FY2019 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 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 will inform both behavioral and pharmacological interventions. We began an initial discussion of translating the basic experimental findings on altered reward sensitivity in ADHD into behavioral management strategies. 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. In addition, we have developed culturally appropriate parenting interventions for Japanese parents and are conducting a multi-site randomized control trial, working with collaborators in England and at Japanese university and community hospitals in Okinawa, Fukui, and Fukuoka prefectures. 

1. Staff

  • Dr. Emi Furukawa, Group Leader
  • Dr. Shizuka Shimabukuro, Staff Scientist
  • Dr. Margaret Fitts, Clinical Psychologist (from August 2019)
  • Dr. Kelly Carrasco, Research Unit Technician (departed February 2019)
  • Dr. Chi-Ching Chuang, Research Unit Technician (transferred to DFA’s Research Group (December 2019)
  • Ms. Shoko Nagatomo, Research Unit Technician (departed August 2019)
  • Ms. Ryoko Uchida, Research Unit Technician 
  • Mr. Paul Fitts, Research Unit Technician (from November 2019)
  • Ms. Emi Nakanishi, Research Unit Technician (part time)
  • Dr. Atsuko Ishii, Research Unit Technician (from June 2019; POC Grant)
  • Ms. Yuko Goto, Project Administrator (from January 2020; POC Grant)
  • Ms. Kaori Yamashiro, 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: Currently analyzing data from 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: Currently collecting data using novel paradigms to examine effects of reward delay and reward cues in classical and instrumental learning/conditioning.
  • 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. 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:
    • Associate Professor Saskia Van der Oord KU Leuven, Belgium
    • Professor Beckers, KU Leuven, Belgium
    • Ms. Hasse de Meyer 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 reinforcement structures have been developed and used for data collection. We are currently developing 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 contributions to social difficulties. We also completed data collection on a pilot study examining cerebellar functioning in ADHD together with the Neuronal Rhythms in Movement Unit. 

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, 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. 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 is underway for a 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. Preliminary analysis of the data collected with children with and without ADHD indicated that the delay resulted in significant difficulties in learning for the both groups of children. We have modified the task to reduce the difficulty level and have begun data collection using the revised task.

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 and Dr. Alves at the University of Massachusetts Dartmouth. The task examines children’s response speed to reward-predicting cues before and after training. Data collection is nearing completion. 

Pavlovian-to-Instrumental Transfer (PIT) tasks 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. We predict children with ADHD will show less response invigoration (response frequency) than controls in the presence of the reward predicting cue during the transfer phase. We are continuing with the development and pilot testing of this task. 

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 van der Oord and Beckers, and Ms. De Meyer 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. 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 completed initial RCT assessed the immediate effects of the program with Okinawan mothers of children demonstrating significant symptoms of ADHD.

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 with a larger sample of mothers from three different sites throughout Japan. In addition to evaluating the program’s effectiveness we are evaluating: 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 has been completed and an initial round of the RCT has been started. We are also developing standardized training and supervision programs for Well Parent Japan, and discussing a school-based implementation.  

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. 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 have combined 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, and the importance of early intervention.

