Inattention and reaction time variability are linked to ventromedial prefrontal volume in adolescents
Open accessAbstract
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.
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A second fronto-striatal circuit involving the nucleus accumbens and orbitofrontal cortex has been proposed to be associated with ADHD.
“a second fronto-striatal circuit involving the nucleus accumbens and orbitofrontal cortex has been proposed to be associated with ADHD (23–25).”
From Abnormal functional connectivity associated with emotional dysregulation in children with attention-deficit/hyperactivity disorder (2025) · cites this paper as [25]
The Introduction reports ADHD-related abnormalities in the basal ganglia and prefrontal cortex, and the Results link ADHD symptoms to orbital lateral prefrontal volume (page numbers unavailable). The paper does not identify a second fronto-striatal circuit involving the nucleus accumbens and orbitofrontal cortex. (LLM, conf=0.79)
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Ventromedial prefrontal volume in adolescence predicts hyperactive/inattentive symptoms in adulthood
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Can biomarkers be used to diagnose attention deficit hyperactivity disorder?
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“In a large population-based study on adolescents (n = 1,538), a negative correlation was found between ventromedial PFC volume and self-reported ADHD symptom severity and reaction time variability (6).”
BackgroundRecreational Marijuana Use, Adolescent Cognitive Development, and Schizophrenia Susceptibility
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“…using ADHD as a categorical construct (Albrecht et al., 2013; Epstein et al., 2011; Klein et al., 2006; Ryan et al., 2017; Scheres et al., 2001), and by studies measuring the symptoms of ADHD along a dimensional construct (Albaugh et al., 2017; Gomez-Guerrero et al., 2011; Mairena et al., 2012).”
Mapping causal links between prefrontal cortical regions and intra-individual behavioral variability
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“Accumulated evidence indicates that the intra-individual RT variability is signi fi cantly exaggerated in aging 1,6,8,10 , in neuropsychological disorders and patients af fl icted with brain injuries 4,11 – 15 , and has even been shown to predict the all-cause mortality rate of the elderly 12 .”
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“In the same sample, gray matter volume in an overlapping region of the ventromedial PFC was inversely associated with RT-ISV (Albaugh et al., 2017).”
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“…De Felice and Holland, 2018; Hilborn et al., 2009; West et al., 2002) and in patients afflicted with brain injuries or neuropsychological disorders (Albaugh et al., 2017; Batterham et al., 2014; Hill et al., 2013; Kofler et al., 2013; Panagiotaropoulou et al., 2019; Stuss et al., 2003) and even…”
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“Many studies of ADHD have reported volumetric abnormalities in PFC and indicated that ventromedial prefrontal cortex structure is a biomarker for ADHD symptomatology (Albaugh et al., 2017; Bayard et al., 2020; Restrepo-Lozano et al., 2022).”
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“…such as cortical thinning (Shaw et al. 2011; Ducharme et al. 2012; Mous et al. 2014), putamen (Mous et al. 2015) and prefrontal gray matter volume (Albaugh et al. 2017, 2019), and functional connectivity (Hilger and Fiebach 2019; Rohr et al. 2019) have shown associations with inattention and/or…”
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The ventromedial prefrontal cortex: a putative locus for trait inattention
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“29,30 These results suggest that DLPFC enlargement is not restricted to case ‐ defined ADHD samples and may also be detectable as subtle trait ‐ related neuroanatomical variability within the general population.”
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“, 2015) and volume (Albaugh et al., 2017), presence of amyloid beta pathology (Lu et al.”
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“differences at the fusiform gyrus level (32-36).”
- Authors
- Albaugh, M. D., Orr, C., Chaarani, B., Althoff, R. R., Allgaier, N., D’Alberto, N., Hudson, K., Mackey, S., Spechler, P. A., Banaschewski, T., Brühl, R., Bokde, A. L. W., Bromberg, U., Büchel, C., Cattrell, A., Conrod, P. J., Desrivières, S., Flor, H., Frouin, V., Gallinat, J., Goodman, R., Gowland, P., Grimmer, Y., Heinz, A., Kappel, V., Martinot, J.-L., Paillère Martinot, M.-L., Nees, F., Orfanos, D. P., Penttila¨, J., Poustka, L., Paus, T., Smolka, M. N., Struve, M., Walter, H., Whelan, R., Schumann, G., Garavan, H., & Potter, A. S.
