The review by Diego A. Pizzagalli explores the relationship between increased rostral anterior cingulate cortex (rACC) activity and treatment response in depression. The author presents a meta-analysis showing a robust link between pre-treatment rACC activity and better treatment outcomes, suggesting that elevated rACC activity may foster adaptive self-referential processing and help recalibrate interactions between the default network and task-positive networks. The review also discusses the role of the rACC as a hub in the default network, which is involved in self-referential processes such as introspection, memory, and planning. Additionally, it reviews neuropsychological, electrophysiological, and neuroimaging data on frontocingulate dysfunction in depression, highlighting cognitive and affective abnormalities such as maladaptive rumination, difficulty disengaging from negative information, and emotion dysregulation. The review concludes with a discussion of limitations and future directions, emphasizing the need for more systematic analysis and integration of findings to better understand the mechanisms underlying treatment response in depression.The review by Diego A. Pizzagalli explores the relationship between increased rostral anterior cingulate cortex (rACC) activity and treatment response in depression. The author presents a meta-analysis showing a robust link between pre-treatment rACC activity and better treatment outcomes, suggesting that elevated rACC activity may foster adaptive self-referential processing and help recalibrate interactions between the default network and task-positive networks. The review also discusses the role of the rACC as a hub in the default network, which is involved in self-referential processes such as introspection, memory, and planning. Additionally, it reviews neuropsychological, electrophysiological, and neuroimaging data on frontocingulate dysfunction in depression, highlighting cognitive and affective abnormalities such as maladaptive rumination, difficulty disengaging from negative information, and emotion dysregulation. The review concludes with a discussion of limitations and future directions, emphasizing the need for more systematic analysis and integration of findings to better understand the mechanisms underlying treatment response in depression.