Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis

Christienne G. Damatac; Sourena Soheili-Nezhad; Guilherme Blazquez Freches; Marcel P. Zwiers; Sanne de Bruijn; Seyma Ikde; Christel M. Portengen; Amy C. Abelmann; Janneke T. Dammers; Daan van Rooij; Sophie E.A. Akkermans; Jilly Naaijen; Barbara Franke; Jan K. Buitelaar; Christian F. Beckmann; Emma Sprooten

doi:10.1016/j.nicl.2022.103057

Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis

Christienne G. Damatac^*, Sourena Soheili-Nezhad, Guilherme Blazquez Freches, Marcel P. Zwiers, Sanne de Bruijn, Seyma Ikde, Christel M. Portengen, Amy C. Abelmann, Janneke T. Dammers, Daan van Rooij, Sophie E.A. Akkermans, Jilly Naaijen, Barbara Franke, Jan K. Buitelaar, Christian F. Beckmann, Emma Sprooten

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Variation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18 – 34 years), and using the more physiologically informative fixel-based analysis (FBA). Methods: Data were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined ADHD and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. Results: Clinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (t_max = 1.092, standardized effect[SE] = 0.044, p_FWE = 0.016). Improvement in combined ADHD symptoms over time was associated with more fiber cross-section at follow-up in the lCST (t_max = 3.775, SE = 0.051, p_FWE = 0.019). Conclusions: Aberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory.

Original language	English
Article number	103057
Number of pages	11
Journal	NeuroImage: Clinical
Volume	35
DOIs	https://doi.org/10.1016/j.nicl.2022.103057
Publication status	Published - 24 May 2022

Bibliographical note

Funding Information:
The authors would like to thank all of the families who participated in this study and all of the researchers who collected the data. This study sample is from the DELTA and NeuroIMAGE projects. NeuroIMAGE is the longitudinal follow-up study of the Dutch part of the International Multisite ADHD Genetics (IMAGE) project, which was a multi-site, international effort. NeuroIMAGE was supported by a Dutch Research Council (NWO) Large Investment Grant (no. 1750102007010) and NWO Brain & Cognition an Integrative Approach Grant (no. 433–09-242 to J.K.B.), and grants from Radboud University Medical Center, University Medical Center Groningen and Accare, and VU University Amsterdam. DELTA was funded by a Hypatia Tenure Track Grant from Radboud University Medical Center (to E.S.). Funding agencies had no role in study design, data collection, interpretation or influence on writing. J.N. is supported by an NWO Veni grant (no. VI.Veni.194.032). B.F. has received educational speaking fees from Medice. J.K.B. has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda/Shire, Roche, Medice, Angelini, Janssen, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. E.S. is supported by a Hypatia Tenure Track Grant (Radboudumc), Christine Mohrmann Fellowship (Radboud University), and a NARSAD Young Investigator Grant (Brain and Behavior Research Foundation, Grant No. 25034). All other authors report no biomedical financial interests or potential conflicts of interest.

Publisher Copyright:
© 2022 The Author(s)

Funding

The authors would like to thank all of the families who participated in this study and all of the researchers who collected the data. This study sample is from the DELTA and NeuroIMAGE projects. NeuroIMAGE is the longitudinal follow-up study of the Dutch part of the International Multisite ADHD Genetics (IMAGE) project, which was a multi-site, international effort. NeuroIMAGE was supported by a Dutch Research Council (NWO) Large Investment Grant (no. 1750102007010) and NWO Brain & Cognition an Integrative Approach Grant (no. 433–09-242 to J.K.B.), and grants from Radboud University Medical Center, University Medical Center Groningen and Accare, and VU University Amsterdam. DELTA was funded by a Hypatia Tenure Track Grant from Radboud University Medical Center (to E.S.). Funding agencies had no role in study design, data collection, interpretation or influence on writing. J.N. is supported by an NWO Veni grant (no. VI.Veni.194.032). B.F. has received educational speaking fees from Medice. J.K.B. has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda/Shire, Roche, Medice, Angelini, Janssen, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. E.S. is supported by a Hypatia Tenure Track Grant (Radboudumc), Christine Mohrmann Fellowship (Radboud University), and a NARSAD Young Investigator Grant (Brain and Behavior Research Foundation, Grant No. 25034). All other authors report no biomedical financial interests or potential conflicts of interest.

Keywords

Attention deficit hyperactivity disorder
Diffusion imaging
Magnetic resonance imaging
Microstructure
White matter

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Cite this

Damatac, C. G., Soheili-Nezhad, S., Blazquez Freches, G., Zwiers, M. P., de Bruijn, S., Ikde, S., Portengen, C. M., Abelmann, A. C., Dammers, J. T., van Rooij, D., Akkermans, S. E. A., Naaijen, J., Franke, B., Buitelaar, J. K., Beckmann, C. F., & Sprooten, E. (2022). Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis. NeuroImage: Clinical, 35, Article 103057. https://doi.org/10.1016/j.nicl.2022.103057

