FY2020 Annual Report

Human Developmental Neurobiology Unit
Professor Gail Tripp


The research of the Human Developmental Neurobiology Unit continues to focus on advancing understanding of the nature and causes of Attention Deficit Hyperactivity Disorder (ADHD) and translating this knowledge into effective management. We investigate the nature and etiology of altered reinforcement sensitivity in children and adults with ADHD using behavioral, pharmacological and imaging approaches here in Japan and with our collaborators in New Zealand, Brazil and Belgium. This work informs both behavioral and pharmacological interventions. We are actively working with international experts/colleagues to translate basic research on altered reinforcement sensitivity in ADHD into behavioral management strategies. We continue to evaluate the effectiveness, and cost effectiveness, of our parenting intervention for Japanese parents of children with ADHD (Well Parent Japan) in a multi-site randomized control trial, working with collaborators in England and at Japanese university and community hospitals in Okinawa, Fukui, and Fukuoka prefectures. We are also studying the language and social problem-solving skills of children with ADHD to increase understanding of the nature of their social difficulties to identify appropriate intervention targets.

1. Staff                             

  • Dr. Emi Furukawa, Group Leader
  • Dr. Shizuka Shimabukuro, Staff Scientist
  • Dr. Margaret Fitts, Clinical Psychologist
  • Ms. Ryoko Uchida, Research Unit Technician 
  • Mr. Paul Fitts, Research Unit Technician
  • Ms. Emi Nakanishi, Research Unit Technician (part time)
  • Dr. Atsuko Ishii, Research Unit Technician (June 2019 to March 2021; POC Grant)
  • Ms. Yuko Goto, Project Administrator (POC Grant)
  • Ms. Hend Samniya, PhD student
  • Ms. Machiko Shiomi, Research Unit Administrator

2. Collaborations

2.1 Altered reward sensitivity and its relationship to ADHD and other pathological conditions  

  • Description: Imaging (fMRI) and behavioral studies examining neural responses to reward anticipation and delivery, and effects of medication in ADHD and other disorders of impulse control. 
  • Type of collaboration: Joint research
  • Researchers:
    • Professor Jorge Moll, MD., Ph.D., D'Or Institute for Research and Education (IDOR)
    • Professor Paulo Mattos, MD., Ph.D., IDOR
    • Professor Jeff Wickens, Neurobiology Research Unit, OIST
    • Dr. Emi Furukawa, Unit

2.2 Altered reward sensitivity in children and adults with ADHD

  • Description: Completed a pilot study examining physiological (heart rate) responses to reward anticipation and delivery. 
  • Type of collaboration: Joint research
  • Researchers:
    • Professor Egas Caparelli-Daquer, MD., Ph.D., University of State of Rio de Janeiro (UERJ)
    • Dr. Emi Furukawa, Unit

2.3 Investigating sensitivity to different reward structures in ADHD

  • Description: Novel paradigms are being used to examine the effects of reward delay, reward frequency and reward cues on behavior in classical and instrumental learning paradigms.
  • Type of collaboration: Joint research
  • Researchers:
    • Dr. Brent Alsop, University of Otago, New Zealand
    • Dr. Heloisa Alves, University of Massachusetts Dartmouth, US 
    • Dr. Emi Furukawa, Unit

2.4 Supporting Japanese mothers of children with ADHD

  • Description: Currently conducting a multi-site randomized control trial of Well Parent Japan with Japanese mothers of children with ADHD.  
  • Type of collaboration: Joint research
  • Researchers:
    • Professor David Daley, University of Nottingham, UK
    • Professor Akemi Tomoda, Fukui University
    • Professor Takashi Oshio, Hitotsubashi University, Tokyo 
    • Professor Yushiro Yamashita, Kurme University, Fukuoka, Japan
    • Dr. Satoshi Harada, Ryukyu Hospital, Okinawa
    • Dr. Naohiro Endo, Ryukyu Hospital, Okinawa
    • Dr. Shizuka Shimabukuro, Unit

