Brain mechanisms underlying the emotion processing bias in treatment-resistant depression

Abstract

Depression is associated with a cognitive bias towards negative information and away from positive information. This biased emotion processing may underlie core depression symptoms, including persistent feelings of sadness and a reduced capacity to experience pleasure. The neural mechanisms responsible for this biased emotion processing remain unknown. Here we had a unique opportunity to record stereotactic electroencephalography signals in the amygdala and prefrontal cortex (PFC) from 5 patients with treatment-resistant depression (TRD) and 12 patients with epilepsy (as control) while they participated in an affective bias task in which happy and sad faces were evaluated. First, compared with the control group, patients with TRD showed increased amygdala responses to sad faces in the early stage (around 300 ms) and decreased amygdala responses to happy faces in the late stage (around 600 ms) following the onset of faces. Furthermore, during the late stage of happy-face processing, alpha-band activity in the PFC as well as alpha-phase locking between the amygdala and the PFC were significantly greater in patients with TRD compared with the control group. The increased amygdala activation during the early stage of sad-face processing suggests an overactive bottom-up processing system in TRD. Meanwhile, the reduced amygdala response during the late stage of happy-face processing could be attributed to increased top-down inhibition by the PFC through alpha-band oscillation, which may be relieved following deep brain stimulation in the subcallosal cingulate and the ventral capsule/ventral striatum.