Modulating Oscillations and Working Memory in Patients With Subdural Electrodes

University of North Carolina (UNC)

Status: Invitation-only

Conditions: Epilepsy; Working Memory

Treatments: Device: Direct Cortical Stimulation; Device: Direct Cortical Stimulation Sham

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03111290

1R21NS094988 (U.S. NIH Grant/Contract)

13-2710

1R01MH124387 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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30 participants in 2 patient groups

Sham

Sham Comparator group

Description:

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

Treatment:

Device: Direct Cortical Stimulation Sham

Stimulation

Active Comparator group

Description:

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.

Treatment:

Device: Direct Cortical Stimulation