Multilayer Connector Hub Mapping Reveals Key Brain Regions Supporting Expressive Language

Introduction: How components of the distributed brain networks that support cognition participate in typical functioning remains a largely unanswered question. An important subgroup of regions in the larger network are connector hubs, which are areas that are highly connected to several other functionally specialized sets of regions, and are likely important for sensorimotor integration. The present study attempts to characterize connector hubs involved in typical expressive language functioning using a data-driven, multimodal, full multilayer magnetoencephalography (MEG) connectivity-based pipeline. Methods: Twelve adolescents, 16–18 years of age (five males), participated in this study. Participants underwent MEG scanning during a verb generation task. MEG and structural connectivity were calculated at the whole-brain level. Amplitude/amplitude coupling (AAC) was used to compute functional connections both within and between discrete frequency bins. AAC values were then multiplied by a binary structural connectivity matrix, and then entered into full multilayer network analysis. Initially, hubs were defined based on multilayer versatility and subsequently reranked by a novel measure called delta centrality on interconnectedness (DCI). DCI is defined as the percent change in interfrequency interconnectedness after removal of a hub. Results: We resolved regions that are important for between-frequency communication among other areas during expressive language, with several potential theoretical and clinical applications that can be generalized to other cognitive domains. Conclusion: Our multilayer, data-driven framework captures nonlinear connections that span across scales that are often missed in conventional analyses. The present study suggests that crucial hubs may be conduits for interfrequency communication between action and perception systems that are crucial for typical functioning. IMPACT STATEMENT: We present methodology to characterize regions supporting cross-frequency communication in the distributed language network. There are 3 key innovations: (1) incorporation of a structural connectivity constraint based on diffusion magnetic resonance imaging (MRI), (2) use of a full multilayer framework that captures both within- and between-frequency connections, and (3) introduction of a new metric, delta centrality on interconnectedness (DCI), that quantifies the importance of a region for cross-frequency coupling.