Effect of methylphenidate on executive functioning in adults with attention-deficit/hyperactivity disorder: normalization of behavior but not related brain activity

Schweitzer, Julie B.; Lee, Douglas O.; Hanford, Russell B.; Zink, Caroline F.; Ely, Timothy D.; Tagamets, Malle A.; Hoffman, John M.; Grafton, Scott T.; Kilts, Clinton D.

doi:10.1016/j.biopsych.2004.07.011

Cited by 135Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

Effect of methylphenidate on executive functioning in adults with attention-deficit/hyperactivity disorder: normalization of behavior but not related brain activity

Schweitzer, Julie B., Lee, Douglas O., Hanford, Russell B., Zink, Caroline F., Ely, Timothy D., Tagamets, Malle A., Hoffman, John M., Grafton, Scott T. +1 more·2004·Biological Psychiatry

DOI 10.1016/j.biopsych.2004.07.011

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Abstract

Background We examined the effect of prolonged methylphenidate (MPH) treatment on the functional neuroanatomy of executive functioning in adult men with attention-deficit/hyperactivity disorder (ADHD).Methods Positron emission tomography with [(15)O] water measured alterations of regional cerebral blood flow (rCBF) during the Paced Auditory Serial Addition Task and a control task in 10 ADHD and 11 normal control men. Attention-deficit/hyperactivity disorder men were imaged unmedicated and after a clinically optimal dose of MPH for 3 weeks.Results Methylphenidate improved ADHD task performance, reduced rCBF in the prefrontal cortex (PFC), and increased rCBF in the right thalamus and precentral gyrus. Comparisons between the ADHD and normal control groups showed that normal control participants exhibited greater anterior cingulate cortex and temporal gyrus rCBF than ADHD participants under both conditions. Executive functioning was associated with greater subcortical (basal ganglia and cerebellar vermis) activation in the ADHD than normal control group under both conditions.Conclusions Methylphenidate does not normalize task-related activity in ADHD. Task-related rCBF decreases in the PFC may be due to improved filtering out of task-irrelevant stimuli by way of MPH-mediated dopamine release in the PFC.

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Methylphenidate reduces regional cerebral blood flow in the prefrontal cortex and increases it in the thalamus and precentral gyrus.
“MPH has also been shown to reduce regional CBF in the prefrontal cortex and increase regional CBF in the thalamus and precentral gyrus (176).”
From The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities (2018) · cites this paper as [176]
Neuroimaging studies show abnormal prefrontal and parietal cortex functioning in children with ADHD during working memory tasks.
“Neuroimaging studies reveal abnormal PFC and parietal cortex functioning in children with ADHD during WM tasks [5-9, 39, 40].”
From Will Working Memory Training Generalize to Improve Off-Task Behavior in Children with Attention-Deficit/Hyperactivity Disorder? (2012) · cites this paper as [39]

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Authors: Schweitzer, J. B., Lee, D. O., Hanford, R. B., Zink, C. F., Ely, T. D., Tagamets, M. A., Hoffman, J. M., Grafton, S. T., & Kilts, C. D.
Affiliations: University of Maryland, Baltimore (US)
Emory University (US)
National Institutes of Health (US)
Dartmouth College (US)
Corresponding author: Schweitzer, Julie B.
ORCID: Schweitzer, Julie B.
Ely, Timothy D.
Hoffman, John M.
Grafton, Scott T.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2004-10
Volume: 56
Issue: 8
Pages: 597-606
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2004.07.011
OpenAlex: W1988567169
Cited by: 135
References: 92
Citations by year: 2026: 1 · 2024: 5 · 2023: 3 · 2021: 5 · 2020: 7 · 2019: 8 · 2018: 6 · 2016: 6 · 2015: 6 · 2014: 6 · 2013: 8 · 2012: 15
FWCI: 6.84
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1r03mh055550-01)
National Institute of Mental Health (R03 MH55550, K08 MH 01053, K08MH001053)
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: methylphenidate, attention deficit hyperactivity disorder, executive function, regional cerebral blood flow, prefrontal cortex, thalamus, Paced Auditory Serial Addition Test, functional neuroanatomy, dopamine release, basal ganglia, cerebellar vermis, anterior cingulate cortex, temporal gyrus
MeSH terms: Adult, Central Nervous System Stimulants, Behavioral Symptoms, Brain, Brain Mapping, Female, Humans, Male, Methylphenidate, Neuropsychological Tests, Problem Solving, Regional Blood Flow, Task Performance and Analysis, Case-Control Studies, Attention Deficit and Disruptive Behavior Disorders, Positron-Emission Tomography

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Effect of methylphenidate on executive functioning in adults with attention-deficit/hyperactivity disorder: normalization of behavior but not related brain activity

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