Effect of Subanesthetic Ketamine on Intrinsic Functional Brain Connectivity

Low-dose S(+)-ketamine alters the brain's intrinsic large-scale functional connectivity, as measured by resting-state fMRI. In twelve healthy men, ketamine increased connectivity in the cerebellum and visual cortex while decreasing connectivity in auditory and somatosensory networks, including regions involved in pain sensing and affective processing such as the amygdala, insula, and anterior cingulate cortex. Pain-related connectivity changes occurred in areas responsible for descending pain inhibition, including the anterior cingulate cortex, insula, orbitofrontal cortex, and brainstem. These connectivity changes correspond to ketamine's known effects on analgesia, psychedelic experiences, and other side effects.

Study at a glance

Abstract

Background The influence of psychoactive drugs on the central nervous system has been investigated with positron emission tomography and task-related functional magnetic resonance imaging. However, it is not known how these drugs affect the intrinsic large-scale interactions of the brain (resting-state functional magnetic resonance imaging connectivity). In this study, the effect of low-dose S(+)-ketamine on intrinsic brain connectivity was investigated. Methods Twelve healthy, male volunteers received a 2-h intravenous S(+)-ketamine infusion (first hour 20 mg/70 kg, second hour 40 mg/70 kg). Before, during, and after S(+)-ketamine administration, resting-state brain connectivity was measured. In addition, heat pain tests were performed between imaging sessions to determine ketamine-induced analgesia. A mixed-effects general linear model was used to determine drug and pain effects on resting-state brain connectivity. Results Ketamine increased the connectivity most importantly in the cerebellum and visual cortex in relation to the medial visual network. A decrease in connectivity was observed in the auditory and somatosensory network in relation to regions responsible for pain sensing and the affective processing of pain, which included the amygdala, insula, and anterior cingulate cortex. Connectivity variations related to fluctuations in pain scores were observed in the anterior cingulate cortex, insula, orbitofrontal cortex, and the brainstem, regions involved in descending inhibition of pain. Conclusions Changes in connectivity were observed in the areas that explain ketamine's pharmacodynamic profile with respect to analgesia and psychedelic and other side effects. In addition, pain and ketamine changed brain connectivity in areas involved in endogenous pain modulation.