Lower white matter microstructure in the superior longitudinal fasciculus is associated with increased response time variability in adults with attention-deficit/hyperactivity disorder
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BACKGROUND: Response time variability (RTV) is consistently increased in patients with attention-deficit/hyperactivity disorder (ADHD). A right-hemispheric frontoparietal attention network model has been implicated in these patients. The 3 main connecting fibre tracts in this network, the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the cingulum bundle (CB), show microstructural abnormalities in patients with ADHD. We hypothesized that the microstructural integrity of the 3 white matter tracts of this network are associated with ADHD and RTV. METHODS: We examined RTV in adults with ADHD by modelling the reaction time distribution as an exponentially modified Gaussian (ex-Gaussian) function with the parameters μ, σ and τ, the latter of which has been attributed to lapses of attention. We assessed adults with ADHD and healthy controls using a sustained attention task. Diffusion tensor imaging-derived fractional anisotropy (FA) values were determined to quantify bilateral microstructural integrity of the tracts of interest. RESULTS: We included 100 adults with ADHD and 96 controls in our study. Increased τ was associated with ADHD diagnosis and was linked to symptoms of inattention. An inverse correlation of τ with mean FA was seen in the right SLF of patients with ADHD, but no direct association between the mean FA of the 6 regions of interest with ADHD could be observed. LIMITATIONS: Regions of interest were defined a priori based on the attentional network model for ADHD and thus we might have missed effects in other networks. CONCLUSION: This study suggests that reduced microstructural integrity of the right SLF is associated with elevated τ in patients with ADHD.
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On a neural level, RTV has been associated with smaller white matter tracts in the late developing fronto-parietal attention (superior longitudinal fasciculus) and cortico-thalamic cognitive control tracts and reduced activation in fronto-striatal and superior temporal activation in children and adults with ADHD.
“In line with a role in attention and self-control, on a neural level, RTV has been associated with smaller white matter tracts in the late developing fronto-parietal attention (superior longitudinal fasciculus) and cortico-thalamic cognitive control tracts and reduced activation in fronto-striatal and superior temporal activation in children and adults with ADHD (18, 67–70), suggesting an”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [18]
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Experimental — accuracy not yet measuredStudies of fractional anisotropy using diffusion tensor imaging in adults with ADHD have found that increased RTV is associated with reduced microstructural integrity of the superior longitudinal fasciculus and altered white matter structural properties of the corticothalamic tract.
“Studies of fractional anisotropy using diffusion tensor imaging in adults with ADHD have found that increased RTV is associated with reduced microstructural integrity of the superior longitudinal fasciculus (Wolfers et al. 2015) and altered white matter structural properties of the corticothalamic tract (Kölle et al. 2022).”
From Reaction Time Variability and Electrophysiological Indices of Performance Monitoring in Youths With Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder (2026) · cites this paper as Wolfers et al. 2015
The tau parameter was associated with microstructural integrity of the right superior longitudinal fasciculus.
“Recently, we showed that the tau parameter was associated with the microstructural integrity of the right superior longitudinal fasciculus, a white matter tract implicated in both attention and ADHD (Wolfers et al., 2015).”
From Cognitive heterogeneity in adult attention deficit/hyperactivity disorder: A systematic analysis of neuropsychological measurements (2015) · cites this paper as Wolfers et al., 2015
Ex-Gaussian modeling showed that increased reaction time variability is partly due to overly slow responses.
“More thorough investigation of RTV used ex-Gaussian modeling and showed that increased RTV is partly due to overly slow responses (Feige et al. 2013; Gmehlin et al., 2013; Wolfers et al., 2015).”
From Cognitive heterogeneity in adult attention deficit/hyperactivity disorder: A systematic analysis of neuropsychological measurements (2015) · cites this paper as Wolfers et al., 2015
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Attention regulation in women with ADHD and women with bipolar disorder: An ex-Gaussian approach
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Parlatini, V., Raduà, J., Naianna, R., Lintas, A., Atuk, E., Dell’Acqua, F., de Schotten, M. T., & Murphy, D. (2024) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-024-01927-4 · Cited by 5 · see citing works
A multisite validation of brain white matter pathways of resilience to chronic back painPreprint
Mišić, M., Lee, N., Zidda, F., Sohn, K., Usai, K., Löffler, M., Uddin, M. N., Farooqi, A., Schifitto, G., Zhang, Z., et al. (2024) · eLife · doi:10.7554/elife.96312.3 · Cited by 7 · see citing works
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Altered White-matter Tract Property in Adults with Attention-deficit Hyperactivity Disorder
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Lateralization of attention in adults with ADHD: Evidence of pseudoneglect
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Examination of the Neuroplastic Biomarker Levels in Attention Deficit Hyperactivity Disorder
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“…using diffusion tensor imaging in adults with ADHD have found that increased RTV is associated with reduced microstructural integrity of the superior longitudinal fasciculus (Wolfers et al. 2015) and altered white matter structural properties of the corticothalamic tract (Kölle et al. 2022).”
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Associations between ADHD symptom remission and white matter microstructure: a longitudinal analysisPreprint
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Self-citationBrain white matter pathways of resilience to chronic back pain: a multisite validationPreprint
Mišić, M., Lee, N., Zidda, F., Sohn, K., Usai, K., Löffler, M., Uddin, M. N., Farooqi, A., Schifitto, G., Zhang, Z., et al. (2024) · eLife · doi:10.7554/elife.96312.1
Brain white matter pathways of resilience to chronic back pain: a multisite validationPreprint
Mišić, M., Lee, N., Zidda, F., Sohn, K., Usai, K., Löffler, M., Uddin, M. N., Farooqi, A., Schifitto, G., Zhang, Z., et al. (2024) · eLife · doi:10.7554/elife.96312.2
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Dissociable structural and molecular pathways of age-related variability in sustained attentionPreprint
Subbulakshmi, S., Park, J., Rathmann-Bloch, J. E., Ward, T., Cheng, G. L., Miller, D. S., Schwartz, S. T., Sheng, J., Tran, T., Sha, S. J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.29.735429
- Authors
- Wolfers, T., Onnink, A. M. H., Zwiers, M. P., Arias-Vasquez, A., Hoogman, M., Mostert, J. C., Kan, C. C., Slaats-Willemse, D., Buitelaar, J. K., & Franke, B.
- Affiliations
- Radboud University Nijmegen (NL)
- From the Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
- Radboud University Medical Center (NL)
- ORCID
- Venue
- Journal of Psychiatry and Neuroscience
- Publisher
- Canadian Science Publishing
- Published
- 2015-09
- Volume
- 40
- Issue
- 5
- Pages
- 344-351
- ISSN
- 1180-4882 (ISSN-L)
- 1488-2434
- PMC
- PMC4543097
- OpenAlex
- W2336828789
- Cited by
- 52
- References
- 53
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 8 · 2021: 4 · 2020: 3 · 2019: 8 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 1
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Psychiatry and Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (FP7 2007-2013, 016‐130‐669, 433‐09‐229)
- Hersenstichting
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- attention deficit hyperactivity disorder, reaction time variability, superior longitudinal fasciculus, white matter microstructure, fractional anisotropy, sustained attention, inattention, adult ADHD, diffusion tensor imaging
- MeSH terms
- Adult, Attention, Attention Deficit Disorder with Hyperactivity, Female, Humans, Male, Middle Aged, Models, Neurological, Nerve Fibers, Nerve Net, Neuropsychological Tests, Reaction Time, Anisotropy, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, White Matter
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