Deformation-based morphometry of brain changes in alcohol dependence and abstinence
Introduction
Neuroimaging methodology, including magnetic resonance imaging (MRI), has been used to study atrophy associated with chronic alcohol dependence (for reviews, see e.g., Rosenbloom et al., 1995, Sullivan et al., 2000a, Sullivan et al., 2000b). Common findings are enlarged ventricles and sulci (Jernigan et al., 1991a, Jernigan et al., 1991b, Hayakawa et al., 1992, Pfefferbaum et al., 1992), as well as generalized loss of volume in cortical gray matter (GM), white matter (WM), cerebellum (Shear et al., 1996, Sullivan et al., 2000a), and subcortical structures (Jernigan et al., 1991a, Pfefferbaum et al., 1992, Pfefferbaum et al., 1996, Charness, 1993, Hommer et al., 1995, Sullivan et al., 1995, Sullivan et al., 1996). These studies were usually performed in recovering alcoholics in treatment who, at time of MRI study, were abstinent from alcohol for several weeks to several months. However, baseline atrophy may be underestimated in alcoholics who are abstinent for several weeks as global brain tissue volume has been reported to recover significantly within just a few weeks of sobriety (Gazdzinski et al., 2005a), with the most rapid recovery apparent in those with the greatest baseline atrophy and drinking severity (Pfefferbaum et al., 1995). Thus, in order to describe/capture the full extent of baseline chronic alcohol-induced brain atrophy, it is necessary to study alcoholics as soon as possible after cessation of chronic drinking before significant structural recovery can occur (Gazdzinski et al., 2005b) or to study actively drinking individuals with alcohol use disorders (Cardenas et al., 2005b).
Nearly all of the previous MRI studies of the effects of alcohol on the brain, including our earlier studies (Di Sclafani et al., 1995, Fein et al., 2002), used automated computer segmentation of relatively low resolution images to subdivide the brain into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF), often combined with manual or automated tracing of regions of interest (ROIs), such as cerebral lobes and specific subcortical brain structures.
Deformation tensor morphometry (Davatzikos et al., 1996, Machado et al., 1998, Gaser et al., 1999, Studholme et al., 2001a) is a relatively new MRI processing method that quantifies and visualizes shape differences between brains on a voxel-by-voxel basis without a priori definitions of ROIs. This method should be more sensitive to focal effects of chronic alcohol consumption on brain structure, which is potentially obscured by volumetric quantification of large brain ROIs. As opposed to voxel-based morphometry (VBM, as commonly used in Statistical Parameter Mapping software), which examines image differences that remain after approximate registration, deformation-based morphometry (DBM) aims to detect shape differences directly from consistent patterns in the anatomical displacement fields, deriving measures of shape from registration rather than misregistration. Recent methodological improvements also make registration between serial images obtained from the same individual feasible, leading to direct maps of change over time that can be used for longitudinal DBM. We previously used cross-sectional DBM to describe cross-sectional brain shape changes associated with heavy drinking in treatment-naive individuals vs. light-drinking controls (Cardenas et al., 2005b). The main findings suggest dose-related, focal cortical gray matter losses and diffuse CSF increases in the brains of heavy drinkers, with little-to-no evidence of significant white matter losses.
Chronic alcohol-induced brain tissue loss is at least partially reversible after cessation of drinking, the detection of which may be amenable to serial structural MRI measurements. However, previous studies of brain structure recovery in abstinent alcohol-dependent individuals evaluated only changes in relatively large brain regions using quantitative volumetric MRI (Zipursky et al., 1989, Shear et al., 1994, Pfefferbaum et al., 1995, Trabert et al., 1995, Gazdzinski et al., 2005b). The voxel-based method of DBM can localize/visualize specific spatial patterns of recovery of focal cerebral dysmorphology in abstinent alcoholics and quantify its extent.
The goals of this study were to describe the application of DBM to brain changes in alcohol-dependent individuals during short- and long-term abstinence from alcohol. We have specifically used DBM which examines the derivatives of the displacement fields in order to extract specific measures of local size rather than location from the mappings between anatomies. Atrophy patterns in 1-week-abstinent alcohol-dependent individuals were measured and visualized in comparison to light-drinking controls. Brain morphologic changes during prolonged abstinence (6–9 months) and relapse were compared and described as a function of drinking severity and level of atrophy at approximately 1 week of abstinence. Specifically, we tested the following a priori hypotheses: (1) alcohol dependence is associated with widespread reductions of parietal and temporal GM volumes, with focal frontal GM loss, and with WM losses primarily in the frontal and parietal lobes; (2) GM and WM volume decreases are related positively to drinking severity; (3) abstinence from alcohol over 6–9 months is associated with significant local brain tissue volume increases primarily in the WM and (4) tissue recovery is greatest in individuals with the greatest alcohol consumption severity and the greatest atrophy at approximately 1 week of abstinence.
Section snippets
Participants
Recovering alcoholics (RA) were recruited from the San Francisco VA Medical Center Substance Abuse Day Hospital and the San Francisco Kaiser Permanente Chemical Dependence Recovery Program outpatient clinics, and light-drinking controls (LD) responded to advertisements in the community. Prior to completing any procedure, all participants gave written informed consent, which was approved by review boards of the University of California San Francisco and the San Francisco VA Medical Center. All
RA at 1 week of abstinence vs. LD
RA showed tissue loss compared to LD in the frontal, parietal, temporal, and occipital GM and WM, as well as cerebellum (no figure shown). The threshold at p = 0.05 corrected for multiple comparisons using permutation testing is t < − 5; no voxels exceed this threshold to show significant atrophy after correction. However, cluster analysis using fMRIstat revealed two clusters where RA participants had consistently smaller tissue volumes than LD individuals. The larger and more significant cluster
Discussion
We used deformation-based morphometry to examine brain structure differences between 1-week-abstinent alcoholics and light drinkers and to compare tissue recovery over several months in abstinent alcoholics to normal aging. The major findings of this study are: (1) alcohol dependence in this predominantly male Caucasian cohort is associated with significant reductions of tissue in foci within the frontal and temporal lobes, (2) heavier drinking is associated with greater tissue losses in the
Acknowledgments
This work was supported by R01 AA10788 (D.J.M.), R01 MH65392 (C.S.), and Whitaker foundation award RG-01-0115 (C.S.).
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