Callosal white matter microstructural recovery in abstinent alcoholics: a longitudinal diffusion tensor imaging study

White matter damage from chronic alcohol abuse is a consistent finding in neuropathological and structural magnetic resonance imaging (MRI) studies (Estruch et al., 1997; Harper, 1998; Harper and Kril, 1991; Harper et al., 1985; Hommer et al., 1996; Pfefferbaum et al., 1996). According to postmortem analyses, white matter anomalies associated with alcohol abuse include overall volume reduction, demyelination, microtubule disturbance, and axonal subtraction (Alling and Bostrom, 1980; Harper and Kril, 1989; Harper et al., 1987; Kril et al., 1997; Paula-Barbosa and Tavares, 1985). Pathological evidence also indicates that these white matter anomalies are especially prominent in the frontal lobes (Harper and Kril, 1989; Kril et al., 1997; Torvik, 1987). Consistent with neuropathological research, structural MRI studies report loss in white matter integrity that is associated with shrinkage to the frontal lobes (Dirksen et al., 2006; Oscar-Berman and Marinkovic, 2007; Rosenbloom et al., 2003; Schlaepfer et al., 2006). For example, referring to statistically significant regional brain volume differences measured with MRI, Pfefferbaum and colleagues (1997) described greater white matter deficits in the prefrontal and other frontal regions compared to anterior temporal, anterior parietal, and posterior parietal lobes in chronic alcoholics. Diffusion tensor imaging (DTI) studies have identified decreases in fractional anisotropy values in frontal white matter and limbic pathways (Yeh et al., 2009) as well as in the 5 main subregions of the corpus callosum–the rostrum, genu, body, isthmus, and splenium–with the greatest loss to the genu subregion and less shrinkage to the body and splenium (Pfefferbaum et al., 2000, 2006a). Neuropsychological changes from alcohol exposure parallel modifications in brain structure specified in the neuropathology and neuroimaging studies, especially cognitive deficits associated with frontal lobe dysfunction (Dirksen et al., 2006). Broadly speaking, functional deficiencies in alcohol dependence include deficits in abstract thinking, problem-solving, spatial and verbal learning, working memory, attention, and perceptual motor skills (Grant, 1987; Grant et al., 1979, 1984; Harper and Matsumoto, 2005; Pfefferbaum et al., 2000, 2006a; Rourke and Grant, 2009). More specifically, general disruptions to the integrity of the corpus callosum correlate with impairments in interhemispheric processing speed (Davies et al., 2005; Schulte et al., 2005). Callosal micro-structure integrity also predicts, at least in part, visuospatial global–local integration ability in alcohol-dependent subjects, a function also requiring the integration of information from both hemispheres (Muller-Oehring et al., 2009). DTI studies using fiber tractography as well as postmortem analyses indicate that the genu, the anterior section of the corpus callosum, connects left and right hemispheres of the pre-frontal cortex while the posterior segment, the splenium, connects temporal, parietal, and occipital cortices (Abe et al., 2004; Hofer and Frahm, 2006; Huang et al., 2005; Pandya and Seltzer, 1986; Sullivan et al., 2006). Previous research has found that changes in the genu are associated with alcohol-related neuropsychological impairments on frontal lobe-mediated tasks such as Trail Making and Digit Symbol Tests (Jokinen et al., 2007). Furthermore, deficiencies in the genu, specifically, contribute to deficits in attention and working memory (Jokinen et al., 2007; Pfefferbaum et al., 2000, 2006a). Neuroimaging studies of detoxified alcoholics also report evidence of reversal of alcohol-related structural changes to the brain after the periods of abstinence (Sullivan and Pfefferbaum, 2005). As with the greater original harmful effects in white matter (Harper and Kril, 1991; Harper et al., 1985), recovery is also often observed in the white matter. In their MRI study, Shear and colleagues (1994) discovered that recently detoxified subjects examined 1 month after their last drink and after 3 months of abstinence exhibited white matter volume increases, while those who resumed drinking did not. Another study that used deformation-based morphometry (Cardenas et al., 2007) found that the frontal and temporal lobes are vulnerable to the effects of heavy alcohol consumption and that recovery is observed in these abstinent heavy drinkers compared to relapsers. Finally, a multimodal MRI and DTI study demonstrated that alcohol-dependent subjects showed white matter recovery–both in microstructural integrity and volume–depending on smoking status (Gazdzinski et al., 2010). Additional studies confirm white matter recovery during periods of abstinence through changes in magnetic resonance spectroscopy (MRS) metabolites that have been observed to be correlated with white matter improvements. Ende and colleagues (2005) found a statistically significant increase in choline-containing compounds in their follow-up measurement in abstinent alcohol-dependent patients indicating an improved cerebral metabolism of lipids in membranes and myelin. Bartsch and colleagues (2007) also found that 1H-MRS levels of cerebellar choline and frontomesial N-acetylaspartate were significantly augmented after short-term sobriety, and that these increases were associated with global brain volume recovery. The current study hypothesized that the significant declines in microstructural integrity as measured with DTI in the corpus callosumof recentlydetoxifiedalcohol-dependentpatients (RDA) will be partially ameliorated after a year of abstinence fromalcohol. As previously reported, the frontal lobesmay be especially susceptible tomicrostructural whitematter changes in alcoholic patients. The majority of fibers that connect the 2 sides of the frontal lobes course through the genu and body of the corpus callosum; while the splenium connects temporal and occipital regions. Therefore, the current study hypothesized that, paralleling previous findings of preferential frontal damage, the genu of the corpus callosum would exhibit the greatest white matter disruption in RDA, followed by the body and the splenium. Finally, the current study hypothesized that frontal/executive functions similar to those previously found to be susceptible to the effects of alcohol dependence (Jokinen et al., 2007; Pfefferbaum et al., 2000, 2006a) will show the significant improvements after a year of abstinent that parallels improvements inDTImeasures. 2 sides of the frontal lobes course through the genu and body of the corpus callosum; while the splenium connects temporal and occipital regions. Therefore, the current study hypothesized that, paralleling previous findings of preferential frontal damage, the genu of the corpus callosum would exhibit the greatest white matter disruption in RDA, followed by the body and the splenium. Finally, the current study hypothesized that frontal/executive functions similar to those previously found to be susceptible to the effects of alcohol dependence (Jokinen et al., 2007; Pfefferbaum et al., 2000, 2006a) will show the significant improvements after a year of abstinent that parallels improvements in DTI measures.