Frontal cortical tissue composition in abstinent cocaine abusers: a magnetic resonance imaging study

Abstract

Cocaine abusers exhibit impairment of executive cognitive functions that are mediated by the frontal cortex. This work tested for structural (i.e., tissue composition) abnormalities that may underlie such performance deficits. Research participants were cocaine abusers (n = 14) abstinent for 20 days and a non-drug-using comparison group (n = 11), who underwent magnetic resonance imaging (T1-weighted scans of the brain). Gray matter and white matter tissue densities were determined using voxel-based morphometry with small volume correction based on a priori hypotheses derived from functional imaging of the same subjects. Cocaine abusers had significantly lower gray matter tissue density than did the non drug users in 10 of 13 small volumes analyzed in the frontal cortex [bilateral anterior cingulate gyrus (infragenual and perigenual regions) and medial orbitofrontal cortex and the lateral orbitofrontal cortex and middle/dorsal cingulate gyrus in the right hemisphere]. No group differences were found in white matter density of the frontal cortex. These results extend our previous findings of defective frontal cortical activation (indexed by cerebral blood flow) in cocaine abusers to include abnormalities in gray matter tissue density in the same frontal cortical regions.

Introduction

The possible effects of cocaine on brain function and structure have generated much research interest in recent years, especially with the increased application of neuroimaging techniques, such as positron emission tomography (PET) and magnetic resonance (MR) imaging, to study drug abuse. The use of MR imaging to provide information about brain structure has, in the past few years, begun to provide preliminarily evidence of differences in brain structure and tissue composition in cocaine users compared with non drug users Bartzokis et al 2000a, Bartzokis et al 2000b, Bartzokis et al 2001, Bartzokis et al 2002, Fein et al 2002, Franklin et al 2002a, Jacobsen et al 2001a, Jacobsen et al 2001b, Lim et al 2002, Liu et al 1998, O’Neill et al 2001. Several of the studies have identified such differences in the frontal cortex.

The prefrontal region of the frontal cortex has been implicated in a number of the so-called “executive” functions, including focusing or sustaining of attention, decision-making, and response inhibition (see Stuss and Levine, 2002). Cocaine-dependent individuals have exhibited deficits in executive functions that are mediated by the prefrontal cortex Bolla et al 1998, Bolla et al 2000, Di Sclafani et al 2002, Fein et al 2002, and we have used PET with H₂¹⁵O to show abnormalities in brain activation in cocaine abusers while they perform tasks that require such functions (Bolla et al., in press; Bolla et al., submitted). Compared with non drug users, cocaine abusers exhibit more activation of the right orbitofrontal cortex and less activation of the left medial and right lateral prefrontal cortex during performance of the Iowa Gambling Task (Bolla et al., in press), which involves decision-making (Bechara et al., 1994). The same cocaine abusers showed less activation than the non drug users in the left anterior cingulate gyrus and right lateral prefrontal cortex and greater activation in the right anterior cingulate gyrus during performance of the Stroop Interference Task (Bolla et al., submitted), which requires selective attention with response inhibition (Stroop, 1935).

To relate these functional impairments to possible structural abnormalities in the brains of cocaine-abusing individuals, we used voxel-based morphometry Ashburner and Friston 2000, Wright et al 1995 to assess tissue composition of the frontal cortex. Voxel-based morphometry is a relatively new approach to MR analysis that offers the advantages of being automated and nonbiased, while leaving observed differences in tissue composition subject to interpretation (see Discussion). Using this method of analysis, we determined both gray matter density and white matter density in the same research subjects that participated in our PET blood flow studies. We hypothesized that cocaine abusers would show differences in tissue composition compared to non-drug-abusing individuals and that these differences would be reflected in lower gray matter tissue density in regions of the frontal cortex, where cocaine abusers demonstrated abnormalities in cerebral blood flow during performance of tasks related to executive function (Bolla et al., in press; Bolla et al., submitted). The regions selected for study, therefore, included the anterior cingulate gyrus, lateral prefrontal cortex, and medial and lateral areas of the orbitofrontal cortex.

Previous structural MR imaging studies of cocaine abusers have generally reported smaller volume of the frontal cortex in cocaine abusers than in non drug users Bartzokis et al 2000a, Bartzokis et al 2001, Fein et al 2002, Liu et al 1998, O’Neill et al 2001, but have not examined specific regions based on functional imaging data from the same group of subjects. In addition, a previous study that compared cocaine abusers with a non-drug-using group used voxel-based morphometry (whole-brain analysis) to assess gray matter and white matter densities (Franklin et al., 2002a). That analysis identified the insula, temporal cortex, and frontal regions including the anterior cingulate gyrus and medial orbitofrontal cortex as areas where the cocaine abusers had lower gray matter density. Using a priori hypotheses derived from our PET activation studies, the present work generally confirmed these findings in the frontal cortical regions and extended them to show deficits in both medial and lateral areas of the orbitofrontal cortex and middle/dorsal region of the cingulate gyrus of the right hemisphere and bilaterally, the perigenual region of the anterior cingulate gyrus.