Recent research has demonstrated that alterations in the state of consciousness, e.g., induced by psychedelics or transformative experiences, have positive effects for hedonic responsiveness and wellbeing not only in the general population but also in a wide range of diseases including depression, anhedonia, post-traumatic stress disorder, and addiction[1]. Although the underlying mechanisms are still illusive, there is a growing body of evidence linking benefits to increased neuroplasticity, network complexity, and edge-of-chaos criticality due to changes in the mesocortical and mesolimbic circuit[2-4]. However, causality of this relationship has never been investigated. Ultrasonic brain stimulation is a novel approach which makes it possible to target areas deep within this circuit for causal investigation[5]. As a first step though, we need to systematically evaluate the best targets for stimulation. In this pre-registered project, we will stimulate the main cortical and subcortical areas (e.g., medial frontal cortex, orbitofrontal cortex, nucleus accumbens, caudate) in healthy subjects with verified ultrasound parameter settings to (a) test their behavioral effects on cognitive flexibility, the hedonic experience, and well-being using established tasks and questionnaires and (b) test the effects on network brain interaction using simultaneous fMRI and measures of complexity and variability. A pilot with 5 subjects will be implemented first to assess power and sample size.
1. Vollenweider and Preller, Nature Reviews Neuroscience, 2020. 21(11).
2. Toker, et al., Proc Natl Acad Sci U S A, 2022. 119(7).
3. Ly, et al., Cell Rep, 2018. 23(11).
4. Cools, Neuron, 2019. 104(1).
5. Cain, Crone, Scientific Reports, 2021. 11(1).