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, 9 (4), e01229

A Resting-State Study of Volumetric and Functional Connectivity of the Habenular Nucleus in Treatment-Resistant Depression Patients

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A Resting-State Study of Volumetric and Functional Connectivity of the Habenular Nucleus in Treatment-Resistant Depression Patients

Shu-Xin Luan et al. Brain Behav.

Abstract

Objective: To investigate the volumetric and functional connectivity of the habenular nucleus in treatment-resistant depression (TRD) patients using the resting-state functional magnetic resonance imaging (rs-fMRI) approach.

Methods: A total of 15 TRD patients, who visited the Mental Health Institute of the First Hospital Affiliated with Jilin University between August 2014 and March 2015, along with 15 normal subjects, were enrolled into this study for structural and functional imaging. Functional connectivity analysis was performed using bilateral habenular nuclei as the region of interest in contrast to whole-brain voxels.

Results: No significant difference of absolute volume was found in bilateral habenular nuclei between TRD patients and healthy controls, or after controlling for individual total intracranial volume. However, functional connectivity analysis showed increased connectivity between the right habenular nucleus with the medial superior frontal gyrus, anterior cingulate cortex and medial orbitofrontal gyrus, and decreased connectivity with the corpus callosum in the TRD group. For the left habenular nucleus seed, the brain region with increased functional connectivity in the inferior temporal gyrus and decreased functional connectivity in the insular was found in the TRD patients.

Conclusion: Abnormal functional connectivity was present between the habenular nucleus and the default mode network in TRD patients. Dysfunction in habenular nucleus-related circuitry for processing negative emotion might form the pathological basis for TRD. Significant asymmetric functional connectivity was also found between bilateral habenular nuclei in TRD patients. Such asymmetry suggests potentially divergent strategy for intervention on bilateral habenular nucleus regions in the future management of depression.

Keywords: functional connectivity analysis; habenular nucleus; rs-fMRI; treatment-resistant depression.

Conflict of interest statement

None declared.

Figures

Figure 1
Figure 1
Images of the habenular nuclei. Habenular nuclei in the coronal, transversal, and sagittal planes. Native T1 maps (a) and T1 maps with manually segmented habenular nucleus (b). Right habenular nucleus voxel overlay in green and left habenular nucleus voxel overlay in red
Figure 2
Figure 2
Functional connectivity with bilateral habenular nuclei in healthy subjects. (a) Left lateral view under rs‐fMRI; (b) Right lateral view. Red scale indicates positive to negative connectivity with the habenular nuclei under the resting state. (One‐sample t tests, with a p < 0.001 threshold; Alphasim corrected, Cluster size >13 voxels). rs‐fMRI: resting‐state functional magnetic resonance imaging
Figure 3
Figure 3
Functional connectivity with bilateral habenular nuclei in TRD patients. (a) Left lateral view under rs‐fMRI; (b) Right lateral view. Red scale indicates positive to negative connectivity with the habenular nuclei under the resting state. (One‐sample t tests, with a p < 0.001 threshold; Alphasim corrected, Cluster size >13 voxels). TRD: treatment‐resistant depression; rs‐fMRI: resting‐state functional magnetic resonance imaging
Figure 4
Figure 4
Functional connectivity toward the habenular nuclei between healthy subjects and TRD patients. Brain regions exhibiting increased (red) or decreased (blue) resting‐state functional connectivity with the left (a) and right (b) habenular nuclei in TRD subjects compared with healthy controls were shown in the coronal, sagittal, and axial views with the MNI location. The color bar indicates the t‐value. TRD: treatment‐resistant depression; MNI: Montreal Neurological Institute

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