on the heart. Recent evidence indicates that neuromelanin, a byproduct of catecholamine metabolism, accumulates in the LC through young and mid adulthood, suggesting that LC-MRI contrast may be a useful biomarker of individual differences in habitual LC activation. We found that, across younger and older adults, greater LC-MRI contrast was negatively associated with HF-HRV during fear conditioning and spatial detection tasks. This correlation was not accounted for by individual differences in age or anxiety. These findings indicate that individual differences in LC structure relate to key cardiovascular parameters.

Neuromelanin Locus Coeruleus MRI Contrast in Migraine With Aura

“…It is thus possible that LC signal intensity might reflect the habitual LC activation in young adults. Consistent with this hypothesis, greater LC signal intensity was associated with reduced high frequency heart rate variability, a measure reflecting parasympathetic influences on heart rate, in healthy adults . We thus postulated that repeated LC activation during MWA attack in young adults would result in heightened LC signal intensity compared to healthy controls.…”

“…We did not assess anxiety and depression in included patients/controls, which may be a limitation. Indeed, a previous study showed a weak correlation of LC contrast with anxiety and depression in healthy subjects, which, however, was no longer significant after adjustment in multivariate analysis . Another study reported a reduced LC signal in depression .…”

“…Several methods have been used to measure LC automatically or manually. Some authors segmented LC only on axial slice, where LC appeared to be the brightest, 7 mm below the inferior colliculus, with a round cursor of 1 mm 2 or a cross 3 voxel‐wide and high to cover the 1‐2 mm distribution of LC neurons . However, taking into account the anatomical rostro‐caudal extent of LC with variance in intensity along z‐axis dependent on age, we preferred to analyze LC intensity on several slices so as to evaluate LC in 3D.…”

“…Consistent with this hypothesis, greater LC signal intensity was associated with reduced high frequency heart rate variability, a measure reflecting parasympathetic influences on heart rate, in healthy adults. 20 We thus postulated that repeated LC activation during MWA attack in young adults would result in heightened LC signal intensity compared to healthy controls. We could not confirm this hypothesis as MWA was not associated with increased LC contrast and LC contrast was not correlated with migraine activity.…”

“…Some authors segmented LC only on axial slice, where LC appeared to be the brightest, 7 mm below the inferior colliculus, with a round cursor of 1 mm 2 or a cross 3 voxel-wide and high to cover the 1-2 mm distribution of LC neurons. 18,20,25,26 However, taking into account the anatomical rostro-caudal extent of LC with variance in intensity along z-axis dependent on age, we preferred to analyze LC intensity on several slices so as to evaluate LC in 3D. Other authors drew bounding boxes around LC and delimited it automatically by extracting the 10 brightest connected voxels.…”