As a result of our work and other growing evidence that the overactivation of the LHb is a necessary condition for the state of depression in patients or depressive-like behaviour in animals (Sartorius et al, 2010)—and assuming that high frequency DBS of white matter bundles would lead to a functional inhibition—we decided to use bilateral DBS of the LHb in two patients with severe therapy-refractory depression for whom years of treatment, including electroconvulsive therapy, had failed to have a sustained impact. Here, LHB is linked to major depressive disorder.