Resting-state functional connectivity of the human habenula in healthy individuals: Associations with subclinical depression

• Published in: Human brain mapping Vol. 37; no. 7; pp. 2369 - 2384
• Main Authors: Ely, Benjamin A., Xu, Junqian, Goodman, Wayne K., Lapidus, Kyle A., Gabbay, Vilma, Stern, Emily R.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2016; John Wiley & Sons, Inc; John Wiley and Sons Inc
• Subjects: Adult; Cohort Studies; Connectome; depression; Depression - diagnostic imaging; Depression - physiopathology; Female; functional connectivity; habenula; Habenula - diagnostic imaging; Habenula - physiology; Habenula - physiopathology; high resolution; Humans; Magnetic Resonance Imaging; Male; midbrain; Neural Pathways - diagnostic imaging; Neural Pathways - physiology; Neural Pathways - physiopathology; Pattern Recognition, Automated; Rest; resting state fMRI; seed optimization; substantia nigra; ventral tegmental area (VTA); whole brain; substantia nigra; functional connectivity; midbrain; seed optimization; whole brain; depression; habenula; resting state fMRI; high resolution; ventral tegmental area (VTA)
• ISSN: 1065-9471; 1097-0193
• DOI: 10.1002/hbm.23179

Introduction: The habenula (Hb) is postulated to play a critical role in reward and aversion processing across species, including humans, and has been increasingly implicated in depression. However, technical constraints have limited in vivo investigation of the human Hb, and its function remains poorly characterized. We sought to overcome these challenges by examining the whole‐brain resting‐state functional connectivity of the Hb and its possible relationship to depressive symptomatology using the high‐resolution WU‐Minn Human Connectome Project (HCP) dataset. Methods: Anatomical and resting‐state functional MRI data from 50 healthy subjects with low or high subclinical depression scores (n = 25 each) were analyzed. Using novel semi‐automated segmentation and optimization techniques, we generated individual‐specific Hb seeds and calculated whole‐brain functional connectivity for the entire cohort and the contrast of high vs. low depression groups. Results: In the entire cohort, the Hb exhibited significant connectivity with key brainstem structures (i.e., ventral tegmental area, substantia nigra, pons) as well as the anterior and posterior cingulate cortices, precuneus, thalamus, and sensorimotor cortex. Multiple regions showed differential Hb connectivity based on subclinical depression scores, including the amygdala, insula, and prefrontal, mid‐cingulate, and entorhinal cortices. Conclusions: Hb connectivity findings converged on areas associated with salience processing, sensorimotor systems, and the default mode network. We also detected substantial Hb‐brainstem connectivity, consistent with prior histological and animal research. High and low subclinical depression groups exhibited differences in Hb connectivity with multiple regions previously linked to depression, suggesting the relationship between these structures as a potential target for future research and treatment. Hum Brain Mapp 37:2369–2384, 2016. © 2016 Wiley Periodicals, Inc.