title: Resting-state functional connectivity of the human habenula in healthy individuals: Associations with subclinical depression.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Ely
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.|Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, Translational and Molecular Imaging Institute, New York, New York.|Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Junqian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Wayne K
authors.initials: WK
authors.lastname: Goodman
authors.affiliation: Department of Psychiatry, Stony Brook University, Stony Brook, New York.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Lapidus
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.|Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York.
authors.forename: Vilma
authors.initials: V
authors.lastname: Gabbay
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Stern
mesh_terms: D000328:Adult; D015331:Cohort Studies; D063132:Connectome; D003863:Depression / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D019262:Habenula / Q000000981:diagnostic imaging / Q000502:physiology* / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000502:physiology / Q000503:physiopathology; D010363:Pattern Recognition, Automated; D012146:Rest
keywords: depression; functional connectivity; habenula; high resolution; midbrain; resting state fMRI; seed optimization; substantia nigra; ventral tegmental area (VTA); whole brain