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Altered Volume and Functional Connectivity of the Habenula in Schizophrenia


Altered Volume and Functional Connectivity of the Habenula in Schizophrenia

Lei Zhang et al. Front Hum Neurosci.


The pathogenesis of schizophrenia (SCH) is associated with the dysfunction of monoamine neurotransmitters, the synthesis and release of which are mainly regulated by a key structure, the habenular (Hb) nucleus. However, little is known regarding whether SCH is associated with structural or functional alterations in the Hb. In this study, we combined structural and resting-state functional magnetic resonance imaging to investigate the changes in volume and functional connectivity of the Hb in 15 patients with SCH vs. 16 age- and gender-matched healthy controls (HCs). Morphologically, the absolute volume of the bilateral Hb was significantly lower in the SCH patients than in the HCs. Functionally, the bilateral Hb showed significantly enhanced functional connectivity with the left medial prefrontal cortex (mPFC) in the SCH patients. Additionally, the SCH patients exhibited increased functional connectivity of the left Hb with the left lingual gyrus and right inferior frontal gyrus (IFG). A further exploratory analysis revealed that the SCH patients showed increased functional connectivity between the right Hb and several subcortical regions related to dopaminergic pathways, including the left ventral striatum, caudate and putamen. Finally, the increased functional connectivity of the right Hb with the mPFC was positively correlated with the Brief Psychiatric Rating Scale (BPRS) scores in the patients. Together, these results suggest that the altered volume and functional connectivity of the Hb may be involved in the pathogenesis of SCH and thus that the Hb may serve as a potential target in developing new therapeutic strategies in SCH.

Keywords: functional connectivity; habenular nucleus; morphology; resting-state functional magnetic resonance imaging; schizophrenia.


Figure 1
Figure 1
The habenula regions of interest (ROIs) in native and Montreal Neurological Institute (MNI) spaces. Individual habenula ROIs were first drawn manually on the high-resolution T1-weighted structural images in native space and are shown for a representative participant (A). The resulting ROIs were then transformed from the native space into the MNI space by applying the deformation fields derived from the tissue segmentation of each participant’s T1-weighted image, after which they were summed over all the healthy controls (HCs) (B) and schizophrenia (SCH) patients (C) to demonstrate the consistency of the habenula locations.
Figure 2
Figure 2
Within-group patterns and between-group differences of the RSFC for the bilateral habenula. RSFC of the left habenula nucleus (A) and RSFC of the right habenula nucleus (B). The color bars represent the T scores. HCs, healthy controls; RSFC, resting-state functional connectivity; L, left; R, right; IFG, inferior frontal gyrus; LING, lingual gyrus; mPFC, medial prefrontal cortex.
Figure 3
Figure 3
Enhanced RSFC between the habenula and subcortical regions in the SCH group. ROIs, regions of interest; HCs, healthy controls; L, left; R, right; SN/VTA, substantianigra/ventral tegmental area.
Figure 4
Figure 4
The relationship between the RSFC and clinical data for the SCH group. mPFC, medial prefrontal cortex; BPRS, Brief Psychiatric Rating Scale.

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