Clinical trial NCT04286776: Memory Retrieval and Encoding Investigated by Neural Stimulation
Official title: Memory Retrieval and Encoding Investigated by Neural Stimulation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Epilepsy Intractable
Keywords: episodic memory
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Columbia University
First posted: 2020-02-27
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All enrolled patients are considered eligible to receive direct electrical stimulation. Subjects have the option to receive non stimulation testing only.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: To use direct electrical stimulation to disentangle causal versus correlative biomarkers of verbal and spatial episodic memory
timeFrame: Up to 4 weeks (typical duration of hospital stay)
measure: To develop and test models of human brain dynamics in the presence of electrical stimulation
timeFrame: Up to 4 weeks (typical duration of hospital stay)
measure: To assess how reactivation of prior memories shapes subsequent recall and memory organization, including memory for the content, context and value of experiences.
timeFrame: Up to 4 weeks (typical duration of hospital stay)
measure: To determine whether state-dependent stimulation can separately be used to modulate encoding and retrieval processes
timeFrame: Up to 4 weeks (typical duration of hospital stay)
measure: To determine whether stimulation is more effective at modulating memory when targeted to regions with specific connectivity profiles to the medial temporal lobe
timeFrame: Up to 4 weeks (typical duration of hospital stay)
measure: To determine how simultaneous stimulation at multiple target sites can be optimized to modulate memory
timeFrame: Up to 4 weeks (typical duration of hospital stay)
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Bethesda
country: United States
facility: National Institute of Neurological Disorders and Stroke
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Columbia University
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: University of Pennsylvania
name: Michael Kahana, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.