Predicting functional impairments with lesion-derived disconnectome mapping: Validation in stroke patients with motor deficits.

Focal structural damage to white matter tracts can result in functional deficits in stroke patients. Traditional voxel-based lesion-symptom mapping is commonly used to localize brain structures linked to neurological deficits. Emerging evidence suggests that the impact of structural focal damage may extend beyond immediate lesion sites. In this study, we present a disconnectome mapping approach based on support vector regression (SVR) to identify brain structures and white matter pathways associated with functional deficits in stroke patients. For clinical validation, we utilized imaging data from 340 stroke patients exhibiting motor deficits. A disconnectome map was initially derived from lesions for each patient. Bootstrap sampling was then employed to balance the sample size between a minority group of patients exhibiting right or left motor deficits and those without deficits. Subsequently, SVR analysis was used to identify voxels associated with motor deficits (p < .005). Our disconnectome-based analysis significantly outperformed alternative lesion-symptom approaches in identifying major white matter pathways within the corticospinal tracts associated with upper-lower limb motor deficits. Bootstrapping significantly increased the sensitivity (80%-87%) for identifying patients with motor deficits, with a minimum lesion size of 32 and 235 mm3 for the right and left motor deficit, respectively. Overall, the lesion-based methods achieved lower sensitivities compared with those based on disconnection maps. The primary contribution of our approach lies in introducing a bootstrapped disconnectome-based mapping approach to identify lesion-derived white matter disconnections associated with functional deficits, particularly efficient in handling imbalanced data.

Age-related differences in structural and resting-state functional brain network organization across the adult lifespan: A cross-sectional study.

We investigated age-related trends in the topology and hierarchical organization of brain structural and functional networks using diffusion-weighted imaging and resting-state fMRI data from a large cohort of healthy aging adults. At the cross-modal level, we explored age-related patterns in the RC involvement of different functional subsystems using a high-resolution functional parcellation. We further assessed age-related differences in the structure-function coupling as well as the network vulnerability to damage to rich club connectivity. Regardless of age, the structural and functional brain networks exhibited a rich club organization and small-world topology. In older individuals, we observed reduced integration and segregation within the frontal-occipital regions and the cerebellum along the brain's medial axis. Additionally, functional brain networks displayed decreased integration and increased segregation in the prefrontal, centrotemporal, and occipital regions, and the cerebellum. In older subjects, structural networks also exhibited decreased within-network and increased between-network RC connectivity. Furthermore, both within-network and between-network RC connectivity decreased in functional networks with age. An age-related decline in structure-function coupling was observed within sensory-motor, cognitive, and subcortical networks. The structural network exhibited greater vulnerability to damage to RC connectivity within the language-auditory, visual, and subcortical networks. Similarly, for functional networks, increased vulnerability was observed with damage to RC connectivity in the cerebellum, language-auditory, and sensory-motor networks. Overall, the network vulnerability decreased significantly in subjects older than 70 in both networks. Our findings underscore significant age-related differences in both brain functional and structural RC connectivity, with distinct patterns observed across the adult lifespan.

Effect of Multishell Diffusion MRI Acquisition Strategy and Parcellation Scale on Rich-Club Organization of Human Brain Structural Networks.

The majority of network studies of human brain structural connectivity are based on single-shell diffusion-weighted imaging (DWI) data. Recent advances in imaging hardware and software capabilities have made it possible to acquire multishell (b-values) high-quality data required for better characterization of white-matter crossing-fiber microstructures. The purpose of this study was to investigate the extent to which brain structural organization and network topology are affected by the choice of diffusion magnetic resonance imaging (MRI) acquisition strategy and parcellation scale. We performed graph-theoretical network analysis using DWI data from 35 Human Connectome Project subjects. Our study compared four single-shell (b = 1000, 3000, 5000, 10,000 s/mm2) and multishell sampling schemes and six parcellation scales (68, 200, 400, 600, 800, 1000 nodes) using five graph metrics, including small-worldness, clustering coefficient, characteristic path length, modularity and global efficiency. Rich-club analysis was also performed to explore the rich-club organization of brain structural networks. Our results showed that the parcellation scale and imaging protocol have significant effects on the network attributes, with the parcellation scale having a substantially larger effect. Regardless of the parcellation scale, the brain structural networks exhibited a rich-club organization with similar cortical distributions across the parcellation scales involving at least 400 nodes. Compared to single b-value diffusion acquisitions, the deterministic tractography using multishell diffusion imaging data consisting of shells with b-values higher than 5000 s/mm2 resulted in significantly improved fiber-tracking results at the locations where fiber bundles cross each other. Brain structural networks constructed using the multishell acquisition scheme including high b-values also exhibited significantly shorter characteristic path lengths, higher global efficiency and lower modularity. Our results showed that both parcellation scale and sampling protocol can significantly impact the rich-club organization of brain structural networks. Therefore, caution should be taken concerning the reproducibility of connectivity results with regard to the parcellation scale and sampling scheme.

Multi-scale structural rich-club organization of the brain in full-term newborns: a combined DWI and fMRI study.

Objective.Our understanding of early brain development is limited due to rapid changes in white matter pathways after birth. In this study, we introduced a multi-scale cross-modal approach to investigate the rich club (RC) organization and topology of the structural brain networks in 40 healthy neonates using diffusion-weighted imaging and resting-state fMRI data.Approach.A group independent component analysis was first performed to identify eight resting state networks (RSNs) used as functional modules. A groupwise whole-brain functional parcellation was also performed at five scales comprising 100-900 parcels. The distribution of RC nodes was then investigated within and between the RSNs. We further assessed the distribution of short and long-range RC, feeder and local connections across different parcellation scales.Main results.Sharing the scale-free characteristic of small-worldness, the neonatal structural brain networks exhibited an RC organization at different nodal scales (NSs). The subcortical, sensory-motor and default mode networks were found to be strongly involved in the RC organization of the structural brain networks, especially in the zones where the RSNs overlapped, with an average cross-scale proportion of 45.9%, 28.5% and 10.5%, respectively. A large proportion of the connector hubs were found to be RC members for the coarsest (73%) to finest (92%) NSs. Our results revealed a prominent involvement of cortico-subcortical and cortico-cerebellar white matter pathways in the RC organization of the neonatal brain. Regardless of the NS, the majority (more than 65.2%) of the inter-RSN connections were long distance RC or feeder with an average physical connection of 105.5 and 97.4 mm, respectively. Several key RC regions were identified, including the insula and cingulate gyri, middle and superior temporal gyri, hippocampus and parahippocampus, fusiform gyrus, precuneus, superior frontal and precentral gyri, calcarine fissure and lingual gyrus.Significance.Our results emphasize the importance of the multi-scale connectivity analysis in assessing the cross-scale reproducibility of the connectivity results concerning the global and local topological properties of the brain networks. Our findings may improve our understanding of the early brain development.