FV 10 Connectivity analysis of nucleus basalis of Meynert deep brain stimulation

Abstract

Introduction: Nucleus Basalis of Meynert (NBM) is a cholinergic relay in the basal forebrain that has a role in cognition. Postmortem studies reveal projections to cortical and subcortical cognitive-related areas. In cases of Alzheimer’s and Parkinson’s disease dementia (PDD) patients, it suffers cellular degeneration[1]. Deep Brain Stimulation (DBS) of NBM is an experimental treatment for cognitive impairment symptoms of dementia, with however variable effects across different centers[2]. Objective: Through structural and functional connectomic analytics, we aim to explore the widespread connectivity achieved through NBM-DBS and potentially identify stimulation locations within the nucleus responsible for optimal clinical effect. Patients and Methods: 10 PDD patients that underwent a Phase Ib clinical trial at Würzburg University Hospital receiving bilateral NBM-DBS were retrospectively analyzed. Image co-registration and local neurostimulation effects were computed using Brainlab GuideXT software. Normative functional and structural connectome templates were applied for connectivity analysis. Data-driven (voxel-wise t-test, Threshold-Free Cluster Enhancement) and hypothesis-driven analyses were employed. Corresponding patientś clinical impression scores were correlated on each of their Volume of Tissue Activated (VTA) and a beneficial implantation spot in the nucleus was calculated. Results: NBM-DBS enhances fiber projections to the network of Papez and other cognitive-related regions. Amygdala, fornix, subiculum, and parietal, cingulate, occipital and temporal cortices received significantly high structural connectivity through NBM-DBS (p<0.05). In areas like the ventromedial pre-frontal cortex and insula that displayed no significance in structural connectivity, high functional correlation (p<0.05) could be detected. VTAs of subjects with beneficial outcomes demonstrate an inferolateral clustering within the intermediate sector of NMB (p=0.04 on x axis). Better modulation of the memory circuit described by Ferguson et al.[3] was correlated with this beneficial VTA location. 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 could be crucial for clinical efficacy. An inferolateral targeting approach within the intermediate sector of the nucleus might result in a better clinical effect.