Large-scale brain systems in ADHD: beyond the prefrontal–striatal model
Open accessAbstract
Attention-deficit/hyperactivity disorder (ADHD) has long been thought to reflect dysfunction of prefrontal-striatal circuitry, with involvement of other circuits largely ignored. Recent advances in systems neuroscience-based approaches to brain dysfunction have facilitated the development of models of ADHD pathophysiology that encompass a number of different large-scale resting-state networks. Here we review progress in delineating large-scale neural systems and illustrate their relevance to ADHD. We relate frontoparietal, dorsal attentional, motor, visual and default networks to the ADHD functional and structural literature. Insights emerging from mapping intrinsic brain connectivity networks provide a potentially mechanistic framework for an understanding of aspects of ADHD such as neuropsychological and behavioral inconsistency, and the possible role of primary visual cortex in attentional dysfunction in the disorder.
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Higher cortical centers involved in motor control, monitoring for salient stimuli, and shifting attention flexibly may play a more indirect role in emotion dysregulation in ADHD.
“Higher cortical centers involved in motor control (supplementary motor areas, motor cortex), monitoring for salient stimuli (temporoparietal junction, frontal operculum) and in shifting attention flexibly (frontal eye fields, intraparietal sulcus) may play a more indirect role (109).”
From Emotion Dysregulation in Attention Deficit Hyperactivity Disorder (2014) · cites this paper as [109]
The Motor network and dorsal and ventral attentional networks sections identify the cited motor regions and describe the named attentional regions as monitoring salient stimuli or shifting attention. Our copy does not say these regions play an indirect role in emotion dysregulation in ADHD; that connection goes beyond what the source reports. (LLM, conf=0.84)
Experimental — accuracy not yet measuredResearch has demonstrated hypoactivity and reduced connectivity within the Central Executive Network (CEN) in adults with ADHD, which correlates with deficits in executive functioning, cognitive flexibility, and goal-directed behavior.
“Research has demonstrated hypoactivity and reduced connectivity within the CEN in adults with ADHD, which correlates with deficits in executive functioning, cognitive flexibility, and goal-directed behavior”
From ADHD in Adulthood: Clinical Presentation, Comorbidities, and Treatment Perspectives (2025) · cites this paper as [79]
The Fronto-parietal network section describes the executive control circuit as supporting goal-directed processes and flexibility, and reports hypoactivation during inhibitory tasks in children with ADHD. It does not establish reduced connectivity within that network in adults with ADHD or show that both abnormalities correlate with the stated deficits. The Default network section discusses connectivity and performance, but does not establish that adult-specific CEN relationship. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThese impairments often manifest as increased distractibility or elevated mind-wandering, as well as hyperactivity of the default network and weaker anticorrelations with networks involved in external attention.
“These impairments often manifest as increased distractibility or elevated levels of mind-wandering,212,228–231 as well as hyperactivity of the DN and weaker anticorrelations with networks involved in external attention.146–148,229,232–235”
From The default network and self-generated thought: component processes, dynamic control, and clinical relevance (2014) · cites this paper as [232]
Individuals with ADHD exhibit elevated response-time variability, supporting theories that the default network interferes with maintenance of external task goals by periodically disrupting on-task attention.
“In addition to these manifestations, individuals with ADHD also exhibit elevated response-time variability,236 supporting theories that the DN interferes with maintenance of external task goals by periodically disrupting on-task attention.146,232”
From The default network and self-generated thought: component processes, dynamic control, and clinical relevance (2014) · cites this paper as [232]
It is unlikely that significant functional brain abnormalities characterizing ADHD would be evident regardless of the mental state of the test subject during the scan.
“It is also unlikely that significant functional brain abnormalities characterizing ADHD would be evident regardless of the mental state of the test subject, during the scan (Castellanos and Proal, 2012; Hammer et al., 2015).”
From Functional neuroimaging of visuospatial working memory tasks enables accurate detection of attention deficit and hyperactivity disorder (2015) · cites this paper as Castellanos and Proal, 2012
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Adıgüzel Akman, Ö., & Bıyıklı, C. (2026) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.70151
- Authors
- Castellanos, F. X., & Proal, E.
- Affiliations
- Nathan Kline Institute for Psychiatric Research (US)
- NYU Langone Health (US)
- Corresponding author
- Castellanos, F. Xavier
- Venue
- Trends in Cognitive Sciences
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 16
- Issue
- 1
- Pages
- 17-26
- ISSN
- 1364-6613 (ISSN-L)
- PMC
- PMC3272832
- OpenAlex
- W2131578768
- Cited by
- 831
- References
- 104
- Citations by year
- 2026: 133 · 2025: 60 · 2024: 37 · 2023: 38 · 2022: 48 · 2021: 52 · 2020: 56 · 2019: 52 · 2018: 47 · 2017: 51 · 2016: 65 · 2015: 62 · 2014: 71 · 2013: 37 · 2012: 22
- FWCI
- 5.44
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Trends in Cognitive Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH083246, R01MH081218)
- National Institute on Drug Abuse (R01DA016979)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- attention deficit hyperactivity disorder, large-scale brain networks, resting-state networks, frontoparietal network, dorsal attention network, motor network, visual network, default mode network, intrinsic brain connectivity, ADHD pathophysiology, primary visual cortex, attentional dysfunction, behavioral inconsistency
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Brain, Brain Mapping, Humans, Magnetic Resonance Imaging, Models, Neurological, Neural Pathways, Visual Cortex
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