This lecture discusses the challenges in treating mental disorders with a focus on brain circuit dysfunctions. Deep brain stimulation (DBS) is explored as a circuit-directed approach, presenting mixed results in mental illness treatment. The instructor presents advancements in developing biomarkers to guide target engagement and designing new stimulation protocols for circuit-level physiological changes. Results show improvements in top-down executive function, cortical electrophysiology, and symptom relief from closed-loop stimulation. The lecture also covers new stimulation techniques in animals that target specific aspects of circuit connectivity, paving the way for rationally designed brain stimulation therapies.