title: Mode of Anisotropy Reveals Global Diffusion Alterations in Attention-Deficit/Hyperactivity Disorder.
abstract: OBJECTIVE
  Diffusion tensor imaging (DTI) can identify structural connectivity alterations in attention-deficit/hyperactivity disorder (ADHD). Most ADHD DTI studies have concentrated on regional differences in fractional anisotropy (FA) despite its limited sensitivity to complex white matter architecture and increasing evidence of global brain differences in ADHD. Here, we examine multiple DTI metrics in separate samples of children and adults with and without ADHD with a principal focus on global between-group differences.
  
  
  METHODS
  Two samples: adults with ADHD (n = 42) and without (n = 65) and children with ADHD (n = 82) and without (n = 80) were separately group matched for age, sex, and head motion. Five DTI metrics (FA, axial diffusivity, radial diffusivity, mean diffusivity, and mode of anisotropy) were analyzed via tract-based spatial statistics. Group analyses tested for diagnostic differences at the global (averaged across the entire white matter skeleton) and regional level for each metric.
  
  
  RESULTS
  Robust global group differences in diffusion indices were found in adults, with the largest effect size for mode of anisotropy (MA; Cohen's d = 1.45). Global MA also differed significantly between groups in the pediatric sample (d = 0.68). In both samples, global MA increased classification accuracy compared to the model with clinical Conners' ADHD ratings alone. Regional diagnostic differences did not survive familywise correction for multiple comparisons.
  
  
  CONCLUSIONS
  Global DTI metrics, particularly the mode of anisotropy, which is sensitive to crossing fibers, capture connectivity abnormalities in ADHD across both pediatric and adult samples. These findings highlight potential diffuse white matter microarchitecture differences in ADHD.
authors.affiliation: New York University, New York.
authors.forename: Yuliya N
authors.initials: YN
authors.lastname: Yoncheva
authors.affiliation: New York University, New York.
authors.forename: Krishna
authors.initials: K
authors.lastname: Somandepalli
authors.affiliation: New York University, New York; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY.
authors.forename: Philip T
authors.initials: PT
authors.lastname: Reiss
authors.affiliation: New York University, New York; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY; Institute of Neuroscience, Trinity College Dublin, Ireland.
authors.forename: Clare
authors.initials: C
authors.lastname: Kelly
authors.affiliation: New York University, New York.
authors.forename: Adriana
authors.initials: A
authors.lastname: Di Martino
authors.affiliation: New York University, New York.
authors.forename: Mariana
authors.initials: M
authors.lastname: Lazar
authors.affiliation: Center for Cognitive Neuroscience, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Nathan Kline Institute for Psychiatric Research, Orangeburg, NY; Child Mind Institute, New York.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Milham
authors.affiliation: New York University, New York; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY. Electronic address: castef01@nyumc.org.
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Castellanos
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D056324:Diffusion Tensor Imaging / Q000379:methods* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D066127:White Matter / Q000000981:diagnostic imaging / Q000502:physiology / Q000503:physiopathology
keywords: ADHD; DTI; adults; biomarkers; fractional anisotropy