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Comparative meta-analyses of brain structural and functional abnormalities during cognitive control in attention-deficit/hyperactivity disorder and autism spectrum disorder
Open accessAbstract
Background: People with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have abnormalities in frontal, temporal, parietal and striato-thalamic networks. It is unclear to what extent these abnormalities are distinctive or shared. This comparative meta-analysis aimed to identify the most consistent disorder-differentiating and shared structural and functional abnormalities. Methods: Systematic literature search was conducted for whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies of cognitive control comparing people with ASD or ADHD with typically developing controls. Regional gray matter volume (GMV) and fMRI abnormalities during cognitive control were compared in the overall sample and in age-, sex- and IQ-matched subgroups with seed-based d mapping meta-analytic methods. Results: Eighty-six independent VBM (1533 ADHD and 1295 controls; 1445 ASD and 1477 controls) and 60 fMRI datasets (1001 ADHD and 1004 controls; 335 ASD and 353 controls) were identified. The VBM meta-analyses revealed ADHD-differentiating decreased ventromedial orbitofrontal ( z = 2.22, p < 0.0001) but ASD-differentiating increased bilateral temporal and right dorsolateral prefrontal GMV ( z s ⩾ 1.64, p s ⩽ 0.002). The fMRI meta-analyses of cognitive control revealed ASD-differentiating medial prefrontal underactivation but overactivation in bilateral ventrolateral prefrontal cortices and precuneus ( z s ⩾ 1.04, p s ⩽ 0.003). During motor response inhibition specifically, ADHD relative to ASD showed right inferior fronto-striatal underactivation ( z s ⩾ 1.14, p s ⩽ 0.003) but shared right anterior insula underactivation. Conclusions: People with ADHD and ASD have mostly distinct structural abnormalities, with enlarged fronto-temporal GMV in ASD and reduced orbitofrontal GMV in ADHD; and mostly distinct functional abnormalities, which were more pronounced in ASD.
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“Comparative meta-analyses show that structural grey matter volume reductions in basal ganglia and insula are disorder-specific relative to OCD in 30 data sets with 1,870 participants (Norman et al., 2016) while medial frontal reductions were specific to ASD in 66 data sets with 3,610 participants (Lukito et al., 2020).”
From The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder (2021) · cites this paper as Lukito et al., 2020
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“The functional under-activations in right inferior frontal cortex and basal ganglia during tasks of cognitive control were disorder-specific relative to OCD in 1,870 participants (Norman et al., 2016), while the inferior frontal dysfunction was specific relative to autism in 3,610 participants (Lukito et al., 2020).”
From The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder (2021) · cites this paper as Lukito et al., 2020
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“A meta-analysis of 21 functional MRI studies with 607 participants found that those with ADHD showed consistent and replicable under-activation in typical regions of inhibitory control such as right inferior frontal cortex, supplementary motor area and the basal ganglia relative to typically developing individuals (Hart et al., 2013). The inferior frontal under-activation findings were replicated”
From The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder (2021) · cites this paper as Lukito et al., 2020
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“Meta-analyses and systematic reviews showed that the medications used to treat ADHD are not associated with observed deficits in brain structure (Hoogman et al., 2017; Hoogman et al., 2019; Lukito et al., 2020; Norman et al., 2016; Spencer et al., 2013), but with improved brain function, most prominently in inferior frontal and striatal regions (Hart et al., 2013; Lukito et al., 2020; Norman et al”
From The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder (2021) · cites this paper as Lukito et al., 2020
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“Similarly, previous large scale studies and meta-analyses of neuroimaging, neurophysiological and neuropsychological impairments have highlighted areas of overlap, particularly between ADHD and ASD 53-56 .”
From Candidate diagnostic biomarkers for neurodevelopmental disorders in children and adolescents: a systematic review (2023) · cites this paper as [54]
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“Enlarged fronto-temporal GMV in ASD was reported in previous studies [61], which is consistent with our results.”
From Confound Controlled Multimodal Neuroimaging Data Fusion and Its Application to Developmental Disorders (2025) · cites this paper as [61]
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“Recent findings suggest that early brain overgrowth is not a defining characteristic of toddlers with high-risk for developing ASD (Hazlett et al., 2017), and may be specific to boys with regressive autism (Nordahl et al., 2011), who are underrepresented across studies.”
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“The inferior frontal under-activation findings were replicated in two further fMRI meta-analyses of inhibitory control with 33 datasets/1161 participants, and 42 data-sets/2005 participants, respectively (Lukito et al., 2020; Norman et al., 2016).”
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Postural Control in Childhood: Investigating the Neurodevelopmental Gradient Hypothesis
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“Enlarged fronto-temporal GMV in ASD was reported in previous studies [61], which is consistent with our results.”
Metadata
- Authors
- Lukito, S., Norman, L., Carlisi, C., Radua, J., Hart, H., Simonoff, E., & Rubia, K.
- Affiliations
- King's College London (GB)
- National Institutes of Health (US)
- Corresponding author
- Lukito, Steve
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2020-03-27
- Volume
- 50
- Issue
- 6
- Pages
- 894-919
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- PMC
- PMC7212063
- OpenAlex
- W2998651304
- Semantic Scholar
- 149256fab88748ba0bc73fec857807db9020efac
- Cited by
- 248
- References
- 246
- Citations by year
- 2026: 27 · 2025: 43 · 2024: 47 · 2023: 50 · 2022: 38 · 2021: 36 · 2020: 6
- FWCI
- 23.71
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (206459/Z/17/Z, Z/17/Z, 206459)
- Maudsley Charity
- National Institute for Health and Care Research (NF-SI-0514-10073, IS-BRC-1215, BRC-1215-20018, RP-PG-1211-20016, IS-BRC-1215–20018)
- King's College London (IS-BRC-1215-20018, 115300)
- European Commission (115300, CPII19/00009)
- Fondation pour la Recherche Médicale
- Institute of Psychiatry, Psychology and Neuroscience, King’s College London
- Medical Research Council (MR/P012647/1, 115300, MR/P019293/1, MR/R000832/1)
- Economic and Social Research Council (ESRC 003041/1, 003041/1)
- Instituto de Salud Carlos III ((CPII19/00009), PI19/00394)
- European Regional Development Fund (CPII19/00009)
- European Social Fund (CPII19/00009)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- attention deficit hyperactivity disorder, autism spectrum disorder, cognitive control, structural brain abnormalities, functional brain abnormalities, gray matter volume, dorsolateral prefrontal cortex, medial prefrontal cortex, ventrolateral prefrontal cortex, precuneus, anterior insula, response inhibition, seed-based d mapping
- MeSH terms
- Autism Spectrum Disorder, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Brain, Cerebral Cortex, Child, Cognition, Female, Humans, Magnetic Resonance Imaging, Male, Parietal Lobe, Thalamus, Young Adult, Gray Matter
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