Functional connectivity anomalies in medication-naive children with ADHD: Diagnostic potential, symptoms interpretation, and a mediation model

Clin Neurophysiol. 2025 Apr 18;174:212-219. doi: 10.1016/j.clinph.2025.04.011. Online ahead of print.

ABSTRACT

OBJECTIVE: To identify reliable electroencephalography (EEG) biomarkers for attention deficit/hyperactivity disorder (ADHD) by investigating anomalous functional connectivity patterns and their clinical relevance.

METHODS: Resting-state EEG data were collected from 74 children aged 6-12 (33 unmedicated ADHD; 41 typically developing). Functional connectivity was quantified using the imaginary part of coherency (ICOH). Machine learning (ML)-based support vector machine (SVM) modeling, regression, and mediation analyses linked connectivity features to symptom severity and diagnostic classification.

RESULTS: Children with ADHD exhibited beta (β) band hypo-connectivity in frontal regions (Fp2-F4, Fp1-Cz, F7-Cz) and theta (θ) band hyper-connectivity in left parietal-central networks (C3-P7, P3-P7, etc.). An SVM classifier achieved an average area under the curve of 0.89 using three connectivity features. Left parietal θ band hyper-connectivity (C3-P7) correlated with both inattention and hyperactivity/impulsivity and mediated their interrelationship.

CONCLUSIONS: ADHD is characterized by disrupted frontoparietal connectivity, with θ band hyper-connectivity in sensory-integration networks potentially compensating for impaired frontal regulation.

SIGNIFICANCE: These findings highlight C3-P7 θ band connectivity as both a diagnostic and mechanistic biomarker, providing novel target for neurofeedback therapies and enhancing the differential diagnosis in neurodevelopmental disorders.

PMID:40305882 | DOI:10.1016/j.clinph.2025.04.011