Brain Function Study for Epilepsy

Overseen By Krzysztof A Bujarski, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Dartmouth-Hitchcock Medical Center

Disqualifiers: Stroke, Dementia, Psychosis, others

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

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

175 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how different parts of the brain function by studying brain activity in people with and without epilepsy. Participants will perform various tasks related to memory, speech, and emotions. Some will have electrodes on their scalp or implanted in their brain to record activity. People with epilepsy who are considering surgery and experience frequent seizures may be suitable candidates, as well as those without epilepsy who wish to participate as controls. The goal is to gain insights into brain function to potentially improve future treatments. As an unphased study, this trial offers participants a unique opportunity to contribute to groundbreaking research that could enhance understanding and treatment of brain conditions.

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 study team or your doctor.

What prior data suggests that this study's methods are safe for participants?

Research has shown that invasive EEG, which involves placing electrodes inside the brain, can sometimes cause side effects. These may include an increased risk of brain bleeding and temporary brain function problems. However, long-term issues are rare.

In contrast, scalp EEG, where electrodes are placed on the scalp, is generally safe and often used to monitor seizures. It is non-invasive, meaning it doesn’t require surgery, and doesn’t carry the same risks as invasive EEG.

Both methods are important for understanding brain activity, especially in people with epilepsy. Despite some risks with invasive EEG, doctors use it because it can provide essential information. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different brain tasks and EEG recordings, both invasive and non-invasive, can enhance our understanding of epilepsy. Unlike standard treatments that often rely on medication to control seizures, this trial investigates how brain function can be influenced by tasks like attention, memory, and language exercises, alongside EEG monitoring. The potential to pinpoint how specific brain activities relate to epilepsy could pave the way for innovative, targeted therapies in the future. This approach could offer a more personalized treatment plan, tailored to how a patient’s brain uniquely responds to different stimuli.

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

Research has shown that invasive EEG, one of the methods used in this trial, effectively identifies where seizures begin in the brain. One study found that patients who underwent this type of monitoring had a better chance of becoming seizure-free, with 71.6% not experiencing seizures after surgery. In this trial, some participants will undergo invasive EEG. In contrast, scalp EEG, another method used in this trial, is less invasive but also useful for detecting seizures and predicting their recurrence. A model using scalp EEG signals achieved 88.67% accuracy in predicting seizures. Both methods aid in understanding and managing epilepsy by locating seizure activity in the brain. ^{5 6 7 8 9}

Who Is on the Research Team?

Krzysztof A Bujarski, MD

Principal Investigator

Dartmouth-Hitchcock Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with refractory epilepsy who are undergoing clinical intracranial EEG recording as part of their evaluation for epilepsy surgery. It also includes healthy individuals and online participants without epilepsy to serve as controls.

Inclusion Criteria

I am 18 years or older and may need a scalp EEG.

I am 18 years or older and may have an intracranial EEG.

I am 18 years or older and do not have the condition being studied.

Exclusion Criteria

Patients with Scalp EEG must not be able to provide informed consent for any reason

Normal Controls must be determined not to be appropriate normal control for the study population

Patients with Intracranial EEG must not be able to provide informed consent for any reason

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants engage in daily sessions designed to test aspects of human cognition such as memory, speech, language, feeling, movement, attention, sound perception, and emotions, with continuous recording of brain activity using intracranial and scalp EEG.

2 weeks

1-2 daily sessions (30-90 minutes each)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Attention/arousal tasks
• Auditory Tasks
• Brain Stimulation
• Language tasks
• Memory Tasks
• Recording of facial expressions
• Social Emotional Task
• Visuospatial tasks

Trial Overview The study tests various aspects of human cognition in patients with electrodes implanted in the brain or on the scalp, using tasks related to memory, speech, emotions, etc., often involving computers and additional non-invasive monitoring equipment.

How Is the Trial Designed?

Group I: Scalp EEG (electrodes are placed on a participant's scalp) Experimental Treatment 8 Interventions

Patients with non-invasive scalp electrodes who are admitted to the hospital for clinical reasons will be asked to participate in various study tasks with the recording of their EEG (recording of brain waves via electrodes attached to a participant's scalp) during these tasks.

