FY2017 Annual Report

Human Developmental Neurobiology Unit
Professor Gail Tripp

Abstract

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 programs. We are investigating the nature and etiology of altered reward sensitivity in children and adults with ADHD using behavioral, pharmacological and imaging approaches here in Japan and with our collaborators in New Zealand and Brazil. This work will inform both behavioral and pharmacological interventions. 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. Our work developing culturally appropriate parenting interventions for Japanese parents has moved forward to a multi-site randomized control.

1. Staff

  • Dr. Emi Furukawa, Group Leader
  • Dr. Shizuka Shimabukuro, Researcher
  • Dr. Mairin Taylor, Clinical Psychologist
  • Dr. Kelly Carrasco, Research Unit Technician
  • Dr. Chi-Ching Chuang, Research Unit Technician
  • Shoko Nagatomo, Technical Staff
  • Ryoko Uchida, Technical Staff
  • Emi Nakanishi, Technical Staff (part time)
  • Aya Puca, 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, OIST
    • Dr. Emi Furukawa, OIST

2.2 Altered reward sensitivity in children and adults with ADHD

  • Description: Completed analyzing behavioral data collected on computer-based task designed to assess sensitivity to changing reward contingencies (signal detection). Currently analyzing data for the study examining punishment sensitivity (matching law). A pilot study is underway to measure physiological responses to reward anticipation and delivery. 
  • Type of collaboration: Joint research
  • Researchers:
    • Egas Caparelli-Daquer, MD., Ph.D., University of State of Rio de Janeiro (UERJ)
    • Dr. Emi Furukawa, OIST

2.3 Investigating sensitivity to different reward structures in ADHD

  • Description: Manuscripts have been published documenting results from behavioral data collected with English-speaking children on computer-based behavioral tasks designed to assess sensitivity to changing reward contingencies (signal detection) and punishment (matching law). Currently collecting data and developing new paradigms to examine other aspects of reward, including effects of reward delay on learning and classical conditioning.  
  • Type of collaboration: Joint research
  • Researchers:
    • Dr. Brent Alsop, Otago University
    • Dr. Emi Furukawa, OIST
    • Dr. Shizuka Shimabukuro, OIST

2.4 Supporting Japanese mothers of children with ADHD

  • Description: Completed a Proof-of-Concept study and a single-site randomized control trial (RCT) of a Japanese adaptation of the New Forest Parenting Programme (NFPP-J) with Japanese mothers of children with ADHD. A multi-site RCT effectiveness study is in development.
  • Type of collaboration: Joint research
  • Researchers:
    • Professor David Daley, University of Nottingham, UK
    • Dr. Shizuka Shimabukuro, OIST

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

  • Description: Began data collection using a simple free-operant instrumental learning task.
  • Type of collaboration: Joint research
  • Researchers:
    • Associate Professor Saskia Van der Oord at KU Leuven, Belgium
    • Professor Tom Beckers at KU Leuven, Belgium
    • Ms. Hasse de Meyer, Ku Leuven, Belgium/OIST

 

 

3. Activities and Findings

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

We continued to collect data with Japanese-speaking and English-speaking children with ADHD in Okinawa. Data collection involves detailed clinical assessments of children's behavior. Multiple computer-based behavior tasks examining sensitivity to different reward structures have been developed and used for data collection. Parent training programs with Japanese families and related data collection are also 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 contributions to social difficulties. We also began a pilot study examining cerebellar functioning in ADHD.

We hosted 4 interns this year from several universities who observed and assisted in aspects of data collection and participated in other research activities at CRC.  