2.5 Learning under conditions of partial vs. continuous reinforcement in ADHD

  • Description: Currently collecting data using a simple free-operant instrumental learning task to assess the effect of reward frequency on response acquisition.
  • Type of collaboration: Joint research
  • Researchers:
    • Professor Saskia Van der Oord KU Leuven, Belgium
    • Professor Beckers, KU Leuven, Belgium
    • Dr. Hasse de Meyer KU Leuven, Belgium
    • Ms. An-Katrien Hulsbosch (PhD student)

2.6 Frustration responses to partial reinforcement and punishment in ADHD

  • Description: We have established a new collaboration to examine children’s emotional reactions to reinforcement and punishment, using measures of heart rate, activity, and facial expression together with traditional behavioral measures.
  • Type of collaboration: Joint research
  • Researchers:
    • Professor Saskia Van der Oord KU Leuven, Belgium
    • Professor Beckers, KU Leuven, Belgium
    • Ms. An-Katrien Hulsbosch, KU Leuven, Belgium (PhD student)


3. Activities and Findings

3.1 Data collection at the Children's Research Center (CRC) in Okinawa

We continued to collect data with English-speaking children, meeting criteria for ADHD, in Okinawa. This includes detailed clinical assessments of children's behavior as well as participation in multiple computer-based behavioral tasks examining sensitivity to different reinforcement structures. We are piloting several new tasks. Parent training programs with Japanese families and related data collection are ongoing. We have extended earlier research evaluating the social problem-solving skills of children with ADHD to include detailed assessments of the children's language skills to evaluate to their contribution to social difficulties.

This year, we hosted one internship student, Mr. Akinobu Noguchi (December 2020 to March 2021), and two rotation students, Ms. Shannon Hayashi (September 2020 to December 2020) and Ms. Izabela Porębska, Rotation student (January 2021 to April 2021).

3.2 ADHD and Dopamine Transfer Deficit (DTD)  

In the first collaborative imaging study with IDOR, we demonstrated a reciprocal dissociation in ADHD vs. Control groups, with ADHD participants showing increased striatal blood-oxygen-level dependent (BOLD) responses to reward delivery (US), but not to reward-predicting cues (CS), with the reverse pattern observed in the Control participants. The observed BOLD response patterns being consistent with impaired predictive dopamine signaling in ADHD as hypothesized in DTD. In a second study, we examined the effects of stimulant medication (methylphenidate) on the striatal responses to reward-predicting cues and reward delivery in adults with ADHD. Larger differences in the BOLD responses to reward cues versus non-reward cues were observed in the ventral striatum when the ADHD participants were taking methylphenidate compared to placebo. In response to cued-reward outcome, methylphenidate reduced the BOLD time-series correlation between the dorsal striatum and dorsal medial prefrontal cortex. The results suggest that methylphenidates’ therapeutic effects may be mediated by altering neural responses to CS and US. Data collection for a third study examining 1) if altered sensitivity to reward cues and reward delivery, involving monetary incentives generalizes to other types of rewards, and 2) whether the nature and degree of altered reward sensitivity observed in ADHD is shared by those who have a Binge Eating Disorders. Data analysis is continuing.

The results of a pilot study examining heart-rate responses to reward-predicting cues and reward delivery in collaboration with UERJ showed that in typically developing adults, orienting effects are observed in response to non-reward stimuli when preceded by the reward predicting cue after conditioning.  

3.3 Effects of delayed reinforcement on learning

The DTD hypothesis predicts that under conditions of delayed reinforcement, learning in children with ADHD will take place more slowly than in typically developing children, and may fail to occur. 

We are testing this hypothesis by comparing the learning speed of children with and without ADHD using a delayed-reinforcement learning task in collaboration with Dr. Alsop at University of Otago.  Preliminary analysis of the data collected with children with and without ADHD indicated that the delay resulted in significant difficulties in learning for both groups of children. We have modified the task to reduce the difficulty level and are collecting the data using the revised task.

3.4 Waiting behavior in children with and without ADHD

Children with ADHD have been shown to demonstrate stronger preference for immediate over delayed reward. We examined the effects of reward delay and reward-predicting cues on children’s waiting behavior, using a computerized behavioral choice task, in collaboration with Dr. Alsop at University of Otago and Dr. Alves at the University of Massachusetts Dartmouth. The results indicate that children with ADHD are more likely than typically developing children to abandon their efforts to wait, especially when wait times are long.

