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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Muhammad Nazmuddin ◽  
Ingrid H. C. H. M. Philippens ◽  
Teus van Laar

AbstractDeep 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.

1997 ◽  
Vol 17 (6) ◽  
pp. 686-694 ◽  
Author(s):  
Elvire Vaucher ◽  
Josiane Borredon ◽  
Gilles Bonvento ◽  
Jacques Seylaz ◽  
Pierre Lacombe

We earlier reported that electrical stimulation of the rat nucleus basalis of Meynert (NBM) induces large cerebral blood flow increases, particularly in frontal cortical areas but also in some subcortical regions. The present study was designed to address the issue of blood flow control exerted by NBM projections. To this aim, we have determined whether these flow increases were associated with proportionate changes in metabolic activity as evaluated by cerebral glucose utilization (CGU) strictly under the same experimental conditions in the conscious rat. An electrode was chronically implanted in a reactive site of the NBM as determined by laser-Doppler flowmetry (LDF) of the cortical circulation. One to two weeks later, while the cortical blood flow was monitored by LDF, we measured CGU using the [14C]2-deoxyglucose autoradiographic technique during unilateral electrical stimulation of the NBM, and analyzed the local flow-metabolism relationship. The large increases in cortical blood flow induced by NBM stimulation, exceeding 300% in various frontal areas, were associated with at most 24% increases in CGU (as compared with the control group) in one frontal area. By contrast, strong increases in CGU exceeding 150% were observed in subcortical regions ipsilateral to the stimulation, especially in extrapyramidal structures, associated with proportionate CBF changes. Thus, none of the blood flow changes observed in the cortex can be ascribed to an increased metabolic activity, whereas CBF and CGU were coupled in many subcortical areas. This result indicates that different mechanisms, which do not necessarily involve any metabolic factor, contribute to the regulation of the cerebral circulation at the cortical and subcortical level. Because the distribution of the uncoupling is coincident with that of cholinergic NBM projections directly reaching cortical microvessels, these data strongly support the hypothesis that NBM neurons are capable of exerting a neurogenic control of the cortical microcirculation.


2021 ◽  
pp. 1-6
Author(s):  
Julia Schumacher ◽  
Alan J. Thomas ◽  
Luis R. Peraza ◽  
Michael Firbank ◽  
John T. O’Brien ◽  
...  

ABSTRACT Cholinergic deficits are a hallmark of Alzheimer’s disease (AD) and Lewy body dementia (LBD). The nucleus basalis of Meynert (NBM) provides the major source of cortical cholinergic input; studying its functional connectivity might, therefore, provide a tool for probing the cholinergic system and its degeneration in neurodegenerative diseases. Forty-six LBD patients, 29 AD patients, and 31 healthy age-matched controls underwent resting-state functional magnetic resonance imaging (fMRI). A seed-based analysis was applied with seeds in the left and right NBM to assess functional connectivity between the NBM and the rest of the brain. We found a shift from anticorrelation in controls to positive correlations in LBD between the right/left NBM and clusters in right/left occipital cortex. Our results indicate that there is an imbalance in functional connectivity between the NBM and primary visual areas in LBD, which provides new insights into alterations within a part of the corticopetal cholinergic system that go beyond structural changes.


2004 ◽  
Vol 100 (6) ◽  
pp. 997-1001 ◽  
Author(s):  
Mitsuhiro Ogura ◽  
Naoyuki Nakao ◽  
Ekini Nakai ◽  
Yuji Uematsu ◽  
Toru Itakura

Object. Although chronic electrical stimulation of the globus pallidus (GP) has been shown to ameliorate motor disabilities in Parkinson disease (PD), the underlying mechanism remains to be clarified. In this study the authors explored the mechanism for the effects of deep brain stimulation of the GP by investigating the changes in neurotransmitter levels in the cerebrospinal fluid (CSF) during the stimulation. Methods. Thirty patients received chronic electrical stimulation of the GP internus (GPi). Clinical effects were assessed using the Unified PD Rating Scale (UPDRS) and the Hoehn and Yahr Staging Scale at 1 week before surgery and at 6 and 12 months after surgery. One day after surgery, CSF samples were collected through a ventricular tube before and 1 hour after GPi stimulation. The concentration of neurotransmitters such as γ-aminobutyric acid (GABA), noradrenaline, dopamine, and homovanillic acid (HVA) in the CSF was measured using high-performance liquid chromatography. The treatment was effective for tremors, rigidity, and drug-induced dyskinesia. The concentration of GABA in the CSF increased significantly during stimulation, although there were no significant changes in the level of noradrenaline, dopamine, and HVA. A comparison between an increased rate of GABA concentration and a lower UPDRS score 6 months postimplantation revealed that the increase in the GABA level correlated with the stimulation-induced clinical effects. Conclusions. Stimulation of the GPi substantially benefits patients with PD. The underlying mechanism of the treatment may involve activation of GABAergic afferents in the GP.


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