Self-Processing Circuits Among Depressed Youth After Amygdala Neurofeedback Cued to the Self-Face

Major depressive disorder is a significant health concern among adolescents due to its link to suicide and lifetime impairments. Current treatments yield limited success, but real-time functional magnetic resonance imaging (RT-fMRI) neurofeedback (NF) is a promising intervention. We tested the effects of RT-fMRI neurofeedback on the modulation of neural circuitry underlying self-referential processing and emotion regulation in youth trying to up-regulate the amygdala-hippocampus (AMYHIPP) complex. We examined amygdala functional connectivity during a self-other face recognition task before and after RT-fMRI NF from the AMYHIPP complex. (1) Depressed youth showed higher bilateral amygdala to anterior cingulate cortex (ACC), superior temporal and frontal gyri connectivity compared to controls, who showed lower connectivity before NF. Yet after NF, this pattern reversed, with depressed youth showing lower bilateral amygdala connectivity than controls. (2) Depressed youth showed increased right amygdala-cuneus connectivity while controls showed increased left amygdala-cuneus connectivity during self-other face recognition. (3) Lower right amygdala-cuneus connectivity was linked to improved rumination. Higher left amygdala-cuneus connectivity was linked to improved depression. (4) Shifts of less right versus left amygdala to superior middle temporal gyri connectivity after neurofeedback, and of more right versus left amygdala to middle frontal gyrus after NF, were linked to higher AMYHIPP engagement during training. This is suggestive of NF training effects upon implicit versus explicit emotion circuits. Caution is necessary regarding the meaning of symptoms to circuits associations and putative mechanisms of neurofeedback training given the lack of a placebo group.