Abstract

Ketamine is a non-competitive anatognist of the N-methyl-d-aspartate (NMDA) receptor commonly used as an anesthetic and analgesic. In sub-anesthetic doses, it can induce temporary psychotic symptoms and has served as a pharmacological model for schizophrenia. While its acute effects on brain and behavior have been studied, the effects of long-term exposure to ketamine on brain activity have been largely unexplored. In this study, we aimed to examine such effects on spontaneous brain dynamics measure using resting-state functional magnetic resonance imaging (fMRI). Forty-one patients with ketamine dependence and forty-four healthy control subjects were imaged with BOLD fMRI using a 3.0-Tesla Siemens scanner at the Magnetic Resonance Center of Hunan Provincial People's Hospital, analyzed with the regional homogeneity (ReHo) method. Compared with healthy controls, decreased ReHo was found in ketamine users in the right anterior cingulate cortex and increased ReHo was found in left precentral frontal gyrus (p<0.05, cluster-level corrected). We also observed negative correlations between increased ReHo in precentral frontal gyrus and estimated total lifetime ketamine consumption and ketamine craving levels. To our knowledge, this is the first study the long-term effects of ketamine exposure on brain functional activity. Our findings indicate that ketamine dependence is associated with alterations in the functional connectivity of medial and lateral prefrontal cortices.

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