Memory Retrieval and Encoding Investigated by Neural Stimulation (MEMREINS)

November 4, 2024 updated by: University of Pennsylvania
The purpose of this research is to understand biomarkers of human memory through correlational analyses and to use focal electrical stimulation as a causal manipulation to understand how biomarkers of memory relate to other brain states and behavioral measures.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

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

The study protocol outlines fundamental experiments to understand the neural dynamics underlying human memory and use direct brain stimulation as a tool (intervention) to study the relationship between those dynamics and memory performance. The investigators will collect recording and stimulation data from 250 patient volunteers as they perform carefully-matched verbal and spatial memory tasks. During non-stimulation sessions, the investigators will measure correlative neural biomarkers of memory encoding and retrieval using standard clinical depth electrodes and micro-wire recordings. To test the causal role of these biomarkers, the investigators will employ direct brain stimulation to briefly modulate neural activity, and measure ensuing changes in behavioral performance. With a set of causal biomarkers and predictive models in hand, the investigators will finally ask whether model-driven stimulation paradigms offer the investigators the ability to reliably modulate neural activity, and consequent behavior, in real-time.

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.
800

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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado, Denver
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institute of Neurological Disorders and Stroke
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03766
        • Dartmouth-Hitchcock Medical Center
    • New York
      • New York, New York, United States, 10027
        • Columbia University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio

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

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Expected to undergo intracranial implantation and postoperative electroencephalographic monitoring as part of a standard clinical procedure for the treatment of pharmacologically resistant epilepsy
  2. Age 18 or older

Exclusion Criteria:

  1. Any physical or cognitive disability or illness that would limit their ability to perform cognitive tasks
  2. Any medical condition that would, in the investigator's opinion, limit the subject's participation in the study.
  3. Unable or unwilling to provide informed consent
  4. MRI contraindications

Standard clinical care includes a pregnancy test for female patients prior to the surgical implantation of the electrodes. Pregnant women are not surgically implanted.

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: N/A
  • Interventional Model: Single Group 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: Direct Electrical Stimulation
Stimulation will be applied concurrently with the task, if applicable, and stimulation trials will be interleaved with sham trials, where no stimulation is delivered.
Device: Direct electrical stimulation
Stimulation will not exceed 0.75 mA and will be approved prior by study investigators. Each subject will have a safety threshold testing at the beginning of each session and if 'afterdischarges' occur the subject's stimulation threshold will be lowered.

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
To use direct electrical stimulation to disentangle causal versus correlative biomarkers of verbal and spatial episodic memory
Time Frame: Up to 4 weeks (typical duration of hospital stay)
1. We will use linear mixed effects models and L2-penalized logistic regression classifiers to compare periods of successful and unsuccessful performance in our tasks
Up to 4 weeks (typical duration of hospital stay)
To develop and test models of human brain dynamics in the presence of electrical stimulation
Time Frame: Up to 4 weeks (typical duration of hospital stay)
2. We will compare spectral indices of brain activity before and after stimulation as a function of stimulation parameters.
Up to 4 weeks (typical duration of hospital stay)
To assess how reactivation of prior memories shapes subsequent recall and memory organization, including memory for the content, context and value of experiences.
Time Frame: Up to 4 weeks (typical duration of hospital stay)
3. We will mathematical models of neural similarity described in detail in Halpern (2024) and Manning (2011, 2012) to test the reactivation mechanisms described in Lohnas et al. (2014) and Healey and Kahana (2015).
Up to 4 weeks (typical duration of hospital stay)
To determine whether state-dependent stimulation can separately be used to modulate encoding and retrieval processes
Time Frame: Up to 4 weeks (typical duration of hospital stay)
4. We will evaluate the closed-loop stimulation protocol described in Kahana et al. (2023) in both encoding and retrieval.
Up to 4 weeks (typical duration of hospital stay)
To determine whether stimulation is more effective at modulating memory when targeted to regions with specific connectivity profiles to the medial temporal lobe
Time Frame: Up to 4 weeks (typical duration of hospital stay)
5. We will compare recall rates during a free recall experiment with brain stimulation at sites with high network-mediated activation, as described in Solomon et al. (2018), versus low network-mediated activation.
Up to 4 weeks (typical duration of hospital stay)
To determine how simultaneous stimulation at multiple target sites can be optimized to modulate memory
Time Frame: Up to 4 weeks (typical duration of hospital stay)
6. We will compare recall rates during a free recall experiment with no brain stimulation, stimulation at one site, and stimulation at multiple sites.
Up to 4 weeks (typical duration of hospital stay)

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 Pennsylvania

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.
Columbia University
National Institute of Neurological Disorders and Stroke (NINDS)

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: Michael Kahana, PhD, University of Pennsylvania

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)

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.
October 12, 2014

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.
December 31, 2024

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.
December 31, 2024

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).
February 24, 2020

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.
February 24, 2020

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.
February 27, 2020

Study Record Updates

Last Update Posted (Estimated)

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.
November 5, 2024

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.
November 4, 2024

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.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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.
  • 820553
  • 1U01NS113198-01 (U.S. NIH Grant/Contract)
  • 5R01NS106611-05 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified data will be shared in a public repository at regular intervals during the project. De-identified data sets will be anonymized prior to posting on the public repository. These de-identified data are likely to be analyzed for secondary purposes other than those described in this protocol (e.g. seizure prediction). Shared data will include, at a minimum, digital spreadsheets used to summarize all participant behavioral data. De-identified electrophysiology data, demographic information, electrode localization information, and task information (e.g. timing of each trial, timing of responses) will be shared in a central repository. Descriptions of the tasks and stimuli will be shared. De-identified references to individual participant data may also appear in scientific journal publications or presented at scientific meetings.

IPD Sharing Time Frame

Study data will become available within six months of publication of the relevant results, with no planned expiration.

IPD Sharing Access Criteria

Data is freely available, will require a formal request for access.

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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