Neural Mechanisms and Non-invasive Deep Brain Stimulation of Mood and Well-being

Our expectations about the world shape our mood and well-being. In extreme contexts, mood can become pathologically depressed as in mood disorders or dementia. Recent studies have begun to suggest a mechanism for how expectations (and their violation) impact human moods. Unfortunately, this mechanism relies on correlational studies since we currently lack tools able to directly manipulate these circuits in healthy humans. UltraDeepMood will combine cutting-edge ultrasound stimulation with imaging and computational modeling to determine the hypothesis that human moods can be changed by modulating expectation signalling in deep brain subcallosal cingulate circuits.UltraDeepMood will overcome the current major limitations hindering our understanding of mood circuits in humans. First, the lack of non-invasive tools to modulate activity deep in the healthy brain: by using focused transcranial ultrasound stimulation (TUS), a technique I have pioneered in deep primate areas, I will non-invasively manipulate human circuits to causally establish their role in mood. Second, by using TUS to modulate dopamine-projecting areas, I will directly modulate learning and decision processes in the striatum and disentangle them from those underlying mood and well-being in subcallosal anterior cingulate cortex.UltraDeepMood has three key aims: (1) dissociate the contribution of gray versus white matter TUS to mood connectivity; (2) combine TUS with fMRI and computational models to determine the role of deep cingulate circuits to mood; (3) directly manipulate related circuits of learning and decision-making.UltraDeepMood will reveal a novel mechanistic insight into the circuits of moods and well-being in the healthy brain. This non-invasive approach will open an unprecedented avenue in shaping our understanding of deep brain circuits. Determining this is foundational for establishing the basis of mood symptoms and developing new therapies.