Transcallosal White Matter Degradation Detected with Quantitative Fiber Tracking in Alcoholic Men and Women: Selective Relations to Dissociable Functions

Introduction: Excessive alcohol consumption can adversely affect white matter fibers and disrupt transmission of neuronal signals. Here, we examined six anatomically defined transcallosal white matter fiber bundles and asked whether any bundle was specifically vulnerable to alcohol, what aspect of white matter integrity was most affected, whether women were more vulnerable than men, and whether evidence of compromise in specific bundles was associated with deficits in balance, sustained attention, associative learning, and psychomotor function, commonly affected in alcoholics.

Methods: Diffusion tensor imaging quantitative fiber tracking assessed integrity of six transcallosal white matter bundles in 87 alcoholics (59 men, 28 women) and 88 healthy controls (42 men, 46 women). Measures included orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, quantified separately for axial (longitudinal; lambdaL) and radial (transverse; lambdaT) diffusivity. The Digit Symbol Test and a test of ataxia were also administered.

Results: Alcoholism negatively affected callosal FA and lambdaT of all but the sensory-motor bundle. Women showed no evidence for greater vulnerability to alcohol than men. Multiple regression analyses confirmed a double dissociation: higher diffusivity in sensory-motor and parietal bundles was associated with poorer balance but not psychomotor speed, whereas higher diffusivity in prefrontal and temporal bundles was associated with slower psychomotor speed but not balance.

Conclusions: This study revealed stronger alcohol effects for FA and radial diffusivity than axial diffusivity, suggesting myelin degradation, but no evidence for greater vulnerability to alcohol in women than men. The presence of brain-behavior relationships provides support for the role of alcoholism-related commissural white matter degradation as a substrate of cognitive and motor impairment. Identification of a double dissociation provides further support for the role of selective white matter integrity in specific domains of performance.