White matter properties in fronto-parietal tracts predict maladaptive functional activation and deficient response inhibition in ADHD

Abstract

Response inhibition, defined as the ability to suppress inappropriate responses, is a key characteristic of adaptive human behaviour. However, in individuals with attention deficit hyperactivity disorder (ADHD) it is often impaired and is linked to broad life outcomes. Previous neuroimaging investigations have indicated a myriad of brain networks in response inhibition, which limit its utility in understanding and overcoming response inhibition difficulties. More recently, it has been suggested that a specific fronto-parietal functional circuitry between the inferior frontal gyrus (IFG) and the intraparietal sulcus (IPS), dictates the recruitment of the IPS in response inhibition in ADHD. To ascertain the critical role of the IFG-IPS functional circuit and its relevance to response inhibition in ADHD, it is crucial to understand the underlying structural architecture of this circuit so that the functional relevance could be interpreted correctly. Here we investigated the white matter pathways connecting the IFG and IPS using seed-based probabilistic tractography on diffusion data in 42 ADHD and 24 neurotypicals and assessed their impact on both the recruitment of IPS in response inhibition scenarios and on response inhibition performance in a Go/No-go task. Our results showed that individual differences in the structural properties of the IPS-IFG circuit, including tract volume and diffusivity, were linked to IPS activation and even predicted response inhibition performance outside the scanner. These findings highlight the structural-functional coupling of the IFG-IPS circuit in response inhibition in ADHD and confirm a structural basis for maladaptive functional top-down control in deficient inhibition in ADHD. Our results also support the notion of ADHD as a continuum and suggest that individual differences in tract-specific functional and structural connectivity could serve as neuromarkers of ADHD.