Cholinergic Enhancement of Theta

Study Summary

The goal of this study is to learn about the effects of Cobenfy KarXT (xanomeline and trospium chloride) on episodic memory processing, including specific effects on areas of the brain involved in memory and changes it may have on brain activity. The investigators will do this by testing epileptic patients who are already undergoing intracranial surgery for seizure monitoring, and measuring the activity from the brain areas being assessed. The main questions it aims to answer are 1) whether Cobenfy KarXT changes memory activity based on its agonist effect on muscarinic receptors and acetylcholine, and 2) what the nature of these brain activity changes are. This work builds on previous experiments evaluating cholinergic antagonists. Participants will complete two treatment arms. One of these will be with the drug, and the other will be with a placebo pill, so that the participants are unaware which session the actual drug has been received. Patients will complete a verbal serial recall and/or associative recognition task each of the two days. An anesthesiologist or patient nurse will administer either the drug or the placebo at a critical point which addresses both of the research questions. Researchers will compare the brain activity between the two treatment arms to determine what brain activity changes, and whether there is an additional behavioral effect on memory.

Primary Outcome

Memory-related changes in brain electrical activity in participants from baseline at post-intervention (approx. within 1-3 hrs) is measured by comparing the Free recall memory tasks with the electrical readings collected across all bandwidths, but focusing on primarily theta power and oscillatory changes. Other changes, such as phase amplitude coupling, may also be considered.

Interventions

• DRUG Placebo
• DRUG COBENFY KarXT (50/20 mg)