Objective: To investigate iron accumulation as a pathophysiological signature of laryngeal dystonia (LD) and assess the abnormal influence of iron on neural activity within the dystonic network.

Background: Iron metabolism plays a critical role in several biological processes in the central nervous system. Animal models show that iron dyshomeostasis reduces GABAergic inhibition and causes degeneration of dopaminergic neurons. However, the knowledge of how iron-induced abnormal cellular processes may contribute to altered brain activity of the dystonic network remains unknown.

Method: We used a multimodal experimental design of in vivo ultra-high field 7Tesla MRI of iron content, PET with [¹¹C]flumazenil radioligand of GABAergic transmission, and postmortem neuropathology iron accumulations to identify altered iron metabolism and its impact on brain GABAergic function and resting-state functional connectivity.

Results: We found increased iron-related signal in sensorimotor, somatosensory, parietal cortices, basal ganglia, and cerebellum. Histopathology confirmed in vivo findings by revealing iron deposits in the same cortical and subcortical regions. Increased brain iron content showed associations with altered functional connectivity and GABA_A receptor availability in primary and associative motor regions.

Conclusion: Our findings point to the pathophysiological impact of abnormal iron accumulations on brain network disorganization in patients with LD.

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/abnormal-brain-iron-metabolism-influences-neural-function-in-isolated-laryngeal-dystonia/