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, James W. Murrough, Prantik Kundu

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 × 0.5 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.

Original languageEnglish
Article number102148
JournalNeuroImage: Clinical
Volume25
DOIs
StatePublished - 2020
Externally publishedYes

Keywords

  • Anxiety
  • High-field MRI
  • Locus coeruleus
  • Norepinephrine
  • PTSD
  • Structural imaging

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