Substance abuse and white matter: Findings, limitations, and future of diffusion tensor imaging research

Binge-drinking adolescents were found to have lower fractional anisotropy than controls.

“Two independent research groups found that binge-drinking adolescents—compared to controls—had lower FA (Badsberg Jensen & Pakkenberg, 1993; McQueeny et al., 2009).”

• cites Badsberg Jensen & Pakkenberg, 1993Not checked yet

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• cites McQueeny et al., 2009 sourceNot checked yet

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Following prolonged abstinence, alcohol or opiate users can show white matter microstructure that is not significantly different from nonusers.

“Following prolonged abstinence, abusers of alcohol (Pfefferbaum et al., 2014) or opiates (Wang et al., 2011) have white matter microstructure that is not significantly different from nonusers.”

• cites Pfefferbaum et al., 2014 sourceNot checked yet

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• cites Wang et al., 2011 sourceNot checked yet

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Opiate-abusing individuals consistently exhibit lower fractional anisotropy and lower axial diffusivity relative to non-using controls.

“Relative to non-using controls, opiate-abusing individuals consistently exhibit both lower FA (Bora et al., 2012; Fu et al., 2008; Li et al., 2013; Qiu et al., 2013; Wang et al., 2011) and lower AD (Bora et al., 2012; Qiu et al., 2013).”

• cites Bora et al., 2012Not matched

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• cites Fu et al., 2008Not matched

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• cites Li et al., 2013Not matched

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Alcohol abuse is associated with lower white matter volume.

“Gross anatomical estimations indicate that alcohol-abusing individuals have lower white matter volume (Arnone et al., 2008; Pfefferbaum, Adalsteinsson, & Sullivan, 2006).”

• cites Arnone et al., 2008Not matched

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• cites Pfefferbaum, Adalsteinsson, & Sullivan, 2006Not matched

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The corpus callosum was the most consistently implicated pathway, with nearly half of studies finding at least one significant microstructural difference there.

“nearly half of the studies reviewed found at least one significant microstructural difference in the corpus callosum, as measured by FA.”

Cocaine users were reported to have lower white matter fractional anisotropy than controls in several DTI studies.

“Several recent DTI studies have found that cocaine users had lower white matter FA relative to controls (Azadeh et al., 2016; Romero, Asensio, Palau, Sanchez, & Romero, 2010).”

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• cites Romero, Asensio, Palau, Sanchez, & Romero, 2010 sourceNot checked yet

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Longitudinal studies reviewed suggest that substance abuse may cause changes in white matter, but the permanence of those changes remains uncertain.

“The subsample of longitudinal studies reviewed suggests that substance abuse may cause changes in white matter, though it is unclear to what extent such alterations are permanent.”

Heavy nicotine use has been associated with lower white matter fractional anisotropy in some studies.

“In chronic nicotine users, heavy consumption has been associated with lower FA (Lin, Wu, Zhu, & Lei, 2013) and higher FA (Paul et al., 2008), as well has both lower RD (Wang et al., 2017) and higher RD (Lin et al., 2013).”

• cites Lin, Wu, Zhu, & Lei, 2013Not matched

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• cites Paul et al., 2008Not matched

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• cites Wang et al., 2017Not matched

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For cocaine, longitudinal and related evidence suggests that cocaine use negatively impacts white matter microstructure.

“Together, these studies provide fairly consistent evidence that cocaine abuse negatively impacts white matter microstructure (Ma et al., 2017).”

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The direction of white matter microstructural differences appears to depend on the substance being used.

“The direction of these differences, however, appeared substance-dependent.”

The only longitudinal cannabis study reviewed suggested that cannabis use causes white matter changes.

“For cannabis, the only longitudinal study in this literature similarly suggests that cannabis use causes white matter changes, not the reverse.”

Alcohol abuse likely induces white matter changes rather than the reverse, based on longitudinal evidence.

“Together, these results support the notion that alcohol abuse likely induces white matter changes, not vice versa.”

The authors conclude that substance-related white matter alterations may be at least partly reversible with abstinence.

“It is therefore possible that, at least to some degree, abstinence can reverse effects of substance abuse on white matter.”

Across substances, many studies found differences in major white matter fiber pathways, especially the corpus callosum.

“Across substance of abuse, the majority of the studies reviewed found differences in major white matter fiber pathways such as the corpus callosum, superior and inferior longitudinal fasciculi.”

The review finds a relationship between substance abuse and differences in white matter microstructure, with effects varying by substance and often involving major fiber pathways such as the corpus callosum.

“Across substance, users tended to exhibit differences in the microstructure of major fiber pathways, such as the corpus callosum.”

Many reviewed studies were limited by scanner hardware and acquisition choices such as 1.5 Tesla scanners, unreported head coil information, and too few gradient directions.

“First, several studies used a 1.5 Tesla MRI scanner. This is likely because 3T scanners were less widely available even ten years ago. Nonetheless, 3T scanners have superior signal-to-noise ratio and therefore are preferable”

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The authors recommend probabilistic tractography for examining specific white matter tracts because it is more robust to crossing and kissing fibers.

“Probabilistic tractography is recommended as it has greatly improved robustness to the many kissing and crossing white matter fibers of the brain (Behrens, Berg, Jbabdi, Rushworth, & Woolrich, 2007).”

• cites Behrens, Berg, Jbabdi, Rushworth, & Woolrich, 2007 sourceNot checked yet

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Diffusion tensor imaging is a magnetic resonance imaging technique that estimates white matter in vivo.

“Diffusion tensor imaging (DTI) is a magnetic resonance imaging technique that estimates white matter in vivo (Bihan et al., 2001) and is increasingly being used to study the biology of addiction.”

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The paper provides methodological guidance for future diffusion tensor imaging research on substance abuse.

“We therefore also provide methodological guidance for future research using DTI to study substance abuse.”

The review included articles published through December 2018 that used diffusion weighted or tensor MRI, were published no earlier than 2008, and had enough sample size for at least group-level statistics.

“This search included articles published through December of 2018. Inclusion criteria were: (i) employed diffusion weighted or tensor magnetic resonance imaging; (ii) published no earlier than 2008; (iii) sample size sufficiently powered to conduct at least group level statistics.”

The authors encourage future study of tracts connecting addiction-related brain areas, especially frontostriatal connectivity.

“Specifically, we encourage future study of tracts that connect addiction-related brain areas (Kalivas & Volkow, 2005) such as the ventral striatum, ventral tegmental area, ventral pallidum, the extended amygdala, orbitofrontal cortex, and thalamus.”

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The review aims to examine the relationship, specificity, and directionality of substance-related differences in white matter microstructure across major substances of abuse.

“In this review, we survey the past decade of DTI research with the goal of examining the relationship, specificity, and directionality, of substance-related differences in white matter microstructure.”

The authors searched Web of Science and PubMed with DTI-related white matter terms and substance-of-abuse terms, including alcohol, cannabis, cocaine, nicotine, and opiates.

“We searched the Web of Science database (http://apps.webofknowledge.com/) and PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) using the following Boolean criteria: “white matter” AND (“DTI” OR “DWI” OR “diffusion” OR “dMRI”) AND “[substance of abuse]”.”