Brain Imaging and Behavior

, Volume 12, Issue 2, pp 518–531 | Cite as

Treatment effect of methylphenidate on intrinsic functional brain network in medication-naïve ADHD children: A multivariate analysis

  • Jae Hyun Yoo
  • Dohyun Kim
  • Jeewook Choi
  • Bumseok Jeong
Original Research


Methylphenidate is a first-line therapeutic option for treating attention-deficit/hyperactivity disorder (ADHD); however, elicited changes on resting-state functional networks (RSFNs) are not well understood. This study investigated the treatment effect of methylphenidate using a variety of RSFN analyses and explored the collaborative influences of treatment-relevant RSFN changes in children with ADHD. Resting-state functional magnetic resonance imaging was acquired from 20 medication-naïve ADHD children before methylphenidate treatment and twelve weeks later. Changes in large-scale functional connectivity were defined using independent component analysis with dual regression and graph theoretical analysis. The amplitude of low frequency fluctuation (ALFF) was measured to investigate local spontaneous activity alteration. Finally, significant findings were recruited to random forest regression to identify the feature subset that best explains symptom improvement. After twelve weeks of methylphenidate administration, large-scale connectivity was increased between the left fronto-parietal RSFN and the left insula cortex and the right fronto-parietal and the brainstem, while the clustering coefficient (CC) of the global network and nodes, the left fronto-parietal, cerebellum, and occipital pole-visual network, were decreased. ALFF was increased in the bilateral superior parietal cortex and decreased in the right inferior fronto-temporal area. The subset of the local and large-scale RSFN changes, including widespread ALFF changes, the CC of the global network and the cerebellum, could explain the 27.1% variance of the ADHD Rating Scale and 13.72% of the Conner’s Parent Rating Scale. Our multivariate approach suggests that the neural mechanism of methylphenidate treatment could be associated with alteration of spontaneous activity in the superior parietal cortex or widespread brain regions as well as functional segregation of the large-scale intrinsic functional network.


Attention deficit-hyperactivity disorder Methylphenidate Functional magnetic resonance imaging Resting state networks Machine learning 


Compliance with ethical standards


This research was supported by the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2016M3C7A1914448 to B.J.), and by KAIST Future Systems Healthcare Project from the Ministry of Education, Science and Technology (N11160068 to B.J.)

Conflict of interest

All authors declares that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants and their parents included in the study.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Computational Affective Neuroscience and Development Laboratory, Graduate School of Medical Science and Engineering, KAISTDaejeonRepublic of Korea
  2. 2.KI for Health Science and Technology, KAIST Institute, KAISTDaejeonRepublic of Korea
  3. 3.Department of PsychiatryCatholic University Daejeon St. Mary’s HospitalDaejeonRepublic of Korea

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