FY2018 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 trial.

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: Currently analyzing data for the study examining punishment sensitivity (matching law). A pilot study is ongoing examining physiological (heart rate) 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: Currently collecting data using novel paradigms to examine effects of reward delay on learning and classical conditioning.
Type of collaboration: Joint research
Researchers:
- Dr. Brent Alsop, Otago University
- Dr. Emi Furukawa, OIST

2.4 Supporting Japanese mothers of children with ADHD

Description: Currently conducting effectiveness study of a Japanese adaptation of the New Forest Parenting Programme (NFPP-J) 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
- Dr. Shizuka Shimabukuro, OIST

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

Description: Currently collecting data 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 Beckers, at KU Leuven, Belgium
- Ms. Hasse de Meyer at KU Leuven, Belgium

3. Activities and Findings

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

We have continued to collect data with English-speaking children with ADHD in Okinawa. Data collection involves detailed clinical assessments of children's behavior. Multiple computer-based behavioral 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 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 continue to pilot a paradigm to examine cerebellar functioning in ADHD.

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. In the 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. Data analysis and manuscript drafts have been completed. Data collection is underway for the third imaging study examining 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 analysis is also underway for an initial pilot study to examine 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. Data collection with typically developing children for the control group is ongoing.

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 are carrying out 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 Vander 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 is ongoing. This 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.

3.7 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. For these to be effective, research with large and diverse populations of children with ADHD is needed to identify the predictors and moderators of academic performance. We are combining data previously collected in New Zealand with Unit data collected in Okinawa (native English speakers) to identify predictors and moderators of academic performance in children with ADHD. Analyses to date highlight the importance of language skills and working memory to academic performance, together with the value of early intervention.

4. Publications

4.1 Journals

Furukawa, E., Alsop, B., Caparelli-Dáquer, E.M., Casella, E.B., da Costa, R.Q.M., Queiroz, P.M., Galvão, P.A., Benevides, L.R.S., Jucá-Vasconcelos, H.P., & Tripp, G. (2018). Behavioral adjustment to asymmetric reward availability among children with and without ADHD: Effects of past and current reinforcement contingencies. Attention Deficit and Hyperactivity Disorder (First Online https://doi.org/10.1007/s12402-018-0265-x).
Taylor, M., chuang, D.D., Carrascp, K., Nagatomo, S., & Ricklidge, J. (2018). Dietary and micronutrient treatments for children with neurodevelopmental disorders. Current Developmental Disorders Reports, 1-10. https://doi.org/10.1007/s40474-018-0159-55
Rucklidge, J., Taylor, M., Jphnstone, J.M. (2018). Do diet and nutrition affect ADHD? Facts and clinical considerations. Psychiatric Times, 35(9)

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

Predictors of Academic Achievement in Clinical and Community Samples of Children with ADHD: The Importance of Semantic Language and Verbal Working Memory. 5th EUNETHYDIS International Conference on ADHD, Edinburgh, September 2018. Carrasco, K. D., & Tripp, G.
Methylphenidate effects on correlated fMRI activity during reward processing in adults with ADHD. 5th EUNETHYDIS International Conference on ADHD, Edinburgh, September 2018. Furukawa, E., Costa, R. Bado, P., Hoefle, S., Vigne, P., Monteiro, M., Tripp, G., Wickens, J., Moll, J., & Mattos, P.
Relationships between reward sensitivity and eating behavior in adults with and without ADHD. 5th EUNETHYDIS International Conference on ADHD, Edinburgh, September 2018. Bado, P., Drumond, J., Nazzar, B., Moll, J., Tripp, G., Mattos, P., & Furukawa, E.
Working memory, age, and semantic language skills predict academic achievement in children with ADHD across samples. International School Psychology Association Annual conference, Tokyo, Japan, July, 2018. Carrasco, K.D., & Chuang, C.
Do childhood experiences of abuse predict more difficulties in adulthood among individuals with ADHD? 23rd World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions, Prague, Czech Republic, July, 2018. Taylor, M.R., Chuang, C.C., Rucklidge, J., Boden, J., Tripp, G., Kuijer, R., Farmer, R.
Empirically derived working memory profiles of children with ADHD: linking working memory and academic achievement. Journal of Clinical Child & Adolescent Psychology 2018 Future Directions Forum, June, 2018. Chuang, C., Tripp, G., & Carrasco, K.

5. Intellectual Property Rights and Other Specific Achievements