Cecilia Lee, Illustrations Editor

A Yale researcher has received a grant from the Yale Swebilius Pilot Research Program in Epilepsy to study the effects of ketamine in individuals with epilepsy. 

Sarah Fineberg, an assistant professor of psychiatry at the Yale School of Medicine and an attending psychiatrist at the Connecticut Mental Health Center, will be the principal investigator of a study investigating the impact of ketamine, a short-acting anesthetic, on individuals suffering from epilepsy. Collaborators on the study include Eyiyemisi Damisah, assistant professor of neurosurgery and neuroscience; Alfred Kaye, assistant professor of psychiatry; and John Krystal, professor and chair of the department of psychiatry.

“I love doing work at the intersection of patient experience and neurobiology,” Fineberg said. “This project directly relates experiences that patients can feel and describe to basic elements of neural function.” 

It was in the mid-90s when Krystal, alongside his colleagues, was able to identify that the drug ketamine had the potential to exhibit antidepressant effects. Now, Fineberg hopes to further evaluate ketamine’s antidepressant effects by studying them in relation to individuals with a history of seizures. Since arriving at Yale in 2010 after completing a MD-PhD program at the University of Iowa, Fineberg has focused on clinical research in the context of studying mood symptoms, particularly in groups that have been historically excluded from psychiatric studies, such as individuals with epilepsy.

Studying the neural mechanisms of such disorders as they occur in the brain can be difficult due to the skull acting as a barrier, according to Krystal. To overcome this obstacle, non-invasive neuroimaging techniques, such as EEG or MRI, are used to study brain activity. Still, direct electrical recording of brain activity remains essential. In the case of Fineberg’s study, the team plans to seek out individuals who have previously been treated with chronic intracranial electrodes to help manage their seizures. In doing so, the researchers hope to utilize the intracranial electrodes to measure the participants’ neural signals after taking ketamine to determine how they relate to the emotional states of the participants, as well as how their seizures are responding to the drug. 

“I am thrilled to work with Drs. Fineberg and Damisah and their team in a study that will, for the first time, record directly from human brain circuits as they are exposed to ketamine and relate the ketamine effects to improvements in depression,” Krystal said. “This could shed light on the underlying biology and potentially provide new biomarkers of depression and its treatment.” 

Using these chronic intracranial electrodes could provide crucial insights into the effects that occur after ketamine dosing. Dissociation, or the state of feeling disconnected from the passage of time or one’s own body or thoughts, is a common side effect of taking ketamine. Monitoring the neural signals of the participants in the one to two hour window that dissociation generally takes place in could be essential to deriving its neural basis and in turn, developing a better understanding of both ketamine and depression in the context of epilepsy. 

“Recognition of knowledge of the nonmotor manifestations of epilepsy holds inherent value for the well-being of these patients,” said Shanae Aerts GRD ’26, a graduate student in the interdepartmental neuroscience program at Yale’s Blumenfeld lab — which studies the relationship between consciousness and epilepsy. “By nature, symptoms like depression are more difficult to see yet can have a large impact on quality of life.” 

The initial research into the antidepressant effects of ketamine in the 1990s helped lay the groundwork for the development of the antidepressant Esketamine, commonly known as Spravato, by Janssen Pharmaceuticals.