FY2022 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. Well Parent Japan (WPJ), our parenting intervention for Japanese parents of children with ADHD, is moving to the dissemination phase after completion of a large multi-site randomized trial. Another community-based participatory research study is underway to develop an accessible preventative/early intervention parenting program. We are also conducting research on the role of pragmatic language, expectations, 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 (Until May 2022)
Dr. Catherine Williams, Clinical Psychologist (From September 2022)
Ms. Ryoko Uchida, Research Unit Technician
Mr. Paul Fitts, Research Unit Technician (Until May 2022)
Ms. Emi Nakanishi, Research Unit Technician (part time)
Ms. Juli Cornett, Research Unit Technician (From December 2022)
Ms. Hend Samniya, PhD student
Ms. Izabela Porębska, PhD student (From February 2022)
Ms. Kokila Dilhani Perera, Rotation student/PhD student (From September 2022)
Ms. An-Katrien Hulsbosch visiting research student (From May 2022 – November 2022)
Ms. Miho Tatsuki, Research Intern (From October 2021– June 2022)
Ms. Miki Medorua, Research Intern (From December 2022 – March 2022)
Ms. Anastasia Lado, Research Intern (From April 2022 – September 2022)
Ms. Iryna Vlasiuk, Research Intern (From July 2022 – September 2022)
Mr. Kazuma Takada, Rotation student (May 2022- September 2022)
Ms. Machiko Shiomi, Research Unit Administrator (until November 2022)
Ms. Ayame Munoz, Research Unit Administrator (From February 2023)
Ms. Yuko Goto, Project Administrator (POC Grant)

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:
- Dr. Jorge Moll, MD., Ph.D., D'Or Institute for Research and Education (IDOR)
- Professor Paulo Mattos, MD., Ph.D., IDOR
- Patrícia Bado, PhD., Catholic University of Rio de Janeiro/IDOR
- Raquel Costa, MD., Ph.D., IDOR
- Camila Bernardes, MA., 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. Mayank Aggarwal, RIKEN
- Dr. Jeff Wickens, Neurobiology Research Unit, OIST
- Ms. Silic Bozena, Neurobiology Research Unit, OIST
- Dr. Emi Furukawa, Unit
- Ms. Kokila Dihani Perera, Unit

2.3 Emotional reactivity to discontinuous reinforcement, conditional discrimination, and punishment in ADHD

Description: Currently collecting data using a free-operant instrumental learning task, a conditional discrimination task, and a matching-law punishment task to examine children’s emotional reactions to reinforcement schedules, extinction and punishment. We record 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
- Ms. An-Katrien Hulsbosch, KU Leuven, Belgium (PhD Student)

2.4 Supporting Japanese mothers of children with ADHD

Description: Completed data collection for a pragmatic multi-site effectiveness and cost effectiveness randomized control trial of WPJ with Japanese mothers of children with ADHD. Currently analyzing data and preparing manuscripts. Also supporting the community implementation of WPJ.
Type of collaboration: Joint research (POC-ITR/POC-II grants)
Researchers:
- Professor David Daley, University of Nottingham, UK
- Professor Akemi Tomoda, University of Fukui, Fukui
- Professor Takashi Oshio, Hitotsubashi University, Tokyo
- Professor Yushiro Yamashita, Kurume University, Fukuoka
- Dr. Satoshi Harada, Ryukyu Hospital, Okinawa
- Dr. Takahiro Endo, Ryukyu Hospital, Okinawa
- Dr. Shizuka Shimabukuro, Unit
- Ms. Yuko Goto, Unit
Community organization:
- Life Support Center for families and individuals with neurodevelopmental disorders

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

Description: Using a community-based participatory research approach, we are developing a behavioral management program that will be accessible to parents who are concerned about children’s behavior but may be hesitant to seek help in traditional healthcare settings. The program is informed by our empirical research on altered sensitivity to changing contingencies in children with ADHD. A feasibility trial will be conducted.
Type of collaboration: Joint research (KAKENHI Scientific Research C).
Researchers:
- Dr. Aya Kasai, Miyazaki International College
- Dr. Emi Furukawa, Unit
- Dr. Shizuka Shimabukuro, Unit

2.6 Survey and promotion of multicultural society through supporting children with international roots: creating a community where information can be shared, and trust can be established across cultures and languages

Description: Making assessment and intervention resources for ADHD and other childhood conditions available in multiple languages for parents and teachers in Japan and evaluating their reach, acceptability and effects.
Type of collaboration: Collaborator in the project (Funded by Toyota Foundation).
Researchers:
- Ms. Noriko Yamada, Institute of Future Engineering, University of Ryukyus
- NPO SABJA
- Dr. Emi Furukawa, Unit

