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

Trial Summary

What is the purpose of this trial?

This study will enroll patients with epilepsy who are being evaluated for epilepsy surgery and have electrodes implanted in the brain and/or have electrodes on the scalp. Additionally, this study will recruit normal and online controls (participants who do not have epilepsy). Participants will be asked to participate in 1 to 2 (30-90 minutes) daily sessions designed to test aspects of human cognition such as memory, speech, language, feeling, movement, attention, sound perception, and emotions. Generally, this will involve working on a computer, looking at pictures or watching videos, and answering questions. Additionally, participants may be asked to be hooked up to additional equipment such as eye tracker, electrical stimulator, heart rate monitor, sweat monitor or other non-invasive equipment. The overall aim of this study is to use human intracranial electrophysiology (the recording of the electrical activity of the human brain) to study localization and function of the human brain.

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 data supports the effectiveness of this treatment for epilepsy?

Research shows that Vagus Nerve Stimulation (VNS) can improve working memory and attention in patients with epilepsy, as well as enhance cognitive functions like alertness and arousal. These findings suggest that VNS may have beneficial effects on brain function in epilepsy beyond just reducing seizures. ^{1 2 3 4 5}

Is vagus nerve stimulation (VNS) safe for humans?

Vagus nerve stimulation (VNS) is generally considered safe for humans, as it is an accepted treatment for epilepsy and depression. Studies have shown that while VNS can affect memory and reaction times, these effects are reversible and not significant in clinical settings. ^{1 2 4 5 6}

How does vagus nerve stimulation differ from other treatments for epilepsy?

Vagus nerve stimulation (VNS) is unique because it involves electrical stimulation of the vagus nerve to help control seizures, unlike traditional drug treatments. It not only reduces seizure frequency but also has potential cognitive benefits, such as improving working memory and affecting emotional reactivity, which are not typically associated with standard epilepsy medications. ^{1 2 7 8 9}

Research Team

Krzysztof A Bujarski, MD

Principal Investigator

Dartmouth-Hitchcock Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation improves working memory performance. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Memory alterations during acute high-intensity vagus nerve stimulation. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer's disease: a pilot study. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Facilitates Cortical Arousal and Alertness. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of Vagus Nerve Stimulation on Attention and Working Memory in Neuropsychiatric Disorders: A Systematic Review. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Concurrent brain-responsive and vagus nerve stimulation for treatment of drug-resistant focal epilepsy. [2022]

7. Slovakia pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation outcome prediction: from simple parameters to advanced models. [2022]

8. United States 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. [2023]

9. United States 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. [2023]