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. 2017 Nov 1;82(9):660-668.
doi: 10.1016/j.biopsych.2017.01.003. Epub 2017 Jan 13.

Inattention and Reaction Time Variability Are Linked to Ventromedial Prefrontal Volume in Adolescents

Matthew D Albaugh  1 , Catherine Orr  2 , Bader Chaarani  2 , Robert R Althoff  2 , Nicholas Allgaier  2 , Nicholas D'Alberto  2 , Kelsey Hudson  2 , Scott Mackey  2 , Philip A Spechler  2 , Tobias Banaschewski  3 , Rüdiger Brühl  4 , Arun L W Bokde  5 , Uli Bromberg  6 , Christian Büchel  6 , Anna Cattrell  7 , Patricia J Conrod  8 , Sylvane Desrivières  7 , Herta Flor  9 , Vincent Frouin  10 , Jürgen Gallinat  11 , Robert Goodman  12 , Penny Gowland  13 , Yvonne Grimmer  9 , Andreas Heinz  14 , Viola Kappel  15 , Jean-Luc Martinot  16 , Marie-Laure Paillère Martinot  17 , Frauke Nees  9 , Dimitri Papadopoulos Orfanos  10 , Jani Penttila  18 , Luise Poustka  3 , Tomáš Paus  19 , Michael N Smolka  20 , Maren Struve  9 , Henrik Walter  14 , Robert Whelan  21 , Gunter Schumann  7 , Hugh Garavan  2 , Alexandra S Potter  2
Affiliations

Inattention and Reaction Time Variability Are Linked to Ventromedial Prefrontal Volume in Adolescents

Matthew D Albaugh et al. Biol Psychiatry. .

Abstract

Background: Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have most commonly reported volumetric abnormalities in the basal ganglia, cerebellum, and prefrontal cortices. Few studies have examined the relationship between ADHD symptomatology and brain structure in population-based samples. We investigated the relationship between dimensional measures of ADHD symptomatology, brain structure, and reaction time variability-an index of lapses in attention. We also tested for associations between brain structural correlates of ADHD symptomatology and maps of dopaminergic gene expression.

Methods: Psychopathology and imaging data were available for 1538 youths. Parent ratings of ADHD symptoms were obtained using the Development and Well-Being Assessment and the Strengths and Difficulties Questionnaire (SDQ). Self-reports of ADHD symptoms were assessed using the youth version of the SDQ. Reaction time variability was available in a subset of participants. For each measure, whole-brain voxelwise regressions with gray matter volume were calculated.

Results: Parent ratings of ADHD symptoms (Development and Well-Being Assessment and SDQ), adolescent self-reports of ADHD symptoms on the SDQ, and reaction time variability were each negatively associated with gray matter volume in an overlapping region of the ventromedial prefrontal cortex. Maps of DRD1 and DRD2 gene expression were associated with brain structural correlates of ADHD symptomatology.

Conclusions: This is the first study to reveal relationships between ventromedial prefrontal cortex structure and multi-informant measures of ADHD symptoms in a large population-based sample of adolescents. Our results indicate that ventromedial prefrontal cortex structure is a biomarker for ADHD symptomatology. These findings extend previous research implicating the default mode network and dopaminergic dysfunction in ADHD.

Keywords: Attention-deficit/hyperactivity disorder; Inattention; Multi-informant; Neuroimaging; Reaction time variability; Ventromedial prefrontal cortex.

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Conflict of interest statement

Disclosures

The other authors report no biomedical financial interests or potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Results from whole brain voxel-wise analyses. Age, gender, total gray matter volume (GMV), site, pubertal development, Performance IQ, Verbal IQ, and socio-economic status were controlled for in the analyses. An initial height threshold of p ≤ .005 was implemented at the voxel level, with a corrected family-wise error (FWE; p ≤ .05) subsequently applied to identify significant clusters. To visualize overlap in findings. the image on the right is a composite of all associations.
FIGURE 2
FIGURE 2
Results from whole brain voxel-wise analyses using Hyperactive/Impulsive and Inattentive symptom counts. Age, gender, total gray matter volume (GMV), site, pubertal development, Performance IQ, Verbal IQ, and socio-economic status were controlled for in the analyses. An initial height threshold of p ≤ .005 was implemented at the voxel level, with a corrected family-wise error (FWE; p ≤ .05) subsequently applied to identify significant clusters.
FIGURE 3
FIGURE 3
Figure illustrates region of overlap between parent DAWBA, parent SDQ, youth SDQ, and reaction time variability. Age, gender, total gray matter volume (GMV), site, pubertal development, Performance IQ, Verbal IQ, and socio-economic status were controlled for in the analyses. An initial height threshold of p ≤ .005 was implemented at the voxel level, with a corrected family-wise error (FWE; p ≤ .05) subsequently applied to identify significant clusters.
FIGURE 4
FIGURE 4
Scatter plot depicting the relationship between normalized gene expression values (y axis) and t-statistic value (x axis) corresponding to the association between gray matter volume (GMV) and multi-informant average of ADHD symptoms. Positive t values indicate an inverse association between GMV and symptomatology, whereas negative t values represent a positive association between GMV and ADHD symptomatology.
FIGURE 5
FIGURE 5
Scatter plot depicting the relationship between normalized gene expression values (y axis) and T-statistic value (x axis) corresponding to the association between gray matter volume (GMV) and multi-informant average of ADHD symptoms. Positive t values indicate an inverse association between GMV and symptomatology, whereas negative t values represent a positive association between GMV and ADHD symptomatology.
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