Causal connectivity alterations of cortical-subcortical circuit anchored on reduced hemodynamic response brain regions in first-episode drug-naïve major depressive disorder

Abstract

Some efforts were done to investigate the disruption of brain causal connectivity networks involved in major depressive disorder (MDD) using Granger causality (GC) analysis. However, the homogenous hemodynamic response function (HRF) assumption over the brain may disturb the inference of temporal precedence. Here we applied a blind deconvolution approach to examine the altered HRF shape in first-episode, drug-naïve MDD patients. The regions with abnormal HRF shape in patients were chosen as seeds to detect the GC alterations in MDD. The results demonstrated significantly decreased magnitude of spontaneous hemodynamic response of the orbital frontal cortex (OFC) and the caudate nucleus (CAU) in MDD comparing to healthy controls, suggesting MDD patients likely had alterations in neurovascular coupling and cerebrovascular physiology in these two regions. GC mapping showed increased/decreased GC in OFC-/CAU centered networks in MDD. The outgoing GC values from OFC to anterior cingulate cortex and occipital regions were positively correlated with Hamilton Depression Scale (HAMD) scores, while the incoming GC from insula, middle and superior temporal gyrus to CAU were negatively correlated with HAMD scores of MDD. The abnormalities of directional connections in the cortico-subcortico-cerebellar network may lead to unbalanced integrating the emotional-related information for MDD, and further exacerbating depressive symptoms.

Acupuncture treatment modulates the corticostriatal reward circuitry in major depressive disorder

“…Recent studies found that brains of patients with MDD showed reduced activity in the temporal lobe and caudate during reward / decision-making processing as compared to healthy controls (Segarra et al, 2016; Yang et al, 2016). Resting-state fMRI studies also found that depressive disorders were accompanied by increased amplitude of low-frequency fluctuations in the temporal gyrus (Liu et al, 2011) and lower effective connectivity from the temporal lobe to caudate (Gao, Zou, He, Sun, & Chen, 2016). As the temporal lobe is involved in motor-sensory control and perception (Kilintari, Raos, & Savaki, 2014; Xu et al, 2015), we speculated that the dorsal caudate’s influence on the temporal cortex and visual areas may have an impact on the somatization effects of MDD, including sleep disturbance, and pain conditions such as tension headaches and musculo-tendinous pain.…”

Brain structure alterations in depression: Psychoradiological evidence

“…A functional MRI study showed that a decrease in the OFC circuit connections was associated with unexpected reward receipt tasks and pleasant stimuli in MDD patients. The causal relationship between the OFC and the ACC is positively correlated with the severity of depression . In conclusion, the orbitofrontal circuit may be negatively related to the severity of depression and the source of negative thinking …”

“…Structural connections between cortical and subcortical areas compose several circuits, such as the frontal‐subcortical circuit, basal ganglic‐thalamic‐cortical circuit, prefrontal hippocampus circuit, the limbic‐cortical‐striatal‐thalamic‐cortical circuit, and the limbic‐cortical‐striatal‐pallidal‐thalamic circuit. The most common functional connection in MDD patients is the cortical‐subcortical circuit . According to previous findings, the frontal lobe, parietal lobe, thalamus, putamen, and hippocampus are considered hubs in these circuits …”

Environmental factors linked to depression vulnerability are associated with altered cerebellar resting-state synchronization

“…These observations may partly explain the biological relevance of cerebellar resting-state activity disruptions observed across several psychiatric disorders345678. Notably, recent research findings have consistently suggested cerebellar resting-state connectivity changes in depression, making it one of the best candidate mechanisms to elicit the neural alterations of the depressed brain9101112.…”