Epilepsy Intractable
Conditions
Keywords
episodic memory
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.
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.
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Columbia University
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
All enrolled patients are considered eligible to receive direct electrical stimulation. Subjects have the option to receive non stimulation testing only.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To use direct electrical stimulation to disentangle causal versus correlative biomarkers of verbal and spatial episodic memory | 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 |
| To develop and test models of human brain dynamics in the presence of electrical stimulation | 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. |
| To assess how reactivation of prior memories shapes subsequent recall and memory organization, including memory for the content, context and value of experiences. | 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). |
| To determine whether state-dependent stimulation can separately be used to modulate encoding and retrieval processes | 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. |
| To determine whether stimulation is more effective at modulating memory when targeted to regions with specific connectivity profiles to the medial temporal lobe | 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. |
| To determine how simultaneous stimulation at multiple target sites can be optimized to modulate memory | 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. |
Countries
United States
Outcome results
None listed