Elsevier

Drug and Alcohol Dependence

Volume 151, 1 June 2015, Pages 128-134
Drug and Alcohol Dependence

Full length article
Altered white matter in cocaine-dependent subjects with traumatic brain injury: A diffusion tensor imaging study

https://doi.org/10.1016/j.drugalcdep.2015.03.015Get rights and content

Highlights

Abstract

Background

Diffusion tensor imaging (DTI) is a useful technique for non-invasively investigating the microstructural organization of white matter (WM), and the most consistent DTI finding regarding cocaine-related WM alterations is in the corpus callosum (CC). WM injury has also been observed in subjects with traumatic brain injury (TBI), including in the CC.

Methods

We used DTI to test if the WM microstructure is relatively more impaired in cocaine-dependent subjects who had suffered a mild TBI (mTBI). Fractional anisotropy (FA), which reflects the degree of alignment of cellular structures within fiber tracts and their structural integrity, was compared across cocaine-dependent subjects with mTBI (COCTBI group, n = 9), matched cocaine-dependent subjects without TBI (COC group, n = 12), and matched healthy controls (CTL group, n = 12).

Results

The COCTBI group had significantly lower FA in the genu, body, and splenium of CC, than the CTL group whenever the education was controlled or not. The COC group had significantly lower FA in the left and right anterior corona radiata than the CTL group only when the education was controlled. There was no significant difference in FA between the COC and COCTBI groups.

Conclusion

Cocaine dependence (or mTBI) related WM impairments in the CC were not detectable in this small subject sample. The significant finding in the CC suggests that the concurrence of cocaine dependence and mTBI might result in more severe damage to the CC, which could even be detected in small sample size.

Introduction

Cocaine dependence is associated with white matter (WM) impairment (Moeller et al., 2005, Lim et al., 2008, Ma et al., 2009, Lane et al., 2010, Xu et al., 2010, Bell et al., 2011, Hanlon et al., 2013), which may compromise cognitive functions. Diffusion tensor imaging (DTI), which exploits the directionality of diffusion of water molecules in tissues, is a powerful technique for non-invasively investigating the microstructural organization of WM (Taber et al., 2002). Cocaine-induced alterations in WM are often observed in two of the DTI measures, i.e., fractional anisotropy (FA) (Moeller et al., 2005, Lim et al., 2008, Ma et al., 2009, Lane et al., 2010, Bell et al., 2011) and radial diffusivity (Moeller et al., 2007, Ma et al., 2009, Lane et al., 2010). FA measures deviation from isotropy and reflects the degree of alignment of cellular structures within fiber tracts as well as their structural integrity (Cercignani et al., 2001). Higher radial diffusivity is indicative of greater diffusion perpendicular to the fiber tracts and may be possibly associated with impairment in myelin (Song et al., 2002, Song et al., 2003, Klawiter et al., 2011).

Previous DTI studies have reproducibly shown that cocaine dependence is associated with significant WM deficits. Moeller et al. (2005) reported significantly lower FA in the genu and rostral body of the corpus callosum (CC) in cocaine-dependent subjects compared to controls and an association between FA in the anterior CC and impulsivity within the cocaine-dependent subjects. Lim et al. (2008) found lower FA in the inferior frontal WM in cocaine-dependent subjects compared to control subjects. Ma et al. (2009) observed that cocaine-dependent subjects had significantly higher radial diffusivity in the rostral body and isthmus of the CC than non-drug-using controls. Lane et al. (2010) found lower FA and higher radial diffusivity in the CC, frontal and parietal WM regions in cocaine-dependent subjects compared to non-drug-using controls and an association between the DTI measures in these regions and decision-making. Xu et al. (2010) noted that in cocaine-dependent subjects, worse treatment outcomes were negatively-correlated with FA values and positively-correlated with radial diffusivity across several brain regions including the CC, frontal, parietal, temporal, and occipital lobes, and cerebellum. Bell et al. (2011) found that the cocaine-abstinent subjects had lower FA in genu of the CC, superior longitudinal fasciculus, and the superior corona radiata when compared against non-drug-using controls. So far, the most consistent finding regarding cocaine dependence related WM alterations is in the CC (Moeller et al., 2005, Moeller et al., 2007, Ma et al., 2009, Lane et al., 2010, Xu et al., 2010, Bell et al., 2011). These findings have been replicated in controlled, animal studies (Narayana et al., 2009, Narayana et al., 2014) using DTI.

