Working MemoryNCT03111290
Modulating Oscillations and Working Memory in Patients With Subdural Electrodes
A study testing Direct Cortical Stimulation in people with Working Memory and Epilepsy, run by University of North Carolina, Chapel Hill.
Trial summary
Purpose: To investigate whether rhythmic direct electrical stimulation (DES) causes entrainment of endogenous neural oscillatory activity and whether such activity improve cognition. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Working Memory, Epilepsy
- What is being tested?
- Direct Cortical Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2014to 15 Mar 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of medically intractable epilepsy
- Capable of giving informed consent
- Aged 18 - 80 years, either sex
Who cannot join
- Past or current history of other neurological illnesses including ischemic stroke, intracerebral hemorrhage, brain neoplasm.
- Major systemic illness
- Severe cognitive impairment defined as mini-mental state examination of less than 20
- Severe psychiatric illness
- Excessive use of alcohol or other substances
About this study
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.
Read the 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
- Being tested
- Direct Cortical Stimulation, Direct Cortical Stimulation Sham
- Keywords
- Facial recognition
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Direct Cortical StimulationDevice
A train of periodic electrical pulses is delivered between two local electrodes implanted in the brain
Direct Cortical Stimulation ShamDevice
Sham trials where no electric pulse is delivered
| Study group | Role | What they receive |
|---|---|---|
| Sham | Sham comparator | Device: Direct Cortical Stimulation Sham. Trials in which stimulation is not applied. These trials are initiated using a generic trigger generator. Receives: Device: Direct Cortical Stimulation Sham |
| Stimulation | Active comparator | 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. Receives: Device: Direct Cortical Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Working Memory Task Performance - Accuracy
In this task, a sequence of items (alphabets or numerals) is presented followed by a delay. Following this, a single item which may or may not have been in the sequence is presented and the subject will be asked to indicate whether the item was in the previously presented sequence. A total of 150 trials will be performed with randomly interleaved sham trials where no stimulation is applied. Accuracy will be quantified in percentage correct.
Measured: 1 Hour
Working Memory Task Performance - Reaction Time
In this task, a sequence of items (alphabets or numerals) is presented followed by a delay. Following this, a single item which may or may not have been in the sequence is presented and the subject will be asked to indicate whether the item was in the previously presented sequence. A total of 150 trials will be performed with randomly interleaved sham trials where no stimulation is applied. Reaction times will be quantified in milliseconds.
Measured: 1 Hour
Secondary outcomes (1)
Intracranial EEG
Spectral analysis and functional connectivity analysis of electrophysiology data will be performed using methods like multi-taper fft, wavelets, phase locking, Granger causality etc. The measures will be compared between sham and stimulation trials to identify if stimulation enhances neuronal entrainment. The correlation between the measures described above and the task performance will also be estimated.
Measured: Intracranial EEG will be collected simultaneously when the participants perform the task. 1 Hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2017
- Study startJan 2014
- Primary completion15 Mar 2017 (estimated)
- Study completion15 Mar 2017 (estimated)
Why it stopped: Record erroneously created as an updated trial was initiated \& performed in the same patient population.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Working MemoryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor
- Investigators
- Flavio Frohlich, PhD, Principal investigator, University of North Carolina, Chapel HillHae Won Shin, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03111290
- Sponsor's protocol ID
- 13-2710
- Other IDs
- 1R21NS094988
- Status last verified
- Jan 2025
- First submitted
- 22 Feb 2017
- Last updated
- 19 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: De-identified electrophysiology data and task information (e.g. timing of each trial, timing of responses) will be shared at the end of the study in a central repository (e.g. zenodo)
Publications
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.
PubMed 27023427
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulating Oscillations and Working Memory in Patients With Subdural Electrodes
- ClinicalTrials.gov ID
- NCT03111290
- Acronym / sponsor ID
- 13-2710
- Conditions
- Working Memory, Epilepsy
- Keywords
- Facial recognition
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Record erroneously created as an updated trial was initiated \& performed in the same patient population.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Jan 2014 (actual)
- Primary completion
- 15 Mar 2017 (estimated)
- Study completion
- 15 Mar 2017 (estimated)
- First posted
- 12 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sham | Sham comparator | Device: Direct Cortical Stimulation ShamDevice: Direct Cortical Stimulation Sham. Trials in which stimulation is not applied. These trials are initiated using a generic trigger generator. |
| Stimulation | Active comparator | Device: Direct Cortical StimulationDevice: 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- History of medically intractable epilepsy
- Capable of giving informed consent
- Aged 18 - 80 years, either sex
Key exclusion criteria (5 listed)
- Past or current history of other neurological illnesses including ischemic stroke, intracerebral hemorrhage, brain neoplasm.
- Major systemic illness
- Severe cognitive impairment defined as mini-mental state examination of less than 20
- Severe psychiatric illness
- Excessive use of alcohol or other substances
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Direct Cortical StimulationA train of periodic electrical pulses is delivered between two local electrodes implanted in the brain | Device | Stimulation |
| Direct Cortical Stimulation ShamSham trials where no electric pulse is delivered | Device | Sham |
Primary outcome
Working Memory Task Performance - Accuracy
Time frame: 1 Hour
In this task, a sequence of items (alphabets or numerals) is presented followed by a delay. Following this, a single item which may or may not have been in the sequence is presented and the subject will be asked to indicate whether the item was in the previously presented sequence. A total of 150 trials will be performed with randomly interleaved sham trials where no stimulation is applied. Accuracy will be quantified in percentage correct.
Working Memory Task Performance - Reaction Time
Time frame: 1 Hour
In this task, a sequence of items (alphabets or numerals) is presented followed by a delay. Following this, a single item which may or may not have been in the sequence is presented and the subject will be asked to indicate whether the item was in the previously presented sequence. A total of 150 trials will be performed with randomly interleaved sham trials where no stimulation is applied. Reaction times will be quantified in milliseconds.
1 secondary outcome
Intracranial EEG
Time frame: Intracranial EEG will be collected simultaneously when the participants perform the task. 1 Hour
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2026.
- Background: PubMed 27023427Alagapan 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.
- Individual participant dataSharing planned: Yes. De-identified electrophysiology data and task information (e.g. timing of each trial, timing of responses) will be shared at the end of the study in a central repository (e.g. zenodo)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Flavio Frohlich, PhD principal investigator
University of North Carolina, Chapel Hill
Hae Won Shin, MD principal investigator
University of North Carolina, Chapel Hill
Questions about this trial
What is this clinical trial studying?
A study testing Direct Cortical Stimulation in people with Working Memory and Epilepsy, run by University of North Carolina, Chapel Hill.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Working Memory Task Performance - Accuracy (time frame: 1 Hour). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03111290, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.