Dissecting corticostriatal functional circuits to clarify the heterogeneity of Autism, ADHD symptoms
Poster No:
287
Submission Type:
Abstract Submission
Authors:
Han Byul Cho1, Hyunhoe An2, Shinwon Park3, Seok-Jun Hong1,2,4,5
Institutions:
1Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Republic of Korea, 2Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Republic of Korea, 3Autism Center, Child Mind Institute, New York, United States, 4Life-inspired Neural network for Prediction and Optimization Research Group, Suwon, Republic of Korea, 5Center for the Developing Brain, Child Mind Institute, New York, United States
First Author:
Han Byul Cho
Center for Neuroscience Imaging Research, Institute for Basic Science
Suwon, Republic of Korea
Center for Neuroscience Imaging Research, Institute for Basic Science
Suwon, Republic of Korea
Co-Author(s):
Seok-Jun Hong
Center for Neuroscience Imaging Research, Institute for Basic Science|Department of Biomedical Engineering, Sungkyunkwan University|Life-inspired Neural network for Prediction and Optimization Research Group|Center for the Developing Brain, Child Mind Institute
Suwon, Republic of Korea|Suwon, Republic of Korea|Suwon, Republic of Korea|New York, United States
Center for Neuroscience Imaging Research, Institute for Basic Science|Department of Biomedical Engineering, Sungkyunkwan University|Life-inspired Neural network for Prediction and Optimization Research Group|Center for the Developing Brain, Child Mind Institute
Suwon, Republic of Korea|Suwon, Republic of Korea|Suwon, Republic of Korea|New York, United States
Introduction:
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are highly comorbid developmental conditions sharing several behavioral symptoms, especially in the 'executive function domain' [1-3]. The corticostriatal circuit, which regulates cognitive flexibility, motor persistence and attention, have been suggested as a common biological basis for this comorbidity [4, 5]. However, the specific circuit mechanisms underlying this dysfunction and the relevant cause for their high phenotypic heterogeneity across these conditions remain incompletely understood.
Methods:
From the Healthy Brain Network repository [6], we analyzed a group of clinically diagnosed ASD and ADHD as well as matched neurotypical (NT) individuals (130 male and 67 female; 25 NT, 16 ASD, 123 ADHD, and 33 ASD+ADHD), targeting a battery of their behavioral scores, cognitive performance assessed by NIH toolbox [7] and multimodal neuroimaging data. First, we performed a factor analysis to identify the bases underlying a common variance of behavior symptoms and cognitive performance across all subjects. Next, to understand the relationship between these phenotypic bases and the brain circuit for executive functions, we computed seed-based functional connectivity (FC) between the striatum and the following approximal regions [8]: the frontal and motor cortices, thalamus, amygdala, hippocampus, diencephalon ventral and midbrain. This circuit-level FC was then fed into the partial least squares (PLS) analysis [9] to quantify the multivariate relationship with four factor scores previously derived from the factor analysis. To verify the significance of the partial least squares statistics, 1000 iterations of permutations and bootstrapping were performed.
Results:
The factor analysis identified four major behavioral symptom bases across ASD and ADHD individuals: 'ASD-specific (Factor-1)', 'Externalizing (Factor-2)', 'Internalizing (Factor-3)' symptoms, and 'Executive dysfunction (Factor-4)' [Fig. 1A]. Group comparisons revealed that Factor-1 was mainly associated with ASD-traits, while Factor-2 was linked to ADHD-traits. Factor-3 did not show notable traits related to diagnostic labels, whereas Factor 4, reflecting executive dysfunction, revealed a significantly higher score in the ASD+ADHD groups [Fig. 1B], corroborating high comorbid symptoms in both groups. Next, the PLS analysis identified a latent brain-behavior component capturing the relationship between the corticostriatal network and behavioral factors [Fig. 2A, B]. Identified significant FC loadings (i.e., how much a given connection contributes to make the significant latent component in explaining the behavior) primarily concentrated in the dorsal striatum, dorsomedial nucleus of the thalamus, and dorsal lateral/medial neocortical regions [Fig. 2C]. Factor-1 and Factor-4 showed negative PLS loadings, while Factor-3 exhibited positive PLS loadings. Factor-2 demonstrated relatively lower absolute loadings [Fig. 2D]. This indicates that Factor-1, -3, and -4, together with the FC of the main regions identified in Fig. 2C, significantly contributes to explaining the brain-behavior relationship.
Conclusions:
This study provides preliminary evidence indicating a shared neural axis that crosses the boundaries of clinically diagnosed ASD, ADHD, and their comorbid conditions. The identified brain-behavior relationship enhances our understanding of the phenotypic heterogeneity of these disorders and suggests that dorsal striatum and related networks may play a crucial role as a biomarker to explain these highly comorbid conditions along the unified brain-behavior axis.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Task-Independent and Resting-State Analysis
Keywords:
Attention Deficit Disorder
Autism
Computational Neuroscience
Development
DISORDERS
FUNCTIONAL MRI
1|2Indicates the priority used for review
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2. Simonoff E. et al., (2008) ‘Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample’ Journal of the American Academy of Child and Adolescent Psychiatry 47, 921–929.
3. Uddin LQ, (2021) ‘Cognitive and behavioural flexibility: neural mechanisms and clinical considerations’ Nature Reviews Neuroscience 22(3): 167–79.
4. Di Martino A et al (2011) ‘Aberrant striatal functional connectivity in children with autism’ Biological Psychiatry 69(9): 847–56.
5. Tomasi D et al., (2012) ‘Abnormal functional connectivity in children with Attention-Deficit/Hyperactivity Disorder’ Biological Psychiatry 71 (5): 443–50.
6. Alexander LM et al., (2017) ‘An open resource for transdiagnostic research in pediatric mental health and learning disorders’ Scientific data 4, 170181
7. www.nihtoolbox.org
8. Haber S & Knutson B (2010). The reward circuit: Linking primate anatomy and human imaging
9. Kebets V et al., (2019) ‘Somatosensory-motor dysconnectivity spans multiple transdiagnostic dimensions of psychopathology. Biological Psychiatry 86, 779-791