title: 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: BACKGROUND
  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 (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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  Increased 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Psychiatry, University of Texas Health Science Center at San Antonio San Antonio, Texas ; Research Imaging Institute, University of Texas Health Science Center at San Antonio San Antonio, Texas.
authors.forename: Ashley
authors.initials: A
authors.lastname: Acheson
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine Baltimore, Maryland.
authors.forename: Malle A
authors.initials: MA
authors.lastname: Tagamets
authors.affiliation: Oxford Centre for Functional MRI of the Brain, University of Oxford Oxford, UK ; Department of Psychiatry, Yale University School of Medicine New Haven, Connecticut.
authors.forename: Anderson
authors.initials: A
authors.lastname: Winkler
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine Baltimore, Maryland ; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University Baltimore, Maryland.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Rowland
authors.affiliation: Department of Psychiatry, University of Texas Health Science Center at San Antonio San Antonio, Texas.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Mathias
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine Baltimore, Maryland.
authors.forename: Susan N
authors.initials: SN
authors.lastname: Wright
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine Baltimore, Maryland.
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
authors.affiliation: Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine Baltimore, Maryland.
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.affiliation: Department of Psychiatry, University of Texas Health Science Center at San Antonio San Antonio, Texas.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Dougherty
mesh_terms: D000293:Adolescent; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001931:Brain Mapping; D002648:Child; D003342:Corpus Striatum / Q000503:physiopathology*; D056344:Executive Function / Q000502:physiology; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007266:Inhibition, Psychological; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology; D066244:Proton Magnetic Resonance Spectroscopy; D011597:Psychomotor Performance / Q000502:physiology*; D012815:Signal Processing, Computer-Assisted; D019966:Substance-Related Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D066127:White Matter / Q000473:pathology / Q000503:physiopathology*
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate
keywords: Family history; functional magnetic resonance imaging; go/no-go task; risk; substance use; white matter integrity