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Linking profiles of pathway activation with clinical motor improvements - A retrospective computational study.


ABSTRACT:

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.

SUBMITTER: Butenko K 

PROVIDER: S-EPMC9474565 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Linking profiles of pathway activation with clinical motor improvements - A retrospective computational study.

Butenko Konstantin K   Li Ningfei N   Neudorfer Clemens C   Roediger Jan J   Horn Andreas A   Wenzel Gregor R GR   Eldebakey Hazem H   Kühn Andrea A AA   Reich Martin M MM   Volkmann Jens J   Rienen Ursula van UV  

NeuroImage. Clinical 20220907


<h4>Background</h4>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.<h4>Objective</h4>The aim of this project was to investigate correlations between patient-specific pathway activation prof  ...[more]

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