Abnormal functional asymmetry and its behavioural correlates in adults with ADHD: A TMS-EEG study

Avnit, Amir; Zibman, Samuel; Alyagon, Uri; Zangen, Abraham · 2023 · Crossref

DOI: 10.1371/journal.pone.0285086

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Summary

This study investigates the neural mechanisms underlying abnormal functional brain asymmetry and deficient response inhibition in adults with Attention Deficit Hyperactivity Disorder (ADHD). While response inhibition deficits and right-hemispheric dysfunction are core features of ADHD, the relationship between these symptoms and the underlying cortical excitability and interhemispheric connectivity remains unclear. The authors aimed to determine if abnormal frontal asymmetry is linked to response inhibition deficits and whether these abnormalities stem from reduced right-frontal excitability or compromised interhemispheric connectivity. The researchers employed a combined Transcranial Magnetic Stimulation–Electroencephalography (TMS-EEG) approach in 48 adults with ADHD and 42 non-clinical controls. Participants underwent three assessments: a Stop-Signal Task (SST) to measure response inhibition via Stop-Signal Reaction Time (SSRT); EEG recording during the SST to analyze the N200 event-related potential, which reflects right-lateralized response inhibition; and single-pulse TMS applied to the right frontal cortex to measure local cortical excitability via TMS-Evoked Potentials (TEP) and interhemispheric signal propagation (ISP), which inversely indicates interhemispheric connectivity. Results indicated that the ADHD group exhibited elongated SSRT, reduced right-frontal N200 asymmetry, weaker TEP amplitude, and stronger ISP compared to controls. Crucially, in the ADHD group, N200 right-frontal asymmetry correlated significantly with SSRT, TEP amplitude, and clinical symptom severity. However, ISP and TEP were unrelated to SSRT, and ISP showed no relationship with N200 asymmetry. These findings suggest that while reduced right-frontal excitability (indicated by weaker TEP) and compromised interhemispheric connectivity (indicated by stronger ISP) are present in ADHD, the specific link between abnormal frontal asymmetry and response inhibition deficits is primarily driven by reduced right-frontal excitability rather than interhemispheric connectivity issues. The study concludes that abnormal frontal asymmetry in ADHD is directly related to key cognitive symptoms, specifically response inhibition deficits, and is underlined by reduced excitability in the right frontal cortex. This supports the "asymmetry account" of ADHD, suggesting that the disorder’s pathology involves a disruption in the ratio of activation between hemispheres rather than a simple right-hemisphere deficit. By linking task-based ERP measures with non-task TMS-EEG metrics, the research provides evidence that diminished right-frontal excitability is a critical neuromarker for the functional asymmetry and behavioral symptoms observed in adult ADHD.

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• executive function