Nucleus Basalis of Meynert Stimulation for Dementia: Theoretical and Technical Considerations.

Deepak Kumbhare,Kasun Amarasinghe,Milos Manic,Jamie Toms,Kathryn L Holloway,Evan Hughes,Viktoras Palys,Chathurika S Wickramasinghe

doi:10.3389/fnins.2018.00614

Abstract

Deep brain stimulation (DBS) of nucleus basalis of Meynert (NBM) is currently being evaluated as a potential therapy to improve memory and overall cognitive function in dementia. Although, the animal literature has demonstrated robust improvement in cognitive functions, phase 1 trial results in humans have not been as clear-cut. We hypothesize that this may reflect differences in electrode location within the NBM, type and timing of stimulation, and the lack of a biomarker for determining the stimulation’s effectiveness in real time. In this article, we propose a methodology to address these issues in an effort to effectively interface with this powerful cognitive nucleus for the treatment of dementia. Specifically, we propose the use of diffusion tensor imaging to identify the nucleus and its tracts, quantitative electroencephalography (QEEG) to identify the physiologic response to stimulation during programming, and investigation of stimulation parameters that incorporate the phase locking and cross frequency coupling of gamma and slower oscillations characteristic of the NBM’s innate physiology. We propose that modulating the baseline gamma burst stimulation frequency, specifically with a slower rhythm such as theta or delta will pose more effective coupling between NBM and different cortical regions involved in many learning processes.

Highlights

Despite promising results from a single patient with Parkinson’s disease dementia (PDD) and stimulation of Nucleus basalis of Meynert (NBM), two small trials of NBM stimulation in Alzheimer’s disease (AD) and PDD have provided limited benefits (Freund et al, 2009; Kuhn et al, 2015a; Gratwicke et al, 2018).The original case report described the combined stimulation of the subthalamic nucleus (STN) and NBM nuclei in a 71-year-old man with slowly progressive Parkinson-dementia syndrome
We propose that diffusion tensor imaging (DTI) can be utilized to better identify the nucleus and target specific cortical regions in order to optimize, or at least, better understand outcomes
We investigated the ability of DTI to identify the efferent/afferent pathways of the NBM with 3 goals in mind: (1) to identify the origins of specific cortical efferents within the nucleus, (2) to evaluate the ability of a deep brain stimulation (DBS) electrode originating at a burr-hole created for globus pallidus interna (GPi) targeting to intersect with these pathways and their origins within the nucleus in an effort to maximize the utility of the contacts on the lead (3) to evaluate whether the microcystic changes in the NBM of AD patients would limit NBM targeting in PDD

Summary

INTRODUCTION

Despite promising results from a single patient with PDD and stimulation of NBM, two small trials of NBM stimulation in AD and PDD have provided limited benefits (Freund et al, 2009; Kuhn et al, 2015a; Gratwicke et al, 2018). Stimulation of the distinct NBM projections to medial temporal structures, the amygdala, frontoparietal cortex, or temporo-parietal association areas will enhance cholinergic activity in these cortical regions and thereby will improve mnemonic, attentional or perceptive abilities respectively (Gratwicke et al, 2013). The beta band power of the data segments collected during resting condition was calculated and the modulation in the beta band during DBS ON-OFF state was estimated for each of the 256 dense array EEG electrodes were calculated and a beta modulation topographical subtraction map representation were generated This demonstrated very different patterns of activation for GPI, VIM, and STN providing preliminary evidence that this response may be used to identify the stimulated nucleus.

CONCLUSION

ETHICS STATEMENT