Causal Role of Top-Down Theta Oscillations in Prioritization

April 20, 2026 updated by: University of North Carolina, Chapel Hill

Modulating Oscillations and Working Memory in Patients With Subdural Electrodes

Purpose: The purpose of this pilot study is to investigate the dynamics between theta and alpha oscillations in the control of working memory. These findings will be informative of what types of brain stimulation are most effective at modulating brain activity. Deep brain stimulation and transcranial magnetic stimulation are used for an increasing number of neurological and psychiatric disorders. Participants: Eligible participants are patients who have previously had electrodes implanted to monitor epilepsy (outside of research activity). 50 participants will be recruited, 25 participants for each phase of the study. Procedures (methods): The participants will perform a cognitive control task. During the task, rhythmic trains of direct cortical stimulation will be delivered to the frontal cortex alone or to the frontal and parietal cortex. Electrocorticography will be collected concurrent with stimulation.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

The aim of this study is to investigate the causal role of functional interactions between frontal-theta dependent selection processes and posterior-alpha dependent suppression processes in the context of cognitive control by targeting theta and alpha oscillations in frontal and parietal cortex separately in phase one of the experiment. Theta and alpha oscillations are hypothesized to play complementary roles such that theta oscillations are excitatory (related to active processing) whereas alpha oscillations are inhibitory (related to suppression of processing).

Thus, the investigators hypothesize that rhythmic brain stimulation can be used to drive activity in opposite directions. In the second phase of the experiment the investigators target functional connectivity between these regions. In particular, theta oscillations are hypothesized to play a critical role in orchestrating the prioritization and suppression of information across the cerebral cortex. Thus, the investigators hypothesize that in-phase theta frequency connectivity will be causally related to working memory success, but alpha frequency connectivity will be inconsequential and anti-phase theta connectivity will be detrimental. Together these findings suggest an overall model by which the amplitude of theta oscillations in prefrontal and the amplitude of alpha oscillations in parietal play a causal role in prioritization and suppression respectively, but functional connectivity between frontal and parietal cortex within the theta frequency band alone is critical to these cognitive processes. This experiment is of critical importance to the design of future interventions that use brain stimulation for the treatment of psychiatric and neurological disorders. For example, the use of frequency specific brain stimulation is key to controlling the impact of brain stimulation on neural activity. Design considerations like this one might be fundamental to improving the efficacy of future interventions such as the use of deep brain stimulation for the treatment of Parkinson's disease and for the use of transcranial magnetic stimulation for the treatment of major depressive disorder.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Able to provide informed consent
  • History of medically intractable epilepsy
  • Speak and understand English
  • For the stimulation session, the participant must have electrodes in the relevant locations

Exclusion Criteria:

  • Current diagnosis of other neurological illnesses including ischemic stroke, intracerebral hemorrhage, brain neoplasm
  • Major systemic illness
  • Severe cognitive impairment - diagnosed by clinician in neuropsychiatric evaluation
  • Severe psychiatric illness
  • Excessive use of alcohol or other substances
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Frontal Stimulation
Direct Cortical Stimulation (DCS) in alpha and theta frequencies is applied through electrodes located in the frontal cortex.
Device: Direct cortical stimulation (DCS) Alpha
Rhythmic alpha stimulation
Other Names:
  • CereStim M96
Device: Direct cortical stimulation (DCS) Theta
Rhythmic theta stimulation applied
Other Names:
  • CereStim M96
Device: Sham Direct cortical stimulation (DCS)
Arrhythmic stimulation paradigm applied
Other Names:
  • CereStim M96
Sham Comparator: 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.
Device: Sham Direct cortical stimulation (DCS)
Arrhythmic stimulation paradigm applied
Other Names:
  • CereStim M96
Device: Direct cortical stimulation (DCS) In-Phase Theta
Rhythmic in-phase theta stimulation applied
Other Names:
  • CereStim M96
Device: Direct cortical stimulation (DCS) Anti-Phase Theta
Rhythmic anti-phase theta stimulation applied
Other Names:
  • CereStim M96

