Major depressive disorder (MDD) is a mood disorder which can interfere with daily life, and it is a major contributor to the overall global disease burden. About one third of MDD patients do not respond to established treatments. What is more, reliable biomarkers for depression are needed as a diagnostic tool. The EU-funded UPSIDE project aims to address these issues. To that end, it will research and validate in vivo a hybrid neurotechnology consisting of an epidural focused ultrasound stimulator and a high-density epidural EEG recording system. Project work will lead to a demonstrator, paving the way for personalised treatments for treatment-resistant depression patients.