Identifying Deep-brain Contributions to Consciousness for Clinical Intervention in Severe Brain Damage with Transcranial Focused Ultrasound

The disorders of consciousness (e.g., coma, the vegetative state) which often follow severe brain damage are the medical conditions which arguably pose some of greatest cost on developed societies—both in term of the economic cost and the suffering produced. While advances in the field of long-term intensive care has made the maintenance of life in patients recovering from brain injury highly feasible, little can be done to promote functional recovery in DOC patients who do survive with severe impairments in consciousness or cognitive functioning. This remaining gap in the medical treatment of DOC is contrasted starkly by a rapidly growing scientific understanding of the mechanisms behind impairment in DOC. The distance between the science and treatment of DOC stems from the many as-yet-undiscovered approaches necessary to move what we know about the neural correlates of (un)consciousness in DOC into suitable treatment options. For instance, circuits involving the basal ganglia and thalamus have been highlighted in recent decades for their apparent involvement in the DOC pathology. Prior to this dissertation, however, there were no methods for influencing the function of these nuclei directly without a surgery whose risks preclude use in most DOC patients. The work of this dissertation aims to assess the feasibility of using low intensity focused ultrasound (LIFU) as a way to selectively, but non-invasively, modulate deep brain structures in the context of DOC. LIFU in healthy subjects was used to better understand the neural response to LIFU applied to the deep brain, while acute and chronic doc patients were administered thalamic LIFU and monitored for the observation of changes in responsiveness. We observe significant behavioral improvement in both DOC cohorts, while fMRI data from three cohorts (2 DOC, 1 healthy) suggest acute inhibition may occur during LIFU but that complex changes in connectivity may underlie the observed recovery in DOC. Finally, this dissertation includes the production of a system for rapidly estimating how skull affects LIFU beam properties (an enduring challenge in this field), which should assist newcomers to the technology. In all, this work aims to be a suitable foundation from which to build a better scientific understanding of and treatment options for DOC through LIFU