Reduced fronto-striatal volume in ADHD in two cohorts across the lifespan

Abstract

ObjectiveNeuroimaging studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with altered brain anatomy. However, small and heterogeneous study samples, and the use of region-of-interest and tissue-specific analyses have limited the consistency and replicability of these effects. The present study uses a fully data-driven multivariate approach to investigate alterations in both gray and white matter simultaneously, and capture neuroanatomical features associated with ADHD in two large, independent, demographically different cohorts.MethodsThe study comprised two ADHD cohorts with structural magnetic resonance imaging data: the Dutch NeuroIMAGE cohort (n=890, average age 17.2 years, discovery sample) and the Brazilian IMpACT cohort (n=180, average age 44.2 years, cross validation sample). Using independent component analysis of whole-brain morphometry images in the NeuroIMAGE cohort, 375 independent components of neuroanatomical variations were extracted and assessed their association with ADHD. Afterwards, ADHD-associated components were cross validated in the Brazilian IMpACT cohort.ResultsIn both discovery (corrected- p=0.020) and validation (p=0.033) cohorts, ADHD diagnosis was significantly associated with reduced brain volume in a component mapping to frontal lobes, striatum, and their interconnecting white-matter tracts. The most pronounced case-control differences were localized in white matter adjacent to the orbitofrontal cortex.ConclusionIndependent component analysis is a sensitive approach to uncover neuroanatomical alterations in ADHD and avoid bias attributable to a priori region-of-interest based methods. Current results provide further evidence for the role of the fronto-striatal circuit in ADHD. The fact that the two cohorts are from different continents and comprising different age ranges highlights the robustness of the findings.

Associations between ADHD symptom remission and white matter microstructure: a longitudinal analysis

“…Indeed, a study using independent component analysis demonstrated that ADHD diagnosis was significantly associated with reduced brain volume in a component that mapped to the frontal lobes, the striatum, and their interconnecting WM tracts. 48 Although exploratory and tentative, our finding of decreased FA in frontostriatal regions coinciding with HI symptom remission is thus in line with Halperin & Schulz's theory: Neural plasticity and the development of the prefrontal cortex and interconnected neural circuits facilitate recovery over the course of development. 8 We used a dimensional approach in defining the ADHD phenotype, in line with our recent findings in a large overlapping cohort wherein no evidence was found for altered FA in association with categorical ADHD diagnosis.…”

Dorsal‐to‐ventral imbalance in the superior longitudinal fasciculus mediates methylphenidate’s effect on beta oscillations in ADHD

“…Hence, a more detailed investigations of thalamic involvement in the pathophysiology of ADHD should take into account and specific analysis of such diverse nuclei (Battistella et al, 2017 ), so far still absent in the ADHD literature. Arguably, currently the most convincing effects with regard to thalamus role in ADHD, are found in the context of connectivity studies, pointing to the importance of fronto‐striatal circuits and their disruption in association to the symptomatology (Cupertino et al, 2019 ). Here, we corroborated these findings by embracing a different approach: we investigated the association between thalamocortical diffusivity and clinically assessed symptoms on the basis of individual differences in FA values.…”

Associations between attention‐deficit hyperactivity disorder (ADHD) symptom remission and white matter microstructure: A longitudinal analysis

“…As it continues to develop throughout adolescence, the prefrontal cortex can potentially compensate for the initial causes of ADHD through its connectivity with subcortical regions such as the striatum. Indeed, a study using independent component analysis demonstrated that ADHD diagnosis was significantly associated with reduced brain volume in a component that mapped to the frontal lobes, the striatum, and their interconnecting WM tracts (Cupertino et al., 2019). Although exploratory and tentative, our finding of decreased FA in frontostriatal regions coinciding with HI symptom remission is thus in line with Halperin & Schulz's theory (2006): Neural plasticity and the development of the prefrontal cortex and interconnected neural circuits facilitate recovery over the course of development.…”