2.7 Feasibility study: Implementation of Well Parent Japan (WPJ) in Japanese schools

Description: We are preparing for a feasibility study to evaluate implementation of an evidence-based parent training program, WPJ, in two Japanese/Okinawan schools. School staff will be trained to co-lead the parenting groups. Teachers will be given opportunities to view accompanying educational videos. We have met with school boards and principals to coordinate the implementation.
Type of collaboration: Joint research (KAKENHI Scientific Research C).
Researchers:
- Professor Yushiro Yamashita, Kurume University, Fukuoka
- Dr. Shizuka Shimabukuro, Unit
- Dr. Emi Furukawa, 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 three PhD students, Ms. Hend Samniya, Ms. Izabela Porębska, and Ms. Kokila Dihani Perera. Hend began data collection for three studies evaluating the ability of children with and without ADHD to monitor and repair their social communication. This includes a narrative task, an information gathering (detective task), and an instruction giving task. She will also evaluate the relationship between task performance and the children’s social skills. Izabela successfully defended her PhD research proposal and is preparing for data collection. She will evaluate the expectations of children with and without ADHD for the behavior of others and how they allocate responsibility for good and poor social outcomes. Kokila completed a rotation in the unit before choosing to join the unit for her PhD. She has been learning all about ADHD and is currently developing her research ideas to further understanding of altered reinforcement sensitivity in children with ADHD.

We hosted four research interns, Miho Tatsuki (October 2021– June 2022), Miki Medorua (December 2022 – March 2022), Anastasia Lado (April 2022 – September 2022) and Iryna Vlasiuk (July 2022 – September 2022), two rotation students, Kazuma Takada, (May 2022 – September 2022) and Kokila Dilhani Perera (September 2022 – January 2023) and a visiting research student, An-Katrien Hulsbocsh (May 2022 – November 2022) who is co-supervised by Professor Tripp.

3.2 ADHD and Dopamine Transfer Deficit (DTD)

After COVID-19 delays, we completed our third fMRI study examining 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 to reward cues and reward delivery.

We are developing new computer-based tasks to examine behavioral sensitivity to reward-predicting cues (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.

In collaboration with Dr. Alsop, we are also collecting data for two other experimental tasks. 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. The DTD also predicts that the extinction of learned behavior is faster for children with ADHD, compared to their typically developing peers. We are testing the speed of behavioral extinction after learning under the condition of continuous or delayed reinforcement. Data collection with ADHD participants for these two tasks is complete. We recently resumed control group data collection after COVID-19 linked delays.

3.3 Waiting behavior in children with and without ADHD

We completed a study examining 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 that 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.

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 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, conditional discrimination, 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 joined 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 well powered 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. After COVID-19 delays, data collection and analyses of the effects of WPJ against threatment as usual (TAU), immediately post intervention and at 3-months follow up were completed together with a cost effectiveness analysis. The results show WPJ is superior to TAU in reducing parenting stress and family strain and improving parenting practices and parenting efficacy. Program delivery costs are modest and the program cost-effective. This is the first cost-effectiveness study of a parenting program in Japan.

We have begun collaborating with the Kunigami Education Board to implement a feasibility study of implementation of WPJ through local schools in Okinawa. This version of the program will incorporate a series of educational videos for teachers (being developed with support from the Community and Public Relations section of OIST). Planning is well underway, including development of the teacher video series. This research is funded by a Kakenhi (Scientific Research C) grant.

3.7 Accessible behavioral intervention for Brazilian and Japanese of children with ADHD

Access to empirically supported psychosocial treatment for childrens behavioral and emotional difficulties is limited worldwide. Following a needs assessment in Brazil and a series of focus-group discussions in Japan, we are developing easily accessed, research-informed, treatment programs teaching parents practical behavior management strategies. An initial feasibility study was conducted for the program delivered via social media in Brazil. Preliminary findings suggest encouraging effects of the program on reducing parent-reported child behavior problems and use of negative parenting strategies. The program in Japan is being developed in close collaboration with community members who are providing input on the style and content of the program. Feasibility testing will also be conducted collaboratively.

3.8 Monitoring and repair of language and social communication in children with and without ADHD

Children with ADHD score lower than typically developing (TD) children on standardized measures of structural and pragmatic language. Most pragmatic language measures rely on parent/teacher reports of the child’s language skills, with little known about language use during actual social interactions in children with ADHD. Our first study analyzed recorded conversations between children with and without ADHD and a young adult confederate. Results show that children with ADHD make more off-topic responses and grammar mistakes, exhibit more disfluencies in their speech, and fail to repair these disfluencies compared with their typically developing (TD) peers. In three further studies we are examining (1) social communication during storytelling (narrative discourse), (2) information eliciting (questioning), and (3) instruction giving tasks.

