Clinical trial NCT03111290: Modulating Oscillations and Working Memory in Patients With Subdural Electrodes
Official title: Modulating Oscillations and Working Memory in Patients With Subdural Electrodes
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Working Memory
Epilepsy
Keywords: Facial recognition
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: National Institute of Mental Health (NIMH)
First posted: 2017-04-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Working Memory Task Performance - Accuracy
timeFrame: 1 Hour
measure: Working Memory Task Performance - Reaction Time
timeFrame: 1 Hour
Secondary outcomes:
measure: Intracranial EEG
timeFrame: Intracranial EEG will be collected simultaneously when the participants perform the task. 1 Hour
Other outcomes:
measure: Facial Recognition Task Performance - Accuracy
timeFrame: 1 Hour
measure: Facial Recognition Task Performance - Reaction Time
timeFrame: 1 Hour
Locations:
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Flavio Frohlich, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Hae Won Shin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.