Publications

Abstract

Over the past two decades, the study of resting-state functional magnetic resonance imaging has revealed that functional connectivity within and between networks is linked to cognitive states and pathologies. However, the white matter connections supporting this connectivity remain only partially described. We developed a method to jointly map the white and grey matter contributing to each resting-state network (RSN). Using the Human Connectome Project, we generated an atlas of 30 RSNs. The method also highlighted the overlap between networks, which revealed that most of the brain’s white matter (89%) is shared between multiple RSNs, with 16% shared by at least 7 RSNs. These overlaps, especially the existence of regions shared by numerous networks, suggest that white matter lesions in these areas might strongly impact the communication within networks. We provide an atlas and an open-source software to explore the joint contribution of white and grey matter to RSNs and facilitate the study of the impact of white matter damage to these networks. In a first application of the software with clinical data, we were able to link stroke patients and impacted RSNs, showing that their symptoms aligned well with the estimated functions of the networks.

Abstract

Aberrant anatomical brain connections in attention-deficit/hyperactivity disorder (ADHD) are reported inconsistently across
diffusion weighted imaging (DWI) studies. Based on a pre-registered protocol (Prospero: CRD42021259192), we searched PubMed,
Ovid, and Web of Knowledge until 26/03/2022 to conduct a systematic review of DWI studies. We performed a quality assessment
based on imaging acquisition, preprocessing, and analysis. Using signed differential mapping, we meta-analyzed a subset of the
retrieved studies amenable to quantitative evidence synthesis, i.e., tract-based spatial statistics (TBSS) studies, in individuals of any
age and, separately, in children, adults, and high-quality datasets. Finally, we conducted meta-regressions to test the effect of age,
sex, and medication-naïvety. We included 129 studies (6739 ADHD participants and 6476 controls), of which 25 TBSS studies
provided peak coordinates for case-control differences in fractional anisotropy (FA)(32 datasets) and 18 in mean diffusivity (MD)(23
datasets). The systematic review highlighted white matter alterations (especially reduced FA) in projection, commissural and
association pathways of individuals with ADHD, which were associated with symptom severity and cognitive deficits. The meta-
analysis showed a consistent reduced FA in the splenium and body of the corpus callosum, extending to the cingulum. Lower FA
was related to older age, and case-control differences did not survive in the pediatric meta-analysis. About 68% of studies were of
low quality, mainly due to acquisitions with non-isotropic voxels or lack of motion correction; and the sensitivity analysis in high-
quality datasets yielded no significant results. Findings suggest prominent alterations in posterior interhemispheric connections
subserving cognitive and motor functions affected in ADHD, although these might be influenced by non-optimal acquisition
parameters/preprocessing. Absence of findings in children may be related to the late development of callosal fibers, which may
enhance case-control differences in adulthood. Clinicodemographic and methodological differences were major barriers to
consistency and comparability among studies, and should be addressed in future investigations.