4. Publications

4.1 Journals

  1. Shimabukuro, S., Daley, D., Thompson, M., Laver-Bradbury, D., Lovern, K., & Tripp, G. (2020). Supporting Japanese mothers of children at risk for attention deficit hyperactivity disorder (ADHD): A small scale randomized control trial of Well Parent Japan. Journal of Child and Family Studies. https://doi.org/10.1007/s10826-020-01704-6
  2. da Costa, R.Q.M., Furukawa, E., Hoefle, S., Moll, J., Tripp, G., Mattos, P. (2020). An adaptation of Pavlovian-to-Instrumental transfer (PIT) methodology to examine the energizing effects of reward-predicting cues on behavior in young adults. Frontiers in Psychology. https://doi.org/10.3389/fpsyg.2020.00195
  3. Furukawa, E., da Costa, R.Q.M., Bado, P., Hoefle, S., Vigne, P., Monteiro, M., Wickens, J.R., Moll, J., Tripp, G., Mattos, P. (2020). Methylphenidate modifies reward cue responses in adults with ADHD: An fMRI study. Neuropharmacology, 162. https://doi.org/10.1016/j.neuropharm.2019.107833
  4. Furukawa, E., Alsop, B., Shimabukuro, S., & Tripp, G. (2019). Is increased sensitivity to punishment a characteristic of attention deficit hyperactivity disorder? An experimental study of response allocation in Japanese children. Attention Deficit and Hyperactivity Disorder, 11, 433-443. https://doi.org/10.1007/s12402-019-00307-6
  5. Furukawa, E., Alsop, B., Caparelli-Dáquer, E.M., Barbante Casella, E., da Costa, R.Q.M., de Moura Queiroz, P., Galvão, P.A., da Silva Benevides, L.R., Jucá-Vasconcelos, H.P., & Tripp, G. (2019). Behavioral adjustment to asymmetric reward availability among children with and without ADHD: Effects of past and current reinforcement contingencies. Attention Deficit and Hyperactivity Disorder, 11, 148-158. https://doi.org/10.1007/s12402-018-0265-x
  6. De Meyer, H., Beckers, T., Tripp, G., & van der Oord, S. (2019). Deficits in conditional discrimination learing in children with ADHD are independent of delay aversion and working memory. Journal of Clinical Medicine, 8(9), 1381. https://doi.org/10.3390/jcm8091381
  7. De Meyer, H, Beckers, T., Tripp, G., van der Ooord, S. (2019). Reinforcement contingency learning in children with ADHD: back to the basics of behavior therapy. Journal of Abnormal Child Psychology, 47, 1889-1902. https://doi.org/10.1007/s10802-019-00572-z

4.2 Books and other one-time publications

Nothing to report.

4.3 Oral and Poster Presentations

  1. Increased behavioral sensitivity to repeated experiences of punishment in children with ADHD: Experimental studies using the matching law. The American Professional Society of ADHD and Related Disorders Annual Meeting, Washington, D.C. January 2020. Furukawa, E., Alsop, B., Shimabukuro, S., Sowerby, P., Jensen, S., & Tripp, G.
  2. What is the contribution of altered motivational processing to ADHD? Implications for psychosocial management. 60th annual meeting of the Japanese Society for Child and Adolescent Psychiatry, Okinawa, December 2019. Tripp, G. (keynote presentation).
  3. Effects of reward delay on learning in children with and without ADHD. EUNETHYDIS 26th Network Meeting on ADHD, Nijmegen, September 2019. Furukawa, E., Alsop, B., Nakanishi, E., Carrasco, K., Chuang, C., Vorderstrasse, V., & Tripp, G.
  4. Deficits in conditional discrimination learning in children with ADHD can be remediated by differential outcomes. EUNETHYDIS 26th Network Meeting on ADHD, Nijmegen, September 2019. De Meyer, H., Beckers, T., Tripp, G., & van der Oord, S. 
  5. A pragmatic multisite RCT of a parent training program specific to ADHD in Japan. EUNETHYDIS 26th Network Meeting on ADHD, Nijmegen, September 2019. Shimabukuro, S., Daley, D., Thompson, M., Laver-Bradbury, C., & Tripp G.
  6. Predictors of academic achievement in ADHD. EUNETHYDIS 26th Network Meeting on ADHD, Nijmegen, September 2019. Tripp, G., Carrasco, K., & Chuang, C.
  7. Psychometric properties of the parenting sense of competence (PSOC) scale: A preliminary investigation with Japanese parents of elementary school children. 83rd Annual convention of the Japanese Psychological Association, Osaka, Japan, September, 2019. Chuang, C., Nagatomo, S., Shimabukuro, S., & Tripp, G.
  8. Working memory and emotional regulation predict social functioning in children with ADHD. 41st International School Psychology Association Conference, Basel, Switzerland, July 2019. Carrasco, K., Chuang, C., & Tripp, G.
  9. Do language and working memory skills predict reading success in children with ADHD. 41st International School Psychology Association Conference, Basel, Switzerland, July 2019. Chuang, C., Carrasco, K., & Tripp, G.
  10. Teasing apart the contributions of language and executive functions to social skills in children with ADHD. International Behavioral Neuroscience Society (IBNS) 28th Annual Meeting, Cairns, Australia, June 2019. Carrasco, K., Chuang, C., & Tripp, G.

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report.

6. Meetings and Events

Nothing to report.

7. Other

Nothing to report.