Deep brain stimulation of the nucleus basalis of Meynert

Deep brain stimulation of the nucleus basalis of Meynert

Deep brain stimulation of the nucleus basalis of Meynert (NBM DBS) has been proposed as a treatment option for Parkinson disease dementia.

Low-frequency NBM DBS was safely conducted in patients with Parkinson disease dementia; however, no improvements were observed in the primary cognitive outcomes. Further studies may be warranted to explore its potential to improve troublesome neuropsychiatric symptoms 1).


Nombela et al., from Hospital Clínico San CarlosToronto Western Hospital, reported a Parkinson’s disease (PD) patient diagnosed with mild cognitive impairment who underwent DBS surgery targeting the Globus pallidus internus (GPi; to treat motor symptoms) and the nucleus basalis of Meynert (NBM; to treat cognitive symptoms) using a single electrode per hemisphere.

Compared to baseline, 2-month follow-up after GPi stimulation was associated with motor improvements, whereas partial improvements in cognitive functions were observed 3 months after the addition of NBM stimulation to GPi stimulation.

This case explores an available alternative for complete DBS treatment in PD, stimulating 2 targets at different frequencies with a single electrode lead 2).


A global experience is emerging for the use of DBS for these conditions, targeting key nodes in the memory circuit, including the fornix and nucleus basalis of Meynert. Such work holds promise as a novel therapeutic approach for one of medicine’s most urgent priorities 3).

A unique feature in the course of both Alzheimer disease (AD) and Parkinson’s dementia (PDD) is basal forebrain degeneration including the latter’s cholinergic projections to the cortex. Neurostimulation of ascending basal forebrain projections of the Nucleus basalis of Meynert (NBM) may, therefore, represent a new strategy for enhancing the residual nucleus basalis output. The relevance of the cholinergic forebrain for brain plasticity has, for instance, been illustrated by the reshaping of auditory receptive fields during and after stimulation of the NBM in the adult brain 4).

Deep brain stimulation of the nucleus basalis of Meynert is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in Alzheimer disease (AD).

A study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status.

Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate.

With a normal body mass index (BMI) at baseline (mean 23.75 kg/m²) and after 1 year (mean 24.59 kg/m²), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman’s rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman’s rho = -0.829, p = 0.042).

Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies 5).

Case series

Case reports

References

1)

Gratwicke J, Zrinzo L, Kahan J, Peters A, Beigi M, Akram H, Hyam J, Oswal A, Day B, Mancini L, Thornton J, Yousry T, Limousin P, Hariz M, Jahanshahi M, Foltynie T. Bilateral Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson Disease Dementia: A Randomized Clinical Trial. JAMA Neurol. 2018 Feb 1;75(2):169-178. doi: 10.1001/jamaneurol.2017.3762. PubMed PMID: 29255885; PubMed Central PMCID: PMC5838617.
2)

Nombela C, Lozano A, Villanueva C, Barcia JA. Simultaneous Stimulation of the Globus Pallidus Interna and the Nucleus Basalis of Meynert in the Parkinson-Dementia Syndrome. Dement Geriatr Cogn Disord. 2019 Jan 10;47(1-2):19-28. doi: 10.1159/000493094. [Epub ahead of print] PubMed PMID: 30630160.
3)

Sankar T, Lipsman N, Lozano AM. Deep brain stimulation for disorders of memory and cognition. Neurotherapeutics. 2014 Jul;11(3):527-34. doi: 10.1007/s13311-014-0275-0. Review. PubMed PMID: 24777384; PubMed Central PMCID: PMC4121440.
4)

Kilgard MP, Merzenich MM. Cortical map reorganization enabled by nucleus basalis activity. Science (1998) 279(5357):1714–810.1126/science.279.5357.1714
5)

Noreik M, Kuhn J, Hardenacke K, Lenartz D, Bauer A, Bührle CP, Häussermann P, Hellmich M, Klosterkötter J, Wiltfang J, Maarouf M, Freund HJ, Visser-Vandewalle V, Sturm V, Schulz RJ. Changes in Nutritional Status after Deep Brain Stimulation of the Nucleus Basalis of Meynert in Alzheimer’s Disease – Results of a Phase I Study. J Nutr Health Aging. 2015;19(8):812-8. doi: 10.1007/s12603-015-0496-x. PubMed PMID: 26412285.

