Brain Stimulation for Epilepsy and Memory Control

Overseen By Flavio Frohlich, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of North Carolina, Chapel Hill

Disqualifiers: Stroke, Brain neoplasm, Severe psychiatric, others

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

Compensation: Varies

Number of Visits: 2

50 Participants Needed

Trial Summary

What is the purpose of this trial?

Purpose: The purpose of this pilot study is to investigate the dynamics between theta and alpha oscillations in the control of working memory. These findings will be informative of what types of brain stimulation are most effective at modulating brain activity. Deep brain stimulation and transcranial magnetic stimulation are used for an increasing number of neurological and psychiatric disorders. Participants: Eligible participants are patients who have previously had electrodes implanted to monitor epilepsy (outside of research activity). 50 participants will be recruited, 25 participants for each phase of the study. Procedures (methods): The participants will perform a cognitive control task. During the task, rhythmic trains of direct cortical stimulation will be delivered to the frontal cortex alone or to the frontal and parietal cortex. Electrocorticography will be collected concurrent with stimulation.

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 direct brain stimulation, including scheduled and responsive neurostimulation, can effectively reduce seizures in people with epilepsy. Studies have demonstrated significant seizure reduction when the stimulator is active, and responsive neurostimulation has been shown to help control seizures by delivering targeted electrical pulses when abnormal brain activity is detected. ^{1 2 3 4 5}

Is direct cortical stimulation safe for humans?

Direct cortical stimulation (DCS) is commonly used in epilepsy treatment and presurgical evaluation, and while it can induce seizures, it is generally considered safe when performed under medical supervision. ^{1 2 6 7 8}

How is the treatment 'Direct cortical stimulation (DCS)' for epilepsy and memory control different from other treatments?

Direct cortical stimulation (DCS) is unique because it involves directly applying electrical pulses to specific brain areas to control seizures and potentially improve memory. Unlike traditional drug treatments, DCS targets the brain's electrical activity directly, offering an alternative for patients who cannot undergo surgery or have drug-resistant epilepsy. ^{1 2 3 9 10}

Research Team

Flavio Frohlich, PhD

Principal Investigator

UNC Chapel Hill

Eligibility Criteria

This trial is for patients with medically intractable epilepsy who have had electrodes implanted for monitoring. They must be able to consent, speak English, and not have other major neurological illnesses, severe cognitive or psychiatric conditions, substance abuse issues, or any risk factors that could affect their participation as judged by the investigator.

Inclusion Criteria

I have epilepsy that doesn't respond to treatment.

I have electrodes placed in the correct spots for the stimulation session.

Able to provide informed consent

Exclusion Criteria

Major systemic illness

I do not have any other brain-related illnesses.

Severe cognitive impairment diagnosed by clinician in neuropsychiatric evaluation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase One: Frontal Stimulation

Direct Cortical Stimulation (DCS) in alpha and theta frequencies is applied through electrodes located in the frontal cortex.

1-2 days

1-2 visits (in-person)

Phase Two: Frontal Parietal Stimulation

Direct Cortical Stimulation (DCS) in in-phase and anti-phase theta frequencies is applied through electrodes located in the frontal and parietal cortex.

1-2 days

1-2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after stimulation sessions

4 weeks

Treatment Details

Interventions

• Direct cortical stimulation (DCS) Alpha
• Direct cortical stimulation (DCS) Anti-Phase Theta
• Direct cortical stimulation (DCS) In-Phase Theta
• Direct cortical stimulation (DCS) Theta
• Sham Direct cortical stimulation (DCS)

Trial Overview The study tests how different types of brain stimulation (theta and alpha oscillations) affect working memory control. Participants will undergo direct cortical stimulation while performing a cognitive task to see which stimulation methods best modulate brain activity.

Participant Groups

Group I: Frontal Stimulation Active Control 3 Interventions

Direct Cortical Stimulation (DCS) in alpha and theta frequencies is applied through electrodes located in the frontal cortex.

Group II: Frontal Parietal Stimulation Placebo Group 3 Interventions

Direct Cortical Stimulation (DCS) in in-phase and anti-phase theta frequencies is applied through electrodes located in the frontal and parietal cortex.

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

Temporal Interference (TI) stimulation at 130 Hz non-invasively stimulates the hippocampus, leading to increased physiological brain activity (ripples) and decreased harmful brain activity (Fast Ripples and interictal discharges) in mouse models of epilepsy.

TI stimulation shows better penetration into the human hippocampus compared to traditional transcranial current stimulation (TCS), suggesting its potential as a focused therapeutic approach for treating epilepsy without affecting surrounding brain tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers. Acerbo, E., Jegou, A., Luff, C., et al.[2022]

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) has been shown to be effective in reducing seizure frequency in adults with epilepsy that does not respond to multiple medications, based on a randomized trial involving this treatment.

The U.S. Food and Drug Administration has approved DBS therapy for epilepsy as an adjunctive treatment, specifically for patients aged 18 and older with partial onset seizures that are resistant to three or more antiepileptic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for epilepsy. Salanova, V.[2019]

References

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

Brain stimulation for the treatment of epilepsy. [2010]

2. England pubmed.ncbi.nlm.nih.gov

Brain stimulation for epilepsy: can scheduled or responsive neurostimulation stop seizures? [2013]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers. [2022]

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

Insights Into the Therapeutic Effect of Responsive Neurostimulation Assessed With Scalp EEG Recording: A Case Report. [2018]

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

On-demand pulsatile intracerebral delivery of carisbamate with closed-loop direct neurostimulation therapy in an electrically induced self-sustained focal-onset epilepsy rat model. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Validation of direct cortical stimulation in presurgical evaluation of epilepsy. [2022]

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

Deep brain stimulation for epilepsy. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Seizures induced by direct electrical cortical stimulation--Mechanisms and clinical considerations. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Electrical stimulation for epilepsy: stimulation of hippocampal foci. [2017]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Brain stimulation for surgical epilepsy. [2010]