White matter properties in fronto-parietal tracts predict maladaptive functional activation and deficient response inhibition in ADHD

Abstract Response inhibition is a key characteristic of adaptive human behaviour. However, in attention deficit hyperactivity disorder (ADHD) it is often impaired. Previous neuroimaging investigations implicate a myriad of brain networks in response inhibition, making it more difficult to understand...

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Main Authors: Daniel Smullen, Andrew P. Bagshaw, Lilach Shalev, Shlomit Tsafrir, Tamar Kolodny, Carmel Mevorach
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-02326-y
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author Daniel Smullen
Andrew P. Bagshaw
Lilach Shalev
Shlomit Tsafrir
Tamar Kolodny
Carmel Mevorach
author_facet Daniel Smullen
Andrew P. Bagshaw
Lilach Shalev
Shlomit Tsafrir
Tamar Kolodny
Carmel Mevorach
author_sort Daniel Smullen
collection DOAJ
description Abstract Response inhibition is a key characteristic of adaptive human behaviour. However, in attention deficit hyperactivity disorder (ADHD) it is often impaired. Previous neuroimaging investigations implicate a myriad of brain networks in response inhibition, making it more difficult to understand and overcome response inhibition difficulties. Recently, it has been suggested that a specific fronto-parietal functional circuitry between the inferior frontal gyrus (IFG) and the intraparietal sulcus (IPS), dictates the recruitment of the IPS during response inhibition in ADHD. To ascertain the critical role of the IFG-IPS functional circuit and its relevance to response inhibition in ADHD, it is crucial to understand the underlying structural architecture of this circuit so that the functional relevance could be interpreted correctly. Here we investigated the white matter pathways connecting the IFG and IPS using seed-based probabilistic tractography on diffusion data in 33 ADHD and 19 neurotypicals, assessing their impact on both IPS recruitment during response inhibition and on response inhibition performance in a Go/No-go task. Our results showed that individual differences in the structural properties of the IPS-IFG circuit, including tract volume and diffusivity, were linked to IPS activation and even predicted response inhibition performance outside the scanner. These findings highlight the structural-functional coupling within the IFG-IPS circuit in response inhibition in ADHD and suggest a structural basis for maladaptive functional top-down control in deficient inhibition in ADHD.
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spelling doaj-art-b4f0c712516d46d4a277bdb554d66af72025-08-20T03:10:36ZengNature PortfolioScientific Reports2045-23222025-06-0115111410.1038/s41598-025-02326-yWhite matter properties in fronto-parietal tracts predict maladaptive functional activation and deficient response inhibition in ADHDDaniel Smullen0Andrew P. Bagshaw1Lilach Shalev2Shlomit Tsafrir3Tamar Kolodny4Carmel Mevorach5Centre for Human Brain Health and School of Psychology, University of BirminghamCentre for Human Brain Health and School of Psychology, University of BirminghamConstantiner School of Education and the Sagol School of Neuroscience, Tel-Aviv UniversityClalit Health ServicesDepartment of Cognitive Sciences, The Hebrew University of JerusalemCentre for Human Brain Health and School of Psychology, University of BirminghamAbstract Response inhibition is a key characteristic of adaptive human behaviour. However, in attention deficit hyperactivity disorder (ADHD) it is often impaired. Previous neuroimaging investigations implicate a myriad of brain networks in response inhibition, making it more difficult to understand and overcome response inhibition difficulties. Recently, it has been suggested that a specific fronto-parietal functional circuitry between the inferior frontal gyrus (IFG) and the intraparietal sulcus (IPS), dictates the recruitment of the IPS during response inhibition in ADHD. To ascertain the critical role of the IFG-IPS functional circuit and its relevance to response inhibition in ADHD, it is crucial to understand the underlying structural architecture of this circuit so that the functional relevance could be interpreted correctly. Here we investigated the white matter pathways connecting the IFG and IPS using seed-based probabilistic tractography on diffusion data in 33 ADHD and 19 neurotypicals, assessing their impact on both IPS recruitment during response inhibition and on response inhibition performance in a Go/No-go task. Our results showed that individual differences in the structural properties of the IPS-IFG circuit, including tract volume and diffusivity, were linked to IPS activation and even predicted response inhibition performance outside the scanner. These findings highlight the structural-functional coupling within the IFG-IPS circuit in response inhibition in ADHD and suggest a structural basis for maladaptive functional top-down control in deficient inhibition in ADHD.https://doi.org/10.1038/s41598-025-02326-y
spellingShingle Daniel Smullen
Andrew P. Bagshaw
Lilach Shalev
Shlomit Tsafrir
Tamar Kolodny
Carmel Mevorach
White matter properties in fronto-parietal tracts predict maladaptive functional activation and deficient response inhibition in ADHD
Scientific Reports
title White matter properties in fronto-parietal tracts predict maladaptive functional activation and deficient response inhibition in ADHD
title_full White matter properties in fronto-parietal tracts predict maladaptive functional activation and deficient response inhibition in ADHD
title_fullStr White matter properties in fronto-parietal tracts predict maladaptive functional activation and deficient response inhibition in ADHD
title_full_unstemmed White matter properties in fronto-parietal tracts predict maladaptive functional activation and deficient response inhibition in ADHD
title_short White matter properties in fronto-parietal tracts predict maladaptive functional activation and deficient response inhibition in ADHD
title_sort white matter properties in fronto parietal tracts predict maladaptive functional activation and deficient response inhibition in adhd
url https://doi.org/10.1038/s41598-025-02326-y
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