Increased default-mode variability is related to reduced task-performance and is evident in adults with ADHD

Athanasia M. Mowinckel; Dag Alnæs; Mads L. Pedersen; Sigurd Ziegler; Mats Fredriksen; Tobias Kaufmann; Edmund Sonuga-Barke; Tor Endestad; Lars T. Westlye; Guido Biele

doi:10.1016/j.nicl.2017.03.008

Increased default-mode variability is related to reduced task-performance and is evident in adults with ADHD

Athanasia M. Mowinckel^*, Dag Alnæs, Mads L. Pedersen, Sigurd Ziegler, Mats Fredriksen, Tobias Kaufmann, Edmund Sonuga-Barke, Tor Endestad, Lars T. Westlye, Guido Biele

^*Corresponding author for this work

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

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Abstract

Insufficient suppression and connectivity of the default mode network (DMN) is a potential mediator of cognitive dysfunctions across various disorders, including attention deficit/hyperactivity disorder (ADHD). However, it remains unclear if alterations in sustained DMN suppression, variability and connectivity during prolonged cognitive engagement are implicated in adult ADHD pathophysiology, and to which degree methylphenidate (MPH) remediates any DMN abnormalities. This randomized, double-blinded, placebo-controlled, cross-over clinical trial of MPH (clinicaltrials.gov/ct2/show/NCT01831622) explored large-scale brain network dynamics in 20 adults with ADHD on and off MPH, compared to 27 healthy controls, while performing a reward based decision-making task. DMN task-related activation, variability, and connectivity were estimated and compared between groups and conditions using independent component analysis, dual regression, and Bayesian linear mixed models. The results show that the DMN exhibited more variable activation patterns in unmedicated patients compared to healthy controls. Group differences in functional connectivity both between and within functional networks were evident. Further, functional connectivity between and within attention and DMN networks was sensitive both to task performance and case-control status. MPH altered within-network connectivity of the DMN and visual networks, but not between-network connectivity or temporal variability. This study thus provides novel fMRI evidence of reduced sustained DMN suppression in adults with ADHD during value-based decision-making, a pattern that was not alleviated by MPH. We infer from multiple analytical approaches further support to the default mode interference hypothesis, in that higher DMN activation variability is evident in adult ADHD and associated with lower task performance.

Original language	English
Pages (from-to)	369-382
Number of pages	14
Journal	NeuroImage: Clinical
Volume	16
Early online date	30 Mar 2017
DOIs	https://doi.org/10.1016/j.nicl.2017.03.008
Publication status	E-pub ahead of print - 30 Mar 2017

Keywords

Adult ADHD
Decision-making
DMN
Dopamine
fMRI
Functional networks
Reward

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Mowinckel, A. M., Alnæs, D., Pedersen, M. L., Ziegler, S., Fredriksen, M., Kaufmann, T., Sonuga-Barke, E., Endestad, T., Westlye, L. T., & Biele, G. (2017). Increased default-mode variability is related to reduced task-performance and is evident in adults with ADHD. NeuroImage: Clinical, 16, 369-382. Advance online publication. https://doi.org/10.1016/j.nicl.2017.03.008

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abstract = "Insufficient suppression and connectivity of the default mode network (DMN) is a potential mediator of cognitive dysfunctions across various disorders, including attention deficit/hyperactivity disorder (ADHD). However, it remains unclear if alterations in sustained DMN suppression, variability and connectivity during prolonged cognitive engagement are implicated in adult ADHD pathophysiology, and to which degree methylphenidate (MPH) remediates any DMN abnormalities. This randomized, double-blinded, placebo-controlled, cross-over clinical trial of MPH (clinicaltrials.gov/ct2/show/NCT01831622) explored large-scale brain network dynamics in 20 adults with ADHD on and off MPH, compared to 27 healthy controls, while performing a reward based decision-making task. DMN task-related activation, variability, and connectivity were estimated and compared between groups and conditions using independent component analysis, dual regression, and Bayesian linear mixed models. The results show that the DMN exhibited more variable activation patterns in unmedicated patients compared to healthy controls. Group differences in functional connectivity both between and within functional networks were evident. Further, functional connectivity between and within attention and DMN networks was sensitive both to task performance and case-control status. MPH altered within-network connectivity of the DMN and visual networks, but not between-network connectivity or temporal variability. This study thus provides novel fMRI evidence of reduced sustained DMN suppression in adults with ADHD during value-based decision-making, a pattern that was not alleviated by MPH. We infer from multiple analytical approaches further support to the default mode interference hypothesis, in that higher DMN activation variability is evident in adult ADHD and associated with lower task performance.",

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AU - Pedersen, Mads L.

AU - Ziegler, Sigurd

AU - Fredriksen, Mats

AU - Kaufmann, Tobias

AU - Sonuga-Barke, Edmund

AU - Endestad, Tor

AU - Westlye, Lars T.

AU - Biele, Guido

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AB - Insufficient suppression and connectivity of the default mode network (DMN) is a potential mediator of cognitive dysfunctions across various disorders, including attention deficit/hyperactivity disorder (ADHD). However, it remains unclear if alterations in sustained DMN suppression, variability and connectivity during prolonged cognitive engagement are implicated in adult ADHD pathophysiology, and to which degree methylphenidate (MPH) remediates any DMN abnormalities. This randomized, double-blinded, placebo-controlled, cross-over clinical trial of MPH (clinicaltrials.gov/ct2/show/NCT01831622) explored large-scale brain network dynamics in 20 adults with ADHD on and off MPH, compared to 27 healthy controls, while performing a reward based decision-making task. DMN task-related activation, variability, and connectivity were estimated and compared between groups and conditions using independent component analysis, dual regression, and Bayesian linear mixed models. The results show that the DMN exhibited more variable activation patterns in unmedicated patients compared to healthy controls. Group differences in functional connectivity both between and within functional networks were evident. Further, functional connectivity between and within attention and DMN networks was sensitive both to task performance and case-control status. MPH altered within-network connectivity of the DMN and visual networks, but not between-network connectivity or temporal variability. This study thus provides novel fMRI evidence of reduced sustained DMN suppression in adults with ADHD during value-based decision-making, a pattern that was not alleviated by MPH. We infer from multiple analytical approaches further support to the default mode interference hypothesis, in that higher DMN activation variability is evident in adult ADHD and associated with lower task performance.

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ER -

Increased default-mode variability is related to reduced task-performance and is evident in adults with ADHD

Abstract

Keywords

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