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 group, using a classical conditioning paradigm modeled on animal studies (Furukawa et al., 2014). ADHD participants showed increased striatal blood-oxygen-level dependent (BOLD) responses to reward delivery (US), but not to reward-predicting cues (CS), while the reverse pattern was observed in the Control participants. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD as hypothesized in DTD. Currently, we are analyzing data collected in the second study, examining the effects of stimulant medication (methylphenidate) on the striatal responses to reward-predicting cues and reward delivery in adults with ADHD. We began data collection for the third imaging study to examine 1) whether altered sensitivity to reward cues and reward delivery, involving monetary incentives used almost exclusively to study reward sensitivity in ADHD, 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 Disorder or both a Binge Eating Disorder and ADHD. Data collection is also underway for a pilot study to measure heart-rate responses to reward-predicting cues and reward delivery in collaboration with UERJ.  

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. The children complete a computer-based task that requires them to learn short response sequences. Each occurrence of the correct sequence is rewarded after a short delay. The delay period allows other responses to be made between the correct sequence and the delivery of a reward, as often occurs outside of the laboratory. Data collection for the ADHD sample is complete. We are now focusing on recruiting typically developing children for the control group.

3.4 Sensitivity to cues that predict reward

The DTD hypothesis predicts that individuals with ADHD do not condition to cues that predict reward as effectively as typically developing children, contributing to their stronger preference for immediate over delayed reward. We are testing this hypothesis by comparing the performance of children with and without ADHD using a computerized behavioral choice task in collaboration with Dr. Alsop at University of Otago. The task examines children’s response speed to reward-predicting cues before and after training. Data collection is ongoing.

Pavlovian-to-Instrumental Transfer (PIT) task also provides a means to test the strength of conditioning to cues previously associated with reward. We are developing a PIT task for use with children that will allow us to further evaluate the ability of children with and without ADHD to condition to reward predicting cues. Pilot testing is being carried out with young adult participants. We predict children with ADHD will show less response invigoration (grip strength and grip frequency) than controls in the presence of the reward predicting cue during the transfer phase.

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 began conducting data for a study to examine the performance (learning) of children with ADHD and controls under partial and continuous reinforcement conditions using a simple free-operant instrumental learning task in collaboration with Professors Van der Oord and Beckers, and Ms. De Meyer at KU Leuven.

3.6 Supporting Japanese mothers of children with ADHD

We are following up a successful small-scale randomized control trial (RCT) of Well parent NFPP-J with a larger effectiveness study. Well parent NFPP-J 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 completed RCT assessed the immediate effects of NFPP-J with Okinawan mothers of children demonstrating significant symptoms of ADHD.

The effectiveness study will assess the immediate and longer term (3-month follow-up) effects of the program with a larger sample of mothers from three different sites throughout Japan. In addition to evaluating the program’s effectiveness we will estimate: 1) the cost of delivering the program in Japanese communities; 2) the reduction in ADHD-associated direct and indirect costs as a result of program completion; and 3) the impact of the intervention on future quality of life of the participating mothers. To date group leader training and program implementation has been initiated at one site. We are also developing a standardized training and supervision programs for Well Parent NFPP-J, and discussing a school-based implementation.  

4. Publications

4.1 Journals

  1. Furukawa, E., Shimabukuro, S., Alsop, B., & Tripp, G. (2017). Behavioral sensitivity of Japanese children with and without ADHD to changing reinforce availability: an experimental study using signal detection methodology. Behavioral and Brain Functions, 13:13.
  1. Furukawa, E., Bado, P., Tripp, G., Mattos, P., & Moll, J. (2017). Focusing is hard! Brain responses to reward in attention deficit hyperactivity disorder. Frontiers for Young Minds, 5:18.
  1. Murray, A., Robinson, T., & Tripp, G. (2017). Neurocognitive and symptom trajectories of ADHD from childhood to early adolescence. Journal of Developmental and Behavioral Pediatrics, 38, 465-475.
  1. Thompson, M.J.J., Au, A., Laver-Bradbury, C., Lange, A-M., Tripp, G., Shimabukuro, S., Zhang, J., Shuai, L., Thompson, C. E.T., Daley, D. & Sonuga-Barke, E. J. (2017). Adapting an ADHD parent training intervention to different cultural contexts: The experience of implementing the New Forest Parenting Programme in China, Denmark, Hong Kong, Japan and the UK. PsyCh Journal, 6, 83-97.
  1. Furukawa, E., Alsop, B., Sowerby, P., Jensen, S. & Tripp, G. (2017) Evidence for increased behavioural control by punishment in children with attention-deficit hyperactivity disorder. Journal of Child Psychology and Psychiatry, 58, 248-257.
  1. Shimabukuro, S., Daley, D., Thompson, M., Laver-Bradbury, C., Nakanishi, E. & Tripp, G. (2017). Supporting Japanese mothers of children with ADHD: cultural adaptation of the New Forest Parent Training Programme. Japanese Psychological Research, 59, 35-48.

