The thalamus is the causal hub of intervention in patients with major depressive disorder: Evidence from the Granger causality analysis

Major depressive disorder (MDD) is the leading mental disorder and afflicts more than 350 million people worldwide. The underlying neural mechanisms of MDD remain unclear, hindering the accurate treatment. Recent brain imaging studies have observed functional abnormalities in multiple brain regions in patients with MDD, identifying core brain regions is the key to locating potential therapeutic targets for MDD. The Granger causality analysis (GCA) measures directional effects between brain regions and, therefore, can track causal hubs as po-tential intervention targets for MDD. We reviewed literature employing GCA to investigate abnormal brain connections in patients with MDD. The total degree of effective connections in the thalamus (THA) is more than twice that in traditional targets such as the superior frontal gyrus and anterior cingulate cortex. Altered causal connections in patients with MDD mainly included enhanced bottom-up connections from the thalamus to various cortical and subcortical regions and reduced top-down connections from these regions to the THA, indicating excessive uplink sensory information and insufficient downlink suppression information for negative emotions. We suggest that the thalamus is the most crucial causal hub for MDD, which may serve as the downstream target for non-invasive brain stimulation and medication approaches in MDD treatment.