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.
Highlights
Youths 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 (FHÀ)
We used structural equation modeling (SEM) to test interactions between frontal-striatal regions with elevated activity in FH+ youths during go/no-go task performance that we previously reported (Acheson et al 2014a) and to determine whether increased activity in these regions can be at least partially explained by reduced frontalstriatal white matter integrity findings we previously reported in this same cohort (Acheson et al 2014b,c)
In these models, increased dorsal striatal activity explained most (~75%) of the elevated supplementary motor area (SMA) activity in FH+ youths, whereas increased SMA activity did not significantly explain their increased striatal activity. Both reduced anterior corona radiata fractional anisotropy and N-acetylaspartate were found to partially mediate the increased SMA activity in FH+ youths, and the combined contributions of increased striatal activation, and decreased fractional anisotropy and N-acetylaspartate fully explained the elevated SMA activations. These results suggest the elevated SMA activity is driven both by increased striatal activity via downstream projections in the frontostriatal motor loop and by reduced white matter integrity in frontal cortical projections, the latter likely increasing SMA activity due to increased energy demands required for action potential propagation
Summary
Youths 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 (FHÀ). Adolescents and young adults with family histories of alcohol and other drug use disorders (FH+) are at greatly increased risk for substance-use disorders relative to those with no family histories of substance-use disorders (FHÀ; Sher et al 2004; Sher and Trull 1994; Tarter et al 2003) This risk may be at least partially due to frontostriatal circuitry dysregulations as FH+ youths and young adults have: (1) reduced frontostriatal white matter development (Herting et al 2010; Acheson et al 2014b,c); (2) altered and often increased activity in frontostriatal and other forebrain regions We used structural equation modeling (SEM) analyses on to test: (1) how elevated activity in the SMA and dorsal striatum influence each other; and (2) how reduced frontal white matter integrity contributes to the increased SMA and dorsal striatum activity
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