Detecting Neuroplastic Effects Induced by Ketamine in Healthy Human Subjects: A Multimodal Imaging Approach

Ketamine is increasingly recognized for its rapid and sustained antidepressant effects, but the biological mechanisms responsible for these long-lasting benefits remain incompletely understood.

Authors: Claudio Agnorelli, Joseph Peill, Gabriela Sawicka, Danielle Kurtin, Ekaterina Shatalina, Kirran Ahmad, Matthew B. Wall, Catarina Rua, Kate Godfrey, Natalie Ertl, Graham Searle, Katie Zhou, Martin Osugo, Brandon Weiss, Kyle T. Greenway, Andrea Fagiolini, Robin Carhart-Harris, Paul M. Matthews, Eugenii A. Rabiner, David Nutt, and David Erritzoe

In this study, researchers used integrated PET/MRI, magnetic resonance spectroscopy (MRS), and resting-state fMRI to investigate molecular, cellular, and network-level changes occurring after a single psychedelic dose of ketamine in healthy volunteers.

Although no statistically significant group-level increase in synaptic density markers was observed, ketamine administration produced sustained increases in anterior cingulate cortex glutamate levels and altered functional connectivity between key brain regions. Multimodal analyses also revealed relationships between synaptic plasticity markers and changes in default mode network activity, highlighting the DMN as a potential hub through which ketamine may reorganize brain function. These findings provide new insights into the mechanisms of psychedelic-induced neuroplasticity and demonstrate the value of integrated imaging approaches for studying emerging neuropsychiatric therapies.

Why Read This Publication?

• Reveal the Brain-Wide Effects of Ketamine: Discover how PET, MRS, and fMRI were combined to capture molecular and functional changes associated with ketamine-induced neuroplasticity.
• Gain New Insights into Default Mode Network Remodeling: Learn how alterations in glutamate signaling and functional connectivity may contribute to ketamine’s sustained therapeutic effects and reshape brain hierarchies.
• See the Power of Multimodal Imaging in Psychiatry Research: Explore a proof-of-concept study demonstrating how integrated PET/MRI approaches can advance the understanding of psychedelic and neuropsychiatric therapies.

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