Neurocircuitry in alcoholism: a substrate of disruption and repair

Abstract

The chronic, excessive consumption of alcohol results in significant modification of selective neural systems of the brain structure, physiology, and function. Quantitative MR structural imaging, diffusion tensor imaging (DTI), and functional MRI (fMRI), together with neuropsychological challenges, have enabled rigorous in vivo characterization of the results of alcoholism on the brain in the human condition. Neuroimaging has also enabled longitudinal study for the examination of alcoholism's dynamic course through periods of drinking and sobriety. Controlled studies have revealed compelling evidence for alcohol-related brain structural and functional modification--some longstanding, some transient, and some compensatory. Patterns of circuitry disruption identified through structural and functional MRI studies suggest a central role for degradation of frontocerebellar neuronal nodes and connecting circuitry affecting widespread brain regions and contributing to alcoholism's salient, enduring, and debilitating cognitive and motor deficits--executive dysfunction, visuospatial impairment, and ataxia.

Brain atrophy in long-term abstinent alcoholics who demonstrate impairment on a simulated gambling task

“…In our manuscript reporting gambling task impairments in the samples presented here (Fein et al, 2004b), and in a manuscript on cognitive function in these same subjects (Fein et al, in press), we did not find any associations between performance and duration of abstinence. In the cognition paper, we found that AbsAlc were essentially cognitively normal (except for impairments in spatial functioning which had to be interpreted gingerly because it was the only domain with impairment of 9 domains assessed -yet it was among the domains that are most frequently reported to be impaired in alcoholism and drug addiction (Crews et al, 2005;Munro et al, 2000;Oscar-Berman et al, 1997;Sullivan et al, 2002;Sullivan and Pfefferbaum, 2005). Nonetheless, we found no association between SGT performance and spatial processing ability.…”

In vivo metabolite differences between the basal ganglia and cerebellum of the rat brain detected with proton MRS at 3T

“…(Dreher and Leibfritz, 1999) was introduced as an in vivo method to detect J-coupled resonances with high signal-to-noise ratio (SNR) by using effective homonuclear decoupling. Here, we tested the feasibility of using CT-PRESS optimized for the detection of Glu (Mayer and Spielman, 2005) in the rat to dissociate the biochemical profile of two brain regions affected in alcohol dependence (Koob, 1999;Sullivan and Pfefferbaum, 2005). Based on the hypotheses that the development of alcohol dependence is mediated by basal ganglia circuitry (Koob, 1999), whereas maintenance of alcohol addiction entails changes in frontocerebellar circuitry Sullivan and Pfefferbaum, 2005), we choose to establish baseline levels of major metabolites and neurotransmitters in the basal ganglia and the cerebellum.…”

Proteomic Approaches and Identification of Novel Therapeutic Targets for Alcoholism

“…Analyses of post-mortem brain of long-term alcohol abusers have reported neuronal loss in gray matter and loss of white matter volume (Harper, 2009;Kril and Harper, 1989;Pfefferbaum, 2004;Sullivan and Pfefferbaum, 2005). These effects are less pronounced in motor, temporal, or cingulate cortices, suggesting that alcohol-induced brain damage is likely brain region selective.…”

“…Alcohol has been shown to damage neurons in multiple brain regions, leading to cognitive impairment and other abnormalities of brain function (Harper, 2009;Pfefferbaum, 2004;Sullivan and Pfefferbaum, 2005). The neuronal and behavioral adaptation of the brain to the constant presence of alcohol can lead to severe withdrawal symptoms when alcohol levels suddenly drop.…”