Understanding Prefrontal and Medial Temporal Neuronal Responses to Algorithmic Cognitive Variables in Epilepsy Patients

Epilepsy Clinical Trial

Official title:

Mapping Algorithmic State Space in the Human Brain

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05283811
• Other study ID #: H18112
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2021
• Est. completion date: March 31, 2026

Study information

• Verified date: June 2024
• Source: Baylor College of Medicine
• Contact: Sameer Sheth, MD, PhD
• Phone: 713-798-5060
• Email: sasheth[@]bcm.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Humans have a remarkable ability to flexibly interact with the environment. A compelling demonstration of this cognitive flexibility is human's ability to respond correctly to novel contextual situations on the first attempt, without prior rehearsal. The investigators refer to this ability as 'ad hoc self-programming': 'ad hoc' because these new behavioral repertoires are cobbled together on the fly, based on immediate demand, and then discarded when no longer necessary; 'self-programming' because the brain has to configure itself appropriately based on task demands and some combination of prior experience and/or instruction. The overall goal of our research effort is to understand the neurophysiological and computational basis for ad hoc self-programmed behavior. The previous U01 project (NS 108923) focused on how these programs of action are initially created. The results thus far have revealed tantalizing notions of how the brain represents these programs and navigates through the programs. In this proposal, therefore, the investigators focus on the question of how these mental programs are executed. Based on the preliminary findings and critical conceptual work, the investigators propose that the medial temporal lobe (MTL) and ventral prefrontal cortex (vPFC) creates representations of the critical elements of these mental programs, including concepts such as 'rules' and 'locations', to allow for effective navigation through the algorithm. These data suggest the existence of an 'algorithmic state space' represented in medial temporal and prefrontal regions. This proposal aims to understand the neurophysiological underpinnings of this algorithmic state space in humans. By studying humans, the investigators will profit from our species' powerful capacity for generalization to understand how such state spaces are constructed. The investigators therefore leverage the unique opportunities available in human neuroscience research to record from single cells and population-level signals, as well as to use intracranial stimulation for causal testing, to address this challenging problem. In Aim 1 the investigators study the basic representations of algorithmic state space using a novel behavioral task that requires the immediate formation of unique plans of action. Aim 2 directly compares representations of algorithmic state space to that of physical space by juxtaposing balanced versions of spatial and algorithmic tasks in a virtual reality (VR) environment. Finally, in Aim 3, the investigators test hypotheses regarding interactions between vPFC and MTL using intracranial stimulation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 205
• Est. completion date: March 31, 2026
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 64 Years

Eligibility

Inclusion Criteria:

• Eligible subjects include both male and female patients, between 10 years of age and 64 years of age, who undergo placement of intracranial electrodes for clinical characterization of epilepsy.

Exclusion Criteria:

• Grounds for exclusion would include inability to understand and follow instructions, or inability to concentrate sufficiently to achieve a high proportion of correct responses.

Related Conditions & MeSH terms

• Epilepsy

Intervention

Device:
• NEUROPACE RNS SYSTEM
This device is indicated as a therapy in reducing the frequency of seizures in individuals

Behavioral:
• EMU
Patients are admitted to the Epilepsy Monitoring Unit for observation of seizure activity prior to further treatment

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Utah	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Baylor College of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Behavioral performance (Accuracy as fraction of correct responses)	Patients will be asked to perform a few different novel, computerized tasks where the patients must respond to on-screen stimuli using button presses. Behavior will be assessed in terms of the accuracy of these responses.	7-14 days of behavioral performance collection
Primary	Neurophysiological activity (single-neuron activity in spikes/second)	While patients are performing each behavioral task, the investigators will measure neural activity from BlackRock using depth electrodes with the aim of isolating single-neuron activity (for patients in the EMU) and local-field potential activity (for patients in the RNS patients). Neurophysiological activity will be analyzed with the aim of understanding the neural representations underlying cognitive performance during the task.	7-14 days of neural activity collection