Mike Fox leads the Center for Brain Circuit Therapeutics at the Brigham & Women’s Hospital at Harvard Medical School in Boston. The center is unique in that it houses colleagues from neurosurgery, neurology, psychiatry and neuroradiology under the same roof – with the aim to collaboratively work on novel neuromodulation treatments. It is a great honor to interview Mike about his earlier work with Marc Raichle on anticorrelated networks in the brain, his work on TMS network mapping, lesion network mapping and DBS network mapping. Our conversation was enriched by guest questions of many friends and members of the center, Shan Siddiqi, Aaron Boes, Michael Ferguson, Fred Schaper and Dan Corp. We cover how lesion network mapping originated, why effective invasive and noninvasive neuromodulation targets must be linked by brain networks and ways Mike has taken to uncover those relationships. We talk about what makes causal sources of inference – brain lesions and neuromodulation targets – so unique to study the brain, treatment concepts that can be traced back to basic science work in animals vs. serendipitous findings in humans and discuss why and how brain lesions are set for a comeback – both for treatment and investigation.