Promoting Recovery After Brain Injury Using Focused Ultrasound

Determine neurobehavioral responses to LIFUP in patients with DoC: Coma Recovery Scale - Revised (CRS-R)

Outcome measures collected prior to LIFUP sessions will be compared to outcome measures obtained after LIFUP sessions. The Coma Recovery Scale Revised (CRS-R) ranges from 0 to 23 points, with higher scores indicating better neurobehavioral function and level of consciousness. The CRS-R consists of 6 subscales designed to assess auditory function, receptive and expressive language, visuoperception, communication ability, motor functions, and arousal level. The lowest score on each sub-scale represents reflexive activity; the highest represents behaviors mediated by cognitive input. The total score ranges between 0 (worst) and 23 (best).

Determine neurobehavioral responses to LIFUP in patients with DoC: Disability Rating Scale (DRS)

Outcome measures collected prior to LIFUP sessions will be compared to outcome measures obtained after LIFUP sessions. The DRS ranges from 0 to 30 points, with higher scores indicating more severe disability. DRS subscale scores include eye opening \[score range 0-3\], communication \[score range 0-4\], motor response \[score range 0-5\], cognitive ability for feeding \[score range 0-3\], cognitive ability for toileting \[score range 0-3\], cognitive ability for grooming \[score range 0-3\], level of function \[score range 0-5\], and employability \[score range 0-3\]. Subscale scores are summed to produce the total score.

Determine neurophysiologic responses to LIFUP in patients with DoC

Using electroencephalography (EEG) recordings, we will compute power spectral density within predefined frequency bands and derive ABCD-level classifications, resting-state complexity metrics, and responsiveness indices that quantify the degree of thalamocortical disconnection.

Identify and evaluate ethical perspectives of patient representatives surrounding investigation of therapeutic neuromodulation technologies such as LIFUP in patients with DoC

Family members or surrogate decision-makers (i.e., legally authorized healthcare proxies of study participants with DoC), will be engaged in interviews to capture their expectations, perspectives, and concerns surrounding the use and deployment of neuromodulation techniques in the context of brain injury. The semi-structured interview will center on key themes: hopes and expectations for neuromodulation technology; views on the informed consent process and data privacy related to neural data; considerations of equity in access to neuromodulation therapies; areas of uncertainty or concern regarding risks and benefits; and perceived roles of caregivers and families in the neuromodulation decision-making process. This approach is designed to elicit a nuanced understanding of ethical considerations as viewed by those most impacted, thereby informing a robust ethical framework that aligns research and clinical practices with the values and needs of patients and their families.

Brain MRI-derived responsiveness index (structural-functional signature predicting LIFUP response)

Participants who can safely undergo MRI will receive an advanced brain imaging protocol. The primary quantitative measure will be a composite Brain MRI-derived Responsiveness Index, computed from predefined brain MRI features. Structural and functional metrics will be combined into a single composite index using a prespecified analytic model. The composite index will be reported as a unitless continuous score, with higher values corresponding to imaging patterns associated with greater likelihood of LIFUP responsiveness.