Neural Correlates of the Dual-Pathway Model for ADHD in Adolescents
Chun Shen1, Qiang Luo1, Tianye Jia1
1Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China (Shen, Luo, Jia, Feng, Sahakian); State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science and Human Phenome Institute, Fudan University, Shanghai, China (Luo); Departments of Psychology and Psychiatry and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, U.K. (Sahakian); Medical Research Council-Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Desrivières, Quinlan, Schumann); School of Mathematical Sciences, Fudan University, Shanghai, China (Zhao); Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (Banaschewski, Millenet, Nees); Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin (Bokde); University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Büchel); Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (Flor, Nees); Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany (Flor); Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Kiel, Germany (Nees); NeuroSpin, Commissariat à l'Énergie Atomique, Université Paris-Saclay, Gif-sur-Yvette, France (Frouin, Orfanos); Departments of Psychiatry and Psychology, University of Vermont, Burlington (Garavan); Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, U.K. (Gowland); Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin (Heinz, Walter); Physikalisch-Technische Bundesanstalt Braunschweig and Berlin (Ittermann); Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 1000, Neuroimaging and Psychiatry, University Paris Sud-Paris Saclay, University Paris Descartes, Paris (Martinot, Artiges, Paillère-Martinot); Service Hospitalier Frédéric Joliot, Orsay, France (Martinot, Artiges); Maison de Solenn, Paris (Martinot); Groupe Hospitalier Nord Essonne, Department of Psychiatry, Orsay, France (Artiges); Assistance Publique-Hôpitaux de Paris, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris (Paillère-Martinot); Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto (Paus); Departments of Psychology and Psychiatry, University of Toronto, Toronto (Paus); Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Poustka); Clinic for Child and Adolescent Psychiatry, Medical University of Vienna, Vienna (Poustka); Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany (Fröhner, Smolka); School of Psychology and Global Brain Health Institute, Trinity College Dublin (Whelan); Developmental and Behavioral Pediatric Department and Child Primary Care Department, Ministry of Education-Shanghai Key Lab for Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China (Li, Sahakian); Department of Computer Science, University of Warwick, Coventry, U.K. (Feng); and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Feng).
Objective:
The dual-pathway model has been proposed to explain the heterogeneity in symptoms of attention deficit hyperactivity disorder (ADHD) by two independent psychological pathways based on distinct brain circuits. The authors sought to test whether the hypothesized cognitive and motivational pathways have separable neural correlates.
Methods:
In a longitudinal community-based cohort of 1,963 adolescents, the neuroanatomical correlates of ADHD were identified by a voxel-wise association analysis and then validated using an independent clinical sample (99 never-medicated patients with ADHD, 56 medicated patients with ADHD, and 267 healthy control subjects). The cognitive and motivational pathways were assessed by neuropsychological tests of working memory, intrasubject variability, stop-signal reaction time, and delay discounting. The associations were tested between the identified neuroanatomical correlates and both ADHD symptoms 2 years later and the polygenic risk score for ADHD.
Results:
Gray matter volumes of both a prefrontal cluster and a posterior occipital cluster were negatively associated with inattention. Compared with healthy control subjects, never-medicated patients, but not medicated patients, had significantly lower gray matter volumes in these two clusters. Working memory and intrasubject variability were associated with the posterior occipital cluster, and delay discounting was independently associated with both clusters. The baseline gray matter volume of the posterior occipital cluster predicted the inattention symptoms in a 2-year follow-up and was associated with the genetic risk for ADHD.
Conclusions:
The dual-pathway model has both shared and separable neuroanatomical correlates, and the shared correlate in the occipital cortex has the potential to serve as an imaging trait marker of ADHD, especially the inattention symptom domain.
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