Causal Role of Top-Down Theta Oscillations in Prioritization
Modulating Oscillations and Working Memory in Patients With Subdural Electrodes
2 other identifiers
interventional
50
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Jul 2024
Typical duration for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 1, 2024
CompletedFirst Posted
Study publicly available on registry
February 9, 2024
CompletedStudy Start
First participant enrolled
July 1, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2027
April 22, 2026
April 1, 2026
2.6 years
February 1, 2024
April 20, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Change in Working Memory Task Performance - Pashler's working memory capacity metric (k)
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
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-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)
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 Outcomes (3)
Intracranial EEG Wavelets
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
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
During the 1- to 1.5-hour test at Baseline and Stimulation Session conducted over a 1 to 2 day period
Study Arms (2)
Frontal Stimulation
ACTIVE COMPARATORDirect Cortical Stimulation (DCS) in alpha and theta frequencies is applied through electrodes located in the frontal cortex.
Frontal Parietal Stimulation
SHAM COMPARATORDirect Cortical Stimulation (DCS) in in-phase and anti-phase theta frequencies is applied through electrodes located in the frontal and parietal cortex.
Interventions
Rhythmic alpha stimulation
Rhythmic theta stimulation applied
Arrhythmic stimulation paradigm applied
Rhythmic in-phase theta stimulation applied
Rhythmic anti-phase theta stimulation applied
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Related Publications (2)
Alagapan S, Riddle J, Huang WA, Hadar E, Shin HW, Frohlich F. Network-Targeted, Multi-site Direct Cortical Stimulation Enhances Working Memory by Modulating Phase Lag of Low-Frequency Oscillations. Cell Rep. 2019 Nov 26;29(9):2590-2598.e4. doi: 10.1016/j.celrep.2019.10.072.
PMID: 31775030BACKGROUNDAlagapan S, Lustenberger C, Hadar E, Shin HW, FrÓ§hlich F. Low-frequency direct cortical stimulation of left superior frontal gyrus enhances working memory performance. Neuroimage. 2019 Jan 1;184:697-706. doi: 10.1016/j.neuroimage.2018.09.064. Epub 2018 Sep 27.
PMID: 30268847BACKGROUND
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Flavio Frohlich, PhD
UNC Chapel Hill
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 1, 2024
First Posted
February 9, 2024
Study Start
July 1, 2024
Primary Completion (Estimated)
January 31, 2027
Study Completion (Estimated)
January 31, 2027
Last Updated
April 22, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- beginning 9 and continuing for 36 months following publication
- Access Criteria
- Investigator has approved IRB, IEC, or REB and an executed a data use/sharing agreement with UNC.
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.