- Affiliations
- University of Vermont (US)
- Heidelberg University (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Trinity College Dublin (IE)
- University Medical Center Hamburg-Eppendorf (DE)
- University of Nottingham (GB)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Inserm (FR)
- University of Toronto (CA)
- Neuroimaging Center (DE)
- University College Dublin (IE)
- Corresponding author
- Albaugh, Matthew D.
- ORCID
- Albaugh, Matthew D.
- Orr, Catherine
- Chaarani, Bader
- Althoff, Robert R.
- Allgaier, Nicholas
- D’Alberto, Nicholas
- Hudson, Kelsey
- Mackey, Scott
- Spechler, Philip A.
- Banaschewski, Tobias
- Brühl, Rüdiger
- Bokde, Arun L.W.
- Bromberg, Uli
- Büchel, Christian
- Conrod, Patricia J.
- Desrivières, Sylvane
- Flor, Herta
- Frouin, Vincent
- Gallinat, Jürgen
- Goodman, Robert
- Gowland, Penny
- Grimmer, Yvonne
- Heinz, Andreas
- Martinot, Jean-Luc
- Nees, Frauke
- Orfanos, Dimitri Papadopoulos
- Poustka, Luise
- Paus, Tomáš
- Smolka, Michael N.
- Struve, Maren
- Walter, Henrik
- Whelan, Robert
- Garavan, Hugh
- Potter, Alexandra S.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 82
- Issue
- 9
- Pages
- 660-668
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC5509516
- OpenAlex
- W2572261981
- Cited by
- 63
- References
- 51
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 10 · 2023: 7 · 2022: 5 · 2021: 5 · 2020: 17 · 2019: 4 · 2018: 8 · 2017: 1
- FWCI
- 6.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- GRO (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
- Papyrus : Institutional Repository (Université de Montréal) (submittedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Funders
- Wellcome Trust (U54 EB020403)
- National Institute for Health and Care Research (eMED SysAlc01ZX1311A, SFB 940/1, SM 80/7-2, SM 80/7-1, 01EV0711, 01GS08152, U54 EB020403, SysAlc01ZX1311A)
- European Commission (602450, U54 EB020403, SFB 940, 115300, SM 80/7-2, RO1 MH085772-01A1, 603016, MR/N000390/1, LSHMCT-2007-037286, 01EV0711, 602805)
- Deutsche Forschungsgemeinschaft (SFB) 940/1, LSHM-CT-2007-037286, U54 EB020403, MR/N000390/1, 01GS08152, SM 80/7–2, 602805, RO1 MH085772-01A1, 01EV0711, SM 80/7-1, SFB940)
- Svenska Forskningsrådet Formas (MR/N000390/1)
- Bundesministerium für Bildung und Forschung (eMED SysAlc01ZX1311A, U54 EB020403, RO1 MH085772-01A1, MR/N000390/1, SFB 940/1, LSHM-CT-2007-037286, SFB 940, 01GS08152, SysAlc01ZX1311A, SM 80/7-2, 01EV0711)
- Forskningsrådet om Hälsa, Arbetsliv och Välfärd
- National Institutes of Health (SFB 940, SM 80/7-2, LSHM-CT-2007-037286, 01GS08152, MR/N000390/1, 01EV0711, MH085772‐01A1, EB020403, RO1 MH085772-01A1)
- Medical Research Council (MR/N000390/1, RO1 MH085772-01A1, 115300, LSHM-CT-2007-037286, SFB 940/1, 01EV0711, 01GS08152, 93558, SM 80/7-2, SM 80/7-1, SFB 940, eMED SysAlc01ZX1311A, U54 EB020403)
- National Institute of Mental Health (L40 MH108486, R01MH085772)
- National Institute on Drug Abuse (P50DA036114)
- National Institute of General Medical Sciences (P20GM103644)
- National Institute of Biomedical Imaging and Bioengineering (U54EB020403)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, ventromedial prefrontal cortex, gray matter volume, reaction time variability, inattention, adolescents, dopamine D1 receptor, DRD2, default mode network
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Female, Humans, Male, Reaction Time, Prefrontal Cortex
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