Individualised structural and functional frontostriatal connectivity mapping in adult ADHD

Abundant research from early neurocognitive models to recent mega-analyses has highlighted the central role of frontostriatal circuits in attention deficit hyperactivity disorder (ADHD). However, it remains unclear which specific aspects of functionally organized frontostriatal loops are affected by ADHD and how these disruptions differ across individuals in light of the disorder’s marked heterogeneity. We investigated frontostriatal connectivity in individualised circuits in 40 adults with ADHD and 36 neurotypical controls using a multimodal dataset that included diffusion-weighted magnetic resonance imaging (MRI), as well as functional MRI during working memory updating, resting state, and a naturalistic attention task. Compared with neurotypical controls, adults with ADHD exhibited reduced structural connectivity strength and increased mean, axial, and radial diffusivity in tracks originating from medial and orbital prefrontal areas. Functional data revealed weaker connectivity in the ADHD group during verbal and visuospatial working memory tasks in circuits connecting the striatum with the dorsolateral prefrontal cortex, motor regions, and orbitofrontal cortex, while no group differences were found during resting state or the naturalistic task. Structural and functional aberrancies were only partly overlapping. Comparisons with atlas-based analyses highlighted the precision of individualised connectivity mapping. Together, these findings suggest that (1) frontostriatal functional connectivity aberrancies in ADHD are driven by striatum-dependent cognitive processes such as working memory, (2) functional and structural differences are related to partly different frontostriatal circuits, and (3) precise mapping of frontostriatal pathways can be achieved through individualised connectivity mapping.