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Updated: Jul 14, 2025

The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System
Published on: April 25, 2012
Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological
Sophia Linguiti1, Jacob W Vogel2, Valerie J Sydnor1
1Penn Lifespan Informatics and Neuroimaging Center (PennLINC), Philadelphia, PA, United States; Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.
Abstract:
Functional magnetic resonance imaging (fMRI) is increasingly used to non-invasively study the acute impact of psychedelics on the human brain. While fMRI is a promising tool for measuring brain function in response to psychedelics, it also has known methodological challenges. We conducted a systematic review of fMRI studies examining acute responses to experimentally administered psychedelics in order to identify convergent findings and characterize heterogeneity in the literature. We reviewed 91 full-text papers; these studies were notable for substantial heterogeneity in design, task, dosage, drug timing, and statistical approach. Data recycling was common, with 51 unique samples across 91 studies. Fifty-seven studies (54%) did not meet contemporary standards for Type I error correction or control of motion artifact. Psilocybin and LSD were consistently reported to moderate the connectivity architecture of the sensorimotor-association cortical axis. Studies also consistently reported that ketamine administration increased activation in the dorsomedial prefrontal cortex. Moving forward, use of best practices such as pre-registration, standardized image processing and statistical testing, and data sharing will be important in this rapidly developing field.
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