Where is ADHD in the brain? Evidence for a neurodevelopmental continuum of brain dynamics

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Where is ADHD in the brain? Evidence for a neurodevelopmental continuum of brain dynamics

Authors

Duma, G. M.; Stefanelli, G.; Toffoli, L.; Ferri, G.; Pellegrino, G.; Danieli, A.; Martinez, F.; Tarantino, V.; Astle, D.; Del Popolo Cristaldi, F.; Mento, G.

Abstract

Background Attention-deficit/hyperactivity disorder (ADHD) has traditionally been conceptualized categorically, with efforts to identify disorder-specific neurobiological endophenotypes. However, dimensional models suggest that brain-behavior organization may follow developmental axes that cut across diagnostic boundaries. We tested whether neural dynamics and cortical excitability differentiate those with ADHD diagnoses from typically developing (TD) peers, and whether brain-behavior covariance aligns with diagnostic or developmental dimensions. Methods We studied 84 participants aged 8-17 years (51 ADHD, 33 TD). High-density electrophysiological (hdEEG) measures included task-free source-resolved data used to derive mean global brain fluidity (variance of dynamic functional connectivity) and region-specific cortical excitability. Behavioural measures included self- and parent-report questionnaires, cognitive control (CC) tasks, and neuropsychological tests. Partial least squares (PLS) assessed multivariate brain-behavior associations including age, followed by clustering based on latent component scores. Results Group differences emerged in parent-report questionnaires and CC tasks, but not in neuropsychological measures. ADHD individuals showed higher mean global brain fluidity and increased cortical excitability. The excitability-fluidity relationship was network-dependent: higher excitability predicted higher fluidity in task-positive networks and lower fluidity in default-mode and salience networks, with no group effects. PLS identified a latent dimension linking neural metrics with age, verbal fluency, inhibitory control, and positive affect, but it did not distinguish ADHD from TD. Clustering revealed two neurodevelopmental profiles spanning both groups. Conclusions While ADHD is associated with mean-level differences in neural dynamics, brain-behaviour organization follows a developmental neurocognitive-affective axis that transcends the diagnostic boundary. These findings support a dimensional framework for understanding neurobiological variation in neurodevelopmental conditions.

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