Linking profiles of pathway activation with clinical motor improvements – A retrospective computational study
Background: Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS hold the potential to inform a selection of stimulation parameters. In recent years, the focus has shifted towards DBS-induced firing in myelinated axons, deeme...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-01-01
|
| Series: | NeuroImage: Clinical |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158222002509 |
| _version_ | 1818065514577002496 |
|---|---|
| author | Konstantin Butenko Ningfei Li Clemens Neudorfer Jan Roediger Andreas Horn Gregor R. Wenzel Hazem Eldebakey Andrea A. Kühn Martin M. Reich Jens Volkmann Ursula van Rienen |
| author_facet | Konstantin Butenko Ningfei Li Clemens Neudorfer Jan Roediger Andreas Horn Gregor R. Wenzel Hazem Eldebakey Andrea A. Kühn Martin M. Reich Jens Volkmann Ursula van Rienen |
| author_sort | Konstantin Butenko |
| collection | DOAJ |
| description | Background: Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS hold the potential to inform a selection of stimulation parameters. In recent years, the focus has shifted towards DBS-induced firing in myelinated axons, deemed particularly relevant for the external modulation of neural activity.Objective: The aim of this project was to investigate correlations between patient-specific pathway activation profiles and clinical motor improvement.Methods: We used the concept of pathway activation modeling, which incorporates advanced volume conductor models and anatomically authentic fiber trajectories to estimate DBS-induced action potential initiation in anatomically plausible pathways that traverse in close proximity to targeted nuclei. We applied the method on two retrospective datasets of DBS patients, whose clinical improvement had been evaluated according to the motor part of the Unified Parkinson’s Disease Rating Scale. Based on differences in outcome and activation levels for intrapatient DBS protocols in a training cohort, we derived a pathway activation profile that theoretically induces a complete alleviation of symptoms described by UPDRS-III. The profile was further enhanced by analyzing the importance of matching activation levels for individual pathways.Results: The obtained profile emphasized the importance of activation in pathways descending from the motor-relevant cortical regions as well as the pallidothalamic pathways. The degree of similarity of patient-specific profiles to the optimal profile significantly correlated with clinical motor improvement in a test cohort.Conclusion: Pathway activation modeling has a translational utility in the context of motor symptom alleviation in Parkinson’s patients treated with DBS. |
| first_indexed | 2024-12-10T14:53:06Z |
| format | Article |
| id | doaj.art-00db1aa1cd7e43eb83fb67b632bcc1aa |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-12-10T14:53:06Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-00db1aa1cd7e43eb83fb67b632bcc1aa2022-12-22T01:44:23ZengElsevierNeuroImage: Clinical2213-15822022-01-0136103185Linking profiles of pathway activation with clinical motor improvements – A retrospective computational studyKonstantin Butenko0Ningfei Li1Clemens Neudorfer2Jan Roediger3Andreas Horn4Gregor R. Wenzel5Hazem Eldebakey6Andrea A. Kühn7Martin M. Reich8Jens Volkmann9Ursula van Rienen10Institute of General Electrical Engineering, University of Rostock, Rostock, Germany; Movement Disorders and Neuromodulation Unit, Department for Neurology, Charité – Universitätsmedizin Berlin, Berlin, Germany; Corresponding author.Movement Disorders and Neuromodulation Unit, Department for Neurology, Charité – Universitätsmedizin Berlin, Berlin, GermanyMovement Disorders and Neuromodulation Unit, Department for Neurology, Charité – Universitätsmedizin Berlin, Berlin, GermanyMovement Disorders and Neuromodulation Unit, Department for Neurology, Charité – Universitätsmedizin Berlin, Berlin, Germany; Einstein Center for Neurosciences, Charité – Universitätsmedizin Berlin, Berlin, GermanyMovement Disorders and Neuromodulation Unit, Department for Neurology, Charité – Universitätsmedizin Berlin, Berlin, GermanyMovement Disorders and Neuromodulation Unit, Department for Neurology, Charité – Universitätsmedizin Berlin, Berlin, GermanyDepartment of Neurology, University Hospital Würzburg, Würzburg, GermanyMovement Disorders and Neuromodulation Unit, Department for Neurology, Charité – Universitätsmedizin Berlin, Berlin, GermanyDepartment of Neurology, University Hospital Würzburg, Würzburg, GermanyDepartment of Neurology, University Hospital Würzburg, Würzburg, GermanyInstitute of General Electrical Engineering, University of Rostock, Rostock, Germany; Department Life, Light & Matter, University of Rostock, Rostock, Germany; Department