The main questions this study aims to answer are:
Can low-intensity FUS neuromodulation be safely and feasibly administered to the bilateral central thalamus in patients with disorders of consciousness (DoC)? Does FUS neuromodulation result in short-term improvements in arousal or behavioral responsiveness? Does FUS neuromodulation produce measurable changes in neural activity on EEG and/or fMRI?
Participants will:
Receive two sessions of low-intensity FUS neuromodulation, spaced four weeks apart, plus or minus one week.
Undergo pre- and post-treatment assessments, including planning CT, MRI/fMRI, EEG, and standardized clinical scales such as the Coma Recovery Scale-Revised (CRS-R) and Glasgow Coma Scale (GCS).
Be continuously monitored for safety during and after each FUS treatment. Complete follow-up imaging and clinical assessments approximately 2 weeks after each FUS session, 12 weeks after the second treatment, and at 12 months post-injury when clinically feasible.
Diagnosis of severe traumatic brain injury, hypoxic-ischemic brain injury, or other acute brain injury.
Glasgow coma scale below 13 when off sedation, or on minimal sedation.
Absence of another better explanation for the depressed level of consciousness (e.g,, metabolic abnormality, seizures)
Intracranial pressure (ICP) is within a normal range (< 20 cm H2O), or, a neurosurgeon associated with the study and/or the treating physician agree that ICP is likely < 20 cm H2O based on clinical and neuroimaging information (acknowledging the limitations of non-invasive assessment of ICP53).
Active seizure activity or post-anoxic myoclonus at the time of proposed treatment
Taking full anti-coagulation medication (does not include deep-vein-thrombosis chemoprophylaxis)
Skull anatomy incompatible with safe FUS delivery (as determined by CT)
Medical instability that would preclude safe transport or prolonged supine positioning
Single group
Next Generation Dome Helmet (NGDH)
DeviceParticipants will receive MR-guided focused ultrasound neuromodulation using the Next Generation Dome Helmet (NGDH). Each participant will undergo two treatment sessions spaced four weeks apart. MRI and CT imaging will be used to guide targeting of the bilateral centromedian/parafascicular nuclei of the thalamus. Continuous monitoring will be performed during each session, and follow-up clinical, EEG, and MRI assessments will be conducted to evaluate safety, feasibility, and preliminary effects.
Feasibility of Bilateral Central Thalamic FUS Neuromodulation
Feasibility will be defined as the proportion of enrolled participants who complete both focused ultrasound (FUS) neuromodulation sessions without protocol deviation or occurrence of a serious adverse event (SAE) related to the procedure.
Safety of FUS Next Generation Dome Helmet (NGDH) to Perform Neuromodulation in Patients with Disorders of Consciousness
Safety will be assessed by the frequency, type, and severity of adverse events (AEs) and serious adverse events (SAEs) following FUS treatment. Events of interest include seizures, autonomic instability, new focal neurological deficits, clinical deterioration, or structural abnormalities detected on post-treatment MRI.
Change in Behavioral Responsiveness (Coma Recovery Scale-Revised, CRS-R)
The Coma Recovery Scale-Revised (CRS-R) is a standardized behavioral assessment used to measure level of consciousness in patients with disorders of consciousness. The CRS-R consists of 6 subscales (Auditory, Visual, Motor, Oromotor/Verbal, Communication, and Arousal) that evaluate reproducible signs of awareness. Total scores range from 0 to 23, with higher scores indicating greater behavioral responsiveness and higher levels of consciousness.
Change in Glasgow Coma Scale (GCS)
The Glasgow Coma Scale (GCS) is a standardized clinical tool used to assess a patient's level of consciousness, particularly after brain injury. It evaluates three components of responsiveness: eye opening, verbal response, and motor response. Each component is scored individually and then summed to produce a total score ranging from 3 to 15. Higher scores indicate better neurological function and greater levels of consciousness, while lower scores reflect more severe impairment.
Change in Rancho Los Amigos Scale Level
The Rancho Los Amigos Scale (also known as the Rancho Los Amigos Levels of Cognitive Functioning Scale) is an 8-level clinical scale used to assess cognitive recovery and behavioral responsiveness following severe brain injury. The scale ranges from Level I (No Response) to Level VIII (Purposeful and Appropriate Response). Higher levels indicate greater cognitive functioning, improved awareness, and more appropriate and consistent behavioral responses. Only participants who scored 23 on CRS-R will complete The Rancho Los Amigos Scale.
Change in EEG Measures of Neural Activity
Electroencephalography (EEG) will be used to assess changes in neural activity before and after focused ultrasound (FUS) neuromodulation. EEG measures will include spectral power (frequency band power across delta, theta, alpha, beta, and gamma ranges), spectral entropy (a measure of signal complexity and cortical activation), and event-related responses during task-based paradigms (e.g., motor imagery and passive auditory language tasks). Higher spectral entropy and increased task-related cortical responses are generally interpreted as reflecting greater cortical activation and improved network engagement associated with arousal and awareness. Changes in resting-state spectral power and task-evoked responses will be assessed relative to baseline.
Click on the lead sponsor to view all of their trials.
