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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how certain brain waves, such as theta and alpha, affect memory and how brain stimulation might help manage epilepsy and improve memory control. It uses direct brain stimulation (Direct Cortical Stimulation, or DCS) in various ways to determine the most effective method. Participants will perform tasks while receiving stimulations to specific brain areas. Ideal candidates for this trial are individuals with epilepsy who already have electrodes in place from previous treatments. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research on brain stimulation and memory control.

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 brain stimulation method is safe for epilepsy and memory control?

In a previous study, researchers used direct cortical stimulation (DCS) safely in patients with epilepsy. This method sends small electrical pulses to the brain to help manage seizures. For example, the Neuropace RNS system employs a similar approach and is already available for epilepsy patients. Research shows that this type of brain stimulation is generally well-tolerated.

Additionally, studies suggest that direct stimulation can aid memory tasks by boosting brain activity. The reviewed studies have not reported significant serious side effects linked to this kind of brain stimulation, suggesting it is a relatively safe treatment option for conditions like epilepsy and memory control.

Overall, data from past research show that DCS has been safely tested, particularly for managing seizures and improving memory functions. However, like all treatments, individual responses can vary, and participants in clinical trials may experience different effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these brain stimulation techniques because they offer a fresh approach to treating epilepsy and memory control issues. Unlike standard medications that often focus on altering neurotransmitter levels, Direct Cortical Stimulation (DCS) involves applying electrical impulses directly to specific brain regions, which may lead to more precise control of brain activity. The use of different frequencies—alpha and theta—also opens up the possibility of customizing treatments based on individual needs, potentially improving efficacy and reducing side effects. This innovative approach could lead to faster and more targeted relief for patients who haven't responded well to existing options.

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

This trial will compare different approaches to direct cortical stimulation (DCS) for epilepsy and memory control. Research has shown that DCS can influence brain activity and improve working memory. Participants may receive DCS targeting the frontal cortex at alpha and theta frequencies, which studies suggest can enhance memory tasks by affecting brain rhythms. Alternatively, some participants will receive DCS targeting both the frontal and parietal cortex at in-phase and anti-phase theta frequencies. Evidence suggests that DCS at specific frequencies helps coordinate memory processing. Additionally, researchers have used DCS to identify brain areas involved in seizures, indicating potential for epilepsy treatment. These findings suggest that DCS might effectively improve memory and manage epilepsy symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Flavio Frohlich, PhD

Principal Investigator

UNC Chapel Hill

Are You a Good Fit for This Trial?

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

Able to provide informed consent

Speak and understand English

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

Exclusion Criteria

Major systemic illness

Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study

Severe cognitive impairment diagnosed by clinician in neuropsychiatric evaluation

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10680685/

Direct cortical stimulation induces short-term plasticity of ... Patterned brain stimulation is commonly employed as a tool for eliciting plasticity in brain circuits and treating neuropsychiatric disorders.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053811918319360

Low-frequency direct cortical stimulation of left superior ... Our results provide evidence for SFG playing a functional role in working memory and suggest that SFG may coordinate working memory through low-frequency ...

3. cell.com cell.com/cell-reports/fulltext/S2211-1247(19)31394-4

Network-Targeted, Multi-site Direct Cortical Stimulation ... We test whether electrically stimulating frontal and parietal regions at the frequency of interaction is effective in modulating working memory.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8793936/

Direct Cortical Stimulation to Probe the Ictogenicity of the ... These results support targeted mapping of SOZ in LAFA onset patterns by performing DCS in high EI nodes to distinguish seizure generators (true responders)

5. mdpi.com mdpi.com/2077-0383/14/6/1956

Mapping the Epileptogenic Brain Using Low-Frequency ... In this review, we examine the past two decades of innovation in low-frequency stimulation as it pertains to pre-surgical evaluation.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5007190/

Safety of transcranial Direct Current Stimulation: Evidence ... This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6692891/

Direct Electrical Stimulation in Electrocorticographic Brain ... Closed loop stimulation to control seizures is currently clinically available to epilepsy patients through the Neuropace RNS system (Morrell, 2011; Lee et al., ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0960982217303263

Direct Brain Stimulation Modulates Encoding States and ... Free recall is a complex task that recruits multiple core episodic memory processes [20]. We show that stimulation increases encoding states by ...

9. cell.com cell.com/current-biology/fulltext/S0960-9822(17)30326-3

Direct Brain Stimulation Modulates Encoding States and ... Here, we test the hypothesis that targeted electrical stimulation can modulate neural encoding states and subsequent memory outcomes. Using recordings from ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S2214751925001215

Optimizing high-frequency and low-frequency deep brain ... Experimental models have shown that high-frequency stimulation reduces seizure activity, likely by disrupting cortical synchronization, whereas low-frequency ...