Transcranial focused ultrasound for epilepsy

s Brain Stimulation 14 (2021) 1708e1752 and complete dependence, typically acquired after severe brain injury, which can last from days to decades. These conditions are also associated with great emotional and financial strain on families, increased burn-out rates of care-taking personnel, and pose complex medical, legal, and ethical questions. On the basis of a theoretical understanding of DOC as a functional and/or structural “disconnection” of thalamo-cortical circuits, experimental interventions are typically aimed at upregulating thalamic output. Yet, despite great advances in our understanding of these conditions, there is no accepted treatment for chronic DOC. Surgical interventions for direct thalamic stimulation (e.g., deep brain stimulation) have shown remarkable results, but are inapplicable to more than 85% of patients, while non-invasive indirect approaches (e.g., transcranial direct current stimulation) show some promise, but their efficacy remains debated. In light of the above, we launched a first-in-man clinical trial, in both acute (n 1⁄4 11) and chronic (n 1⁄4 10) DOC, aimed at evaluating the feasibility and initial safety and efficacy of non-invasive focused ultrasound neuromodulation of thalamus. First, with respect to safety we observed no Serious Adverse Events, confirming the safety record of this technique. Second, although this feasibility trial was open label with no sham control, both cohorts exhibited significant improvement in neurobehavioral measurements (i.e., Coma Recovery Scale e Revised, CRS-R, and CRS-R-index) following ultrasound. In the chronic cohort, which received two doses of ultrasound at a weeks distance, a significant linear trend was observed, suggesting an additive effect of multiple sonications. These exciting data provide a strong first step towards careful clinical investigation of the effectiveness of this approach as a therapeutic intervention for patients with a Disorder of Consciousness.