Subcortical Arousal in Perceptual Awareness
Purpose
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.
Condition
- Epilepsy
Eligibility
- Eligible Ages
- Over 13 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
A. The following are the inclusion/exclusion criteria for healthy participants age 18
years and up (Aim 1 and 2):
Inclusion: (1) normal vision with or without the use of corrective lenses; (2) normal
hearing not needing an assistive hearing device.
Exclusion: (1) past history of diagnosis of a psychiatric or neurologic disease; (2)
current psychiatric or neurologic disease; (3) requires hard contact lenses or glasses to
maintain normal vision (prevents accurate pupil and eye gaze measurements); (4) pregnant
or nonremovable ferrous metal objects inside or on the body (prevents MRI).
B. The following are the inclusion/exclusion criteria for epilepsy patients with thalamic
electrodes age 13 years and up (Aim 3A):
Inclusion: (1) normal vision with or without the use of corrective lenses; (2) normal
hearing not needing an assistive hearing device.
Exclusion: (1) requires hard contact lenses or glasses to maintain normal vision
(prevents accurate pupil and eye gaze measurements); (2) unable to perform the perception
task due to cognitive impairment
C. The following are the inclusion/exclusion criteria for epilepsy patients with thalamic
electrodes age 18 year and up (Aim 3B):
Inclusion: (1) normal vision with or without the use of corrective lenses; (2) normal
hearing not needing an assistive hearing device.
Exclusion: (1) unable to perform the perception task due to cognitive impairment
Study Design
- Phase
- N/A
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Thalamic Recording (Aim 3A) |
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. |
|
|
Experimental Thalamic Stimulation (Aim 3B) |
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. |
|
|
Experimental fMRI with report + no-report perception paradigms (Aims 1 and 2) |
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. |
|
Recruiting Locations
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Yale University
Detailed Description
The goal of the planned studies is to investigate the role of shared subcortical arousal systems in perception, including visual, auditory and tactile perception. We will investigate shared subcortical arousal circuits in perception using techniques with complementary strengths including fMRI, pupil and eye gaze measurements, behavioral testing, and direct recording and stimulation of the thalamus. Aims 1 and 2 will investigate subcortical arousal systems in visual, auditory and tactile perception using fMRI, pupil and eye gaze measurements and behavioral testing in healthy normal adult participants. We will collect data from participants for auditory (N=65) and tactile (N=65) perception, and will use an existing data set previously collected and published by our group for visual perception (N=65). For Aim 1 we will analyze fMRI changes in subcortical arousal areas comparing perceived vs not perceived stimuli, and will perform conjunction and disjunction analyses to combine results across visual, auditory and tactile tasks. For Aim 2 we will repeat this analysis but using report-independent perception data based on machine learning classification of eye metrics. Sample size estimates are based on our recent fMRI studies of visual perception which obtained robust statistically significant results in subcortical arousal areas with sample size of 65 participants (Kronemer et al., 2022). Testing is replicated in each participant on two different scanning days, counterbalanced across task-relevant stimulus type on each day. Data for the Visual Report + No Report perception task have already been collected and are publicly available through nitrc.org. Therefore, to obtain comparable data sets for auditory and tactile perception for Aims 1 and 2, we will recruit an additional 65 + 65 = 130 participants, each studied on two days of testing with Report + No Report Paradigms. Aim 3 will investigate the role of the thalamic intralaminar region in visual perception using direct recording and stimulation from patients with chronically implanted thalamic electrodes previously placed for treatment of epilepsy. We will collect data from 32 patients for thalamic recordings only (Aim 3A) and from 16 patients for both thalamic recording and stimulation (Aim 3B). For Aim 3A we will analyze thalamic event related potentials in perceived vs not perceived stimuli, classified as in Aim 2 based on eye metrics. For Aim 3B, we will analyze the probability of perception for visual stimuli presented under three different conditions: thalamic stimulation simultaneous with the visual stimulus, thalamic stimulation delayed until 2s after the visual stimulus, and no thalamic stimulation. Sample size calculations for Aim 3A begin with our prior significant results with N=65 for scalp EEG in the Report + No Report Paradigm. Because we saw robust ERPs with N=7 in the thalamus using the Report Paradigm (Kronemer et al., 2022), as a reasonable conservative intermediate sample size for Report + No Report thalamic icEEG we will plan N=32, leveraging recruitment across multiple planned sites to achieve this number. For Aim 3B, preliminary data with thalamic stimulation show a mean effect size of ~20% ± 20% on probability of perception. Therefore, with 80% power and two-sided significance of p<0.05, we will require N=16 participants as a conservative estimate of sample size. Human subjects research for Aims 1 and 2 will be performed at Yale University School of Medicine. For Aim 3, the study subject population will consist of epilepsy patients with electrodes previously implanted in the intralaminar thalamus (surgical implants are not part of the present study). Aim 3A will include patients with thalamic recording, eye metric, scalp EEG and behavioral measurements (N=32). Aim 3B will include patients with thalamic recording, thalamic stimulation, scalp EEG and behavioral measurements (N=16). Due to the special patient population planned for Aim 3, data will be collected at multiple sites (up to 11). This will be done by visits from Yale research personnel to each site, in collaboration with local site investigators. Site investigators will identify epilepsy patient participants with chronically implanted thalamic intralaminar electrodes to be recruited for the research.