Investigating Near-Threshold Perception During Ultrasonic Deep Brain Stimulation

NCT07840521 | Not Yet Recruiting FDA Device

• 2 other identifiers: HUM002517692R01GM103894
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This research is studying changes in awareness and metabolism in the brain that may take place in various brain regions stimulated with ultrasound (low-intensity focused ultrasound pulsation or LIFUP) while undergoing magnetic resonance imaging (MRI)-based brain measurements.

Conditions

Consciousness, Level Altered

Outcome Measures

Primary Outcomes (1)

• Blood Oxygen Level Dependent (BOLD) response to visual stimuli

  Changes in task-evoked blood oxygen level-dependent responses to visual stimuli will be measured using functional MRI before, during, and after LIFUP across the five stimulation parameter conditions.

  Approximately 70 minutes

Secondary Outcomes (2)

• Perceptual criterion (c) derived from the Signal Detection Theory (SDT)

  Approximately 65-75 minutes

• Perceptual sensitivity (d') derived from the Signal Detection Theory (SDT)

  Approximately 75 minutes

Study Arms (3)

LIFUP-fMRI

EXPERIMENTAL

Participants assigned to the fMRI arm will complete five visits, with a different brain region targeted at each visit. Each visit will include seven consecutive 10-minute scanning periods: one pre-LIFUP baseline fMRI scan, five fMRI scans conducted during LIFUP using five predefined combinations of duty cycle and pulse repetition frequency, and one post-LIFUP baseline fMRI scan. The five stimulation parameter combinations will be labeled Combination 1 through Combination 5. The order of the five parameter combinations will be randomized within each visit. The total planned scanning time for these seven periods is approximately 70 minutes, excluding structural imaging, participant positioning, transducer placement, safety checks, and other required study procedures.

Device: Low-intensity focused ultrasound pulsation (LIFUP); Device: Functional Magnetic Resonance Imaging (fMRI)

LIFUP-magnetic resonance spectroscopy (MRS)

EXPERIMENTAL

Participants assigned to the MRS arm will also complete five visits, with a different brain region targeted at each visit. Each visit will include a pre-LIFUP baseline MRS acquisition, an excitatory LIFUP condition, a post-excitatory non-LIFUP MRS acquisition, an inhibitory LIFUP condition, and a post-inhibitory non-LIFUP MRS acquisition. Each MRS acquisition period will last approximately 13 minutes and will include approximately 5 minutes of glutamate plus glutamine measurement and 8 minutes of gamma-aminobutyric acid (GABA) measurement. The order of the excitatory and inhibitory LIFUP conditions will be randomized across participants.

Device: Low-intensity focused ultrasound pulsation (LIFUP); Device: Magnetic Resonance Spectroscopy

LIFUP-Glymphatic MRI

EXPERIMENTAL

Participants assigned to the glymphatic MRI arm will complete up to five visits, with a different prespecified brain region targeted at each visit. Tissue-to-fluid water exchange, velocity spectrum imaging, and cerebral perfusion using arterial spin labeling will be assessed before, during, and after LIFUP. The planned imaging periods total approximately 1.5 hours per visit, excluding participant positioning, structural imaging, transducer placement, safety checks, and other required study procedures.

Device: Low-intensity focused ultrasound pulsation (LIFUP); Device: Multi-modal glymphatic function MRI

Interventions

Low-intensity focused ultrasound pulsation (LIFUP) DEVICE

LIFUP will be used to stimulate specific brain regions and assess their causal involvement in the control of conscious state and contents.

LIFUP-Glymphatic MRI; LIFUP-fMRI; LIFUP-magnetic resonance spectroscopy (MRS)

Functional Magnetic Resonance Imaging (fMRI) DEVICE

Whole-brain functional images will be acquired using a multiband gradient-echo echo-planar imaging sequence with the following parameters: 60 slices, repetition time (TR) = 800 ms, echo time (TE) = 30 ms, flip angle = 52°, multiband acceleration factor = 6, slice thickness = 2.4 mm, in-plane resolution = 2.4 × 2.4 mm, FOV = 216 × 216 mm, and image matrix = 90 × 90. MRI acquisition and associated study procedures will be completed within a scanning visit lasting no more than approximately 2 hours.

LIFUP-fMRI

Magnetic Resonance Spectroscopy DEVICE

Single-voxel proton magnetic resonance spectroscopy will be performed. A nominal 15 × 15 × 10 mm spectroscopy voxel will be positioned at the prespecified brain target using the participant's anatomical MRI. Glutamate plus glutamine (Glx) will be measured using a short-echo-time spectroscopy sequence with an acquisition time of approximately 5 minutes. GABA will be measured using an edited spectroscopy sequence with an acquisition time of approximately 8 minutes. An unsuppressed water-reference scan will also be acquired for signal correction and metabolite quantification. Voxel placement, shimming, and other sequence parameters may be adjusted slightly based on target anatomy, scanner requirements, and data quality while maintaining the planned procedures and approximate acquisition times.

LIFUP-magnetic resonance spectroscopy (MRS)

Multi-modal glymphatic function MRI DEVICE

The study team will collect three separate measurements related to glymphatic function. (i) Multi-delay pseudo-continuous arterial spin labeling (PCASL) MRI with a 3D stack of spirals (SOS) gradient and spin echo (GRASE) read-out. Labeling durations from 500 to 2000 ms, TR = 6 sec., background suppression. FOV = 24 cm with 3x3x5 mm resolution. (ii) Tissue-to-fluid Water exchange rate using T2 selective saturation labeling pulses using the same resolution parameters. (iii) Velocity Spectrum Imaging using velocity selective preparation pulses followed by spherical spiral projection imaging (FOV = 24 cm, velocity bandwidth = \[-1, 1\] cm/s, isotropic spatial resolution = 3.5 mm).

LIFUP-Glymphatic MRI

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must be right-handed, English-speaking, and capable of providing written informed consent.
• Participants must have normal or corrected-to-normal vision while wearing contact lenses,
• Participants must have a body mass index of less than 30
• Participants must not be taking medications for any neurological, psychological, or psychiatric condition.

You may not qualify if:

• Participants will be excluded if they have any contraindication to MRI scanning, including possible pregnancy, current breastfeeding BMI greater than 30, metallic substances or implants in the body, claustrophobia, anxiety that would prevent MRI scanning, Participants with tattoos in the head or neck region will also be excluded, while tattoos in other locations will be evaluated by the investigators to determine whether they pose a safety concern.
• cardiopulmonary disease, or an intracranial structural abnormality identified on T1-weighted MRI.
• Women of childbearing potential will be required to complete a study-funded pregnancy test before participation and must have a negative result.
• vision that is not 20/20 or corrected to 20/20 with contact lenses, a history of significant head injury involving loss of consciousness
• a learning disability or other developmental disorder
• any sensory or motor impairment, activity, condition, or circumstance that, in the judgment of the study coordinator or Principal Investigators, would prevent satisfactory completion of the study protocol.

Sponsors & Collaborators

• University of Michigan: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Consciousness Disorders

Interventions

Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Zirui Huang

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy McKinney

CONTACT

734-647-8129; adrongo@med.umich.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Associate Professor, Anesthesiology

Study Record Dates

• First Submitted: September 18, 2026
• First Posted: September 25, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): March 1, 2032
• Study Completion (Estimated): March 1, 2032
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)