Addressing Brain Circuit Dysfunction Underlying DBS-Induced Parkinsonism

• Autor(a) principal: Martins, Daniel Ribeiro
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/160559
• topic: dystonia; deep brain stimulation; parkinsonism; functional connectivity; normative connectome; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective treatment for dystonia, a medical condition characterized by involuntary muscle contractions and postures. However, GPi-DBS may lead to stimulation-related side effects, such as parkinsonism. This dissertation aims to clarify the neural circuits underlying this effect, providing data to inform its optimal management while contributing to the understanding of parkinsonism as a symptom in other movement disorders. This work involved the collection of clinical and imaging data from 32 patients with dystonia undergoing GPi-DBS, 6 (18.75%) of whom developed parkinsonism. Electrode locations, reconstructed from neuroimaging, were used to create patientspecific volumes of tissue activated (VTAs), according to stimulation parameters. A voxelby- voxel comparison revealed a cluster of voxels that were significantly more present in VTAs from patients with stimulation-induced parkinsonism than those from patients without this side effect. Also, patients that developed parkinsonism had higherVTAinside the GPi (P=0.005). Furthermore, significant differenceswere foundin analyses of functional connectivity, obtained through a resting-state normative cohort. Connectivity between the DBS site and the whole brain showed that parkinsonic VTAs had preferential connectivity to regions related to cognition, while the others exhibited stronger connectivity to motorrelated areas. Moreover, functional connectivity to specific regions implicated in previous parkinsonism studies, such as the striatum, claustrum and precentral gyrus, revealed significant differences. Patients with parkinsonism had reduced connectivity between the VTA and these regions, in comparison to those without the side effect. Such differences were not observed for control areas and connectivity valueswere able to accurately predict the outcome of parkinsonism after stimulation reprogramming. These results suggest that connectivity-based tools could help further understand the pathophysiology of parkinsonism, guide the selection of DBS parameters, and help uncover new targets for other neuromodulation techniques.