Effects of early ketamine exposure on cerebral gray matter volume and functional connectivity

Abstract

Ketamine has been used for medical purposes, most typically as an anesthetic, and recent studies support its use in the treatment of depression. However, ketamine tends to be abused by adolescents and young adults. In the current study, we examined the effects of early ketamine exposure on brain structure and function. We employed MRI to assess the effects of ketamine abuse on cerebral gray matter volume (GMV) and functional connectivity (FC) in 34 users and 19 non-users, employing covariates. Ketamine users were categorized as adolescent-onset and adult-onset based on when they were first exposed to ketamine. Imaging data were processed by published routines in SPM and AFNI. The results revealed lower GMV in the left precuneus in ketamine users, with a larger decrease in the adolescent-onset group. The results from a seed-based correlation analysis show that both ketamine groups had higher functional connectivity between left precuneus (seed) and right precuneus than the control group. Compared to controls, ketamine users showed decreased GMV in the right insula, left inferior parietal lobule, left dorsolateral prefrontal cortex/superior frontal gyrus, and left medial orbitofrontal cortex. These preliminary results characterize the effects of ketamine misuse on brain structure and function and highlight the influence of earlier exposure to ketamine on the development of the brain. The precuneus, a structure of central importance to cerebral functional organization, may be particularly vulnerable to the influences of early ketamine exposure. How these structural and functional brain changes may relate to the cognitive and affective deficits remains to be determined with a large cohort of participants.

Figure 1

T-score map shows significant smaller gray matter volume in ketamine users than general adults. The clusters were calculated by Monte Carlo simulation with all significant criteria corrected to p_alpha < .05. Bottom bar graph shows that ketamine users have decreased effect in the right insula, left inferior parietal lobule, left dorsolateral prefrontal cortex, and left medial orbitofrontal cortex. The significance level of the analyses were corrected with age, gender, and years of education as covariates. ***LSD-corrected p < .001. **LSD-corrected p < 0.01. (Both post hoc tests follow analysis of covariance).

Figure 2

T-score map showing significant functional connectivity differences between ketamine users and healthy adults. The clusters were calculated by Monte Carlo simulation with all significant criteria corrected to p_alpha < .05. Bottom bar graph shows that ketamine users have greater effect in the left DLPFC-right IFG, left DLPFC-right STG, left MOFC-right insula, and left MOFC-right ITG. The significance level of the analyses were corrected with age, gender, and years of education as covariates. ***LSD-corrected p < .001. (Post hoc test follow analysis of covariance).

Figure 3

F-score map showing significant differences in left precuneus for the three groups according to ketamine use onset time. The first bar graph shows the adolescent-onset group has decreased gray matter volume in left precuneus compared to the other groups (bottom left). The differences remain after controlling for years of ketamine usage (bottom right). All of the above results were corrected for multiple comparison with all significant criteria corrected to p_alpha < .05.

Figure 4

F-score map showing significant functional connectivity differences from left precuneus to right precuneus for the three groups. The first bar graph shows that the adolescent-onset group and the adult-onset group have significantly higher functional connectivity than the control group (bottom left). The group differences do not exist after controlling for years of ketamine usage (bottom right). All of the above results were corrected for multiple comparison with all significant criteria corrected to p_alpha < .05.