Detecting neuroplastic effects induced by ketamine in healthy human subjects: A multimodal approach

TY - JOUR

T1 - Detecting neuroplastic effects induced by ketamine in healthy human subjects

T2 - A multimodal approach

AU - Agnorelli, Claudio

AU - Peill, Joseph

AU - Sawicka, Gabriela

AU - Kurtin, Danielle

AU - Shatalina, Ekaterina

AU - Ahmad, Kirran

AU - Wall, Matthew B

AU - Rua, Catarina

AU - Godfrey, Kate

AU - Ertl, Natalie

AU - Searle, Graham

AU - Zhou, Katie

AU - Osugo, Martin

AU - Weiss, Brandon

AU - Greenway, Kyle T

AU - Fagiolini, Andrea

AU - Carhart-Harris, Robin

AU - Matthews, Paul M

AU - Rabiner, Eugenii A

AU - Nutt, David

AU - Erritzoe, David

PY - 2026/3/21

Y1 - 2026/3/21

N2 - We investigated ketamine’s neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1–8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven male participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (glutamate and GABA) and resting-state fMRI (intrinsic brain activity, functional connectivity), before and after ketamine. While group-level analyses showed no significant increases in PET synaptic markers, ketamine administration resulted in significantly elevated glutamate levels within the anterior cingulate cortex (ACC). Functional connectivity analyses revealed reduced coupling between the ACC and the dorsolateral prefrontal cortex (dlPFC) and increased coupling between the ACC and the amygdala in the days following ketamine administration. Our multimodal analysis revealed that participants showing an increase in [11C]-UCBJ volume distribution (VT), a putative index of synaptic plasticity, showed a correlated reduction in intrinsic activity within regions belonging to the default mode network (DMN). By linking molecular, cellular and network-level changes, our results point to the DMN as a central hub where ketamine may reshape brain hierarchies in the long term, providing new directions for understanding its therapeutic mechanisms and developing targeted treatments.

AB - We investigated ketamine’s neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1–8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven male participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (glutamate and GABA) and resting-state fMRI (intrinsic brain activity, functional connectivity), before and after ketamine. While group-level analyses showed no significant increases in PET synaptic markers, ketamine administration resulted in significantly elevated glutamate levels within the anterior cingulate cortex (ACC). Functional connectivity analyses revealed reduced coupling between the ACC and the dorsolateral prefrontal cortex (dlPFC) and increased coupling between the ACC and the amygdala in the days following ketamine administration. Our multimodal analysis revealed that participants showing an increase in [11C]-UCBJ volume distribution (VT), a putative index of synaptic plasticity, showed a correlated reduction in intrinsic activity within regions belonging to the default mode network (DMN). By linking molecular, cellular and network-level changes, our results point to the DMN as a central hub where ketamine may reshape brain hierarchies in the long term, providing new directions for understanding its therapeutic mechanisms and developing targeted treatments.

UR - https://www.scopus.com/pages/publications/105033487761

U2 - 10.1177/0271678X261431447

DO - 10.1177/0271678X261431447

M3 - Article

SN - 0271-678X

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

ER -