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

  1. Development of parent training program for children with ADHD: Japanese version of the New Forest Parenting Program. 9th Japanese ADHD Conference, Toyko, Japan, March, 2018. Shimabukuro, S. (talk in Japanese).
  1. A randomized controlled trial of NFPP-Japan with mothers of children with attention deficit hyperactivity disorder. EUNETHYDIS 25th Network meeting, Cologne, Germany, October, 2017. Tripp, G. & Shimabukuro, S.
  1. Reward and Punishment: Integrating the two sides of the coin in the pathophysiology of ADHD. 6th World Congress on ADHD, Vancouver, Canada, April, 2017
  1. Methylphenidate effects on reward processing in adults with ADHD: an fMRI study. EUNETHYDIS 25th Network meeting, Cologne, Germany, October, 2017. Furukawa, E., Tripp, G., Moll, J., Hoefle, S., Costa, R., Wickens, J., Vigne, P., Monteiro, M., Bado, P., & Mottos, P.
  1. Behavioral sensitivity of Japanese children with and without ADHD to changing reinforcer availability. EUNETHYDIS 25th Network meeting, Cologne, Germany, October, 2017. Tripp, G., Furukawa, E., Alsop, B., & Shimabukuro, S.
  1. Rhythmic abilities in adults with attention-deficit/hyperactivity disorder (ADHD). The Neurosciences and Music IV- Music, Sound and Health, in Boston USA, June, 2017. Engel, A., Monteiro, M., Hoefle, S., Furukawa, E., Villringer, A, Hove, M.J., Keller, P. E., and Mattos, P.
  2. Behavioral sensitivity to changing reward frequency among Brazilian children with and without Attention-Deficit/Hyperactivity Disorder. 6th World Congress on ADHD. Vancouver, April, 2017. Furukawa, E., Alsop B., Casella B., Caparelli-Dáquer, E., Costa, R., Galvão, P. , Benevides, L. , Jucá-Vasconcelos, H., Queiroz, P., Tripp, G.

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report

6. Meetings and Events

6.1 Round table discussion amongst Okinawan researchers at Junku-do bookstore.

  • Date: March, 2018
  • Venue: OIST Media Section sponsored event to enhance connections between Okinawan community and people of OIST, Naha, Okinawa
  • Speaker: Dr. Shizuka Shimabukuro (OIST)

6.2 Dissemination of the intervention program for children with ADHD and families.

  • Date: December, 2017
  • Venue: OIST/Junku-do collaborative seminar series by Okinawan researchers, Naha City, Okinawa, Japan
  • Speaker: Dr. Shizuka Shimabukuro (OIST)

6.3 Adolescents with ADHD

  • Date: November, 2017
  • Venue: Public Lecture, OIST Auditorium, Okinawa, Japan
  • Speaker: Associate Professor Saskia Van de Oord, UK Leuven, Faculty of Psychology and Educational Science, Belgium

6.4 Motivation matters: reward, punishment and ADHD.

  • Date: November, 2017
  • Venue: United States Department of Defense Teachers Education Day
  • Speaker: Prof. Gail Tripp, Dr. Marin Taylor (OIST)

6.5 Understanding and managing ADHD – a practical guide for parents and teachers

  • Date: July, 2017
  • Venue: Onna-son, Okinawa, Japan
  • Speaker: Prof. Gail Tripp (OIST)

 

7. Other

Nothing to report.