Neuronal Mechanisms of Learning and Utilizing Abstract Representations

The purpose of this study is to examine how memories of past experiences are used to guide behavior in novel situations through the cognitive process of abstraction. This project examines how abstract representations are learned, whether and how they support generalization to novel situations, and whether and how they support analogical reasoning.

Study Overview

• Status: Not yet recruiting
• Conditions: Epilepsy Intractable
• Intervention / Treatment: Behavioral: Cedrus RB-844 response pad; Adtech Behnke-Fried micro-electrodes; Neurolynx electrophysiology system; Blackrock Cerestim stimulator

Detailed Description

Despite the importance of abstraction for human cognition, little is known about the underlying mechanisms and their disruption by disease or injury. The goal of this research is to develop a circuit-level understanding of abstraction to enable the development of new treatments for the devastating effects of cognitive disorders in which abstraction fails. As part of this study, investigators will conduct experiments that utilize the rare opportunity to record in-vivo from human single neurons simultaneously in multiple brain areas in patients undergoing treatment for drug resistant epilepsy.

Researchers will investigate three overarching hypotheses on the neural substrate of abstraction. Aim 1: to determine the dynamics of learning abstract representations. Aim 2: to decipher how abstract representations facilitate generalization. Aim 3: to decipher how abstract representations facilitate analogical reasoning.

The expected outcomes of this work are a characterization of how abstract neural representations are formed, how they enable generalization to novel stimuli and tasks, and how they enable analogical reasoning.

Participants in this study are patients undergoing invasive monitoring for suspected focal epilepsy with depth electrodes. Subjects will conduct a variety of cognitive tests on a computer placed in front of them during their hospital stay. Participating hospitals in this study are Cedars-Sinai, UC Davis, and Barrow Neurological Institute.

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mia Coordinator; Phone Number: 424-315-2642; Email: mia.mazer@cshs.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
      • Contact: Mia Coordinator; Phone Number: 424-315-2642; Email: mia.mazer@cshs.org
      • Principal Investigator: Adam Mamelak, MD
      • Principal Investigator: Ueli Rutishauser, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Intractable epilepsy, undergoing invasive monitoring
• Age ≥18
• Full Scale Intelligence Quotient > 70
• Ability to comprehend and perform simple behavioral tasks by pressing buttons on laptop computer in response to questions.

Exclusion Criteria:

• Determination by clinicians and investigators that a patient is unable to complete the behavioral tasks required for the protocol due to either cognitive limits, psychological limits, or pain.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Behavioral Testing; Behavioral testing and neuronal recordings	Behavioral: Cedrus RB-844 response pad; Adtech Behnke-Fried micro-electrodes; Neurolynx electrophysiology system; Blackrock Cerestim stimulator; Devices listed are components of a single intervention that includes: Record patient responses (Cedrus RB-844), record neuronal activity (Neurolynx) from electrodes (Adtech Behnke-Fried), apply intermittent electrical stimulation (Blackrock Cerestim)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuronal population activity	Proportion of experiment sessions in which abstract representation emerged following successful learning of the task by the subject.	3 years
Facilitation of generalization	Strength of correlation between the presence of abstract representations at the neuronal level and the subjects ability to perform generalization.	3 years
Effect of electrical stimulation	Proportion of experiment sessions in which electrical stimulation to the hippocampus disrupted abstract representations.	3 years

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Collaborators: University of California, Los Angeles; Columbia University; University of California, Davis; National Institute on Deafness and Other Communication Disorders (NIDCD); Barrow Neurological Institute
• Investigators: Principal Investigator: Ueli Rutishauser, PhD, Cedars-Sinai Medical Center; Principal Investigator: Adam Mamelak, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Epilepsy; Memory; Decision-making; Depth Electrode
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Drug Resistant Epilepsy; Epilepsy
• Other Study ID Numbers: Study00000572 Part 1; R61DC022835 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No