Towards Causal Mapping of Episodic Memory iEEG Networks Via Multi-method Brain Stimulation

January 26, 2026 updated by: University of Chicago
Human intracranial electroencephalography (EEG) can provide brain-activity correlates of memory with high spatial and temporal resolution. This project will test functional relevance of these neural signals for memory behavioral performance using novel noninvasive and invasive stimulation methods. Findings will advance understanding of brain mechanisms for memory, as is needed to accelerate progress in the treatment of memory disorders.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Episodic memory impairment occurs when diseases impact the hippocampus and its network of interacting brain areas. Better understanding of brain mechanisms for memory is required to development treatments. This project will develop experimental approaches that use stimulation to manipulate brain-behavior relationships in humans and thereby directly test how the hippocampal network supports memory. Intracranial electroencephalography (iEEG) provides opportunities to study the neural basis of memory with high spatial and temporal resolution. Many experiments have identified iEEG signals associated with memory, for instance by comparing instances of memory success to failure. However, the functional relevance of these signals remains unclear, as such comparisons can identify signals of extraneous, co-occurring, cognitive processes. A routine approach to address this limitation in the behavioral neurosciences is via bi-directional manipulations, i.e., exogenous enhancement or inhibition of the putative neural process and tests of corresponding enhancement or inhibition of behavioral performance. This approach has been underutilized in human iEEG memory research, in part due to difficulties in reliably influencing memory or neural signals given currently available manipulations, such as direct electrical stimulation (DES) through iEEG electrodes. As a route to achieve bi-directional manipulation experiments in human iEEG memory research, this project utilizes a noninvasive electromagnetic stimulation tool that reliably and robustly influences hippocampal network activity and memory performance, called "hippocampal indirectly targeted stimulation" (HITS). HITS will be used with iEEG for the first time to identify activity patterns of the hippocampal network related to memory behavioral performance enhancement versus impairment. To rigorously test for behavioral relevance, we will use a closed-loop machine-learning approach to identify DES parameters that reproduce the hippocampal-network iEEG activity patterns generated by HITS, and then test whether delivery of DES to enhance or inhibit these hippocampal-network iEEG activity patterns produces corresponding enhancement versus impairment of memory behavioral performance. Thus, bidirectional manipulation will be used to directly/causally test iEEG signals of memory behavior. Group-level modeling of DES parameters that mimic the effects of HITS will be used to broaden the accessibility of bidirectional manipulations for future research that tests memory mechanisms in larger iEEG samples across multiple sites that lack the technical capability for HITS. Across three sites, will test whether bi-directional manipulations of hippocampal-network activity involvement in memory performance are more successful for HITS-informed DES versus DES based on a priori hypotheses. This exploratory project will thus build a foundation for future studies to rigorously test hippocampal-network support of memory behavioral performance using bi-directional experimental manipulations and will establish a collaboration of multidisciplinary researchers across multiple institutions to perform this innovative mechanistic memory research.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
44

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
    • Missouri
      • St Louis, Missouri, United States, 63130
        • Washington University in St. Louis

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18+ years old
  • Native English speakers
  • Normal or corrected-to-normal near and far vision

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: TMS stimulation using HITS
Hippocampal indirectly targeted stimulation (HITS) will be applied in patients with epilepsy undergoing intracranial electroencephalography (iEEG) monitoring. iEEG signals of episodic memory behavioral performance will be obtained from clinical macroelectrodes and research microelectrodes in a specialized memory task involving encoding and retrieval of naturalistic scenes along with eye-movement tracking. Memory behaviors of interest will include recollection during old/new decisions and spatiotemporal replay of eye-movement patterns. HITS will be applied for ~2 s immediately before each scene onset during encoding, using parameters that have yielded enhanced versus impaired performance in this experiment design
Other: TMS electrical stimulation parameters during cognitive and memory demands
Study conditions will involve electrical stimulation delivered through non-invasive TMS. These different stimulation parameters will include the presence of stimulation (no stimulation versus stimulation) and the location of stimulation.
Experimental: DES stimulation using HITS parameters
We will test the behavioral significance of iEEG correlates of memory enhancement and impairment using a rigorous approach involving DES. Direct electrical stimulation (DES) parameters will be identified that reproduce as closely as possible the iEEG signatures of memory enhancement or impairment caused by HITS. This will be accomplished using a closed-loop machine learning approach to maximize the similarity of the iEEG signals evoked by DES and the iEEG signals evoked by HITS, during memory encoding.
Other: DES electrical stimulation parameters during cognitive and memory demands
Study conditions will involve direct electrical stimulation delivered through implanted iEEG electrodes. These different stimulation parameters will include the presence of stimulation (no stimulation versus stimulation) and the location of stimulation across the same electrode or a different electrode.
Experimental: Normative model of DES
We will develop, test, and refine for future experiments a normative model of DES parameters to achieve experimental bi-directional manipulation of iEEG correlates of episodic memory. We will identify common features of the DES parameters that were algorithmically determined to mimic the iEEG signals of memory enhancement or impairment by HITS in the Experiment 2 dataset. Analyses will account for individual differences in stimulated electrode locations, in iEEG functional connectivity of stimulated electrodes, in the success of behavioral modification, and in the accuracy of mimicking the iEEG effects of HITS, to enable predictions about how to apply DES parameters in stimulation-naïve subjects given their idiosyncratic electrode placements and brain activity patterns.
Other: DES electrical stimulation parameters during cognitive and memory demands
Study conditions will involve direct electrical stimulation delivered through implanted iEEG electrodes. These different stimulation parameters will include the presence of stimulation (no stimulation versus stimulation) and the location of stimulation across the same electrode or a different electrode.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Power of theta-band hippocampal iEEG activity
Time Frame: Measured during the performance of the task while research activities are completed. Measurement will take 2 to 4 hours on a single day
iEEG is used to measure local brain electrical activity evoked by task conditions. We will record and analyze the power of theta-band hippocampal iEEG activity
Measured during the performance of the task while research activities are completed. Measurement will take 2 to 4 hours on a single day
iEEG activity between hippocampus and the stimulated electrode
Time Frame: Measured during the performance of the task while research activities are completed. Measurement will take 2 to 4 hours on a single day
iEEG is used to measure local brain electrical activity evoked by task conditions. We will record and analyze the synchrony of iEEG activity between hippocampus and the stimulated electrode.
Measured during the performance of the task while research activities are completed. Measurement will take 2 to 4 hours on a single day
Memory task performance
Time Frame: The memory task is administered before, during and/or after stimulation from transcranial magnetic stimulation (TMS) or direct electrical stimulation (DES). The memory task will take 2 to 4 hours in a single day.
Subjects attempt to discriminate studied from novel (foil) scenes and object images
The memory task is administered before, during and/or after stimulation from transcranial magnetic stimulation (TMS) or direct electrical stimulation (DES). The memory task will take 2 to 4 hours in a single day.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Chicago

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Washington University School of Medicine
Northwestern University, Chicago, IL

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Joel Voss, PhD, University of Chicago

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 15, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 16, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 30, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 30, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB24-0486

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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