YNICL Journal 2020 Journal Article
Sub-millimeter variation in human locus coeruleus is associated with dimensional measures of psychopathology: An in vivo ultra-high field 7-Tesla MRI study
- Laurel S. Morris
- Aaron Tan
- Derek A. Smith
- Mora Grehl
- Kuang Han-Huang
- Thomas P. Naidich
- Dennis S. Charney
- Priti Balchandani
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. 5 mm 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 postmortem anatomic definitions of the LC. There was variation of LC size in healthy subjects (125. 7 +/- 59. 3 mm3), 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<0. 025), trans-diagnostically across the full sample. This study combined high-resolution and quantitative MR with a mixture of supervised and unsupervised computational techniques to provide robust, sub-millimeter measurements of the LC in vivo, which were additionally related to common psychopathology. This work has wide-reaching applications for a range of neurological and psychiatric disorders characterized by expected LC dysfunction.