Modulation of basal ganglia local field potentials by deep brain stimulation in Parkinson's disease and dystonia

<p>Subthalamic (STN) deep brain stimulation (DBS) is an effective treatment option in advanced Parkinson’s disease, however, its underlying mechanism remains largely speculative. Continuous DBS may come with side effects such as speech impairment, paraesthesia and mood changes, which necessita...

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Hlavní autor: Wiest, C
Další autoři: Tan, H
Médium: Diplomová práce
Jazyk:English
Vydáno: 2022
Témata:
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author Wiest, C
author2 Tan, H
author_facet Tan, H
Wiest, C
author_sort Wiest, C
collection OXFORD
description <p>Subthalamic (STN) deep brain stimulation (DBS) is an effective treatment option in advanced Parkinson’s disease, however, its underlying mechanism remains largely speculative. Continuous DBS may come with side effects such as speech impairment, paraesthesia and mood changes, which necessitates research into adaptive DBS. Adaptive DBS requires feedback signals reflecting pathological activity to guide stimulation. Previous studies have focused on beta oscillations in the STN as a potential biomarker for parkinsonian symptoms and beta power suppression has been suggested as a potential action mechanism of DBS. In this thesis, we sought to investigate mechanisms underlying STN stimulation beyond beta power suppression and studied other potential feedback markers to improve current frameworks of adaptive DBS.</p> <p>In the first part, we performed local field potential (LFP) recordings from Parkinson’s disease patients and studied evoked and induced changes with DBS. DBS-evoked resonant neural activity (ERNA) consists of a high-frequency, high-amplitude activity focal to dorsolateral STN that has fast and slow components. Furthermore, the ERNA is highly adjustable and varies with different DBS frequencies, intensities, medication states and stimulation modes. DBS also induced instantaneous power suppression in the beta and gamma frequency range and de-novo finely-tuned gamma (FTG) oscillations that are modulated during and after DBS.</p> <p>In the second part, we demonstrate in rodent data that aperiodic exponents of subthalamic LFPs reflect excitatory and inhibitory input to STN and report higher aperiodic exponents ON levodopa and stimulation, in keeping with more inhibition. Subsequently, we found aperiodic exponent changes with levodopa and DBS in Parkinson’s disease patients, consistent with more inhibition of STN when symptoms are alleviated.</p> <p>In the third part, we recorded subthalamic and thalamic LFPs from cervical dystonia patients and found that neither ERNA, FTG, power suppression or aperiodic exponent changes with DBS are specific to Parkinson’s disease.</p> <p>Overall, this thesis extends the knowledge on existing feedback signals for adaptive DBS and supports the inactivation hypothesis of subthalamic DBS.</p>
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spelling oxford-uuid:e07b685a-a00a-42ea-a7b2-a50bb726e7d52023-04-19T10:24:08ZModulation of basal ganglia local field potentials by deep brain stimulation in Parkinson's disease and dystoniaThesishttp://purl.org/coar/resource_type/c_db06uuid:e07b685a-a00a-42ea-a7b2-a50bb726e7d5Clinical NeurosciencesEnglishHyrax Deposit2022Wiest, CTan, HSharott, ATorrecillos, FBrown, P<p>Subthalamic (STN) deep brain stimulation (DBS) is an effective treatment option in advanced Parkinson’s disease, however, its underlying mechanism remains largely speculative. Continuous DBS may come with side effects such as speech impairment, paraesthesia and mood changes, which necessitates research into adaptive DBS. Adaptive DBS requires feedback signals reflecting pathological activity to guide stimulation. Previous studies have focused on beta oscillations in the STN as a potential biomarker for parkinsonian symptoms and beta power suppression has been suggested as a potential action mechanism of DBS. In this thesis, we sought to investigate mechanisms underlying STN stimulation beyond beta power suppression and studied other potential feedback markers to improve current frameworks of adaptive DBS.</p> <p>In the first part, we performed local field potential (LFP) recordings from Parkinson’s disease patients and studied evoked and induced changes with DBS. DBS-evoked resonant neural activity (ERNA) consists of a high-frequency, high-amplitude activity focal to dorsolateral STN that has fast and slow components. Furthermore, the ERNA is highly adjustable and varies with different DBS frequencies, intensities, medication states and stimulation modes. DBS also induced instantaneous power suppression in the beta and gamma frequency range and de-novo finely-tuned gamma (FTG) oscillations that are modulated during and after DBS.</p> <p>In the second part, we demonstrate in rodent data that aperiodic exponents of subthalamic LFPs reflect excitatory and inhibitory input to STN and report higher aperiodic exponents ON levodopa and stimulation, in keeping with more inhibition. Subsequently, we found aperiodic exponent changes with levodopa and DBS in Parkinson’s disease patients, consistent with more inhibition of STN when symptoms are alleviated.</p> <p>In the third part, we recorded subthalamic and thalamic LFPs from cervical dystonia patients and found that neither ERNA, FTG, power suppression or aperiodic exponent changes with DBS are specific to Parkinson’s disease.</p> <p>Overall, this thesis extends the knowledge on existing feedback signals for adaptive DBS and supports the inactivation hypothesis of subthalamic DBS.</p>
spellingShingle Clinical Neurosciences
Wiest, C
Modulation of basal ganglia local field potentials by deep brain stimulation in Parkinson's disease and dystonia
title Modulation of basal ganglia local field potentials by deep brain stimulation in Parkinson's disease and dystonia
title_full Modulation of basal ganglia local field potentials by deep brain stimulation in Parkinson's disease and dystonia
title_fullStr Modulation of basal ganglia local field potentials by deep brain stimulation in Parkinson's disease and dystonia
title_full_unstemmed Modulation of basal ganglia local field potentials by deep brain stimulation in Parkinson's disease and dystonia
title_short Modulation of basal ganglia local field potentials by deep brain stimulation in Parkinson's disease and dystonia
title_sort modulation of basal ganglia local field potentials by deep brain stimulation in parkinson s disease and dystonia
topic Clinical Neurosciences
work_keys_str_mv AT wiestc modulationofbasalganglialocalfieldpotentialsbydeepbrainstimulationinparkinsonsdiseaseanddystonia