Cue-Induced Brain Activation in Chronic Ketamine-Dependent Subjects, Cigarette Smokers, and Healthy Controls: A Task Functional Magnetic Resonance Imaging Study

Abstract

BackgroundObservations of drug-related cues may induce craving in drug-dependent patients, prompting compulsive drug-seeking behavior. Sexual dysfunction is common in drug users. The aim of the study was to examine regional brain activation to drug (ketamine, cigarette smoking) associated cues and natural (sexual) rewards.MethodsA sample of 129 [40 ketamine use smokers (KUS), 45 non-ketamine use smokers (NKUS) and 44 non-ketamine use non-smoking healthy controls (HC)] participants underwent functional magnetic resonance imaging (fMRI) while viewing ketamine use related, smoking and sexual films.ResultsWe found that KUS showed significant increased activation in anterior cingulate cortex and precuneus in response to ketamine cues. Ketamine users (KUS) showed lower activation in cerebellum and middle temporal cortex compared with non-ketamine users (NKUS and HC) in response to sexual cues. Smokers (KUS and NKUS) showed higher activation in the right precentral frontal cortex in response to smoking cues. Non-ketamine users (NKUS and HC) showed significantly increased activation of cerebellum and middle temporal cortex while viewing sexual cues.ConclusionThese findings clearly show the engagement of distinct neural circuitry for drug-related stimuli in chronic ketamine users. While smokers (both KUS and NKUS) showed overlapping differences in activation for smoking cues, the former group showed a specific neural response to relevant (i.e., ketamine-related) cues. In particular, the heightened response in anterior cingulate cortex may have important implications for how attentionally salient such cues are in this group. Ketamine users (KUS) showed lower activation in response to sexual cues may partly reflect the neural basis of sexual dysfunction.

Brain Changes Associated With Long-Term Ketamine Abuse, A Systematic Review

“…We included 16 studies in our review, totaling 440 chronic ketamine users with a mean ketamine use of 2-9.7 years and 2.4 grams per day, compared to 259 drug-free controls and 44 poly-drug controls. Five studies were based on the same sample (Liao et al, 2010(Liao et al, , 2011(Liao et al, , 2012(Liao et al, , 2016(Liao et al, , 2018. The included studies described structural gray matter and white matter differences, differences in brain functionality and differences in neurotransmitter receptor binding.…”

“…Because of these heterogenous results, we could not perform a quantitative bias analysis. Bias could play a role, since the 5 studies by Liao et al (2010Liao et al ( , 2011Liao et al ( , 2012Liao et al ( , 2016Liao et al ( , 2018 were based on the same sample. For that reason, we compared the results if four of these five studies were left out of the analysis, to the situation in which all five studies were included.…”

“…They found a higher activation in the anterior cingulate cortex (ACC) in response to ketamine cues. Also, ketamine subjects showed lower activation in the cerebellum and the middle temporal cortex in response to natural rewarding (sexual) cues (Liao et al, 2018). Li et al (2017) assessed resting-state functional connectivity of the subgenual anterior cingulate cortex (sgACC) in relation to depression scores of 36 chronic ketamine users with an average ketamine use of 4.9 years (dose not reported) compared to 20 drug-free controls.…”

Non-Opioid Anesthetics Addiction: A Review of Current Situation and Mechanism

“…The rsFC can provide a valuable tool for exploring large-scale brain networks and their interactions and identifying the neural circuit disorders behind SUD [ 121 , 123 ]. Using fMRI, we found that ketamine could significantly increase neuronal activity, especially in the PFC, anterior cingulate cortex, precuneus, and precentral frontal gyrus [ 99 , 100 , 101 ]. Chronic ketamine use can also alter rsFC, especially in the thalamus, basal ganglia, and higher cortex [ 97 ].…”

Neurobiological mechanisms and related clinical treatment of addiction: a review

“…Imaging studies found that cannabis, cocaine, and heroin users all showed abnormal activation in the anterior insula, DLPFC, and inferior parietal lobe compared with healthy control participants using a cue-induced craving task (Zilverstand et al ., 2018 ). One study found ketamine addicts exhibited increased activation in the anterior cingulate gyrus and precuneus than healthy control when exposed to ketamine-related clips, while the anterior central frontal gyrus was mainly activated under smoking-related cues (Liao et al ., 2018a ).…”