From neurons to brain networks, pharmacodynamics of stimulant medication for ADHD

Parlatini, Valeria; Bellato, Alessio; Murphy, Declan; Cortese, Samuele

doi:10.1016/j.neubiorev.2024.105841

Cited by 26Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

From neurons to brain networks, pharmacodynamics of stimulant medication for ADHD

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Parlatini, Valeria, Bellato, Alessio, Murphy, Declan, Cortese, Samuele·2024·Neuroscience & Biobehavioral Reviews

DOI 10.1016/j.neubiorev.2024.105841

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Abstract

Stimulants represent the first line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) and are among the most prescribed psychopharmacological treatments. Their mechanism of action at synaptic level has been extensively studied. However, it is less clear how their mechanism of action determines clinically observed benefits. To help bridge this gap, we provide a comprehensive review of stimulant effects, with an emphasis on nuclear medicine and magnetic resonance imaging (MRI) findings. There is evidence that stimulant-induced modulation of dopamine and norepinephrine neurotransmission optimizes engagement of task-related brain networks, increases perceived saliency, and reduces interference from the default mode network. An acute administration of stimulants may reduce brain alterations observed in untreated individuals in fronto-striato-parieto-cerebellar networks during tasks or at rest. Potential effects of prolonged treatment remain controversial. Overall, neuroimaging has fostered understanding on stimulant mechanism of action. However, studies are often limited by small samples, short or no follow-up, and methodological heterogeneity. Future studies should address age-related and longer-term effects, potential differences among stimulants, and predictors of treatment response.

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Studies using acute administration of stimulants demonstrated that neural activity in adults with ADHD can be modulated towards similar levels as those of adults without ADHD in various tasks (Parlatini et al., 2024).
“Studies using acute administration of stimulants demonstrated that neural activity in adults with ADHD can be modulated towards similar levels as those of adults without ADHD in various tasks (Parlatini et al., 2024).”
From Are prediction error modifications domain specific in autism but domain general in ADHD? (2025) · cites this paper as Parlatini et al., 2024
The discussion of fMRI findings (p. 7) reports that acute stimulants alter activation during attention, inhibition and other tasks, and suggests that activity in people with ADHD moves toward that of neurotypical peers. It does not establish this pattern specifically across tasks in adults; the review also notes conflicting working-memory findings. The claim is therefore more age-specific and more definitive than the source. (LLM, conf=0.86)
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“This has been noted to be reduced in individuals with ADHD (Forssberg et al., 2006, Volkow et al., 2001, Volkow et al., 2007a), although this was not confirmed by all studies (Cherkasova et al., 2014).”
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Role of neurotrophic factors in attention deficit hyperactivity disorder.
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No Significant Association Between Genetic Variants in 7 Candidate Genes and Response to Methylphenidate Treatment in Adult Patients With ADHD
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Methylphenidate Alters Functional Connectivity of Default Mode Network in Drug-Naive Male Adults With ADHD
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Authors: Parlatini, V., Bellato, A., Murphy, D., & Cortese, S.
Affiliations: King's College London (GB)
University of Nottingham (GB)
Corresponding author: Parlatini, Valeria
ORCID: Parlatini, Valeria
Bellato, Alessio
Murphy, Declan
Cortese, Samuele
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 2024-09
Volume: 164
Pages: 105841
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/j.neubiorev.2024.105841
OpenAlex: W4401306218
Cited by: 26
References: 230
Citations by year: 2026: 10 · 2025: 15 · 2024: 1
FWCI: 2.08
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion, cc-by)
PubMed (publishedVersion)
ePrints Soton (University of Southampton) (submittedVersion)
Funders: iMinds
British Association for Psychopharmacology
Aims2Cure (AIMS-2-TRIALS, 115300, 777394)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: attention deficit hyperactivity disorder, stimulant medication, pharmacodynamics, dopamine signaling, brain networks, default mode network, salience, long-term treatment outcomes, predictors of treatment response
MeSH terms: Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Brain, Humans, Nerve Net, Neurons

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