Research Article: Alcohol’s Effects on the Brain: Neuroimaging Results in Humans and Animal Models

Date Published: , 2017

Publisher: National Institute on Alcohol Abuse and Alcoholism

Author(s): Natalie M. Zahr, Adolf Pfefferbaum.



Brain imaging technology has allowed researchers to conduct rigorous studies of the dynamic course of alcoholism through periods of drinking, sobriety, and relapse and to gain insights into the effects of chronic alcoholism on the human brain. Magnetic resonance imaging (MRI) studies have distinguished alcohol-related brain effects that are permanent from those that are reversible with abstinence. In support of postmortem neuropathological studies showing degeneration of white matter, MRI studies have shown a specific vulnerability of white matter to chronic alcohol exposure. Such studies have demonstrated white-matter volume deficits as well as damage to selective gray-matter structures. Diffusion tensor imaging (DTI), by permitting microstructural characterization of white matter, has extended MRI findings in alcoholics. MR spectroscopy (MRS) allows quantification of several metabolites that shed light on brain biochemical alterations caused by alcoholism. This article focuses on MRI, DTI, and MRS findings in neurological disorders that commonly co-occur with alcoholism, including Wernicke’s encephalopathy, Korsakoff’s syndrome, and hepatic encephalopathy. Also reviewed are neuroimaging findings in animal models of alcoholism and related neurological disorders. This report also suggests that the dynamic course of alcoholism presents a unique opportunity to examine brain structural and functional repair and recovery.

Partial Text

Since the early 1980s, conventional structural MRI has allowed researchers to visualize the living human brain. Detailed images of the brain are possible in part because the different brain tissue types (i.e., gray matter, white matter, and cerebrospinal fluid [CSF]) contain different proportions of water (Rumboldt et al. 2010). With MRI, the brain can be viewed from bottom to top (axial), from front to back (coronal), from left to right (sagittal), or at any oblique angle to these planes. This flexibility also enables greater accuracy in aligning images with internal landmarks, an essential consideration for ensuring consistency of data from replicate images from the same individual (Rohlfing 2006).

An important initial report in the rodent MRI literature was the demonstration that brain growth continues beyond what would be considered adulthood in rats bred to prefer alcohol (i.e., alcohol-preferring rats, or P rats). Indeed, whole-brain volume in such rats continued to grow until approximately postnatal day 450 (Sullivan et al. 2006a), well past adulthood, which is typically considered as postnatal day 90 (Bell et al. 2013). Baseline studies (in the absence of alcohol [i.e., EtOH] exposure) also suggest that brains of alcohol-preferring rats are different relative to their wild-type counterparts, including reduced gray-matter volume in thalamus, ventral tegmental area, and insular and cingulate cortices (Gozzi et al. 2013).

A number of sources provide extensive descriptions of the principles of DTI (Basser and Jones 2002; Chien et al. 1990; Gerig et al. 2005; Jones 2005; LeBihan 2001, 2003; Pierpaoli et al. 1996; Poupon et al. 1999; Sullivan and Pfefferbaum 2011). Briefly, DTI takes advantage of the fact that MR images of the brain are predominantly maps of water protons with contrast created by their immediate environment and their motility. In regions with few or no constraints imposed by physical boundaries, such as CSF in the ventricles, water movement is random and uniform in every direction and is therefore isotropic. In contrast to CSF, the path of a water molecule along a white-matter fiber is constrained by physical boundaries such as the axon sheath, causing greater movement along the long axis of the fiber than across it. This movement is called anisotropic; diffusion along the long axis of a fiber (axial or longitudinal diffusion) is greater than diffusion across the fiber (radial or transverse diffusion) (Song et al. 2002).

Although MRI primarily depicts the distribution of water protons, similar technology can also be used to obtain information about chemical constituents other than water, primarily due to a small frequency shift, or “chemical shift,” relative to the water signal. The acquisition of MR-detectable signals other than those of water and fat is referred to as MRS and is an in vivo application of traditional laboratory-based NMR spectroscopy.

Imaging investigations of alcohol-related brain disorders show unique neuropathology (as outlined in table 1), offering a framework for examining pathology in uncomplicated alcoholism. Because brains affected by AUD can show mild effects in the regions aggressively targeted by overt disease, animal models have been useful in distinguishing the etiology of pathology and differentiating brain regions specifically targeted by thiamine deficiency versus hyperammonemia, for example. Individuals with AUD may show more prominent effects in some regions compared with others, suggesting a propensity for one diagnosis over another (e.g., an alcoholic may be more vulnerable to thiamine deficiency than to liver damage). What remains unresolved, and what animal models can help determine, is why certain brain regions are differentially vulnerable to certain pathologies. For example, are the colliculi sensitive to thiamine deficiency because of their relatively high metabolic rate (Landau et al. 1955; Sokoloff et al. 1977)? Is the pons susceptible to CPM because of its proximity to the basilar artery? Does dopamine explain why basal ganglia are targets of liver disease (Mousseau et al. 1993)?





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