Frontal white matter abnormalities following chronic ketamine use: a diffusion tensor imaging study

Abstract

Ketamine abuse has been shown to have a deleterious impact on brain function. However, the precise mechanisms of ketamine dependence-induced pathological change remain poorly understood. Although there is evidence for white matter changes in drug abuse, the presence of white matter abnormalities in chronic ketamine users has not been studied. White matter volumes were measured using in vivo diffusion tensor magnetic resonance imaging data in 41 ketamine-dependent subjects and 44 drug-free healthy volunteers. White matter changes associated with chronic ketamine use were found in bilateral frontal and left temporoparietal cortices. There was also evidence that frontal white matter fractional anisotropy correlated with the severity of drug use (as measured by estimated total ketamine consumption). We provide direct evidence for dose-dependent abnormalities of white matter in bilateral frontal and left temporoparietal regions following chronic ketamine use. The findings suggest a microstructural basis for the changes in cognition and experience observed with prolonged ketamine use. Moreover, the similarities of these changes to those observed in chronic schizophrenia have implications for the glutamate model of this illness.

Abnormalities in White Matter Microstructure Associated with Chronic Ketamine Use

“…The other previous study of white matter abnormalities in ketamine users found bilateral frontal cortex differences in FA, but also differences in the left temporoparietal cortex (Liao et al, 2010). The differences between that study and our findings could be because of several factors.…”

“…We also examined whether the variation across individuals in the mean D P within each cluster was associated with total lifetime ketamine use, recency of ketamine use, or scores on the OLIFE and DES questionnaires using the bivariate correlation analysis (using an adjusted alpha level of 0.01 because of multiple comparisons). However, this did not reveal any significant correlations between the ketamine-use data or questionnaire scores, in contrast to the only other investigation of chronic ketamine use and white matter microstructure (Liao et al, 2010).…”

“…We also found evidence that dissociative symptoms in ketamine users were related to differences in connectivity between the caudate and the prefrontal cortex. To date, there has only been one report examining white matter structure in chronic ketamine users (Liao et al, 2010). This identified three areas where FA differed in ketamine users compared with controls, located bilaterally in the frontal cortex.…”

“…Liao et al reported significant reductions in FA in the bilateral frontal cortex and the left temporoparietal cortex in chronic ketamine users compared with controls. Individual variability in the level of FA in the frontal cortex was found to correlate negatively with lifetime ketamine consumption (Liao et al, 2010). Another study also reported decreased bilateral frontal gray matter volume in chronic ketamine users (Liao et al, 2011).…”

“…A recent study explored whether chronic ketamine users exhibited changes in brain white matter microstructure using magnetic resonance diffusion tensor imaging (DTI) (Liao et al, 2010). This technique uses the passive diffusion of water molecules in the brain tissue to infer properties of the underlying microarchitecture (Basser et al, 1994).…”