Group II: Invasive EEG (electrodes are implanted in a participant's brain) Experimental Treatment 9 Interventions

Patients with intracranial electrodes (electrodes are implanted in a participant's brain) undergoing pre-surgical evaluation for clinical reasons will be asked to participate in various study tasks with the recording of intracranial EEG (recording of brain waves via electrodes implanted in a participant's brain) during these tasks.

Group III: Normal Controls Active Control 7 Interventions

Normal controls will be recruited from family members of patients, from advertisements, or from online tools. There will be no EEG recordings obtained from these participants.

Group IV: Online Controls Active Control 7 Interventions

Certain control subjects will be recruited through Amazon Mechanical Turk. These participants will be given their task on the online platform using Qualtric survey function. The task design will be identical to normal controls who are recruited in-person, with the exception of identifiers. There will be no EEG recordings obtained from these participants.

Who Is Running the Clinical Trial?

Dartmouth-Hitchcock Medical Center

Lead Sponsor

Trials

548

Recruited

2,545,000+

Dartmouth College

Collaborator

Trials

93

Recruited

1,415,000+

Brown University

Collaborator

Trials

480

Recruited

724,000+

Published Research Related to This Trial

In a study involving 60 participants, transcutaneous auricular vagus nerve stimulation (taVNS) for 20 minutes improved reaction times in tasks requiring quick responses, indicating enhanced cortical arousal and alertness.

taVNS was found to reduce high-frequency alpha oscillations in the brain, which correlated with better performance in target detection tasks, suggesting a potential mechanism for its effects on cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Facilitates Cortical Arousal and Alertness. Chen, Y., Lu, X., Hu, L.[2023]

Acute vagal nerve stimulation (VNS) significantly reduces power in specific brain wave frequency bands, particularly showing a notable 4.9% decrease in theta band activity, which suggests a mechanism of action for VNS in reducing epileptiform activity.

The study analyzed electrocorticography (ECoG) data from 22 patients with both VNS and responsive neurostimulation (RNS) devices, providing evidence that VNS leads to desynchronization in brain activity, which could inform better programming for neurostimulators in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrocorticography Analysis in Patients With Dual Neurostimulators Supports Desynchronization as a Mechanism of Action for Acute Vagal Nerve Stimulator Stimulation. Ernst, LD., Steffan, PJ., Srikanth, P., et al.[2023]

This study analyzed data from 124 patients with drug-resistant epilepsy and found that direct electrical cortical stimulation (ECS) of the cingulate cortex evoked 329 responses, highlighting its involvement in various functions such as sensory, motor, and affective responses.

The cingulate sulcus visual area (CSv) was identified as a key region for integrating sensory, motor, vestibular, and visual information, indicating the cingulate cortex's complex role in brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptomatic responses elicited by electrical stimulation of the cingulate cortex: Study of a cohort of epileptic patients and literature review. Xue, Y., Yan, H., Hao, G., et al.[2023]

In a pilot study involving 10 patients with Alzheimer's disease, vagus nerve stimulation (VNS) showed a positive effect on cognitive function, with 70% of patients improving on the Alzheimer's Disease Assessment Scale (ADAS-cog) and 90% on the Mini-Mental State Examination (MMSE) after 3 months.

VNS was well tolerated by patients, with only mild and transient side effects reported, suggesting it is a safe intervention for cognitive enhancement in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer's disease: a pilot study. Sjögren, MJ., Hellström, PT., Jonsson, MA., et al.[2022]

Vagus nerve stimulation (VNS) can reduce seizure frequency by more than 50% in at least 50% of patients with refractory partial epilepsy, but complete seizure freedom is rare and 25% of patients may not benefit from the treatment.

Younger patients and those with specific types of epilepsy, such as posttraumatic epilepsy or tuberous sclerosis, tend to have better outcomes with VNS, and advanced brain imaging techniques can help predict individual responses to the therapy, although their use is limited by the need for specialized equipment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation outcome prediction: from simple parameters to advanced models. Chrastina, J., Novak, Z., Zeman, T., et al.[2022]

A systematic review of 20 studies on vagus nerve stimulation (VNS) in patients with neuropsychiatric disorders showed mixed results, with some studies indicating improvements in attention and working memory, but overall, the evidence is not strong enough to confirm VNS as an effective treatment.

