Subcortical Arousal Study for Epilepsy

Recruiting at 7 trial locations

Overseen By Kristine Dacosta

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Disqualifiers: Severe vision impairment, Cognitive impairment, Pregnancy

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how certain brain circuits affect visual perception in people with epilepsy. It tests two approaches: recording brain activity during a visual task and using gentle brain stimulation to observe its influence on perception. The trial seeks epilepsy patients with thalamic electrodes who have normal vision (with or without glasses) and can complete perception tasks without cognitive difficulties. Eligible participants may find this trial a good fit. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could enhance understanding of epilepsy and visual perception.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that these techniques are safe for investigating subcortical arousal circuits in visual perception?

Previous studies have found recordings from the thalamus to be safe, with no negative side effects reported. Patients did not experience any harmful effects from the procedure. Similarly, research on thalamic stimulation, which involves sending small electrical pulses to the brain, shows it is generally safe. Long-term studies have demonstrated that this method can effectively reduce seizures without causing serious side effects. Both treatments show promise in managing epilepsy, suggesting they are well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how the thalamus, a deep brain structure, influences visual perception in epilepsy patients. Unlike standard epilepsy treatments, which often involve medications or surgery, this study uses intracranial and surface EEG recordings to analyze brain activity during specific visual tasks. Additionally, the trial tests the effects of direct electrical stimulation of the thalamus to see how it impacts visual perception, potentially revealing new ways to understand and treat epilepsy. This approach could lead to innovative therapies that target brain circuits more precisely, offering hope for more effective management of epilepsy symptoms.

What evidence suggests that this trial's treatments could be effective for epilepsy?

This trial will explore the effects of thalamic stimulation on epilepsy. Research has shown that stimulating the thalamus might benefit people with epilepsy. In earlier studies, this type of stimulation reduced seizure severity and improved participants' overall well-being. On average, participants experienced a 3.5-point improvement in seizure severity on a 10-point scale. Another study found that 71% of participants had at least half as many seizures after receiving thalamic stimulation for six months or more. These results suggest that thalamic stimulation could help control seizures and enhance the quality of life for those with epilepsy. ^{6 7 8 9 10}

Who Is on the Research Team?

Hal Blumenfeld, MD, Phd

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals with normal vision and hearing, including those with epilepsy who have thalamic electrodes. Participants must be aged 13 or older, capable of consenting, not pregnant, using reliable birth control if applicable, and able to perform perception tasks without cognitive impairments unrelated to epilepsy.

Inclusion Criteria

Normal vision with or without the use of corrective lenses

Normal hearing not needing an assistive hearing device

Normal vision with or without the use of corrective lenses

Exclusion Criteria

Severe vision impairment even with correction preventing ability to see stimuli (prevents accurate pupil and eye gaze measurements)

Pregnancy

I am 13 or older with epilepsy and have thalamic electrodes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Thalamic Recording (Aim 1)

Participants perform the visual behavioral task with intracranial EEG brain recordings and surface EEG recordings to analyze thalamic event-related potentials.

4 weeks

Multiple visits for EEG recordings

Thalamic Stimulation (Aim 2)

Participants are tested during the Visual Report Paradigm with thalamic stimulation conditions randomized across trials.

4 weeks

Multiple visits for stimulation sessions

Follow-up

Participants are monitored for safety and effectiveness after the intervention

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Behavioral task
• EEG
• Eye Tracking

Trial Overview The study examines how subcortical arousal circuits affect visual perception in people with epilepsy. It uses EEGs for brain activity monitoring, eye tracking to follow gaze and pupil changes, and behavioral tasks to assess awareness. Conducted across multiple U.S. sites, it builds on initial promising results.

How Is the Trial Designed?

Group I: Thalamic Stimulation (Aim 2) Experimental Treatment 3 Interventions

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.

Group II: Thalamic Recording (Aim 1) Experimental Treatment 3 Interventions

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.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Citations

1. academic.oup.com academic.oup.com/braincomms/advance-article/8196834

Thalamocortical network neuromodulation for epilepsy The median improvement in seizure severity was 3.5 out of 10 points (P = 0.0312), life satisfaction 4.5 points (P = 0.0312) and quality of sleep 3 points (P = ...

2. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2022.910345/full

Responsive Thalamic Neurostimulation: A Systematic ... Of the subjects who received responsive thalamic stimulation for ≥6 months, 17/24 subjects experienced greater than or equal to 50% reduction, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10942513/

Thalamic stimulation induced changes in network connectivity ... Thalamic stimulation delivered for >1.5 hours significantly reduced pulse evoked potential amplitudes in connected areas compared to baseline, ...

4. nature.com nature.com/articles/s41467-025-64922-w

Thalamocortical hodology to personalize electrical ... Thalamic electrical stimulation offers a therapeutic approach for refractory epilepsy patients ineligibles for resective surgery.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8379668/

Effects of anterior thalamic nuclei stimulation on ... We extend previous work [16] showing an immediate and continuous suppression of interictal epileptiform discharges with thalamic stimulation during inpatient ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1059131117304934

Long-term follow-up of anterior thalamic deep brain ... Long-term follow-up data for epilepsy patients treated with DBS is scarce. Very recently, long-term efficacy and safety data from the SANTE trial (Stimulation ...

7. thejns.org thejns.org/pediatrics/view/journals/j-neurosurg-pediatr/35/4/article-p361.xml

Thalamic stereo-electroencephalography exploration in ... Collecting more patient data during phase II SEEG will be crucial for accurately determining the final placement of neuromodulation targets.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12098681/

Inter-seizure variability in thalamic recruitment and its ... Our results suggest that by analyzing electrical activity during seizures, we can better predict which parts of the thalamus are involved.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10316776/

Multisite thalamic recordings to characterize seizure ... Our approach for multisite thalamic sampling was safe and caused no adverse events. Intracranial EEG recordings confirmed SOZ in medial temporal lobe, insula, ...

10. aesnet.org aesnet.org/abstractslisting/utility-and-safety-of-thalamic-nuclei-stereotactic-eeg-to-guide-rns-placement-or-epilepsy-surgery

utility and safety of thalamic nuclei stereotactic eeg to guide ... Thalamic intracranial monitoring targets in SEEG planning resulted in thalamic-targeted treatment in 62% of subjects. No serious adverse events were seen ...