FY2021 Annual Report

Human Developmental Neurobiology Unit
Professor Gail Tripp

Abstract

The research of the Human Developmental Neurobiology Unit seeks to advance understanding of the nature and causes of Attention Deficit Hyperactivity Disorder (ADHD) and to translate this knowledge into effective management strategies. We investigate reinforcement sensitivity and learning in children and adults with ADHD using behavioral, physiological and imaging approaches here in Japan and with collaborators in New Zealand, Brazil and Belgium. We are working with local and international colleagues to incorporate these findings into psychosocial interventions for families of children with ADHD. We recently completed data collection for a multi-site randomized trial of Well Parent Japan (WPJ), our parenting intervention for Japanese parents of children with ADHD. This study evaluates the effectiveness and cost effectiveness of WPJ compared with routine clinical care in Japanese mental health services. The study is the first of its kind in Japan, representing a collaborative effort with researchers in England and Japan, incorporating research sites in Okinawa, Fukui and Fukuoka. Study findings will be available in the summer of 2022. We are also conducting studies on the role of pragmatic language and perspective taking skills in the social difficulties of children with ADHD, again with the long-term goal of improved interventions.

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)
  • Ms. Naruyo Yoshimoto (POC Grant)
  • Ms. Yuko Goto, Project Administrator (POC Grant)
  • Ms. Hend Samniya, PhD student
  • Ms. Izabela Porębska, PhD student (From February 2022)
  • Ms. Miyu Nambu, Rotation student (September 2021- March 2022)
  • Mr. Akinobu Noguchi, Visiting Research Student (May 2021 – March 2022)
  • Ms. Miho Tatsuki, Research Intern (From October 2021)
  • Ms. Nanami Okada, Research Intern (December 2021- March 2022)
  • Ms. Machiko Shiomi, Research Unit Administrator

2. Collaborations

2.1 Altered motivational processes in ADHD: Experimental to translational research

  • Description: (1) Imaging (fMRI) studies examining neural responses to reward anticipation and delivery and (2) translation of behavioral and neuroimaging findings to a brief psychoeducational /behavior management program delivered via social media.
  • 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 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

2.3 Emotional reactivity to discontinuous reinforcement and punishment in ADHD

  • Description: Currently collecting data using a free-operant instrumental learning task and a matching-law punishment task to examine children’s emotional reactions to reinforcement schedules, extinction and punishment. We measure heart rate, activity levels, 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)

2.4 Supporting Japanese mothers of children with ADHD

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

 2.5 Translational research: Incorporating experimental evidence on altered reward and punishment sensitivity into behavioral management strategies for ADHD

  • Description: Currently reviewing empirical findings on altered reinforcement sensitivity in ADHD to identify modifications to traditional behavioral management strategies for children with ADHD. This will be used incorporated into a needs assessment and an intervention feasibility trial.
  • Type of collaboration: Resulted in a successful Kakenhi (Scientific Research C) grant (to commence in FY 2022).
  • Researchers:
    • Dr. Aya Kasai, Miyazaki International College
    • Dr. Emi Furukawa, Unit
    • Dr. Shizuka Shimabukuro, Unit

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 the children's behavior together with participation in multiple computer-based behavioral tasks examining sensitivity to different reinforcement structures. We are piloting several new tasks.

We are currently home to two PhD students Ms. Hend Samniya and Ms. Izabela Porębska. Following a successful proposal defense, Hend began pilot data collection evaluating children’s social communication and discourse skills. In particular, Hend is interested in the ability of children with and without ADHD to monitor and repair their social communications and how this contributes to social difficulties in children with ADHD. Izabela joined us in February 2022 and is currently developing her research ideas to further understanding of social functioning of children with ADHD.

We hosted two research interns, Nanami Okada (December - April 2021) and Ms. Miho Tatsuki, (October 2021~), and a rotation student Ms. Miyu Nambu, (September - December 2021),

3.2 ADHD and Dopamine Transfer Deficit (DTD)

In collaborative imaging studies with IDOR, we previously reported that adults with ADHD show increased striatal blood-oxygen-level dependent (BOLD) responses to monetary reward delivery (US), but not to reward-predicting cues (CS). The opposite pattern was observed in the Control participants. We also showed that methylphenidate modulates the cortico-striatal responses to the US and CS among adults with ADHD. These response patterns are consistent with impaired predictive dopamine signaling in ADHD as hypothesized in DTD. In a third study, we examined whether altered sensitivity to reward cues and reward delivery, involving monetary incentives, generalizes to other types of reward. Results indicate reduced striatal responses to affiliative reward cues together with increased responses to delivery of affiliative reward stimuli in adults with ADHD. Interestingly, these response alternations were not found with food reward stimuli. Reward modality may differentially impact neural responses cues and reward delivery.

