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..

Yuanjia
Fangfang
Lu
Peiyun
Hu
Xu
Xing
Zhuang