In epilepsy, one randomized controlled trial found no significant cognitive differences between active and control VNS, while some nonrandomized trials and cohort studies reported improvements, highlighting the need for more rigorous research to clarify VNS's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Vagus Nerve Stimulation on Attention and Working Memory in Neuropsychiatric Disorders: A Systematic Review. Aniwattanapong, D., List, JJ., Ramakrishnan, N., et al.[2022]

In a study of 20 patients with refractory epilepsy, vagus nerve stimulation (VNS) was found to significantly improve working memory performance, as indicated by reduced errors on tasks requiring working memory (odds ratio = 0.63).

VNS also influenced emotional reactivity, leading to longer reaction times and increased brain activity in response to emotional distractions, suggesting that VNS has immediate effects on both cognitive function and emotional processing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation improves working memory performance. Sun, L., Peräkylä, J., Holm, K., et al.[2018]

In a study of 64 patients with drug-resistant focal-onset seizures, concurrent use of the RNS® System and VNS® System resulted in a significant median reduction in seizure frequency of 43% at one year and 64% at last follow-up, with responder rates of 49% and 67%, respectively.

The combination of RNS and VNS was found to be safe, with no negative interactions reported, although VNS was associated with more stimulation-related side effects (30%) compared to RNS (2%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent brain-responsive and vagus nerve stimulation for treatment of drug-resistant focal epilepsy. Brown, MG., Sillau, S., McDermott, D., et al.[2022]

In a study involving 11 patients with pharmacoresistant epilepsy, high-intensity left cervical vagus nerve stimulation (VNS) for 4.5 minutes led to a temporary decline in figural memory but did not affect verbal memory, suggesting specific cognitive impacts of VNS.

The study also indicated that VNS might accelerate decision-making times, but since the cognitive effects were reversible, significant side effects in clinical use are unlikely, highlighting the need for further research on varying stimulation conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memory alterations during acute high-intensity vagus nerve stimulation. Helmstaedter, C., Hoppe, C., Elger, CE.[2019]

Citations

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Seizure outcomes and complications associated with ... Invasive monitoring in epilepsy includes both stereoelectroencephalography (SEEG) and subdural electrodes (SDE). While SEEG utilizes thin, depth ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10558161/

Intracranial EEG Structure-Function Coupling and Seizure ... Brain areas implanted with iEEG electrodes had stronger structure-function coupling in seizure-free patients compared with those with seizure ...

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Surgical outcomes related to invasive EEG monitoring with ... In lesional cases, Engel I outcome was 57.3% in SDG-group, while in SEEG-group, it was 71.6%. •. In the temporal cases, seizure-freedom achieved 56.7% in SDG- ...

4. thejns.org thejns.org/view/journals/j-neurosurg/141/2/article-p372.xml

Comparative effectiveness of stereotactic, subdural, or hybrid ... Patients in the SEEG group were more likely to have their SOZ localized and patients in the SDE group were more likely to undergo resection.

5. mdpi.com mdpi.com/2227-9059/12/11/2597?

Methods for Identifying Epilepsy Surgery Targets Using ... We included studies presenting an experimental method for invasive EEG analysis, aiming to complement clinicians in identifying the epilepsy surgery targets.

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Invasive electroencephalography monitoring: Indications ... iEEG can be defined as electroencephalography (EEG) recording utilizing invasive methods or using invasive intracranial electrodes placed surgically.

7. sciencedirect.com sciencedirect.com/science/article/pii/S105913112300153X

Safety profile of subdural and depth electrode ... The use of subdural electrodes was associated with a higher risk of hemorrhage and transient neurological symptoms. However persistent deficits were rare with ...

8. neurology.org neurology.org/doi/10.1212/WNL.0000000000209428

Feasibility, Safety, and Performance of Full-Head Subscalp ... Recording full-head subscalp EEG for localization and monitoring purposes is feasible up to 9 days in humans using minimally invasive techniques.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37302157/

Safety profile of subdural and depth electrode ... The use of subdural electrodes was associated with a higher risk of hemorrhage and transient neurological symptoms.