3.9 Social functioning in children with and without ADHD: conflict resolution, expectations of others, and allocation of responsibility

Many children with ADHD experience social difficulties. The existing literature and clinical reports suggest that children with ADHD may have unrealistic expectations of their partners in social interactions, fail to recognize their own short-comings, and are more likely to blame others for negative outcomes. We are undertaking three studies to assess predictors of social problem solving/conflict resolution skills in children with ADHD, children’s expectations of others in social interactions, and how they allocate responsibility for good and poor social interaction outcomes. Preliminary results from the first study indicate that in children with ADHD, their working memory is important to their understanding of the nature of social problems, while their cognitive and language skills predict their ability generate and choose solutions to social problems.

4. Publications

4.1 Journals

Furukawa, E., Alsop, B., Alves, H., Vorderstrasse, V., Carrasco, K., Chuang, C., Tripp, G. (2023). Disrupted waiting behavior in ADHD: exploring the impact of reward availability and predictive cues. Child Neuropsychology, 29, 76-95.
Silic, B., Aggarwal, M., Liyanagama, K., Tripp, G., Wickens, J.R. (2023). Conditioned approach behavior of SHR and SD rats during Pavlovian conditioning. Behavioral Brain Research, 443 (available online Feb 14^th).
Furukawa, E., Bado, P., da Costa, R., Melo, B., Erthal, P., de Oliveira, I., Wickens, J., Moll, J., Tripp, G., Mattos, P. (2022) Reward modality modulates striatal responses to reward anticipation in ADHD: Effects of affiliative and food stimuli. Psychiatry Research: Neuroimaging (327), 111561.
Furukawa, E., Uchida, R., Tatsuki, M., Fitts, M., Tripp, G. (2022) Wishes of Children of ADHD. Frontiers in Psychiatry (13), 885496.
Figueiredo, T., Tortes, D., Ayrao, V., Bernardes, C., Oloveira, N., Soares, R., da Costa, R. Q. M., Sudo, F., Tripp, G., Serra-Pinheiro, M. A., Mattos, P. (2022). Use of the Brazilian version of the Interpersonal Negotiation Strategies Interview (INSI) in a child and adolescent sample: a pilot study. Trends in Psychiatry and Psychotherapy, 44. doi.org/10.47626/2237-6089-2020-0136
Shimabukuro, S. Daley, D., Endo, T., Harada, S., Tomoda, A., Yamashita, Y., Oshio, T., Guo, B., Ishii, A., Izumi, M., Nakahara, Y., Yamamoto, K., Yao, A., Tripp, G. (2022). The effectiveness and cost-effectiveness of Well Parent Japan for Japanese mothers of children with ADHD: Protocol for a Randomized Controlled Trial, JMIR Research Protocols, Vol 11 No 4.

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

How co-production helped to shape Well Parent Japan: A culturally appropriate parenting intervention for mothers of children with ADHD. Symposium theme: The value of co-production in international neurodiversity research and practice. The 31^st European Congress of Psychiatry, Paris France, March 2023. Shimabukuro, S.
Behavioral management in a classroom, Miyako Island, March 2023. Shimabukuro, S.
Innovative Parenting Program: Developed for and by Brazilians. February 2023. Brazilian embassy and consulates in Japan. Furukawa, E.
Social Discourse Monitoring and Repair: Structural and Pragmatic Language, Fluency, and the Communication Cycle in Children with and without ADHD. Guest lecture in the course “Discourse and Conversation”. The University of Haifa, Haifa, Israel, December 2022. Samniya, H.
Social Discourse Monitoring and Repair: Structural and Pragmatic Language, Fluency, and the Communication Cycle in Children with and without ADHD. Guest lecture in the course “Theoretical and Clinical Aspects”. The University of Haifa, Haifa, Israel, December 2022. Samniya, H.
Social Discourse Monitoring and Repair: Structural and Pragmatic Language, Fluency, and the Communication Cycle in Children with and without ADHD. Guest lecture in the course “Communication Disorders in Bilingual populations”. The University of Haifa, Haifa, Israel, December 2022. Samniya, H.
The power of positive reinforcement: why rewards trump punishments for students with ADHD. ADDitude Podcast #421. September 2022. Tripp, G.
Community-based Participatory Research. September 2022. Myojo Yochien, Furukawa, E.
Considering ADHD-specific additions to Parent Training Core Platform, July 2022. Myojo Yochien, Furukawa, E.
ADHD and Brain Functioning: Impacts on Parenting. June 2022. Myojo Yochien, Furukawa, E.
Interpersonal Negotiation Strategies: background, theory, and applications. First Brazilian Conference of Social Neuroscience, April 2022. Tripp, G.

5. Intellectual Property Rights and Other Specific Achievements