We are developing new computer-based tasks to examine behavioral sensitivity to CS in children with and without ADHD in collaboration with Dr. Brent Alsop at University of Otago, Dr. Mayank Aggarwal of RIKEN, and Dr. Jeff Wickens and Ms. Silic Bozena of the OIST Neurobiology Research Unit.

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 the University of Otago. 

3.3 Waiting behavior in children with and without ADHD

Children with ADHD 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 the University of Otago and Dr. Alves at the University of Massachusetts Dartmouth. Study findings indicate disrupted waiting behavior in ADHD. Compared to their typically developing peers, children with ADHD are more likely to terminate their wait for a large delayed reward by collecting a small, immediately available reward, or attempting to collect the large reward early. Cues signaling availability of the large reward disrupted waiting in children with ADHD when they no longer consistently predicted reward. These findings highlight the importance of looking beyond a simple preference for immediacy.

3.4 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. In collaboration with Professors van der Oord and Beckers, Dr. De Meyer, and Ms. Hulsbosch (KU Leuven), we recently completed a well powered study comparing learning and response to extinction in children, with and without ADHD, under conditions of partial and continuous reinforcement. Children with ADHD showed a reduced partial reinforcement extinction effect as predicted by our DTD hypothesis.

3.5 Emotional reactivity to discontinuous reward and punishment in ADHD.

We are supporting Ms. An-Katrien Hulsbosch’s data collection for her PhD thesis (co-supervised by Professor Tripp) entitled “Reinforcement learning and emotional lability in ADHD. Following delays due to Covid-19, Ms. Hulsbosch will join the Research Unit for 6 months during 2022.

3.6 Supporting Japanese mothers of children with ADHD

Following a successful small-scale randomized control trial (RCT) of Well Parent Japan (WPJ), we undertook a pragmatic multi-site RCT of the program 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 was conducted across three sites in Japan, Fukui, Fukuoka, and Okinawa with our research collaborators. Data analysis is currently underway evaluating the immediate and longer term (3-month follow-up) effects of the program, and the program’s cost effectiveness (delivery cost, reduction in ADHD associated direct and indirect costs, impact on quality of life). Study completion was delayed by approximately 12 months due to Covid-19.

We are also planning a school-based implementation of the program, which will be supported by a Kakenhi (Scientific Research C) grant (to commence in FY 2022).

3.7 Psychosocial treatment needs of Brazilian families of children with ADHD

Access to empirically supported psychosocial treatment is limited among families living in low- to middle-income countries. We conducted a qualitative needs assessment to identify the treatment needs of Brazilian families with children demonstrating symptoms of ADHD, and the barriers families face in accessing psychosocial treatment. Common themes were identified via semi-structured phone interviews with parents of children with ADHD, as well as educators and healthcare providers. The study showed that existing services are not meeting the needs of children with ADHD and their families. Easily accessed, research-informed, treatment programs teaching practical behavior management strategies are highly desired.

3.8 Wishes of children with ADHD

Understanding the desires and motivations of children with ADHD is important in helping them thrive. We examined the wishes of children diagnosed with ADHD using the Three Wishes task. While many of the wishes reported were for immediate fulfillment and reflected material desires, affiliative wishes, highlighting the children’s desire for positive interpersonal relationships, were also common. Some wishes reflected self-actualization and altruistic desires. The study highlighted the diversity and typicality of the self-reported needs, desires, and hopes of children with ADHD.

4. Publications

4.1 Journals

  1. Carrasco KD, Chuang CC, Tripp G (2022). Shared Predictors of Academic Achievement in Children with ADHD: A Multi-Sample Study. J Atten Disord, 26(4), 573-586. https://doi.org/10.1177/10870547211012039
  2. Figueiredo, T, Sudo F, Serra-Pinheiro MA, Tripp G, Mattos P (2022). Interpersonal Negotiation Skills in ADHD. Social Neuroscience, 17(1), 86-93. https://doi.org/10.1080/17470919.2021.2025424
  3. Hulsbosch AK, De Meyer H, Beckers T, Danckaerts M, Van Liefferinge D, Tripp G, Van der Oord S (2021). Systematic Review: Attention-Deficit/Hyperactivity Disorder and Instrumental Learning. J Am Acad Child Adolesc Psychiatry,60(11), 1367-1381. https://doi.org/10.1016/j.jaac.2021.03.009
  4. Furukawa, E, Alsop B, Shimabukuro S, Sowerby P, Jensen S, Tripp G (2021). Increased Behavioral Sensitivity to Repeated Experiences of Punishment in Children with ADHD: Experimental Studies Using the Matching Law. J Atten Disord, 25(12), 1665. (published abstract) https://doi.org/10.1177/1087054720914384
  5. De Meyer H, Tripp G, Beckers T, Van der Oord, S (2021). Conditional Learning Deficits in Children with ADHD can be Reduced through Reward Optimization and Response-Specific Reinforcement. Res Child Adolesc Psychopathol, 49, 1165-1178. 10.1007/s10802-021-00781-5
  6. Carruthers S, Taylor L, Sadiq H, Tripp G (2021). The Profile of Pragmatic Language Impairments in Children with ADHD: A Systematic Review. Dev Psychopathol, 1-23. https://doi.org/10.1017/S0954579421000328
  7. Sayão A, Alves H, Furukawa E, Wenk TS, Cagy M, Gutierrez-Arango S, Tripp G, Caparelli-Dáquer E (2021). Development of a Classical Conditioning Task for Humans Examining Phasic Heart Rate Responses to Signaled Appetitive Stimuli: A Pilot Study. Front Behav Neurosci, 15. https://doi.org/10.3389/fnbeh.2021.639372
  8. De Meyer, H., Tripp, G., Beckers, T., van der Oord, S. (2021). Operamt :erem bij kinderen met ADHD. Terug Naar de basis van gedragstherapie Gedragstherapie: tijdschrift voor gedragstherapie en cognitieve therapie, 54(3), 139-164. (Dutch translation/publication).

