Ketamine Alters Tuning of Neural and Behavioral Spatial Working Memory Precision
Masih Rahmati, Flora Moujaes, Nina Purg Suljič, Jie Lisa Ji, Lucie Berkovitch, Kangjoo Lee, Clara Fonteneau, Charles Schleifer, Brendan Adkinson, Aleksandar Savič, Nicole Santamauro, Zailyn Tamayo, Caroline Diehl, Antonija Kolobaric, Morgan Flynn, Terry Camarro, Clayton E. Curtis, Grega Repovš, Sarah K. Fineberg, Peter T Morgan, Katrin H. Preller, John H. Krystal, John D. Murray, Youngsun T. Cho, Alan Anticevic
bioRxiv Preprint Server February 10, 2025 preprint DOI: 10.1101/2025.02.10.637233 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pharmacological fMRI study |
|---|---|
| Population | Healthy humans |
| Intervention | Ketamine |
| Topics | Esketamine Ketamine |
| Keywords | Memory deficits:memory problems Poorer memory Memory impairment Memory loss Spatial tuning Neural precision Brain function Brain circuit disruptions Brain disorders:neurological conditions Cognitive disorders Neuropharmacology:drug effects Psychopharmacology Cognitive modulators Neuroimaging:brain imaging FMRI Brain scans |
| Citations | 1 |
| Key points | Ketamine broadens neural spatial tuning, attenuates activation across multiple brain regions, and worsens spatial working memory performance in healthy humans. |
Abstract
Deficits in working memory (WM) are a hallmark of neuropsy-chiatric disorders such as schizophrenia, yet their neurobiological basis remains poorly understood. Glutamate N-methyl-D-aspartate receptors (NMDARs) are critical for spatial WM (sWM), with NMDAR antagonist ketamine known to attenuate task-evoked activation and reduce sWM accuracy. Cortical microcircuit models hypothesize that NMDAR antagonism impairs sWM by broadening neural spatial tuning, but this mechanism has not been directly tested in humans. Using a pharmacological fMRI approach, we showed how ketamine broadened neural spatial tuning, attenuated activation across visual, parietal, and frontal areas, and worsened sWM performance in healthy humans. Ketamine-induced changes in tuning were more consistent across individuals and brain regions than changes in overall activation and correlated with individual differences in sWM performance. These findings provide empirical evidence linking NMDAR antagonism to disruptions in cortical microcircuit dynamics, the resulting neural tuning alterations, and sWM impairments, advancing frameworks for therapeutic development.
Comparable studies
Other experimental studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine activates psychosis and alters limbic blood flow in schizophrenia Schizophrenic individuals | 1995 | Experimental study | |
| The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine Healthy participants | 2019 | Controlled experimental study | n = 15 |
| Ketamine Increases Human Motor Cortex Excitability to Transcranial Magnetic Stimulation Normal human subjects | 2003 | Experimental study | n = 7 |
| Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Human participants | 2015 | Experimental study | |
| Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment‐resistant bipolar depression Patients with treatment-resistant bipolar depression | 2012 | Population pharmacokinetic analysis | n = 9 |
Citations in the library
Cites 6
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Elife October 25, 2018
- Glutamate and the Neural Basis of the Subjective Effects of Ketamine Archives of General Psychiatry February 1, 2008
- Linking Microcircuit Dysfunction to Cognitive Impairment: Effects of Disinhibition Associated with Schizophrenia in a Cortical Working Memory Model Cerebral Cortex November 29, 2012
- Ketamine induces multiple individually distinct whole-brain functional connectivity signatures. Elife April 17, 2024
and 1 more in the library