Using Direct Brain Stimulation to Study Cognitive Electrophysiology

Study Overview
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Brief Summary
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This project forms a multi-site research collaboration to carry out verbal and spatial memory experiments in patient volunteers to better understand the neural bases of human memory, employing direct electrical brain stimulation as a tool to study those dynamics and their relationship to memory performance.

Detailed Description
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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.

Official Title
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Using Direct Brain Stimulation to Study Cognitive Electrophysiology

Conditions
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Epilepsy Intractable

Intervention / Treatment
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* Other: Direct electrical stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be enrolled who are expected to undergo intracranial electroencephalographic monitoring as part of a standard clinical procedure for the treatment of pharmacologically resistant epilepsy. Exclusion Criteria: The following individuals will be excluded: Any cognitive impairments that would limit their ability to participate in the memory testing, Any physical disability that would limit their ability to perform cognitive tasks within normal limits, Any psychiatric condition that would limit their ability to provide informed consent or to perform cognitive tasks within normal limits, Any medical condition that would, in the investigator's opinion, limit the subject's participation in the study, Who are pregnant, Unable or unwilling to provide informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: All enrolled patients are considered eligible to receive direct electrical stimulation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Direct Electrical Stimulation<br>Stimulation will be applied concurrently with the task, if applicable, and stimulation trials will be interleaved with sham trials, where no stimulation is delivered. | Other: Direct electrical stimulation<br>* Stimulation lasting from 500 to 2000 milliseconds on bipolar target electrode pairs at one of two target frequencies (e.g. 10 Hz and 200 Hz), up to 1.5 milliamperes in amplitude on depth contacts and 3.5 milliamperes in amplitude on surface contacts. (Pulse shape - Charge-balanced biphasic rectangular pulses with pulse width of 300 microseconds in duration per phase).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Memory performance | To measure memory performance, participants will perform a custom episodic memory task (verbal, spatial), with performance compared between sham and stimulation trials to identify if stimulation modulates memory. The primary outcome measure is memory performance, such as the percentage of recalled items. | Up to 4 weeks (typical duration of hospital stay) | 
| Intracranial electrophysiological recordings: Intracranial Electroencephalogram (iEEG), Spectral Power | Spectral power will be compared between sham and stimulation trials to identify whether stimulation modulates neuronal biomarkers of memory. Spectral power is measured in microvolts squared. | Up to 4 weeks (typical duration of hospital stay) | 
| Intracranial electrophysiological recordings: Intracranial Electroencephalogram (iEEG), Synchrony | Phase and power based synchrony of iEEG data (across or within electrodes) will be compared between sham and stimulation trials to identify whether stimulation modulates neuronal biomarkers of memory. Synchrony can be measured as the length of a resultant vector in complex space and the correlation [-1 to 1] between two time series. | Up to 4 weeks (typical duration of hospital stay) | 
| Intracranial electrophysiological recordings: Unit Activity, Firing Rate | Analysis of unit activity data collected on microwire electrodes will be performed, with firing rates compared between sham and stimulation trials to identify if stimulation modulates the inhibitory-excitatory balance as reflected by decreased or increased firing rates. Firing rate is measured in Hz. | Up to 4 weeks (typical duration of hospital stay) | 
| Intracranial electrophysiological recordings: Unit Activity, Synchrony | Synchrony of spike trains collected on microwire electrodes will be compared between sham and stimulation trials to identify if stimulation modulates neuronal biomarkers of memory. Synchrony will be measured between different neurons and with the phase of the ongoing local field potential. Synchrony can be measured as the length of a resultant vector in complex space and as the correlation [-1 to 1] between two time series. | Up to 4 weeks (typical duration of hospital stay) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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episodic memory