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

NCT07378332 | Enrolling By Invitation DMC

• 1 other identifier: IRB24-0486
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Memory Performance; Hippocampal Activity

Outcome Measures

Primary Outcomes (3)

• Power of theta-band hippocampal iEEG activity

  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

  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

  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.

Study Arms (3)

TMS stimulation using HITS

EXPERIMENTAL

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

DES stimulation using HITS parameters

EXPERIMENTAL

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

Normative model of DES

EXPERIMENTAL

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

Interventions

DES electrical stimulation parameters during cognitive and memory demands OTHER

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.

DES stimulation using HITS parameters; Normative model of DES

TMS electrical stimulation parameters during cognitive and memory demands OTHER

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.

TMS stimulation using HITS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

Sponsors & Collaborators

• University of Chicago: lead
• Northwestern University, Chicago, IL: collaborator
• Washington University School of Medicine: collaborator

Study Sites (3)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

Study Officials

• Joel Voss, PhD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2026
• First Posted: January 30, 2026
• Study Start: September 15, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: January 30, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)