Subcortical Arousal in Perceptual Awareness

Yale University

Status: Not yet enrolling

Conditions: Epilepsy

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06934356

2000037710

1R01NS134655-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The study is a multi-site study and will be conducted at up to 11 investigative sites in the United States. The study will investigate subcortical arousal circuits in visual perception using techniques with complementary strengths based on promising initial studies.

Full description

The study will investigate subcortical arousal circuits in visual perception using techniques with complementary strengths based on promising initial studies. This study is expected to shed important light on the precise relationship between transient increases in subcortical arousal and perceptual awareness, generalizable across the visual modality. This research will therefore provide important general potential benefits, including 1. Identification of subcortical arousal systems in perception, which can benefit treatment of many disorders where perceptual deficits are common, e.g. traumatic brain injury, Alzheimer's disease, stroke, developmental disorders, schizophrenia, epilepsy and others. 2. Understanding the role of specific subcortical arousal circuits in perception may help target improved treatments, including transient thalamic stimulation like that planned for the present investigations, or less invasive treatments (TMS, tDCS, designer drugs) to improve function of these circuits. 3. The planned no-report paradigms may detect perceptual awareness in severe brain damage and anesthesia, where people are unable to overtly respond.

The main hypotheses are that 1. the thalamic awareness potential (TAP) will be associated with visual perception independent of report, and 2. thalamic intralaminar stimulation at the time of stimulus presentation will augment the probability of perceptual awareness.

Enrollment: 72 estimated patients

Sex: All

Ages: 13+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

The following are the inclusion/exclusion criteria for epilepsy patients with thalamic electrodes age 13 years and up (Aim 1):

Inclusion Criteria:

• normal vision with or without the use of corrective lenses
• normal hearing not needing an assistive hearing device

Exclusion Criteria:

• severe vision impairment even with correction preventing ability to see stimuli (prevents accurate pupil and eye gaze measurements)
• unable to perform the perception task due to cognitive impairment other than due to the participant's epilepsy. All participants must be capable of consenting for themselves.

The following are the inclusion/exclusion criteria for epilepsy patients with thalamic electrodes age 18 years and up (Aim 2):

Inclusion Criteria:

• normal vision with or without the use of corrective lenses
• normal hearing not needing an assistive hearing device
• a female subject must have a negative pregnancy test and if sexually active, must be using a reliable form of birth control for the duration of the trial, be surgically sterile, or be at least two years post-menopausal.

Exclusion Criteria:

• severe vision impairment even with correction preventing ability to see stimuli (prevents accurate pupil and eye gaze measurements)
• unable to perform the perception task due to cognitive impairment other than due to participant's epilepsy. All participants must be capable of consenting for themselves.
• pregnancy

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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72 participants in 2 patient groups

Thalamic Recording (Aim 1)

Experimental group

Description:

Participants will perform the visual behavioral task with intracranial electroencephalogram (EEG) brain recordings carried out in parallel with surface EEG recordings. For Aim 1, 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.

Treatment:

Device: Behavioral task

Device: EEG

Device: Eye Tracking

Thalamic Stimulation (Aim 2)

Experimental group

Description:

We will test participants during the Visual Report Paradigm, while recording from the intralaminar thalamus with simultaneous scalp EEG as in Aim 1. 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.

Treatment:

Device: Behavioral task

Device: EEG

Device: Eye Tracking