Memory Retrieval and Encoding Investigated by Neural Stimulation

Epilepsy Intractable Clinical Trial

— MEMREINS  

Official title:

Memory Retrieval and Encoding Investigated by Neural Stimulation

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04286776
• Other study ID #: 820553
• Secondary ID: 1U01NS113198-015
• Status: Enrolling by invitation
• Phase: N/A
• Start date: October 12, 2014
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2024
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 800
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Drug Resistant Epilepsy
• Epilepsy Intractable

Intervention

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.

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	University of Colorado, Denver	Aurora	Colorado
United States	National Institute of Neurological Disorders and Stroke	Bethesda	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Columbia University	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (3)

Lead Sponsor	Collaborator
University of Pennsylvania	Columbia University, National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Ezzyat 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. — View Citation

Kragel 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)