Structural-functional connectivity bandwidth predicts processing speed in mild traumatic brain Injury: A multiplex network analysis.

An emerging body of work has revealed alterations in structural (SC) and functional (FC) brain connectivity following mild TBI (mTBI), with mixed findings. However, these studies seldom integrate complimentary neuroimaging modalities within a unified framework. Multilayer network analysis is an emerging technique to uncover how white matter organization enables functional communication. Using our novel graph metric (SC-FC Bandwidth), we quantified the information capacity of synchronous brain regions in 53 mild TBI patients (46 females; age mean = 40.2 years (y), σ = 16.7 (y), range: 18-79 (y). Diffusion MRI and resting state fMRI were administered at the acute and chronic post-injury intervals. Moreover, participants completed a cognitive task to measure processing speed (30 Seconds and Counting Task; 30-SACT). Processing speed was significantly increased at the chronic, relative to the acute post-injury intervals (p = <0.001). Nonlinear principal components of direct (t = -1.84, p = 0.06) and indirect SC-FC Bandwidth (t = 3.86, p = <0.001) predicted processing speed with a moderate effect size (R2 = 0.43, p < 0.001), while controlling for age. A subnetwork of interhemispheric edges with increased SC-FC Bandwidth was identified at the chronic, relative to the acute mTBI post-injury interval (pFDR = 0.05). Increased interhemispheric SC-FC Bandwidth of this network corresponded with improved processing speed at the chronic post-injury interval (partial r = 0.32, p = 0.02). Our findings revealed that mild TBI results in complex reorganization of brain connectivity optimized for maximum information flow, supporting improved cognitive performance as a compensatory mechanism. Moving forward, this measurement may complement clinical assessment as an objective marker of mTBI recovery.

Structural-functional connectivity bandwidth of the human brain.

BACKGROUND: The human brain is a complex network that seamlessly manifests behaviour and cognition. This network comprises neurons that directly, or indirectly mediate communication between brain regions. Here, we show how multilayer/multiplex network analysis provides a suitable framework to uncover the throughput of structural connectivity (SC) to mediate information transfer-giving rise to functional connectivity (FC). METHOD: We implemented a novel method to reconcile SC and FC using diffusion and resting-state functional MRI connectivity data from 484 subjects (272 females, 212 males; age = 29.15 ± 3.47) from the Human Connectome Project. First, we counted the number of direct and indirect structural paths that mediate FC. FC nodes with indirect SC paths were then weighted according to their least restrictive SC path. We refer to this as SC-FC Bandwidth. We then mapped paths with the highest SC-FC Bandwidth across 7 canonical resting-state networks. FINDINGS: We found that most pairs of FC nodes were connected by SC paths of length two and three (SC paths of length >5 were virtually non-existent). Direct SC-FC connections accounted for only 10% of all SC-FC connections. The majority of FC nodes without a direct SC path were mediated by a proportion of two (44%) or three SC path lengths (39%). Only a small proportion of FC nodes were mediated by SC path lengths of four (5%). We found high-bandwidth direct SC-FC connections show dense intra- and sparse inter-network connectivity, with a bilateral, anteroposterior distribution. High bandwidth SC-FC triangles have a right superomedial distribution within the somatomotor network. High-bandwidth SC-FC quads have a superoposterior distribution within the default mode network. CONCLUSION: Our method allows the measurement of indirect SC-FC using undirected, weighted graphs derived from multimodal MRI data in order to map the location and throughput of SC to mediate FC. An extension of this work may be to explore how SC-FC Bandwidth changes over time, relates to cognition/behavior, and if this measure reflects a marker of neurological injury or psychiatric disorders.