There is a close association between substance use disorders (SUD) and traumatic brain injury (TBI). It has been well documented that individuals with SUD are more prone to TBI through motor vehicle accidents, violence, or falls (Taylor et al., 2003). Thus SUD can increase the risk of TBI (Cherpitel, 2007, Taylor et al., 2003). Preliminary results from our group have shown that subjects with cocaine dependence have a higher incidence of TBI compared to non-drug using controls and occurrence of TBI preceded initiation of cocaine use (Ramesh et al., 2015). In addition, previous DTI studies have consistently found that patients with TBI showed impaired WM microstructure than controls, especially in the CC (see Hulkower et al., 2013 for review). However, it is yet to be determined if subjects with co-morbid cocaine dependence and TBI have additional impairments in the WM structure. In this study, we used DTI to test if the WM microstructure is relatively more impaired in cocaine-dependent subjects with mild TBI (mTBI).

Section snippets

Subjects

The present study was approved by the local university Committee for the Protection of Human Subjects (CPHS) and was performed in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). Informed consent was obtained from each subject before including in this study.

Cocaine-dependent subjects and healthy controls were recruited via newspaper advertisements, and were initially screened by a brief telephone interview. Following the phone screen, eligible

Non-imaging measures

The education level (years) of the COC group was significantly shorter than that of the CTL group (p = 0.008, t = 2.94, DoF = 22). There was no significant difference in education between the COCTBI group and CTL group (p = 0.28, t = 1.10, DoF = 19), and between the COCTBI group and the COC group (p = 0.11, t = 1.66, DoF = 19). The COC subjects (p = 0.020, t = 2.52, DoF = 22) and the COCTBI subjects (p = 0.030, t = 2.34, DoF = 19) consumed significantly more alcohol (kg) than CTL subjects. However, there was no significant

Discussion

This study investigated the potential role of mTBI in the altered WM microstructure in cocaine-dependent subjects, which has been consistently reported in the literature (Moeller et al., 2005, Lim et al., 2008, Ma et al., 2009, Lane et al., 2010, Xu et al., 2010, Bell et al., 2011, Li et al., 2013, Lebel et al., 2013). Using TBSS, we examined whether the WM microstructure was altered in cocaine-dependent subjects with mTBI by comparing their DTI measures with matched non-drug using controls and

Role of funding source

Nothing declared.

Contributors

All authors edited and reviewed the manuscript. Liangsuo Ma analyzed all data, and wrote up the manuscript. Divya Ramesh and Lori Keyser-Marcus provided close head injury measures for all subjects. Liangsuo Ma, Joel L. Steinberg, Ponnada A. Narayana, and F. Gerard Moeller designed the experiment. F. Gerard Moeller designed the 13-item self-report measure of close head injury.

Conflict of interest

No conflict declared.

Acknowledgements

This work is financially supported by National Institute on Drug Abuse (NIDA) Grants no. R01 DA034131 (LM), U54 DA038999 (FGM/JLS), P50 DA009262 (FGM/JLS), and MCRR Shared Instrumentation Grant no. 1 S10 RR019186-01 (PAN). We thank Zahra N. Kamdar, Vipulkumar S. (Vips) Patel, and Edward A. Zuniga for their excellent technical support. We also thank the anonymous reviewers for their constructive comments which have resulted in significant improvement of this article.

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