Striatal activity and reduced white matter increase frontal activity in youths with family histories of alcohol and other substance‐use disorders performing a go/no‐go task

Abstract

IntroductionYouths with a family history of alcohol and other drug use disorders (FH+) are at greater risk of developing substance-use disorders relative to those with no such family histories (FH−). We previously reported that FH+ youths have elevated activity in the supplementary motor area (SMA) and dorsal striatum while performing go/no-go tasks and have reduced frontal white matter integrity. A better understanding of relationships between these variables would provide insight into how frontostriatal circuitry is altered in FH+ youths, which may be an important contributor to their elevated risk.MethodsIn this study, we used structural equation modeling (SEM) to test interactions between activity in the SMA and dorsal striatum in 72 FH+ and 32 FH− youths during go/no-go task performance and to determine whether increased activity in these regions in FH+ youths can be at least partially explained by reduced frontal white matter integrity, as indexed by anterior corona radiata fractional anisotropy and N-acetylaspartate.ResultsIncreased dorsal striatum activity explained most (∽75%) of the elevated SMA activity in FH+ youths, and the combined contributions of increased dorsal striatal activity, and decreased white matter integrity fully explained the elevated SMA activity.ConclusionsThese results suggest the elevated frontal cortical activity in FH+ youths is driven both by their increased striatal activity via downstream projections and reduced white matter integrity in frontal cortical projections, the latter likely increasing frontal cortical activity due to increased energy demands required for action potential propagation. As part of our ongoing longitudinal studies we will examine how these frontostriatal alterations relate to risk for developing substance-use disorders.

Multi‐level prediction of substance use: Interaction of white matter integrity, resting‐state connectivity and inhibitory control measured repeatedly in every‐day life

“…55 Relevantly, this region was also found to mediate abnormal activation during an inhibition task among individuals with a family history of substance misuse, a population at high risk of developing SUD. 56 In addition to replicating the involvement of the corpus callosum and the corona radiata in inhibition using mobile testing, our study emphasized a strong link between brain anatomy and functioning. In our overall sample, higher FA within both clusters was linked to higher connectivity in right occipital-frontal connections that we previously highlighted as benefitting inhibition functioning (Chirokoff et al submitted).…”

“…In addition to its compromise in the SUD population, integrity within the anterior corona radiata also predicts better inhibition functioning assessed via classic Stroop testing in healthy populations 55 . Relevantly, this region was also found to mediate abnormal activation during an inhibition task among individuals with a family history of substance misuse, a population at high risk of developing SUD 56 …”

Chronic oxycodone induces axonal degeneration in rat brain

“…Reduction of brain white matter has also been demonstrated in alcohol and other drug addicts: alcohol abuse [ 74 ], alcohol and drug abuse [ 75 , 76 ], cannabinoids [ 77 , 78 ]. Also, methamphetamine [ 79 , 80 ] and cocaine were shown to induce degeneration of myelinated fibers and axons [ 81 ].…”

Miniature pig model of human adolescent brain white matter development

“…FA is also a valuable phenotype in neuropsychiatric disorders. Reduced FA has been found in adolescents with high clinical risk for development of psychosis (Karlsgodt et al, 2009, 2012, 2015), schizophrenia (Wright et al, 2015; Nazeri et al, 2013; Perez-Iglesias et al, 2010; Friedman et al, 2008; Alba-Ferrara and de Erausquin, 2013; Phillips et al, 2012; Kubicki et al, 2007; Glahn et al, 2013; Ellison-Wright and Bullmore, 2009), and substance use disorders (Acheson et al, 2015, 2014a,b). FA is a simple and empirical parameter but it lacks biological specificity and that makes interpretation of FA findings difficult (Alba-Ferrara and de Erausquin, 2013; Pierpaoli and Basser, 1996).…”