Role of the rostral anterior cingulate cortex in emotion processing in Treatment Resistant Depression

The rostral anterior cingulate cortex (rACC) has been identified as a key region in treatment-resistant depression (TRD), potentially influencing the adaptive interplay between the default mode network and other critical neural networks. This study aims to further uncover the role of the rACC in TRD by investigating its differential connectivity during tasks that evoke conscious and non-conscious emotional responses. Thirty-nine TRD patients, 35 treatment-sensitive depression (TSD) patients, and 38 healthy controls (HC) underwent 3T fMRI while performing tasks designed to elicit emotional responses to facial expressions under supraliminal and subliminal conditions. Connectivity patterns of the rACC were analyzed using seed-based and region-of-interest (ROI) approaches. During the processing of positive emotions in the subliminal task, TRD patients showed increased rACC connectivity to the cerebellum and middle temporal gyrus, compared to HC and TSD. Furthermore, significant hypoconnectivity between the rACC and hippocampus was found in the TRD, during the supraliminal processing of positive emotions, compared to TSD and HC. Altered neural connectivity to both subliminal and supraliminal processing of positive facial emotion distinguishes TRD from healthy individuals and patients who respond to depression treatments. This observation fits with anhedonia symptoms that persist in TRD and our findings identify that the underlying mechanism for this inability to process positive emotions is via altered connectivity of the rACC to regions involved in regulating or contextualising emotions.