Journal Article

Head Motion and Inattention/Hyperactivity Share Common Genetic Influences: Implications for fMRI Studies of ADHD

McMahon, Katie L., Couvy-Duchesne, Baptiste, Hickie, Ian B., Wright, Margaret J., Ebejer, Jane L., Gillespie, Nathan A., de Zubicaray, Greig I., Martin, Nicholas G., Medland, Sarah E., Thompson, Paul M., Duffy, David L.

2016

Overview

Head motion (HM) is a well known confound in analyses of functional MRI (fMRI) data. Neuroimaging researchers therefore typically treat HM as a nuisance covariate in their analyses. Even so, it is possible that HM shares a common genetic influence with the trait of interest. Here we investigate the extent to which this relationship is due to shared genetic factors, using HM extracted from resting-state fMRI and maternal and self report measures of Inattention and Hyperactivity-Impulsivity from the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour (SWAN) scales. Our sample consisted of healthy young adult twins (N = 627 (63% females) including 95 MZ and 144 DZ twin pairs, mean age 22, who had mother-reported SWAN; N = 725 (58% females) including 101 MZ and 156 DZ pairs, mean age 25, with self reported SWAN). This design enabled us to distinguish genetic from environmental factors in the association between head movement and ADHD scales. HM was moderately correlated with maternal reports of Inattention (r = 0.17, p-value = 7.4E-5) and Hyperactivity-Impulsivity (r = 0.16, p-value = 2.9E-4), and these associations were mainly due to pleiotropic genetic factors with genetic correlations [95% CIs] of rg = 0.24 [0.02, 0.43] and rg = 0.23 [0.07, 0.39]. Correlations between self-reports and HM were not significant, due largely to increased measurement error. These results indicate that treating HM as a nuisance covariate in neuroimaging studies of ADHD will likely reduce power to detect between-group effects, as the implicit assumption of independence between HM and Inattention or Hyperactivity-Impulsivity is not warranted. The implications of this finding are problematic for fMRI studies of ADHD, as failing to apply HM correction is known to increase the likelihood of false positives. We discuss two ways to circumvent this problem: censoring the motion contaminated frames of the RS-fMRI scan or explicitly modeling the relationship between HM and Inattention or Hyperactivity-Impulsivity.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adolescent / Adult / Attention / Attention Deficit Disorder with Hyperactivity - diagnosis / Attention Deficit Disorder with Hyperactivity - genetics / Attention Deficit Disorder with Hyperactivity - physiopathology / Attention deficit hyperactivity disorder / Brain - physiopathology / Brain research / Child & adolescent psychiatry / Connectivity / Correlation / Diagnosis / Diseases in Twins - diagnosis / Diseases in Twins - genetics / Diseases in Twins - physiopathology / Environmental factors / Error analysis / Female / Females / Functional magnetic resonance imaging / Genetic aspects / Genetic factors / Genetics / Group effects / Head / Head movement / Head Movements / Health aspects / Humans / Hyperactivity / Hyperkinesis - diagnosis / Hyperkinesis - genetics / Hyperkinesis - physiopathology / Impulsive Behavior / Impulsivity / Magnetic resonance imaging / Magnetic Resonance Imaging - statistics & numerical data / Male / Medical imaging / Medical research / Methods / Mothers / Movement (Physiology) / Neuroimaging / Neuroimaging - statistics & numerical data / Neurology / Noise / Nuisance / Phenotype / Physiological aspects / Pleiotropy / Self Report / Studies / Twins, Dizygotic / Twins, Monozygotic