Defining the neural substrate of the adult outcome of childhood ADHD: a multimodal neuroimaging study of response inhibition
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OBJECTIVE: Understanding the neural processes tied to the adult outcome of childhood attention deficit hyperactivity disorder (ADHD) could guide novel interventions to improve its clinical course. It has been argued that normalization of prefrontal cortical activity drives remission from ADHD, while anomalies in subcortical processes are "fixed," present even in remission. Using multimodal neuroimaging of inhibitory processes, the authors tested these hypotheses in adults followed since childhood, contrasting remitted against persistent ADHD. METHOD: Adult participants (persistent ADHD, N=35; remit-ted ADHD, N=47; never affected, N=99) were scanned with functional MRI (fMRI) (N=85), magnetoencephalography (N=33), or both (N=63) during a response inhibition task. RESULTS: In fMRI analyses, during inhibition, right caudate anomalies reflected a childhood ADHD history and were present even among those who remitted. By contrast, differences related to adult outcome emerged in cortical (right inferior frontal and inferior parietal/precuneus) and cerebellar regions. The persistent ADHD group showed under-activation, whereas the remitted ADHD group did not differ significantly from the never-affected group. Magnetoencephalography showed that the association between adult symptom severity and prefrontal neuronal activity was confined to the time window covering the act of inhibition (300 ms-350 ms). Group differences in cerebellar and parietal neuronal activity occurred during the time window of performance monitoring processes (500 ms-600 ms). CONCLUSIONS: By combining fMRI and magnetoencephalography, the location and time window of neuronal activity that underpins the adult outcome of ADHD was pinpointed. Thus, the cortico-cerebellar processes tied to the clinical course of ADHD are separated from the subcortical processes that are not.
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These studies also reported that ADHD symptom remission is linked to normalized brain activities in anterior cingulate cortex and cerebellar regions.
“However, these studies also reported that ADHD symptom remission also link to normalized brain activities in anterior cingulate cortex and cerebellar regions (Francx et al., 2015; Szekely et al., 2017).”
From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Szekely et al., 2017
The Discussion section on the adult outcome of childhood ADHD reports partial normalization of cerebellar activity with remission. The Results and Discussion identify inferior frontal and parietal regions, but do not report normalized activity in the anterior cingulate cortex; the Results mention a posterior cingulate cluster instead. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNonstimulants may improve deficits in response inhibition and tendencies for impulsive choices in ADHD individuals.
“and may in turn, improve deficits in response inhibition and tendencies for impulsive choices in ADHD individuals”
From Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: A comparative neuroimaging analysis (2024) · cites this paper as Szekely, Sudre, Sharp, Leibenluft, & Shaw, 2017
The Discussion’s Clinical implications section (page unavailable) suggests that pharmacological interventions targeting prefrontal or cerebellar functions may help address ADHD-related deficits, and the Introduction links motor inhibition to impulsivity. It does not identify nonstimulants as beneficial or assess improvement in impulsive choices; the study used a response-inhibition task, not a treatment comparison. (LLM, conf=0.83)
Experimental — accuracy not yet measuredCaudate underactivation was associated with childhood ADHD.
“while caudate underactivation was associated with childhood ADHD (Szekely et al., 2017)”
From Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation (2018) · cites this paper as Szekely et al., 2017
Only ADHD persisters in adulthood had underactivation in ventrolateral prefrontal cortex, parietal regions, anterior cingulate and cerebellum, while non-persisters did not differ from controls.
“only the ADHD persisters in adulthood had underactivation in ventrolateral prefrontal cortex, parietal regions (Schulz et al., 2017; Szekely et al., 2017), anterior cingulate (Schulz et al., 2017) and cerebellum (Szekely et al., 2017), while non-persisters did not differ from controls (Schulz et al., 2017; Szekely et al., 2017).”
From Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation (2018) · cites this paper as Szekely et al., 2017
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A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD)
Luo, Y., Weibman, D., Halperin, J. M., & Li, X. (2019) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2019.00042 · Cited by 394 · see citing works
“, 2015) and EFs subserved by these circuits (Halperin et al., 2008; Rajendran et al., 2013; Szekely et al., 2017).”
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“…et al., 2017), only the ADHD persisters in adulthood had underactivation in ventrolateral prefrontal cortex, parietal regions (Schulz et al., 2017; Szekely et al., 2017), anterior cingulate (Schulz et al., 2017) and cerebellum (Szekely et al., 2017), while non-persisters did not differ from…”
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- Authors
- Szekely, E., Sudre, G. P., Sharp, W., Leibenluft, E., & Shaw, P.
- Affiliations
- From the Section on Neurobehavioral and Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, Md.; and the Section on Bipolar Spectrum Disorders, Emotion and Development Branch, National Institute of Mental Health, Bethesda, Md.
- National Human Genome Research Institute (US)
- Venue
- American Journal of Psychiatry
- Published
- 2017-09-01
- Volume
- 174
- Issue
- 9
- Pages
- 867-876
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC5744256
- OpenAlex
- W2725740712
- Cited by
- 47
- References
- 58
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 3
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 MH999999)
- 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
- childhood ADHD, persistent ADHD, response inhibition, caudate nucleus, prefrontal cortex, cerebellum, inferior frontal cortex, inferior parietal cortex, precuneus, performance monitoring, neural correlates
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Caudate Nucleus, Cerebellum, Cerebral Cortex, Female, Humans, Inhibition, Psychological, Magnetic Resonance Imaging, Male, Remission Induction, Magnetoencephalography, Case-Control Studies, Young Adult, Functional Neuroimaging
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