Memory Replay

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.

Down syndrome is a chromosomal abnormality associated with significant deficits across multiple cognitive domains, including a disproportionate deficit in hippocampally-dependent memory. In other words, individuals with Down syndrome may have a particular difficulty remembering specific details from past events. One way this manifests itself is in overgeneral autobiographical memory, or a tendency to remember the general gist of an event or cluster of events, rather than a single, isolated event. This overgeneral memory makes it difficult for individuals with Down syndrome to access their past, can interfere with attempts to becoming more independent, and increases anxiety and depression. In the current VIRTUAL study, the investigators test whether a new digital memory prosthetic-HippoCamera-can enhance specific autobiographical memory in individuals with Down syndrome. In HippoCamera, users are asked to record and replay events from their daily lives. This replay is curated by a research-based algorithm in HippoCamera that optimizes consolidation of these events over time and has been shown to enhance memory specificity in other populations with memory impairments, particularly those that stem from hippocampal disfunction. It is, therefore, likely that similar enhancements in autobiographical memory specificity will be identified in individuals with Down syndrome, highlighting the benefits of this applications in this population.