Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects

Objective: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. Method: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. Results: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. Conclusions: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine

Differential effects of left and right prefrontal high frequency rTMS on resting state fMRI in healthy individuals

High frequency repetitive transcranial magnetic stimulation (HF-rTMS) has gained great interest in multiple clinical and research fields and is believed to accomplish its effect by influencing neuronal networks. The dlPFC is frequently chosen as the cortical target for HF-rTMS. However very little is known about the differential effect of HF-rTMS over the left and right dlPFC on intrinsic functional connectivity networks in patients or in healthy individuals. The current study assessed the differential effects of left or right HF-rTMS (corrected for sham) on intrinsic Independent Component Analysis (ICA) defined functional connectivity networks in a sample of 45 healthy individuals. All subjects had a first scanning session wherein baseline functional connectivity was assessed. During the second session, individuals received one session of either left, right or sham dlPFC HF-rTMS (60 5 second trains of 10Hz at 110% motor threshold). The sham condition was used in order to correct for time and placebo effects. ICAs were performed to assess baseline differences and stimulation effects on within and between network functional connectivity. Stimulation of the left dlPFC resulted in decreased functional connectivity in the salience network whereas right dlPFC stimulation resulted in increased functional connectivity within this network. No differences between left or right dlPFC stimulation were found in between network connectivity. These results suggest that left and right HF-rTMS may have differential effects and more research is needed on the clinical consequence