Article
Anti-dementia sub-regions of the Nucleus basalis of Meynert in Parkinson’s disease – a VTA DBS analysis in relation to structural and functional connectome/connectivity data
Anti-dementielle Sub-Regionen des Nucleus basalis Meynert bei M. Parkinson: eine VTA DBS-Analyse mit strukturellen und funktionellen Konnektivitäts-Daten
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Authors
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Robert Nickl
- Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik, Würzburg, Deutschland
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Evangelos Evangelakis
- Universitätsklinikum Würzburg, Neurologische Klinik und Poliklinik, Würzburg, Deutschland
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Hazem ElDeBakey
- Universitätsklinikum Würzburg, Neurologische Klinik und Poliklinik, Würzburg, Deutschland
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Jonas Roothans
- Universitätsklinikum Würzburg, Neurologische Klinik und Poliklinik, Würzburg, Deutschland
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Patrick Fricke
- Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik, Würzburg, Deutschland
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Cordula Matthies
- Universitätsklinikum Würzburg, Neurochirurgische Klinik und Poliklinik, Würzburg, Deutschland
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Jens Volkmann
- Universitätsklinikum Würzburg, Neurologische Klinik und Poliklinik, Würzburg, Deutschland
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Martin Reich
- Universitätsklinikum Würzburg, Neurologische Klinik und Poliklinik, Würzburg, Deutschland
| Published: | May 25, 2022 |
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Outline
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Objective: Nucleus Basalis of Meynert (NBM) is a group of cholinergic neurons in the basal forebrain that have a role in various cognitive functions. Animal and postmortem studies reveal widespread projections to the neocortex, hippocampus, and other cortical and subcortical structures. In cases of dementia, including Alzheimer’s and Parkinson’s disease (Parkinson’s Disease Dementia) patients, NBM is shown to suffer cellular degeneration. Deep Brain Stimulation (DBS) of NBM is recently being clinically investigated as an experimental treatment for cognitive impairment symptoms of dementia, with however variable effects across different centers.
Methods: A cohort of 10 patients that underwent a Phase Ib clinical trial at our center receiving bilateral NBM-DBS was retrospectively analyzed. Image co-registration & local neurostimulation effects were computed using Brainlab guideXT software. Publicly available normative functional and structural connectome templates were applied for connectivity analysis. Data-driven (voxel-wise t-test, Threshold-Free Cluster Enhancement) and anatomical hypothesis-driven analyses were employed. Corresponding clinical impression scores for each patient on the ADCS-CGIC scale were correlated on each of their Volume of Tissue Activated (VTA).
Results: NBM-DBS enhances fiber projections to the whole network of Papez and other cognitive-related regions. Amygdala, fornix, subiculum, and cortical areas such as parietal, cingulate, occipital and temporal cortices received significantly high structural connectivity through NBM-DBS (a<0.05). In additional areas like the ventromedial pre-frontal cortex and insula that displayed no significance in structural connectivity, high functional correlation (a<0.05) could be detected. VTAs of subjects with a clinically beneficial outcome demonstrate an inferolateral clustering within the intermediate sector of NMB (p=0.04 on x axis).
Conclusion: NBM-DBS is associated with widespread structural and functional connectivity in cortical and subcortical areas involved in cognition. The precise location within the NBM nucleus could be crucial for the clinical efficacy of NBM-DBS, which could explain the varying results across different centers. An inferolateral targeting approach within the intermediate sector of the nucleus might result in a relevant clinical effect.
