The impact of methylphenidate on choice impulsivity is inversely associated with corpus callosum fiber integrity across sexes

Background: Choice impulsivity represents preference towards smaller immediate rewards over larger delayed rewards. Extensive literature demonstrates that choice impulsivity can be manipulated using dopaminergic agonists such as methylphenidate (MPH), and that females exhibit elevated choice impulsi...

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Main Authors: Maryana Daood, Leehe Peled-Avron, Rachel Ben-Hayun, Michael Nevat, Judith Aharon-Peretz, Rachel Tomer, Roee Admon
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:NeuroImage
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Online Access:http://www.sciencedirect.com/science/article/pii/S1053811925001995
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author Maryana Daood
Leehe Peled-Avron
Rachel Ben-Hayun
Michael Nevat
Judith Aharon-Peretz
Rachel Tomer
Roee Admon
author_facet Maryana Daood
Leehe Peled-Avron
Rachel Ben-Hayun
Michael Nevat
Judith Aharon-Peretz
Rachel Tomer
Roee Admon
author_sort Maryana Daood
collection DOAJ
description Background: Choice impulsivity represents preference towards smaller immediate rewards over larger delayed rewards. Extensive literature demonstrates that choice impulsivity can be manipulated using dopaminergic agonists such as methylphenidate (MPH), and that females exhibit elevated choice impulsivity compared to males. Sex differences are also frequently reported with respect to brain white matter (WM) fiber integrity. It has yet to be determined whether sex differences also exist in the impact of MPH on choice impulsivity, and whether these putative differences are accounted for by the integrity of differential WM fibers. Methods: Forty-eight healthy young adults completed the delay discounting (DD) task twice during MRI-DTI scans after receiving either MPH or placebo in a double-blind, placebo-controlled, within-subject design. WM fiber integrity was assessed using automated fiber quantification (AFQ) and tract-based spatial statistics (TBSS). Results: Compared to placebo, MPH yielded significantly reduced choice impulsivity in males but not in females. DTI data revealed reduced integrity in multiple WM fibers in females compared to males. Interestingly, the impact of MPH on choice impulsivity was negatively associated with fiber integrity in the forceps major of the corpus callosum for males only and positively associated with fiber integrity in the forceps minor of the corpus callosum for females only. Conclusions: Taken together, results uncover sex-specific effects of MPH on choice impulsivity, accounted for by inverse associations between choice impulsivity under MPH and the structural integrity of distinct segments of the corpus callosum. These findings highlight the need to consider sex differences in the neurobiological mechanisms of impulsivity.
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spelling doaj-art-bd51dd7363524df5a161e4fb439c5a1e2025-08-20T03:18:41ZengElsevierNeuroImage1095-95722025-05-0131112119610.1016/j.neuroimage.2025.121196The impact of methylphenidate on choice impulsivity is inversely associated with corpus callosum fiber integrity across sexesMaryana Daood0Leehe Peled-Avron1Rachel Ben-Hayun2Michael Nevat3Judith Aharon-Peretz4Rachel Tomer5Roee Admon6School of Psychological Sciences, University of Haifa, Haifa, Israel; Tandon School of Engineering, New York University, New York City, NY, United States of AmericaSchool of Psychological Sciences, University of Haifa, Haifa, Israel; Department of Psychology & Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, IsraelStroke and Cognition Institute, Department of Neurology, Rambam Health Care Campus, Haifa, Israel; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, IsraelSchool of Psychological Sciences, University of Haifa, Haifa, IsraelStroke and Cognition Institute, Department of Neurology, Rambam Health Care Campus, Haifa, Israel; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, IsraelSchool of Psychological Sciences, University of Haifa, Haifa, Israel; The Integrated Brain and Behavior Research Center (IBBRC), University of Haifa, Haifa, IsraelSchool of Psychological Sciences, University of Haifa, Haifa, Israel; The Integrated Brain and Behavior Research Center (IBBRC), University of Haifa, Haifa, Israel; Corresponding author at: School of Psychological Sciences, University of Haifa, 199 Aba Khoushy Ave. Mount Carmel, Haifa, 31905, Israel.Background: Choice impulsivity represents preference towards smaller immediate rewards over larger delayed rewards. Extensive literature demonstrates that choice impulsivity can be manipulated using dopaminergic agonists such as methylphenidate (MPH), and that females exhibit elevated choice impulsivity compared to males. Sex differences are also frequently reported with respect to brain white matter (WM) fiber integrity. It has yet to be determined whether sex differences also exist in the impact of MPH on choice impulsivity, and whether these putative differences are accounted for by the integrity of differential WM fibers. Methods: Forty-eight healthy young adults completed the delay discounting (DD) task twice during MRI-DTI scans after receiving either MPH or placebo in a double-blind, placebo-controlled, within-subject design. WM fiber integrity was assessed using automated fiber quantification (AFQ) and tract-based spatial statistics (TBSS). Results: Compared to placebo, MPH yielded significantly reduced choice impulsivity in males but not in females. DTI data revealed reduced integrity in multiple WM fibers in females compared to males. Interestingly, the impact of MPH on choice impulsivity was negatively associated with fiber integrity in the forceps major of the corpus callosum for males only and positively associated with fiber integrity in the forceps minor of the corpus callosum for females only. Conclusions: Taken together, results uncover sex-specific effects of MPH on choice impulsivity, accounted for by inverse associations between choice impulsivity under MPH and the structural integrity of distinct segments of the corpus callosum. These findings highlight the need to consider sex differences in the neurobiological mechanisms of impulsivity.http://www.sciencedirect.com/science/article/pii/S1053811925001995Delay discounting (DD)Diffusion tensor imaging (DTI)Methylphenidate (MPH)Tract-based spatial statistics (TBSS)Corpus callosum
spellingShingle Maryana Daood
Leehe Peled-Avron
Rachel Ben-Hayun
Michael Nevat
Judith Aharon-Peretz
Rachel Tomer
Roee Admon
The impact of methylphenidate on choice impulsivity is inversely associated with corpus callosum fiber integrity across sexes
NeuroImage
Delay discounting (DD)
Diffusion tensor imaging (DTI)
Methylphenidate (MPH)
Tract-based spatial statistics (TBSS)
Corpus callosum
title The impact of methylphenidate on choice impulsivity is inversely associated with corpus callosum fiber integrity across sexes
title_full The impact of methylphenidate on choice impulsivity is inversely associated with corpus callosum fiber integrity across sexes
title_fullStr The impact of methylphenidate on choice impulsivity is inversely associated with corpus callosum fiber integrity across sexes
title_full_unstemmed The impact of methylphenidate on choice impulsivity is inversely associated with corpus callosum fiber integrity across sexes
title_short The impact of methylphenidate on choice impulsivity is inversely associated with corpus callosum fiber integrity across sexes
title_sort impact of methylphenidate on choice impulsivity is inversely associated with corpus callosum fiber integrity across sexes
topic Delay discounting (DD)
Diffusion tensor imaging (DTI)
Methylphenidate (MPH)
Tract-based spatial statistics (TBSS)
Corpus callosum
url http://www.sciencedirect.com/science/article/pii/S1053811925001995
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