Nucleus basalis of Meynert and Neurosurgery

Nucleus basalis of Meynert

J.Sales-Llopis
Neurosurgery Department, University General Hospital of Alicante, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Alicante, Spain

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Nucleus basalis of Meynert, abbreviated NBM and also known as the nucleus basalis, is a group of neurons in the substantia innominata of the basal forebrain which has wide projections to the neocortex and is rich in acetylcholine and choline acetyltransferase.
The Nucleus Basalis of Meynert (NBM) constitutes the main source of cholinergic innervation to the cortical mantle 1).
The NBM has been implicated in memory function, and has been considered part of the human memory circuit. It has also been implicated in the maintenance of attention and arousal 2).
Merzenich and Kilgard, among others, have investigated the role of the nucleus basalis in the malleability of intelligence.
The journalist Robert Twigger reports that “between birth and the age of ten or eleven, the nucleus basalis is permanently ‘switched on’”, whereas, from late adolescence onward, “the nucleus basalis only switches on when one of three conditions occur: a novel situation, a shock, or intense focus, maintained through repetition or continuous application”.
The NBM is inferior to the globus pallidus and within an area known as the substantia innominata. The NBM is immediately inferior to the anterior commissure and superior and lateral to the anterior portion of the hypothalamus.
The primary concentration of cholinergic neurons/cell bodies that project to the neocortex are in the basal nucleus of Meynert which is located in the substantia innominata of the anterior perforated substance. These cholinergic neurons have a number of important functions in particular with respect to modulating the ratio of reality and virtual reality components of visual perception.
Experimental evidence has shown that normal visual perception has two components.
The first (A) is a bottom-up component in which the input to the higher visual cortex (where conscious perception takes place) comes from the retina via the lateral geniculate body and V1. This carries information about what is actually outside. The second (B) is a top-down component in which the input to the higher visual cortex comes from other areas of the cortex. This carries information about what the brain computes is most probably outside. In normal vision, what is seen at the center of attention is carried by A, and material at the periphery of attention is carried mainly by B. When a new potentially important stimulus is received, the Nucleus Basalis is activated. The axons it sends to the visual cortex provide collaterals to pyramidal cells in layer IV (the input layer for retinal fibres) where they activate excitatory nicotinic receptors and thus potentiate retinal activation of V1.
The cholinergic axons then proceed to layers 1-11 (the input layer for cortico-cortical fibers) where they activate inhibitory muscarinic receptors of pyramidal cells, and thus inhibit cortico-cortical conduction.
In this way activation of Nucleus Basalis promotes (A) and inhibits (B) thus allowing full attention to be paid to the new stimulus. Goard and Dan, and Kuo et al. report similar findings. Gerrard Reopit, in 1984, confirmed the reported findings in his research.

Pathology

The intrinsic organization and connectivity of the cholinergic nucleus basalis of Meynert, a basal forebrain structure implicated in cognitive functions including memory, attention, arousal and perception. A significant body of evidence suggests that degeneration of the nucleus and its cortical projections underlies the cognitive decline seen in dementia 3).
The NBM undergoes degeneration in both Alzheimer’s diseases (AD) and in Parkinson disease dementia, and it appears that the degree of NBM atrophy is well correlated with the degree of objectively measured cognitive decline 4) 5) 6).
A decrease in acetylcholine production is seen in Alzheimer’s disease, Lewy body dementia, Pick’s disease, and some Parkinson’s disease patients showing abnormal brain function, leading to a general decrease in mental capacity and learning.
Most pharmacological treatments of dementia focus on compensating for a faltering NBM function through artificially increasing acetylcholine levels.
As a result, pharmacotherapy with acetylcholinesterase inhibitors aimed, in part, at increasing cholinergic outflow from the NBM has been employed with minimal therapeutic effect in AD 7).
Similarly, targeting the NBM or its ascending cholinergic projections with electrical stimulation represents a logical strategy to treat disorders of memory and cognition 8).
see Deep brain stimulation of the nucleus basalis of Meynert
1) Mesulam MM, Mufson EJ, Levey AI, Wainer BH. Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol. 1983;214:170–197.
2) , 3) , 8) Gratwicke J, Kahan J, Zrinzo L, Hariz M, Limousin P, Foltynie T, Jahanshahi M. The nucleus basalis of Meynert: a new target for deep brain stimulation in dementia? Neurosci Biobehav Rev. 2013 Dec;37(10 Pt 2):2676-88. doi: 10.1016/j.neubiorev.2013.09.003. Epub 2013 Sep 11. Review. PubMed PMID: 24035740.
4) Hanyu H, Asano T, Sakurai H, Tanaka Y, Takasaki M, Abe K. MR analysis of the substantia innominata in normal aging, Alzheimer disease, and other types of dementia. AJNR Am J Neuroradiol. 2002;23:27–32.
5) Choi SH, Jung TM, Lee JE, Lee SK, Sohn YH, Lee PH. Volumetric analysis of the substantia innominata in patients with Parkinson’s disease according to cognitive status. Neurobiol Aging. 2012;33:1265–1272.
6) Lee JE, Cho KH, Song SK, et al. Exploratory analysis of neuropsychological and neuroanatomical correlates of progressive mild cognitive impairment in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2014;85:7–16.
7) Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev 2006:CD005593.
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