In brief
- A Yale team used fMRI to measure how ketamine alters the precision of spatial working memory in 40 healthy adults.
- Under the influence of ketamine, neural tuning when locating a stimulus widens, and this broadening is associated with poorer task performance.
- This is a mechanistic study involving healthy volunteers; it does not measure clinical treatment or outcomes.
A study published in Biological Psychiatry offers a concrete explanation for why ketamine makes it difficult to remember the location of an object. According to the authors at the Yale University School of Medicine, the drug causes populations of neurons to respond less specifically to a location, and this “widening” is linked to poorer results in spatial memory tasks.
What was measured
Working memory is the ability to hold information in mind for a few seconds, such as the position of an object that has just disappeared. Ketamine blocks NMDA glutamate receptors, and previous work with humans has already shown that this blockade reduces brain activation during tasks and decreases spatial memory precision.
What was missing, according to the paper, was empirical confirmation in humans of a hypothesis derived from animal studies and computational models of cortical circuits: that blocking these receptors impairs memory because neurons lose spatial selectivity. Measuring individual neurons in humans is not feasible non-invasively, so the team combined pharmacological manipulation with functional magnetic resonance imaging (fMRI) and computational models. Instead of focusing only on how much a brain region “lights up,” they modeled how a population of neurons represents each position.
What they found
Forty healthy adults participated in the study. Under the influence of ketamine, spatial neural tuning widened in visual perception and working memory networks, and this widening was linked to worse performance in spatial working memory. The authors also highlight that the changes in tuning were more consistent across individuals and brain regions than changes in the magnitude of activation, which points to an effect shared by location-sensitive areas.
The paper’s abstract presents this as the first empirical evidence in humans linking altered neural tuning to NMDA antagonism and the impairment of spatial working memory. This is a claim made by the authors themselves.
What it implies
The value of this work is primarily explanatory. It provides a concrete mechanism for a cognitive effect of ketamine that has been known for some time, and the authors relate it to the working memory deficits frequently seen in psychiatric disorders such as schizophrenia. Understanding the mechanism, they note, is key to designing better treatments for those deficits.
It is important to read these findings within their limits. The sample size is 40 healthy people and the task is laboratory-based; the study does not evaluate clinical or recreational doses, the duration of effects after the session, or consequences in daily life. Furthermore, this is not a study on depression, so it says nothing about antidepressant efficacy. For those interested in the clinical side, we have gathered the rest of the evidence in our Ketamine and Dissociatives Guide, and regarding another recent mechanism, you can see our news report on the habenula and the speed of ketamine’s antidepressant effect.
Source
- Rahmati M, Anticevic A et al. Ketamine Alters Tuning of Neural and Behavioral Spatial Working Memory Precision. Biological Psychiatry, published online September 28, 2026.
Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.