4.2 Books and other one-time publications

Nothing to report.

4.3 Oral and Poster Presentations

  1. From research to clinical practice: applying what we know about altered reinforcement sensitivity to the management of ADHD. Plenary Address American Professional Society for ADHD and Associated Difficulties (APSARD). January 2022. Tripp G.
  2. Autism Spectrum Disorder in Preschool and Elementary School. January 2022 Child Development Center, OIST Fitts, M.
  3. Autism Spectrum Disorder in Infants and Toddlers. January 2022 Child Development Center, OIST Fitts, M.
  4. Attention deficit hyperactivity disorder (ADHD). A short course/recorded lecture for Graduate School of University of Ryukyus Medical School, January 2022. Tripp, G.
  5. From research to clinical practice: applying what we know about altered reinforcement sensitivity to the management of ADHD. (Adapted version of APSARD Plenary talk) Recorded lecture for Graduate School of University of Ryukyus Medical School, January 2022. Tripp, G.
  6. Results from Behavioral and Imaging Experimental Findings and Their Clinical Implications. OIST Mini-Symposium Zoom Meeting January 2022. Furukawa E, Tripp G.
  7. Use of Reward and Punishment in Japan: Challenges in Adopting NFPP to Japanese Population. OIST Mini-Symposium Zoom Meeting January 2022. Shimabukuro, S.
  8. Well Parent Japan (WPJ) Parent Training for ADHD: Preliminary analysis of maternal Expressed Emotion. The 12th Japanese ADHD Parenting Conference. December 2021. Shimabukuro, S.
  9. Pragmatic multi-center randomized controlled trial of Well Parent Japan (WPJ) for mother of children with ADHD - Getting research into the real world. The 63rd Annual Meeting of the Japanese Society of Child Neurology May 2021. Shimabukuro, S.
  10. A definitive test of partial reinforcement learning in ADHD: Does frequency matter? Eunethydis, Virtual Conference, September 2021. Hulsbosch, AK, De Meyer, H., Beckers, T., Danckaerts, M., Van Liefferinge, D., Tripp, G., van der Oord, S.
  11. ADHD en operant leren: een review en implicaies voor de praktijk. VGCt Najaarscongres, Veldhoven, the Netherlands November 2021. Hulsbosch, AK, De Meyer, H., Beckers, T., Danckaerts, M., Van Liefferinge, D., Tripp, G., van der Oord, S.

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, postponed once to January 2022, and again to January 2023. In January 2022, participants agreed to have a preliminary zoom meeting, each presenting relevant work and ideas for translational work.

Zoom Meeting Presentations:

  1. Effects of Elements of Behavioral Parent Training and Moderators of Effects by Reward/Punishment Sensitivity. Van der Oord S, Van den Hoofdakker B, Luman M. 
  2. Developing Psychoeducation+ Program in Brazil.  Da Costa R, Bernardes C.
  3. How NFPP Teaches Reward and Punishment, Challenges in Providing Reward and Punishment Advice to Parents, Especially to Families with Children with ADHD. Delay D.
  4. Use of Reward and Punishment in Japan, Challenges in Adopting NFPP to Japanese Population. Shimabukuro S.
  5. Relationship between Procrastination and Preference for Immediate Reward in Japanese University Students with Elevated ADHD Symptoms. Oguchi M.
  6. School-Based Universal Intervention for Enhancing Adolescents’ Reward Sensitivity. Takahashi F.
  7. Choice Delay Paradigm Effects Cross Studies and Cultures. Bado P.
  8. Results from Behavioral and Imaging Experimental Findings and Their Clinical Implications. Furukawa E, Tripp P.

7. Other

Nothing to report.