Decreased resting-state functional connectivity of the habenula-cerebellar in a major depressive disorder

Abstract

BackgroundIn animal experiments, the habenula and septal nuclei are known as the key brain areas of depression. However, there are few magnetic resonance imaging (MRI) studies on the functional connectivity between these areas and the subcortical areas in humans with major depression. We aimed to investigate the difference in resting-state functional connectivity (RSFC) among the major regions of interest (ROI) in the subcortical areas, including both the habenula and septal nuclei.MethodsWe performed the seed-to-voxel analysis to investigate the RSFC between both the habenula and septal nucleus, as well as other subcortical regions. Furthermore, ROI-to-ROI analysis was performed among the combinations of ROI pairs in the subcortical areas.ResultsThe seed-to-voxel analysis showed a lower RSFC between the left habenula and the cerebellum in major depressive disorder (MDD) than in healthy controls (HCs). As a result of ROI-to-ROI analysis in subcortical areas, a total of 31 pairs of FCs in the MDD group showed a lower RSFC than in the HCs group.ConclusionThis study revealed a lower RSFC between the left habenula and cerebellum in patients with MDD and reduced RSFC among numerous subcortical areas. These new findings on the neural circuitry of MDD might contribute to an in-depth understanding of depression.

The disappointment centre of the brain gets exciting: A systematic review of habenula dysfunction in depression

“…Indeed, both left and right Hb activation has been shown to increase in healthy controls when exposed to a negative outcome (95, 96). However, those with a diagnosis of MDD recorded either no or attenuated change in Hb activation following exposure to the same negative stimuli (95, 96). Similarly, in an error prediction learning task, adolescents with MDD exhibited a reduction in negative related signalling in the Hb when compared to controls (98).…”

“…Considering the Hb signals negative stimuli, it is expected that Hb activity would increase in response to a negative outcome. Indeed, both left and right Hb activation has been shown to increase in healthy controls when exposed to a negative outcome (95, 96). However, those with a diagnosis of MDD recorded either no or attenuated change in Hb activation following exposure to the same negative stimuli (95, 96).…”

“…Considering the variety of networks projecting from the Hb, it is possible that some circuitry may be hyperactive and others hypoactive in depressive states. For instance, while overall Hb activation was consistently elevated in depression, specific connections to the cerebellum and calcarine sulcus were found to be reduced compared to controls (96,101). Interestingly, a post-mortem human study identified individuals that died with depression displayed a reduction in total Hb volume and cell count (104).…”

“…Compared to controls and those with subclinical depression, individuals with a diagnosis of major depression showed greater functional connectivity between the posterior parietal thalamus (region containing Hb) and the inferior temporal gyrus. Individuals with depression also showed greater functional connectivity between the left Hb and the inferior temporal and superior frontal gyrus but reduced connectivity to the calcarine sulcus (100) and cerebellum (96); no change was recorded in the right Hb. Interestingly, Barreiros et al (92) identified that patients with treatment-resistant depression exhibited greater functional connectivity between the left Hb and precuneus cortex.…”

Recent Advances in Habenula Imaging Technology: A Comprehensive Review

“…In 2016, asymmetry of functional connectivity of the human Hb was found for the first time through fMRI 42 . Studies in humans using resting‐state fMRI have shown that the Hb has extensive functional connections with areas such as the VTA, SN, RN, periaqueductal gray, medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex, and cerebellum (Table S2 in the Supplemental Material) 40,41,43–55 . In a previous study, the bilateral Hb in the 15 patients with schizophrenia showed a markedly stronger resting‐state functional connectivity (RSFC) than did that in the 16 healthy controls (Fig.…”