When patients survive a severe brain injury but fail to fully recover, they often enter a Disorder of Consciousness (DoC) --that is, a set of related conditions of decreased awareness and arousal including the Vegetative State (VS) and the Minimally Conscious State (MCS). When these conditions become chronic, there are no approved treatments to help bolster any further recovery. In prior work, we have shown the clinical feasibility and potential of Low Intensity Focused Ultrasound Pulsation (LIFUP) as a remarkably safe form of non-invasive brain stimulation in these conditions.

In the present study, we propose taking the "next step" to assess whether LIFUP can affect objective and validated markers of DoC patient impairment (in the direction of lesser impairment). Specifically, patients will be admitted at Casa Colina Hospital for a 10-day (in-patient) protocol, and two follow-up sessions, conducted remotely (e.g., over the phone) at 7 and 30-days post-discharge. The full length of the study is 40 days from admission. Over the admission period, patients will undergo multiple measurements of validated biomarkers, including behavioral testing, brain metabolism (using Positron Emission Tomography), and electroencephalography, before and after one session of LIFUP to thalamus.

Inclusion Criteria:

1. Diagnosis of VS or MCS based on the CRS-R .

2. Chronic status:

   • 3 months post-injury for non-traumatic etiologies
   • 12 months post-injury for traumatic etiology

3. 18 years of age or older.

4. If on a psychotropic medication regimen, that regimen will be stable for at least 4 weeks prior to entry to the study and the patient will be willing to remain on a stable regimen during the protocol.

Exclusion Criteria:

1. History of neurological disorder (other than the brain injury).
2. Unsuitability to undergo Magnetic Resonance (MR) assessment (e.g., non-MR compatible implants).
3. Unsuitability to undergo LIFUP neuromodulation (e.g., presence of non-bone implant or absence of bone under the expected positioning of the device by the left temporal bone window).
4. Manifest continuous spontaneous movement (which would prevent imaging)
5. Participation in another concurrent clinical trial.
6. Having undergone PET, CT, or other exam involving the use of ionizing radiation in the 12 months prior to the date of scheduled admission to Casa Colina.
7. Dependence on ventilator.