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| ID | Type | Description | Link |
|---|---|---|---|
| 1K23NS140495 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
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The overall aim of this study is to develop an intervention that can help recovery in patients surviving severe brain injury but failing to fully recover. In particular, this project aims to (1) determine neurobehavioral responses to low-intensity focused ultrasound (LIFUP) in patients with disorders of consciousness (DoC) following brain injury, (2) determine neurophysiologic (EEG) responses to LIFUP in patients with DoC and (3) identify and evaluate ethical perspectives of patient representatives (family members and surrogate decision-makers) surrounding investigation of therapeutic neuromodulation technologies such as LIFUP in patients with DoC.
Aim 1: Determine neurobehavioral responses to LIFUP in patients with DoC. Aim 2: Determine neurophysiologic (EEG) responses to LIFUP in patients with DoC.
Aim 3: Identify and evaluate ethical perspectives of patient representatives (family members and surrogate decision-makers) surrounding investigation of therapeutic neuromodulation technologies such as LIFUP in patients with DoC.
Advanced MRI will be obtained to determine predictive neuroimaging signatures of responsiveness. This project will crucially inform the groundwork for a personalized, connectome-based approach to impactful therapeutic intervention for patients affected by DoC due to diverse pathologies across the brain injury care continuum and will inform an ethical framework for responsible development and deployment of therapeutic neuromodulation technologies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LIFUP group | Experimental | Participants will receive low-intensity focused ultrasound intervention. Participants are also anticipated to undergo advanced MRI and EEG. Surrogate decision makers (family members) and recovered patients will undergo a semi-structured interview. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low-intensity focused ultrasound | Device | Low-intensity focused ultrasound pulsations (LIFUP) will be delivered to the brain, along with advanced MRI and EEG. Surrogate decision makers (family members) and recovered patients will undergo a semi-structured interview. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Days 1-3 |
| 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. | Days 1-3 |
| 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. | Days 1-3 |
| Identify and evaluate ethical perspectives of patient representatives surrounding investigation of therapeutic neuromodulation technologies such as LIFUP in patients with DoC |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Michael Young, MD, MPhil | Contact | 410-808-1196 | michael.young@mgh.harvard.edu | |
| Jason Lew, DO | Contact | 617-724-9247 | jlew3@mgb.org |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital (The General Hospital Corp.) | Recruiting | Boston | Massachusetts | 02114 | United States |
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| ID | Term |
|---|---|
| D003244 | Consciousness Disorders |
| D018458 | Persistent Vegetative State |
| D000070642 | Brain Injuries, Traumatic |
| D020521 | Stroke |
| D002534 | Hypoxia, Brain |
| D003128 | Coma |
| ID | Term |
|---|---|
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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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.
| Days 1-3 |
| Day 1 |
| Spaulding Rehabilitation Hospital Corporation, Inc. | Recruiting | Cambridge | Massachusetts | 02138 | United States |
|
| D013568 | Pathological Conditions, Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D001925 | Brain Damage, Chronic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D014474 | Unconsciousness |
| D001930 | Brain Injuries |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D002561 | Cerebrovascular Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000860 | Hypoxia |
| D012818 | Signs and Symptoms, Respiratory |