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Working Memory Task Performance - Pashler's working memory capacity metric (k)
Time Frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
The participant will be presented with three colored squares in both visual fields during a practice session. Then the participant is presented with an informative retro-cue, an arrow to the left or right, that is 100% predictive of the upcoming probe, or an uninformative neural cue, an arrow pointing in both directions. Finally, in the probe epoch participants are presented with an array of squares on the left or the right side of the screen. Participants must determine if the array of colored squares is the same or different from those held in memory. Performance will be defined as: k=N*(HR*FA)/(1-FA) where N is the number of the items that are held in memory. HR is the hit rate defined as the percent correct for trials where the probe does not match the encoding array. FA is the false alarm rate defined as the percent incorrect for trials where the probe does match the encoding array.
During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Change in Working Memory Task Performance - Reaction Time
Time Frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
The participant will be presented with three colored squares in both visual fields during a practice session. Then the participant is presented with an informative retro-cue, an arrow to the left or right, that is 100% predictive of the upcoming probe, or an uninformative neural cue, an arrow pointing in both directions. Finally, in the probe epoch participants are presented with an array of squares on the left or the right side of the screen. Participants must determine if the array of colored squares is the same or different from those held in memory. Reaction times will be quantified in milliseconds.
During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Intracranial EEG Multi-taper fft
Time Frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Time-frequency analysis of electrophysiology data will be performed using methods like multi-taper fft. This will be compared between sham (arrhythmic) and stimulation trials to identify if stimulation enhances neuronal entrainment.
During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Intracranial EEG weighted phase lag index (wPLI)
Time Frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Functional connectivity will be measured using weighted phase lag index (WPLI). To calculate WPLI, first Morlet wavelet convolution is performed to extract instantaneous phase and amplitude for the frequency of interest for the two target sites. Next, the cross-spectral density is calculated (one signal multiplied by the complex conjugate of the other). From the cross-spectral density the imaginary component of the resulting signal is extracted. Then those imaginary values are averaged over the time frame of instance (here, the second half of the stimulation train). Finally, the magnitude of the resulting vector is taken to be the wPLI. This metric quantifies the consistency of phase lag between the two target regions and is weighted towards signals with a 90 or 270 degree offset to address a common confound in electrophysiology, volume conduction.
During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intracranial EEG Wavelets
Time Frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Spectral analysis and functional connectivity analysis of electrophysiology data will be performed using methods like wavelets. This will be compared between sham (arrhythmic) and stimulation trials to identify if stimulation enhances neuronal entrainment.
During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Intracranial EEG phase locking
Time Frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Spectral analysis and functional connectivity analysis of electrophysiology data will be performed using methods like phase locking. This will be compared between sham (arrhythmic) and stimulation trials to identify if stimulation enhances neuronal entrainment.
During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Intracranial EEG Granger causality
Time Frame: During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Spectral analysis and functional connectivity analysis of electrophysiology data will be performed using methods like Granger causality. This will be compared between sham (arrhythmic) and stimulation trials to identify if stimulation enhances neuronal entrainment.
During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of North Carolina, Chapel Hill

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Flavio Frohlich, PhD, UNC Chapel Hill

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2024

Primary Completion (Estimated)

January 31, 2027

Study Completion (Estimated)

January 31, 2027

Study Registration Dates

First Submitted

February 1, 2024

First Submitted That Met QC Criteria

February 1, 2024

First Posted (Actual)

February 9, 2024

Study Record Updates

Last Update Posted (Actual)

April 22, 2026

Last Update Submitted That Met QC Criteria

April 20, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23-1652
  • 5R01MH124387 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

IPD Sharing Time Frame

beginning 9 and continuing for 36 months following publication

IPD Sharing Access Criteria

Investigator has approved IRB, IEC, or REB and an executed a data use/sharing agreement with UNC.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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