Effect of Subanesthetic Ketamine on Intrinsic Functional Brain Connectivity

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 con- nectivity). In this study, the effect of low-dose S(?)-ket- amine 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 connec- tivity was measured. In addition, heat pain tests were per- formed 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 impor- tantly in the cerebellum and visual cortex in relation to the medial visual network. A decrease in connectivity was ob- served in the auditory and somatosensory network in relation to regions responsible for pain sensing and the affective pro- cessing of pain, which included the amygdala, insula, and anterior cingulate cortex. Connectivity variations related to fluctuations in pain scores were observed in the anterior cin- gulate 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.