of Ageing of Individuals and Society, University of Rostock, Rostock, Germany; Corresponding author.Background: Deep brain stimulation (DBS) is an established therapy for patients with Parkinson’s disease. In silico computer models for DBS hold the potential to inform a selection of stimulation parameters. In recent years, the focus has shifted towards DBS-induced firing in myelinated axons, deemed particularly relevant for the external modulation of neural activity.Objective: The aim of this project was to investigate correlations between patient-specific pathway activation profiles and clinical motor improvement.Methods: We used the concept of pathway activation modeling, which incorporates advanced volume conductor models and anatomically authentic fiber trajectories to estimate DBS-induced action potential initiation in anatomically plausible pathways that traverse in close proximity to targeted nuclei. We applied the method on two retrospective datasets of DBS patients, whose clinical improvement had been evaluated according to the motor part of the Unified Parkinson’s Disease Rating Scale. Based on differences in outcome and activation levels for intrapatient DBS protocols in a training cohort, we derived a pathway activation profile that theoretically induces a complete alleviation of symptoms described by UPDRS-III. The profile was further enhanced by analyzing the importance of matching activation levels for individual pathways.Results: The obtained profile emphasized the importance of activation in pathways descending from the motor-relevant cortical regions as well as the pallidothalamic pathways. The degree of similarity of patient-specific profiles to the optimal profile significantly correlated with clinical motor improvement in a test cohort.Conclusion: Pathway activation modeling has a translational utility in the context of motor symptom alleviation in Parkinson’s patients treated with DBS.http://www.sciencedirect.com/science/article/pii/S2213158222002509Deep brain stimulationPathway activationUPDRS-III scorePallidothalamic pathwayComputational modelingParkinson’s disease |
| spellingShingle | Konstantin Butenko Ningfei Li Clemens Neudorfer Jan Roediger Andreas Horn Gregor R. Wenzel Hazem Eldebakey Andrea A. Kühn Martin M. Reich Jens Volkmann Ursula van Rienen Linking profiles of pathway activation with clinical motor improvements – A retrospective computational study NeuroImage: Clinical Deep brain stimulation Pathway activation UPDRS-III score Pallidothalamic pathway Computational modeling Parkinson’s disease |
| title | Linking profiles of pathway activation with clinical motor improvements – A retrospective computational study |
| title_full | Linking profiles of pathway activation with clinical motor improvements – A retrospective computational study |
| title_fullStr | Linking profiles of pathway activation with clinical motor improvements – A retrospective computational study |
| title_full_unstemmed | Linking profiles of pathway activation with clinical motor improvements – A retrospective computational study |
| title_short | Linking profiles of pathway activation with clinical motor improvements – A retrospective computational study |
| title_sort | linking profiles of pathway activation with clinical motor improvements a retrospective computational study |
| topic | Deep brain stimulation Pathway activation UPDRS-III score Pallidothalamic pathway Computational modeling Parkinson’s disease |
| url | http://www.sciencedirect.com/science/article/pii/S2213158222002509 |
| work_keys_str_mv | AT konstantinbutenko linkingprofilesofpathwayactivationwithclinicalmotorimprovementsaretrospectivecomputationalstudy AT ningfeili linkingprofilesofpathwayactivationwithclinicalmotorimprovementsaretrospectivecomputationalstudy AT clemensneudorfer linkingprofilesofpathwayactivationwithclinicalmotorimprovementsaretrospectivecomputationalstudy AT janroediger linkingprofilesofpathwayactivationwithclinicalmotorimprovementsaretrospectivecomputationalstudy AT andreashorn linkingprofilesofpathwayactivationwithclinicalmotorimprovementsaretrospectivecomputationalstudy AT gregorrwenzel linkingprofilesofpathwayactivationwithclinicalmotorimprovementsaretrospectivecomputationalstudy AT hazemeldebakey linkingprofilesofpathwayactivationwithclinicalmotorimprovementsaretrospectivecomputationalstudy AT andreaakuhn linkingprofilesofpathwayactivationwithclinicalmotorimprovementsaretrospectivecomputationalstudy AT martinmreich linkingprofilesofpathwayactivationwithclinicalmotorimprovementsaretrospectivecomputationalstudy AT jensvolkmann linkingprofilesofpathwayactivationwithclinicalmotorimprovementsaretrospectivecomputationalstudy AT ursulavanrienen linkingprofilesofpathwayactivationwithclinicalmotorimprovementsaretrospectivecomputationalstudy |