No Association between Cortical Gyrification or Intrinsic Curvature and Attention-deficit/Hyperactivity Disorder in Adolescents and Young Adults.

Natalie J Forde,Catharina A Hartman,Aaron F Alexander-Bloch,Pieter J Hoekstra,Marcel P Zwiers,Jaap Oosterlaan,Dirk J Heslenfeld,Jan K Buitelaar,Stephen V Faraone,Lisa Ronan

doi:10.3389/fnins.2017.00218

Abstract

Magnetic resonance imaging (MRI) studies have highlighted subcortical, cortical, and structural connectivity abnormalities associated with attention-deficit/hyperactivity disorder (ADHD). Gyrification investigations of the cortex have been inconsistent and largely negative, potentially due to a lack of sensitivity of the previously used morphological parameters. The innovative approach of applying intrinsic curvature analysis, which is predictive of gyrification pattern, to the cortical surface applied herein allowed us greater sensitivity to determine whether the structural connectivity abnormalities thus far identified at a centimeter scale also occur at a millimeter scale within the cortical surface. This could help identify neurodevelopmental processes that contribute to ADHD. Structural MRI datasets from the NeuroIMAGE project were used [n = 306 ADHD, n = 164 controls, and n = 148 healthy siblings of individuals with ADHD (age in years, mean(sd); 17.2 (3.4), 16.8 (3.2), and 17.7 (3.8), respectively)]. Reconstructions of the cortical surfaces were computed with FreeSurfer. Intrinsic curvature (taken as a marker of millimeter-scale surface connectivity) and local gyrification index were calculated for each point on the surface (vertex) with Caret and FreeSurfer, respectively. Intrinsic curvature skew and mean local gyrification index were extracted per region; frontal, parietal, temporal, occipital, cingulate, and insula. A generalized additive model was used to compare the trajectory of these measures between groups over age, with sex, scanner site, total surface area of hemisphere, and familiality accounted for. After correcting for sex, scanner site, and total surface area no group differences were found in the developmental trajectory of intrinsic curvature or local gyrification index. Despite the increased sensitivity of intrinsic curvature, compared to gyrification measures, to subtle morphological abnormalities of the cortical surface we found no milimeter-scale connectivity abnormalities associated with ADHD.

Highlights

IntroductionAttention-deficit/hyperactivity disorder (ADHD) has been proposed to be a dysconnectivity disorder (Konrad and Eickhoff, 2010) where neural circuits are implicated rather than regions, and there has been a move toward investigating ADHD, and other disorders, in terms of connectivity and integration instead of segregation; where specific regional abnormalities are implicated (Friston, 2011)
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder affecting∼5% of the school age population (Polanczyk et al, 2007) and characterized by pervasive inattention and/or hyperactivity and impulsivity leading to impairments of functioning (American Psychiatric Association, 2013).ADHD has been proposed to be a dysconnectivity disorder (Konrad and Eickhoff, 2010) where neural circuits are implicated rather than regions, and there has been a move toward investigating ADHD, and other disorders, in terms of connectivity and integration instead of segregation; where specific regional abnormalities are implicated (Friston, 2011)
We found no difference between the groups with respect to either intrinsic curvature or local gyrification index within any of the regions investigated

Summary

Introduction

ADHD has been proposed to be a dysconnectivity disorder (Konrad and Eickhoff, 2010) where neural circuits are implicated rather than regions, and there has been a move toward investigating ADHD, and other disorders, in terms of connectivity and integration instead of segregation; where specific regional abnormalities are implicated (Friston, 2011) This shift has come in both functional and structural studies, with recent diffusion magnetic resonance imaging (dMRI) analysis concentrating on network connectivity based on white matter tracts as opposed to the traditional voxel-based or region-of-interest analyses (Cao et al, 2013; Hong et al, 2014). A meta-analysis and contemporary review of the available dMRI data revealed that multiple white matter tracts are affected in ADHD, including the anterior corona radiata, forceps minor, and superior and inferior longitudinal fasciculi (Liston et al, 2011; van Ewijk et al, 2012) These white matter tracts consist of bundles of long-range axonal fibers that connect distant gray matter regions (e.g., cortical to sub-cortical structures, inter-hemispheric connections, or frontal to parietal lobes, etc.). Within this study we ask; are these long range abnormalities echoed in the short range connections within the cortex?

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Conclusion