Habenula functional connectivity variability increases with disease severity in individuals with major depression
Ziqing Zhu1, Sibin Wang2, Tatia M C Lee3
1Cognitive Control and Brain Healthy Laboratory, Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China.
Insights
Major depressive disorder (MDD) is linked to abnormal brain connectivity in the Habenula (Hb). Dynamic functional connectivity (dFC) alterations in the Hb correlate with depressive symptoms, offering new insights for MDD treatment.
Area of Science:
- Neuroscience
- Psychiatry
- Medical Imaging
Background:
- Major Depressive Disorder (MDD) is increasingly associated with neural abnormalities in the Habenula (Hb).
- Previous research primarily focused on static functional connectivity (sFC) between the Hb and the brain.
- Dynamic functional connectivity (dFC) patterns, crucial for understanding brain function, remain under-explored in MDD.
Purpose of the Study:
- To investigate both static (sFC) and dynamic functional connectivity (dFC) of the Habenula (Hb) in individuals with Major Depressive Disorder (MDD).
- To explore the relationship between aberrant Hb connectivity patterns and depressive symptomatology.
- To identify potential neural underpinnings of cognitive and motor deficits in MDD.
Main Methods:
- Utilized seed-based resting-state fMRI to calculate sFC and dFC between the Habenula and the whole brain.
- Included 51 participants diagnosed with MDD and 45 healthy controls (HCs).
- Analyzed correlations between connectivity patterns and cognitive/symptomatic measures.
Main Results:
- MDD patients showed altered sFC, with increased connectivity from the left Hb to the right inferior temporal gyrus and left superior frontal gyrus (SFG), and decreased sFC to the right calcarine gyrus.
- MDD patients exhibited weaker dFC between the left Hb and several brain regions, including the right supplementary motor area, right postcentral gyrus (PoCG), left inferior frontal gyrus, and left occipital gyrus.
- sFC between the Hb and SFG correlated with attention deficits, while dFC between the Hb and PoCG correlated with depressive severity.
Conclusions:
- Aberrant neural circuitry of the Habenula (Hb) may contribute to impaired attention, emotional regulation, and motor control in Major Depressive Disorder (MDD).
- These findings suggest that dynamic connectivity alterations in the Hb are implicated in core depressive symptoms like rumination and psychomotor retardation.
- This research opens new avenues for understanding MDD neuropathology and developing targeted treatment strategies.
Background:
Increasing evidence has suggested the significant relationships between major depressive disorder (MDD) and the neural abnormalities of the Habenula (Hb). Yet, previous research on the relationships between Hb and MDD mainly focuses on the static descriptions of their functional connectivity. However, recent work suggests that the connectivity patterns are indeed dynamic, though related analysis and interpretation remain scarce.
Methods:
Using seed-based resting-state fMRI, the static (sFC) and dynamic functional connectivity (dFC) between the Hb and whole-brain were calculated, including 51 clinical participants (MDDs) and 45 healthy controls (HCs). Association between the aberrant connectivity patterns and depressive symptomatology was also analyzed.
Results:
Compared with the HCs, MDDs exhibited increased sFC from the left Hb to the right inferior temporal gyrus and left superior frontal gyrus (SFG), while sFC to the right calcarine gyrus decreased. Notably, we observed that dFC between the left Hb and the right supplementary motor area, right postcentral gyrus (PoCG), left inferior frontal gyrus as well as left occipital gyrus was weak in MDDs. Furthermore, sFC between the Hb and SFG correlated positively with the measured attention-related cognitive deficits. Importantly, there was a positive correlation between dFC between the Hb and PoCG and depressive severity.
Conclusions:
The findings indicate that the anomalous neural circuitry of Hb may underpin impaired attention disengagement, emotional modulation and motor inhibition associated with depressive symptoms such as rumination disposition and psychomotor retardation. This may open new avenues for studying the neuropathology mechanisms and guiding new treatment strategies for MDD.
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