3.5 Learning under conditions of partial vs. continuous reinforcement

A small number of early studies identified deficits in reinforcement learning in children with ADHD under conditions of partial (not every correct response rewarded), but not continuous, reinforcement. These results are consistent with the predictions of the DTD theory. However, methodological issues limit the conclusions that can be drawn from these studies. We are extending this research in collaboration with Professors van der Oord and Beckers, Dr. De Meyer, and Ms. Hulsbosch from KU Leuven. Data collection is ongoing. 

3.6 Supporting Japanese mothers of children with ADHD

We are following up a successful small-scale randomized control trial (RCT) of Well Parent Japan with a multi-site RCT funded through an OIST Proof of Concept (POC) grant. Well Parent Japan is a 13-session group delivered Japanese language adaptation of the New Forest Parenting Programme for ADHD (NFPP) augmented with strategies to improve participant’s psychological wellbeing.

The multi-site RCT is being conducted across three sites in Japan, Fukui, Kurume and Okinawa with our research collaborators. This RCT assesses the immediate and longer term (3-month follow-up) effects of the program in a larger sample.  In addition, we are evaluating the program’s cost effectiveness (delivery cost, reduction in ADHD associated direct and indirect costs, impact on quality of life). Data collection is expected to be completed in FY 2021.

3.6 Predictors of academic performance in children with ADHD 

Academic difficulties are frequently comorbid with ADHD, highlighting the need for academic remediation programs for children with ADHD. Identifying common predictors of academic difficulties is important to identify appropriate targets of intervention. We combined data previously collected in New Zealand with Unit data (native English speakers living in Okinawa) to identify predictors and moderators of academic performance in children with ADHD. Study findings indicate semantic language, age at testing and verbal working memory as consistent predictors of academic achievement across subjects and samples. We recommend classroom interventions accommodate reduced working memory and address language weaknesses.

4. Publications

4.1 Journals

  1. Faraone, SV., Banaschewski, T., Coghill, D., Zheng, Y., Biederman, J., ...& Tripp, G…. (2021). The world federation of ADHD international consensus statement: 208 evidence-based conclusions about the disorder. Neuroscience & Biobehavioral Reviews. https://doi.org/10.1016/j.neubiorev.2021.01.022
  2. Van der Oord, S., Tripp, G. (2020). How to Improve Behavioral Parent and Teacher Training for Children with ADHD: Integrating Empirical Research on Learning and Motivation into Treatment. Clinical Child and Family Psychology Review volume 23, pages 577–604. https://link.springer.com/article/10.1007/s10567-020-00327-z
  3. Tripp, G., Furukawa, E. (2020). International Sessions: What is the contribution of altered motivational processing to ADHD? Implications for psychosocial management. Japanese Journal of Child and Adolescent Psychiatry: 61(3), 225-242.

4.2 Books and other one-time publications

Nothing to report.

4.3 Oral and Poster Presentations

  1. An Analysis of Emotional Expression Data of Mothers of Children with Attention Deficit Hyperactivity Disorder (ADHD), March 2021, University of the Ryukyus, Noguchi, A. (Internship supervisors: Shimabukuro, S., Tripp, G)
  2. ADHD and Instrumental Learning: A Systematic Review. APSARD Annual Meeting, Virtual Conference. January 2021. Hulsbosch, AK., De Meyer, H., Beckers, T., Danckaerts, M., Van Liefferinge, D., Tripp, G., Van der Oord, S.
  3. Introduction to ADHD, April/May 2020, Child Development Center, OIST, Tripp, G.
  4. ADHD in the School Setting, May 2020, Child Development Center, OIST, Tripp, G.
  5. Introduction to Autism Spectrum Disorder, April 2020, Child Development Center, OIST, Fitts, M.
  6. Behavior Detective Work, April 2020, Child Development Center at OIST, Fitts, P.

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report.

6. Meetings and Events

We had planned a mini symposium “Translating evidence on altered motivational processes in ADHD into behavioral management strategies: Toward new research ideas” in 2020, subsequently postponed to January 2022.

7. Other

Nothing to report.