Modulating Oscillations and Working Memory in Patients With Subdural Electrodes

NCT ID: NCT03111290

Last Updated: 2025-01-08

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2026-01-31

Brief Summary

Purpose: To investigate whether rhythmic direct electrical stimulation (DES) causes entrainment of endogenous neural oscillatory activity and whether such activity improve cognition.

Participants: Drug-resistant epilepsy patients undergoing epilepsy surgery cortical mapping with continuous electrocorticography (ECoG) with intracranial electrodes.

Procedures (methods): Rhythmic electrical stimulation will be delivered via intracranial electrodes during routine extra-operative cortical mapping. Long-term ECoG, Pre-stimulation ECoG, peri-stimulation ECoG, and post-stimulation ECoG data will be analyzed to assess for entrainment of neural oscillations.

Detailed Description

The aim of this study is to characterize the entrainment of endogenous neural oscillatory activity using direct electrical stimulation (DES) of the brain and understand the effects on cognition.

In this study, the investigators will apply rhythmic DES to patients who are undergoing routine DES for cortical mapping as a part of their epilepsy surgery evaluation with the aim of entraining cortical neural oscillations at specific frequencies relevant to cognitive processing and neuropsychiatric disease. The investigators hypothesize that rhythmic DES within a naturally occurring oscillatory frequency will cause entrainment at that frequency (e.g. 10Hz rhythmic DES will entrain a 10 Hz alpha oscillation). Also, the investigators posit that rhythmic DES at the theta (5Hz), alpha(10Hz), and gamma (50Hz) frequencies will cause enhancement of neural oscillations in the gamma band.

The study follows a within-participant crossover design. Participants will perform one of the tasks described below and each task consists of multiple trials of varying difficulty. Stimulation will be applied concurrently through electrodes implanted for clinical determination of seizure focus. Equal number of stimulation and sham trials will be pseudo-randomly interleaved to get a balanced design (balanced across trial difficulty and trial type).

The investigators will apply electrical stimulation in the form of pulse trains. The applied electrical stimulation intensity, duration and frequency follow the parameters used for clinical assessments of language and seizure focus and fall below the clinically approved limits.

The investigators will measure participants performance on a simple working memory task during the above-described cortical electrical stimulation protocol. Alternately, participants can perform a face recognition task.

Conditions

Working Memory; Epilepsy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Sham

Device: Direct Cortical Stimulation Sham. Trials in which stimulation is not applied. These trials are initiated using a generic trigger generator.

Group Type: SHAM_COMPARATOR

Direct Cortical Stimulation Sham

Intervention Type: DEVICE

Sham trials where no electric pulse is delivered

Stimulation

Device: Direct Cortical Stimulation. 150 stimulations with stimulations lasting 5 seconds at different target electrodes at two target frequencies (e.g. 5 Hz and 10 Hz) 2 milliampere in amplitude (Pulse shape - Biphasic square pulse 200 microsecond in duration per phase). Stimulation will be applied concurrently with the task and stimulation trials will be randomly interleaved with sham trials.

Group Type: ACTIVE_COMPARATOR

Direct Cortical Stimulation

Intervention Type: DEVICE

A train of periodic electrical pulses is delivered between two local electrodes implanted in the brain

Interventions

Direct Cortical Stimulation

A train of periodic electrical pulses is delivered between two local electrodes implanted in the brain

Intervention Type: DEVICE

Direct Cortical Stimulation Sham

Sham trials where no electric pulse is delivered

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. History of medically intractable epilepsy

2. Capable of giving informed consent

3. Aged 18 - 80 years, either sex

Exclusion Criteria

1. Past or current history of other neurological illnesses including ischemic stroke, intracerebral hemorrhage, brain neoplasm.

2. Major systemic illness

3. Severe cognitive impairment defined as mini-mental state examination of less than 20

4. Severe psychiatric illness

5. Excessive use of alcohol or other substances

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Flavio Frohlich, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Hae Won Shin, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

References

Alagapan S, Schmidt SL, Lefebvre J, Hadar E, Shin HW, Frӧhlich F. Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation Is State-Dependent. PLoS Biol. 2016 Mar 29;14(3):e1002424. doi: 10.1371/journal.pbio.1002424. eCollection 2016 Mar.

Reference Type: BACKGROUND

PMID: 27023427 (View on PubMed)

Study Documents

Document Type: Summary Data Set

Dataset supporting Alagapan et al. 2016 PLoS Biology

View Document

Other Identifiers

1R21NS094988

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01MH124387

Identifier Type: NIH

Identifier Source: secondary_id

View Link

13-2710

Identifier Type: -

Identifier Source: org_study_id