Subcortical Arousal in Perceptual Awareness

NCT06934356 | Recruiting DMC FDA Device

• 2 other identifiers: 20000377101R01NS134655-01A1
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 8

Brief Summary

The study consists of prospective enrollment of healthy participants and patients with epilepsy, as well as analysis of an existing data set. Healthy participants will be studied with fMRI, eye metrics and behavioral testing at Yale. Patients will be studied with thalamic recording and stimulation, eye metrics and behavioral testing.

Conditions

Epilepsy

Outcome Measures

Primary Outcomes (4)

• Subcortical event-related signals

  Subcortical event-related signals will be recorded by icEEG to assess electrical activity from the cerebral cortex using currently implanted electrodes during the behavioral task

  Immediately after the intervention

• Perceptual Sensitivity

  measured by the percentage of correctly perceived trials for each participant (Aim 3B)

  Immediately after the intervention

• Activity changes

  Measured using functional magnetic resonance imaging (fMRI) during task onset and off-set to fixation and compare them to fMRI changes during conscious perception of a stimulus vs. not-reported stimuli (Aims 1 and 2)

  Immediately after the intervention

• Functional connectivity

  Measured using fMRI to establish networks actively engaged during task vs. fixation and consciously-reported vs. not-reported stimuli (Aims 1 and 2).

  Immediately after the intervention

Secondary Outcomes (1)

• Cortical Event Related Potentials

  Immediately after the intervention

Study Arms (3)

Thalamic Recording (Aim 3A)

EXPERIMENTAL

Participants will perform the visual behavioral task with intracranial electroencephalogram (EEG) brain recordings carried out in parallel with surface EEG recordings. For Aim 3A, we will analyze thalamic event related potentials in perceived vs not perceived stimuli, classified as in perception of no report visual stimuli based on eye metrics.

Device: EEG; Device: Eye Tracking; Device: Behavioral task

Thalamic Stimulation (Aim 3B)

EXPERIMENTAL

We will test participants during the Visual Report Paradigm, while recording from the intralaminar thalamus with simultaneous scalp EEG as in Aim 3A. Three thalamic stimulation conditions will be tested, randomized across trials: 1. No stimulation; 2. Stimulation Concurrent with visual stimuli; 3. Stimulation Delayed to 2s after visual stimuli. Stimulation will be a 100Hz train lasting 300ms, with biphasic square wave pulses 120μs per phase, current adjusted previously by clinicians to maximum tolerated level without side effects (typically \~3mA). The electrical stimulation is being delivered for research purposes to understand the causal role of thalamus in regulating visual perception.

Device: EEG; Device: Eye Tracking; Device: Behavioral task

fMRI with report + no-report perception paradigms (Aims 1 and 2)

EXPERIMENTAL

Participants will consist of healthy adults undergoing fMRI, eye metric and behavioral testing with report + no-report perception paradigms. This will include prospective data collection for the auditory paradigm, tactile paradigm, as well as analysis of an existing data set for the visual paradigm.

Device: EEG; Device: Eye Tracking; Device: Behavioral task; Diagnostic Test: fMRI

Interventions

Behavioral task DEVICE

For the visual perceptual awareness task, the participant will be presented with barely perceptible visual stimuli. After a variable delay, the participant will be asked to report perception of each stimulus and identify its location.

Thalamic Recording (Aim 3A); Thalamic Stimulation (Aim 3B); fMRI with report + no-report perception paradigms (Aims 1 and 2)

fMRI DIAGNOSTIC_TEST

Visual, auditory or tactile behavioral task will be performed during fMRI at the Yale MR Center. The subject will be asked to lie still in a 3T magnet scanner for up to 15-minute blocks. Each subject will have a sagittal T1-weighted localizer scan (3 minutes) and axial-oblique T1-weighted images (3 min). Multiple 5-15-minute imaging runs will be repeated up to 10 times. The subjects' responses will be recorded by a computer that is linked to the button box. The stimuli will be presented in blocks of 5 to 15 minutes throughout the MR imaging sequences.

fMRI with report + no-report perception paradigms (Aims 1 and 2)

EEG DEVICE

Participants will have scalp EEG recorded with the international 10-20 system sampled at 256Hz using EEG amplifiers for purposes of surface event related potential analysis

Thalamic Recording (Aim 3A); Thalamic Stimulation (Aim 3B); fMRI with report + no-report perception paradigms (Aims 1 and 2)

Eye Tracking DEVICE

An eye-tracking device may be used during the perceptual awareness task. Pupillary and gaze location measurements are recorded using either a ViewPoint\~VoltagePro.EyeLink 1000 Plus system, or Argus Science ETVision system. If using the ViewPoint\~VoltagePro system or the Argus Science ETVision system, participants will be asked to wear an eye tracker during the perceptual awareness task (similar to wearing sunglasses). If using the EyeLink 1000 Plus system, participants may be asked to place their head inside of a padded head-chin rest to stabilize head position

Thalamic Recording (Aim 3A); Thalamic Stimulation (Aim 3B); fMRI with report + no-report perception paradigms (Aims 1 and 2)

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Yale University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (8)

Yale School of Medicine

New Haven, Connecticut, 06520, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

Mayo Clinic

Rochester, Minnesota, 55901, United States

RECRUITING

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

NOT YET RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15260, United States

NOT YET RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37235, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Epilepsy

Interventions

Electroencephalography; Eye-Tracking Technology; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Eye Movement Measurements; Diagnostic Techniques, Ophthalmological; Tomography; Diagnostic Imaging

Study Officials

• Hal Blumenfeld, MD, Phd

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hal Blumenfeld, MD, PHD

CONTACT

(203) 785-3865; Hal.blumenfeld@yale.edu

Kristine Dacosta

CONTACT

kristine.dacosta@yale.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2025
• First Posted: April 18, 2025
• Study Start: October 13, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)