Memory Retrieval and Encoding Investigated by Neural Stimulation
MEMREINS
3 other identifiers
interventional
800
1 country
11
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Oct 2014
Longer than P75 for not_applicable
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 12, 2014
CompletedFirst Submitted
Initial submission to the registry
February 24, 2020
CompletedFirst Posted
Study publicly available on registry
February 27, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2024
CompletedNovember 5, 2024
November 1, 2024
10.2 years
February 24, 2020
November 4, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
To use direct electrical stimulation to disentangle causal versus correlative biomarkers of verbal and spatial episodic memory
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
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.
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
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
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
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)
Study Arms (1)
Direct Electrical Stimulation
EXPERIMENTALStimulation will be applied concurrently with the task, if applicable, and stimulation trials will be interleaved with sham trials, where no stimulation is delivered.
Interventions
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.
Eligibility Criteria
You may qualify if:
- Expected to undergo intracranial implantation and postoperative electroencephalographic monitoring as part of a standard clinical procedure for the treatment of pharmacologically resistant epilepsy
- Age 18 or older
You may not qualify if:
- Any physical or cognitive disability or illness that would limit their ability to perform cognitive tasks
- Any medical condition that would, in the investigator's opinion, limit the subject's participation in the study.
- Unable or unwilling to provide informed consent
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Pennsylvanialead
- National Institute of Neurological Disorders and Stroke (NINDS)collaborator
- Columbia Universitycollaborator
Study Sites (11)
University of Colorado, Denver
Aurora, Colorado, 80045, United States
Emory University Hospital
Atlanta, Georgia, 30322, United States
National Institute of Neurological Disorders and Stroke
Bethesda, Maryland, 20892, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03766, United States
Columbia University
New York, New York, 10027, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
UT Southwestern Medical Center
Dallas, Texas, 75390, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Related Publications (3)
Ezzyat Y, Kragel JE, Solomon EA, Lega BC, Aronson JP, Jobst BC, Gross RE, Sperling MR, Worrell GA, Sheth SA, Wanda PA, Rizzuto DS, Kahana MJ. Functional and anatomical connectivity predict brain stimulation's mnemonic effects. bioRxiv [Preprint]. 2023 Aug 11:2023.07.27.550851. doi: 10.1101/2023.07.27.550851.
PMID: 37609181BACKGROUNDEzzyat Y, Wanda PA, Levy DF, Kadel A, Aka A, Pedisich I, Sperling MR, Sharan AD, Lega BC, Burks A, Gross RE, Inman CS, Jobst BC, Gorenstein MA, Davis KA, Worrell GA, Kucewicz MT, Stein JM, Gorniak R, Das SR, Rizzuto DS, Kahana MJ. Closed-loop stimulation of temporal cortex rescues functional networks and improves memory. Nat Commun. 2018 Feb 6;9(1):365. doi: 10.1038/s41467-017-02753-0.
PMID: 29410414BACKGROUNDKragel JE, Ezzyat Y, Lega BC, Sperling MR, Worrell GA, Gross RE, Jobst BC, Sheth SA, Zaghloul KA, Stein JM, Kahana MJ. Distinct cortical systems reinstate the content and context of episodic memories. Nat Commun. 2021 Jul 21;12(1):4444. doi: 10.1038/s41467-021-24393-1.
PMID: 34290240BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michael Kahana, PhD
University of Pennsylvania
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 24, 2020
First Posted
February 27, 2020
Study Start
October 12, 2014
Primary Completion
December 31, 2024
Study Completion
December 31, 2024
Last Updated
November 5, 2024
Record last verified: 2024-11
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- Study data will become available within six months of publication of the relevant results, with no planned expiration.
- Access Criteria
- Data is freely available, will require a formal request for access.
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.