In this engaging conversation with Casey Halpern, a functional neurosurgeon at Penn Medicine. Casey is a pioneer in both deep brain stimulation and focused ultrasound and with his lab has recently had some fantastic breakthroughs, especially, but not exclusively in the field of loss-of-control eating in severe obesity. We cover a lot of ground from optogenetics at Stanford, basic science research about the nucleus accumbens and translation of findings into patients, serendipitous discoveries in humans, to stereo-EEG procedures in patients with epilepsy. We discuss what made his recent Nature paper about an appetite mediating circuit in the human hippocampus so special, how he took his findings from 2013 in rodent work – across several stages – into a human clinical trial for eating disorders. We also cover Casey’s ongoing trial in DBS for OCD, where he adopts an approach to probe the brain with multiple electrodes to then identify optimal target areas for each individual patient – in line with other current advances of psychiatric neurosurgery. We also talk about MR guided focused ultrasound and the potential future of this treatment option in a tight relationship with DBS. As always, I learned a lot in this conversation and I hope you find it as enjoyable as I did. Thank you so much for tuning in – for this round episode number 40 of stimulating brains!