Sub-millimeter variation in human locus coeruleus is associated with dimensional measures of psychopathology: An in vivo ultra-high field 7-Tesla MRI study

Abstract The locus coeruleus (LC) has a long-established role in the attentional and arousal response to threat, and in the emergence of pathological anxiety in pre-clinical models. However, human evidence of links between LC function and pathological anxiety has been restricted by limitations in discerning LC with current neuroimaging techniques. We combined ultra-high field 7-Tesla and 0.4×0.4×0.5mm quantitative MR imaging with a computational LC localization and segmentation algorithm to delineate the LC in 29 human subjects including subjects with and without an anxiety or stress-related disorder. Our automated, data-driven LC segmentation algorithm provided LC delineations that corresponded well with post-mortem anatomic definitions of the LC. There was variation of LC size in healthy subjects (125.7 +/- 59.3mm (Kessler et al., 2005)), which recapitulates histological reports. Patients with an anxiety or stress-related disorder had larger LC compared to controls (Cohen's d=1.08, p=0.024). Larger LC was additionally associated with poorer attentional and inhibitory control and higher anxious arousal (FDR-corrected p's