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title = "Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis",

abstract = "Background: Variation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18 – 34 years), and using the more physiologically informative fixel-based analysis (FBA). Methods: Data were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined ADHD and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. Results: Clinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (tmax = 1.092, standardized effect[SE] = 0.044, pFWE = 0.016). Improvement in combined ADHD symptoms over time was associated with more fiber cross-section at follow-up in the lCST (tmax = 3.775, SE = 0.051, pFWE = 0.019). Conclusions: Aberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory.",

keywords = "Attention deficit hyperactivity disorder, Diffusion imaging, Magnetic resonance imaging, Microstructure, White matter",

author = "Damatac, {Christienne G.} and Sourena Soheili-Nezhad and {Blazquez Freches}, Guilherme and Zwiers, {Marcel P.} and {de Bruijn}, Sanne and Seyma Ikde and Portengen, {Christel M.} and Abelmann, {Amy C.} and Dammers, {Janneke T.} and {van Rooij}, Daan and Akkermans, {Sophie E.A.} and Jilly Naaijen and Barbara Franke and Buitelaar, {Jan K.} and Beckmann, {Christian F.} and Emma Sprooten",

note = "Funding Information: The authors would like to thank all of the families who participated in this study and all of the researchers who collected the data. This study sample is from the DELTA and NeuroIMAGE projects. NeuroIMAGE is the longitudinal follow-up study of the Dutch part of the International Multisite ADHD Genetics (IMAGE) project, which was a multi-site, international effort. NeuroIMAGE was supported by a Dutch Research Council (NWO) Large Investment Grant (no. 1750102007010) and NWO Brain & Cognition an Integrative Approach Grant (no. 433–09-242 to J.K.B.), and grants from Radboud University Medical Center, University Medical Center Groningen and Accare, and VU University Amsterdam. DELTA was funded by a Hypatia Tenure Track Grant from Radboud University Medical Center (to E.S.). Funding agencies had no role in study design, data collection, interpretation or influence on writing. J.N. is supported by an NWO Veni grant (no. VI.Veni.194.032). B.F. has received educational speaking fees from Medice. J.K.B. has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda/Shire, Roche, Medice, Angelini, Janssen, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. E.S. is supported by a Hypatia Tenure Track Grant (Radboudumc), Christine Mohrmann Fellowship (Radboud University), and a NARSAD Young Investigator Grant (Brain and Behavior Research Foundation, Grant No. 25034). All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = may,

day = "24",

doi = "10.1016/j.nicl.2022.103057",

language = "English",

volume = "35",

journal = "NeuroImage: Clinical",

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Damatac, CG, Soheili-Nezhad, S, Blazquez Freches, G, Zwiers, MP, de Bruijn, S, Ikde, S, Portengen, CM, Abelmann, AC, Dammers, JT, van Rooij, D, Akkermans, SEA, Naaijen, J, Franke, B, Buitelaar, JK, Beckmann, CF & Sprooten, E 2022, 'Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis', NeuroImage: Clinical, vol. 35, 103057. https://doi.org/10.1016/j.nicl.2022.103057

TY - JOUR

T1 - Longitudinal changes of ADHD symptoms in association with white matter microstructure

T2 - A tract-specific fixel-based analysis

AU - Damatac, Christienne G.

AU - Soheili-Nezhad, Sourena

AU - Blazquez Freches, Guilherme

AU - Zwiers, Marcel P.

AU - de Bruijn, Sanne

AU - Ikde, Seyma

AU - Portengen, Christel M.

AU - Abelmann, Amy C.

AU - Dammers, Janneke T.

AU - van Rooij, Daan

AU - Akkermans, Sophie E.A.

AU - Naaijen, Jilly

AU - Franke, Barbara

AU - Buitelaar, Jan K.

AU - Beckmann, Christian F.

AU - Sprooten, Emma

N1 - Funding Information: The authors would like to thank all of the families who participated in this study and all of the researchers who collected the data. This study sample is from the DELTA and NeuroIMAGE projects. NeuroIMAGE is the longitudinal follow-up study of the Dutch part of the International Multisite ADHD Genetics (IMAGE) project, which was a multi-site, international effort. NeuroIMAGE was supported by a Dutch Research Council (NWO) Large Investment Grant (no. 1750102007010) and NWO Brain & Cognition an Integrative Approach Grant (no. 433–09-242 to J.K.B.), and grants from Radboud University Medical Center, University Medical Center Groningen and Accare, and VU University Amsterdam. DELTA was funded by a Hypatia Tenure Track Grant from Radboud University Medical Center (to E.S.). Funding agencies had no role in study design, data collection, interpretation or influence on writing. J.N. is supported by an NWO Veni grant (no. VI.Veni.194.032). B.F. has received educational speaking fees from Medice. J.K.B. has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda/Shire, Roche, Medice, Angelini, Janssen, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. E.S. is supported by a Hypatia Tenure Track Grant (Radboudumc), Christine Mohrmann Fellowship (Radboud University), and a NARSAD Young Investigator Grant (Brain and Behavior Research Foundation, Grant No. 25034). All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2022 The Author(s)

PY - 2022/5/24

Y1 - 2022/5/24

N2 - Background: Variation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18 – 34 years), and using the more physiologically informative fixel-based analysis (FBA). Methods: Data were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined ADHD and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. Results: Clinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (tmax = 1.092, standardized effect[SE] = 0.044, pFWE = 0.016). Improvement in combined ADHD symptoms over time was associated with more fiber cross-section at follow-up in the lCST (tmax = 3.775, SE = 0.051, pFWE = 0.019). Conclusions: Aberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory.

AB - Background: Variation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18 – 34 years), and using the more physiologically informative fixel-based analysis (FBA). Methods: Data were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined ADHD and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. Results: Clinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (tmax = 1.092, standardized effect[SE] = 0.044, pFWE = 0.016). Improvement in combined ADHD symptoms over time was associated with more fiber cross-section at follow-up in the lCST (tmax = 3.775, SE = 0.051, pFWE = 0.019). Conclusions: Aberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory.

KW - Attention deficit hyperactivity disorder

KW - Diffusion imaging

KW - Magnetic resonance imaging

KW - Microstructure

KW - White matter

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DO - 10.1016/j.nicl.2022.103057

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AN - SCOPUS:85131043545

SN - 2213-1582

VL - 35

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

M1 - 103057

ER -

Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis

Abstract

Bibliographical note

Funding

Keywords

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