Human Cognition During Surgery: Stimulation-based and Cholinergic Modulation

Summary

This is a research study to determine how COBENFY KarXT (FDA approved), a drug which has been approved for treatment of certain disorders, affects brain activity and cognitive tasks which may be regulated by the cholinergic system.

This study aims to answer: 1) how cholinergic circuitries act during task performance in humans, and 2) develop a better understanding of how cognitive control interacts with learning, memory and decision making in the setting of cholinergic manipulation.

Participants will complete a single treatment arm, regardless of which surgical procedure they are to receive. An anesthesiologist or other clinical staff will administer either the drug or the saline at a critical point which addresses the research questions, prior to patient surgery. This will be either with the drug, or the placebo pill. Half of the participants will be randomized to receive the drug, and the other half of these the placebo. Participants will be unaware whether the actual drug has been received.

Essential tremor patients who participate will complete a cognitive task during an awake surgery. Epilepsy patients who participate will have a resting state recording during the procedure from the deep cortical layers of the brain. A probe will be used during the surgery to measure the effects of this drug and other procedures of the study on the cholinergic system. This probe is the clinical probe known as the AlphaOmega, which is FDA approved for standard of care procedures.

Researchers will compare the brain activity between treatment arms to determine what brain activity changes based on the cholinergic manipulation.

Conditions

• Epilepsy
• Essential Tremor
• Seizures
• Memory Consolidation
• Memory Disorders
• Memory Replay
• Memory Encoding
• Cognitive Control
• Motor Abilities

Interventions

DRUG

Cobenfy KarXT pill (50/20 mg)

Subjects will receive Cobenfy KarXT pill (50/20 mg) 2 hours prior to surgery.

DRUG

Placebo

Subjects will receive placebo pill (equivalent of 50/20mg) 2 hours prior to surgery.

Sponsors & Collaborators

• Peter O'Donnell Jr. Brain Institute

  collaborator UNKNOWN

• University of Texas Southwestern Medical Center

  lead OTHER

Principal Investigators

• Bradley C Lega, MC · University of Texas Southwestern Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-10-31

Primary Completion

2030-09-30

Completion

2030-09-30

FDA Drug

Yes

Countries

• United States

Study Locations