Resting-State fMRI to Identify the Brain Correlates of Treatment Response to Medications in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Lessons From the CUNMET Study

Neuroimaging research seeks to identify biomarkers to improve the diagnosis, prognosis, and treatment of attention-deficit/hyperactivity disorder (ADHD), although clinical translation of findings remains distant. Resting-state functional magnetic resonance imaging (R-fMRI) is increasingly being used...

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Autores principales:	Victor Pereira-Sanchez, Alexandre R. Franco, Pilar de Castro-Manglano, Maria A. Fernandez-Seara, Maria Vallejo-Valdivielso, Azucena Díez-Suárez, Miguel Fernandez-Martinez, M. Reyes Garcia de Eulate, Michael Milham, Cesar A. Soutullo, Francisco X. Castellanos
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	attention-deficit/hyperactivity disorder (ADHD) resting state fMRI stimulants functional connectivity reproducibility Psychiatry RC435-571
Acceso en línea:	https://doaj.org/article/b9a410d99d3c449bba60e4789fecae33
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spelling	oai:doaj.org-article:b9a410d99d3c449bba60e4789fecae332021-11-16T05:11:46ZResting-State fMRI to Identify the Brain Correlates of Treatment Response to Medications in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Lessons From the CUNMET Study1664-064010.3389/fpsyt.2021.759696https://doaj.org/article/b9a410d99d3c449bba60e4789fecae332021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fpsyt.2021.759696/fullhttps://doaj.org/toc/1664-0640Neuroimaging research seeks to identify biomarkers to improve the diagnosis, prognosis, and treatment of attention-deficit/hyperactivity disorder (ADHD), although clinical translation of findings remains distant. Resting-state functional magnetic resonance imaging (R-fMRI) is increasingly being used to characterize functional connectivity in the brain. Despite mixed results to date and multiple methodological challenges, dominant hypotheses implicate hyperconnectivity across brain networks in patients with ADHD, which could be the target of pharmacological treatments. We describe the experience and results of the Clínica Universidad de Navarra (Spain) Metilfenidato (CUNMET) pilot study. CUNMET tested the feasibility of identifying R-fMRI markers of clinical response in children with ADHD undergoing naturalistical pharmacological treatments. We analyzed cross-sectional data from 56 patients with ADHD (18 treated with methylphenidate, 18 treated with lisdexamfetamine, and 20 treatment-naive patients). Standard preprocessing and statistical analyses with attention to control for head motion and correction for multiple comparisons were performed. The only results that survived correction were noted in contrasts of children who responded clinically to lisdexamfetamine after long-term treatment vs. treatment-naive patients. In these children, we observed stronger negative correlations (anticorrelations) across nodes in six brain networks, which is consistent with higher across-network functional segregation in patients treated with lisdexamfetamine, i.e., less inter-network interference than in treatment-naive patients. We also note the lessons learned, which could help those pursuing clinically relevant multidisciplinary research in ADHD en route to eventual personalized medicine. To advance reproducible open science, our report is accompanied with links providing access to our data and analytic scripts.Victor Pereira-SanchezVictor Pereira-SanchezAlexandre R. FrancoAlexandre R. FrancoAlexandre R. FrancoPilar de Castro-ManglanoMaria A. Fernandez-SearaMaria Vallejo-ValdivielsoAzucena Díez-SuárezMiguel Fernandez-MartinezM. Reyes Garcia de EulateMichael MilhamMichael MilhamCesar A. SoutulloFrancisco X. CastellanosFrancisco X. CastellanosFrontiers Media S.A.articleattention-deficit/hyperactivity disorder (ADHD)resting statefMRIstimulantsfunctional connectivityreproducibilityPsychiatryRC435-571ENFrontiers in Psychiatry, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	attention-deficit/hyperactivity disorder (ADHD) resting state fMRI stimulants functional connectivity reproducibility Psychiatry RC435-571
