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Symptom-guided multimodal neuroimage fusion patterns in children with attention-deficit/hyperactivity disorder and its potential “brain structure–function-cognition–behavior” pathological pathways

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Abstract

The “brain-cognition-behavior” process is an important pathological pathway in children with attention-deficit/hyperactivity disorder (ADHD). Symptom guided multimodal neuroimaging fusion can capture behaviorally relevant and intrinsically linked structural and functional features, which can help to construct a systematic model of the pathology. Analyzing the multimodal neuroimage fusion pattern and exploring how these brain features affect executive function (EF) and leads to behavioral impairment is the focus of this study. Based on gray matter volume (GMV) and fractional amplitude of low frequency fluctuation (fALFF) for 152 ADHD and 102 healthy controls (HC), the total symptom score (TO) was set as a reference to identify co-varying components. Based on the correlation between the identified co-varying components and EF, further mediation analysis was used to explore the relationship between brain image features, EF and clinical symptoms. This study found that the abnormalities of GMV and fALFF in ADHD are mainly located in the default mode network (DMN) and prefrontal-striatal-cerebellar circuits, respectively. GMV in ADHD influences the TO through Metacognition Index, while fALFF in HC mediates the TO through behavior regulation index (BRI). Further analysis revealed that GMV in HC influences fALFF, which further modulates BRI and subsequently affects hyperactivity-impulsivity score. To conclude, structural brain abnormalities in the DMN in ADHD may affect local brain function in the prefrontal-striatal-cerebellar circuit, making it difficult to regulate EF in terms of inhibit, shift, and emotional control, and ultimately leading to hyperactive-impulsive behavior.

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Data availability

In our study, the neuroimaging data collected involves brain scans of children diagnosed with ADHD. Due to privacy concerns and ethical considerations, we are unable to make these data publicly available. Our research was conducted in accordance with the ethical declaration submitted for approval, which explicitly stated that the data would be used exclusively for clinical research purposes at Bei**g University Sixth Hospital and would not be disseminated.

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Acknowledgements

This work was supported by the National Natural Sciences Foundation of China (L.S., 81971284; 81771479 ); the Key scientific research projects of capital health development (L.S., 2020-1-4111); the Bei**g Municipal Science and Technology Program (L.S., Z171100001017089); the National Natural Sciences Foundation of China (J.S., 82022035; 62373062); the National Natural Science Foundation of China (L.L., 81873802); the Capital's Funds for Health Improvement and Research (L.L., CFH: 2022-2-4114). We thank all the authors for their contributions in this study and all the children and their parents who participated in the experiment.

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Authors and Affiliations

  1. Peking University Sixth Hospital/Institute of Mental Health, No.51, North Huayuan Road, Haidian District, Bei**g, 100191, China

    Yuan Feng, Yu Zhu, **aojie Guo, **angsheng Luo, Chen Dang, Lu Liu & Li Sun

  2. National Clinical Research Center for Mental Disorders and Key Laboratory of Mental Health, Ministry of Health (Peking University), Bei**g, 100191, China

    Yuan Feng, Yu Zhu, **aojie Guo, **angsheng Luo, Chen Dang, Lu Liu & Li Sun

  3. State Key Laboratory of Cognitive Neuroscience and Learning, Bei**g Normal University, No.19, **njiekouwai Street, Haidian District, Bei**g, 100088, China

    Dongmei Zhi & **g Sui

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  1. Yuan Feng
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Contributions

Li Sun, **g Sui, and Yuan Feng developed the study concept. Yuan Feng, Yu Zhu, **aojie Guo, **angsheng Luo and Chen Dang performed testing and data collection. Yuan Feng and Dongmei Zhi performed the data analysis and interpretation. Yuan Feng and Dongmei Zhi drafted the manuscript. Li Sun, **g Sui and Lu Liu provided critical revisions. All authors approved the final version of the manuscript for submission.

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Feng, Y., Zhi, D., Zhu, Y. et al. Symptom-guided multimodal neuroimage fusion patterns in children with attention-deficit/hyperactivity disorder and its potential “brain structure–function-cognition–behavior” pathological pathways. Eur Child Adolesc Psychiatry (2023). https://doi.org/10.1007/s00787-023-02303-8

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