Diffusion Tensor Tractography in Mesencephalic Bundles: Relation to Mental Flexibility in Detoxified Alcohol-Dependent Subjects

Abstract

Components of the corticocerebellar circuit and the midbrain individually play a central role in addictive processes and have been associated with altered volumes and impairment of cognitive flexibility in alcohol-dependent subjects. The microstructure of white matter bundles composing the corticocerebellar network and passing through the midbrain was studied using diffusion tensor imaging in a group of detoxified alcohol-dependent men (n ¼ 20) and a group of healthy men (n ¼ 24). The relationship between properties of these white matter bundles and cognitive flexibility performance was investigated in alcohol-dependent subjects. Bundles connecting two regions of interest were analyzed using a fiber-tracking quantitative approach, which provided estimates of the fractional anisotropy and the apparent diffusion coefficient, as well as the number of tracked fibers normalized by the volume of regions of interest. Within the bundles running between the midbrain and pons, a mean of 18% fewer fibers per unit volume were tracked in alcohol-dependent men than in healthy controls. In addition, the normalized number of these fibers correlated with the performance in the Trail-Making Test part-B. Even though the alcohol-dependent subjects were detoxified and apparently neurologically intact, their earlier excessive use of alcohol seems to be associated with altered neural microstructure of mesencephalic white matter bundles, which may contribute to their cognitive flexibility impairment.

Human Imaging Studies of Brain Circuitry Disrupted by Alcoholism

“…Specifically, alcoholics show an anterior-posterior gradient of commissural abnormalities (Pfefferbaum, Rosenbloom, Adalsteinsson, & Sullivan, 2007;Pfefferbaum, Rosenbloom, Fama, Sassoon, & Sullivan, 2010) and a superior-inferior gradient of association and projection fiber systems abnormalities (Pfefferbaum, Rosenbloom, Rohlfing, & Sullivan, 2009). DTI studies have also identified functional correlates and even double dissociations indicating selectivity between fiber system and function (e.g., Chanraud et al, 2009;Pfefferbaum et al, 2006Pfefferbaum et al, , 2009. For example, greater diffusivity in the genu was selectively predictive of working-memory performance, whereas greater diffusivity in the splenium was selectively predictive of performance on a spatial-reasoning task .…”

“…Rather, chronically alcohol-dependent men and women without obvious complications from nutritional deficiencies or hepatic disorders demonstrate in vivo visually detectable cortical and cerebellar shrinkage relative to the controls (Hayakawa & Kumagai, 1992;Shear, Jernigan, & Butters, 1994;Wang et al, 1993). Specific regions and tissue affected by chronic alcohol exposure and quantified volumetrically include cortical gray and white matter (Cardenas, Studholme, Meyerhoff, Song, & Weiner, 2005;Jernigan et al, 1991;Pfefferbaum et al, 1992), particularly prefrontal areas in older alcoholics (Cardenas, Studholme, Gazdzinski, Durazzo, & Meyerhoff, 2007;Pfefferbaum, Sullivan, Mathalon, & Lim, 1997), mammillary bodies (Shear, Sullivan, Lane, & Pfefferbaum, 1996;Sullivan et al, 1999), hippocampus (Agartz, Momenan, Rawlings, Kerich, & Hommer, 1999;Beresford et al, 2006;Sullivan, Marsh, Mathalon, Lim, & Pfefferbaum, 1995), amygdala (Makris et al, 2008), thalamus (Chanraud et al, 2007;De Bellis et al, 2005;Sullivan, 2003), caudate nucleus and putamen (Sullivan, Deshmukh, De Rosa, Rosenbloom, & Pfefferbaum, 2005), pons (Chanraud et al, 2009;Pfefferbaum, Rosenbloom, Serventi, & Sullivan, 2002;, parietal cortex (Fein, Shimotsu, Chu, & Barakos, 2009), and cerebellum (De Bellis et al, 2005;Sullivan, Deshmukh, Desmond, Lim, & Pfefferbaum, 2000). Longterm abstinent alcoholics with psychiatric comorbidities show more enduring subcortical volume deficits than those free of such psychopathology (Sameti, Smith, Patenaude, & Fein, 2011).…”

“…Using posturography and balance-platform testing, we observed truncal tremor in the 3-5 Hz band and another prominence in the 5-7 Hz band in alcoholic men (Sullivan, Rose, & Pfefferbaum, 2006) and women (Sullivan, Rose, & Pfefferbaum, 2009). The second prominence may be indicative of thalamic damage to cerebellar-thalamic relays (Guehl et al, 2003); indeed, damage to cerebellar-pontine-thalamic structures (Sullivan, 2003;Sullivan et al, 2003) and circuitry (Chanraud et al, 2009) are well documented in uncomplicated alcoholism.…”

“…Yet alterations in cerebellar nodes of the frontocerebellar circuitry can be useful predictors of executive dysfunctioning in prefrontal regions (Chanraud et al, 2009;Sullivan, 2003;Sullivan et al, 2003). For example, the volume of midbrain white matter, a region common to both corticocerebellar and cerebellocortical fibers, was linked to alcohol dependents' performance on tasks of executive function, including card sorting (Chanraud et al, 2007).…”

Analytical fusion of multimodal magnetic resonance imaging to identify pathological states in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats

“…Many previous DTI studies associates the reduction of FA in the genu of the corpus callosum, centrum semiovale (32) and areas in the frontal and superior sites such as frontal forceps, internal and external capsules, and fornix (33) which suggests a demyelination of fiber tract and axonal degeneration (34). Another DTI studies reveal that white matter fibers from midbrain and pons are disrupted by chronic alcohol intake affecting cognitive abilities (35) and abnormalities in motivational and reward related brain areas (36). Alcohol does not affect males and females in the same way.…”