spellingShingle	attention-deficit/hyperactivity disorder (ADHD) resting state fMRI stimulants functional connectivity reproducibility Psychiatry RC435-571 Victor Pereira-Sanchez Victor Pereira-Sanchez Alexandre R. Franco Alexandre R. Franco Alexandre R. Franco Pilar de Castro-Manglano Maria A. Fernandez-Seara Maria Vallejo-Valdivielso Azucena Díez-Suárez Miguel Fernandez-Martinez M. Reyes Garcia de Eulate Michael Milham Michael Milham Cesar A. Soutullo Francisco X. Castellanos Francisco X. Castellanos Resting-State fMRI to Identify the Brain Correlates of Treatment Response to Medications in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Lessons From the CUNMET Study
description	Neuroimaging research seeks to identify biomarkers to improve the diagnosis, prognosis, and treatment of attention-deficit/hyperactivity disorder (ADHD), although clinical translation of findings remains distant. Resting-state functional magnetic resonance imaging (R-fMRI) is increasingly being used to characterize functional connectivity in the brain. Despite mixed results to date and multiple methodological challenges, dominant hypotheses implicate hyperconnectivity across brain networks in patients with ADHD, which could be the target of pharmacological treatments. We describe the experience and results of the Clínica Universidad de Navarra (Spain) Metilfenidato (CUNMET) pilot study. CUNMET tested the feasibility of identifying R-fMRI markers of clinical response in children with ADHD undergoing naturalistical pharmacological treatments. We analyzed cross-sectional data from 56 patients with ADHD (18 treated with methylphenidate, 18 treated with lisdexamfetamine, and 20 treatment-naive patients). Standard preprocessing and statistical analyses with attention to control for head motion and correction for multiple comparisons were performed. The only results that survived correction were noted in contrasts of children who responded clinically to lisdexamfetamine after long-term treatment vs. treatment-naive patients. In these children, we observed stronger negative correlations (anticorrelations) across nodes in six brain networks, which is consistent with higher across-network functional segregation in patients treated with lisdexamfetamine, i.e., less inter-network interference than in treatment-naive patients. We also note the lessons learned, which could help those pursuing clinically relevant multidisciplinary research in ADHD en route to eventual personalized medicine. To advance reproducible open science, our report is accompanied with links providing access to our data and analytic scripts.
format	article
author	Victor Pereira-Sanchez Victor Pereira-Sanchez Alexandre R. Franco Alexandre R. Franco Alexandre R. Franco Pilar de Castro-Manglano Maria A. Fernandez-Seara Maria Vallejo-Valdivielso Azucena Díez-Suárez Miguel Fernandez-Martinez M. Reyes Garcia de Eulate Michael Milham Michael Milham Cesar A. Soutullo Francisco X. Castellanos Francisco X. Castellanos
author_facet	Victor Pereira-Sanchez Victor Pereira-Sanchez Alexandre R. Franco Alexandre R. Franco Alexandre R. Franco Pilar de Castro-Manglano Maria A. Fernandez-Seara Maria Vallejo-Valdivielso Azucena Díez-Suárez Miguel Fernandez-Martinez M. Reyes Garcia de Eulate Michael Milham Michael Milham Cesar A. Soutullo Francisco X. Castellanos Francisco X. Castellanos
author_sort	Victor Pereira-Sanchez
title	Resting-State fMRI to Identify the Brain Correlates of Treatment Response to Medications in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Lessons From the CUNMET Study
title_short	Resting-State fMRI to Identify the Brain Correlates of Treatment Response to Medications in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Lessons From the CUNMET Study
title_full	Resting-State fMRI to Identify the Brain Correlates of Treatment Response to Medications in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Lessons From the CUNMET Study
title_fullStr	Resting-State fMRI to Identify the Brain Correlates of Treatment Response to Medications in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Lessons From the CUNMET Study
title_full_unstemmed	Resting-State fMRI to Identify the Brain Correlates of Treatment Response to Medications in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Lessons From the CUNMET Study
title_sort	resting-state fmri to identify the brain correlates of treatment response to medications in children and adolescents with attention-deficit/hyperactivity disorder: lessons from the cunmet study
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b9a410d99d3c449bba60e4789fecae33
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Resting-State fMRI to Identify the Brain Correlates of Treatment Response to Medications in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Lessons From the CUNMET Study

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