Response inhibition deficits in unmedicated youth with ADHD: An ERP/sLORETA study

Yixuan Xu; Yexian Zeng; Weizhen Yin; Tong Fu; Danping Hong; Han Yang; Zhihang Zhu; Daomeng Cheng; Caiping Dang; Yan Song; Miancong Li; Yanling Zhou; Chanjuan Yang

doi:10.1016/j.jad.2025.119880

Response inhibition deficits in unmedicated youth with ADHD: An ERP/sLORETA study

J Affect Disord. 2025 Jul 11:119880. doi: 10.1016/j.jad.2025.119880. Online ahead of print.

Authors

Yixuan Xu¹, Yexian Zeng², Weizhen Yin², Tong Fu³, Danping Hong², Han Yang⁴, Zhihang Zhu², Daomeng Cheng², Caiping Dang⁵, Yan Song⁶, Miancong Li⁷, Yanling Zhou⁸, Chanjuan Yang⁹

Affiliations

¹ The Affiliated Brain Hospital, Guangzhou Medical University, China; School of Health Management, Guangzhou Medical University, China.
² The Affiliated Brain Hospital, Guangzhou Medical University, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China; Institute of Psychiatry and Psychology, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
³ Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ The Affiliated Brain Hospital, Guangzhou Medical University, China.
⁵ The Affiliated Brain Hospital, Guangzhou Medical University, China; School of Health Management, Guangzhou Medical University, China; Institute of Psychiatry and Psychology, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
⁶ State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China. Electronic address: songyan@bnu.edu.cn.
⁷ Lin Feng'e Primary School, Liwan District, Guangzhou, China.
⁸ The Affiliated Brain Hospital, Guangzhou Medical University, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China; Institute of Psychiatry and Psychology, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address: zhouylivy@aliyun.com.
⁹ The Affiliated Brain Hospital, Guangzhou Medical University, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, China; Institute of Psychiatry and Psychology, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address: yangw2020@gzhmu.edu.cn.

PMID: 40652975
DOI: 10.1016/j.jad.2025.119880

Abstract

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is characterized by impairments in executive functioning, particularly response inhibition (RI). This study combines time-domain analysis and source analyses of event-related potentials (ERPs) to explore the underlying neuropsychological mechanisms of RI deficits in unmedicated youth with ADHD, and assesses ERP features as potential biomarkers to differentiate ADHD from healthy controls (HCs).

Methods: The study included 52 unmedicated youth with ADHD (ages 6-12) and 53 HCs. ERPs were recorded using an oddball paradigm, followed by within- and between-group comparisons. Source localization analysis examined regional brain activation during task performance. Significant ERP features were then used in a machine learning classification model.

Results: Compared to HCs, youth with ADHD exhibited prolonged mismatch negativity (MMN) latency at frontal (Fz) and posterior (Pz) electrodes, and reduced latency at the central (Cz) electrode. Source analysis indicated increased activation in the cuneus and superior temporal gyrus during the MMN-deviant condition, and enhanced activation in the superior parietal lobules, inferior frontal gyrus, and rectal gyrus during the MMN-novelty condition. Additionally, ADHD patients showed higher activation in the middle temporal and middle occipital gyri during the P300-target condition, and increased activation in the superior frontal gyrus and cuneus during the P300-non-target condition. Notably, the classification model achieved an area under curve (AUC) of 0.918 using MMN latency features.

Conclusion: Abnormal ERP patterns in unmedicated youth with ADHD may reflect impaired RI and have potential as neurobiological markers for the disorder.

Keywords: Children and adolescents; Event-related potentials; Response inhibition; Source analysis; Unmedicated ADHD.