Effect of subanesthetic ketamine on intrinsic functional brain connectivity: a placebo-controlled functional magnetic resonance imaging study in healthy male volunteers.
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.
Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
Marieke
M
Niesters
Najmeh
N
Khalili-Mahani
Christian
C
Martini
Leon
L
Aarts
Joop
J
van Gerven
Mark A
MA
van Buchem
Albert
A
Dahan
Serge
S
Rombouts
D000328:Adult; D000778:Anesthetics, Dissociative / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D003627:Data Interpretation, Statistical; D006213:Hallucinogens / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D007649:Ketamine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000033:anatomy & histology* / Q000187:drug effects*; D010146:Pain / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects; D016037:Single-Blind Method; D055815:Young Adult
D000778:Anesthetics, Dissociative; D006213:Hallucinogens; D007649:Ketamine; C033419:norketamine