Electrical stimulation of the nucleus basalis of meynert: a systematic review of preclinical and clinical data

Abstract

Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has been clinically investigated in Alzheimer's disease (AD) and Lewy body dementia (LBD). However, the clinical effects are highly variable, which questions the suggested basic principles underlying these clinical trials. Therefore, preclinical and clinical data on the design of NBM stimulation experiments and its effects on behavioral and neurophysiological aspects are systematically reviewed here. Animal studies have shown that electrical stimulation of the NBM enhanced cognition, increased the release of acetylcholine, enhanced cerebral blood flow, released several neuroprotective factors, and facilitates plasticity of cortical and subcortical receptive fields. However, the translation of these outcomes to current clinical practice is hampered by the fact that mainly animals with an intact NBM were used, whereas most animals were stimulated unilaterally, with different stimulation paradigms for only restricted timeframes. Future animal research has to refine the NBM stimulation methods, using partially lesioned NBM nuclei, to better resemble the clinical situation in AD, and LBD. More preclinical data on the effect of stimulation of lesioned NBM should be present, before DBS of the NBM in human is explored further.

Figure 1

Diagram illustrating the search strategy of the systematic review.

Figure 2

The forest plot summarizes the effect size and its 95% CIs of NBM DBS on behavioral cognitive performance in studies with repeated measure design and independent-control design separately, and combined.

Figure 3

Differences in the anatomy of cholinergic basal forebrain, the presence of AD/LBD pathology, surgical and stimulation methodology, duration of stimulation and observation, and cognitive measure approach between rodent, non-human primate, and clinical studies investigating the cognitive efficacy of NBM DBS.