Stepwise functional connectivity reveals altered sensory-multimodal integration in medication-naive adults with attention deficit hyperactivity disorder

Neuroimaging studies indicate that children with attention-deficit/hyperactivity disorder (ADHD) present alterations in several functional networks of the sensationto-cognition spectrum. These alterations include functional overconnectivity within sensory regions and underconnectivity between sensory regions and neural hubs supporting higher order cognitive functions. Today, it is unknown whether this same pattern of alterations persists in adult patients with ADHD who had never been medicated for their condition. The aim of the present study was to assess whether medication-naïve adults with ADHD presented alterations in functional networks of the sensation-to-cognition spectrum. Thirty-one medication-naïve adults with ADHD and twenty-two healthy adults underwent resting-state functional magnetic resonance imaging (rs-fMRI). Stepwise functional connectivity (SFC) was used to characterize the pattern of functional connectivity between sensory seed regions and the rest of the brain at direct, short, intermediate, and long functional connectivity distances, thus covering the continuum from the sensory input to the neural hubs supporting higher order cognitive functions. As compared to controls, adults with ADHD presented increased SFC degree within primary sensory regions and decreased SFC degree between sensory seeds and higher order integration nodes. In addition, they exhibited decreased connectivity degree between sensory seeds and regions of the default-mode network. Consistently, the higher the score in clinical severity scales the lower connectivity degree between seed regions and the default mode network.This work was supported by the Ministerio de Economía y Competitividad research grant (SAF2012-32362) and the Instituto de Salud Carlos III (Miguel Servet Type I (CP16/00096), AES Grant (PI17/00064), and P-FIS Grant (FI18/00255))