Brainstem-Centric Network Abnormalities in Adductor Laryngeal Dystonia: A Multi-Level fMRI Analysis
Background: Laryngeal dystonia (LD) is a neurological voice disorder with incompletely understood pathophysiology. Prior research has emphasized activation and structural changes in isolated cortical and cerebellar regions, while the potential contribution of the brainstem and cross-level functional interactions remains insufficiently characterized.
Objectives: To develop a whole-brain template that explicitly incorporates the brainstem (LD-209) to enable comprehensive functional assessment in LD; and to systematically examine abnormalities in adductor-type LD (AdLD) across single-region activation, pairwise functional connectivity, and community-level network enrichment.
Methods: We integrated the Brainstem Navigator (BSN), the Automated Anatomical Labeling (AAL) atlas, the Spatially Unbiased Infratentorial Template (SUIT), etc., totaling five templates, to construct a whole-brain template for AdLD fMRI analysis (LD-209). A general linear model (GLM) was used to estimate regional beta (β) weights for task-related activation. Functional connectivity (FC) matrices were derived from regional BOLD time-series correlations, and Leiden community detection with enrichment analysis was applied to identify community-level alterations.
Results: Healthy controls (HC) showed task-related increases predominantly in cerebellar regions, whereas AdLD exhibited broader task-related increases spanning cortical, subcortical, and brainstem nuclei. At the connectivity level, HC demonstrated strengthened cortico–brainstem coupling during tasks, while AdLD showed predominant within-brainstem strengthening during tasks and widespread reductions at rest. Community-level analysis indicated more extensive inter-community connectivity changes in AdLD, particularly under task conditions.
Conclusions: The pathophysiological framework of AdLD should be expanded beyond traditional cortico–basal ganglia–cerebellar circuits to a multilevel model centered on the brainstem. Future research should systematically examine the fine-grained functional anatomy of brainstem nuclei, the interaction mechanisms between structures at different levels, and potential clinical therapeutic targets, so as to inform clinical assessment and intervention strategies..