scholarly journals The Stereological Analysis and Spatial Distribution of Neurons in the Human Subthalamic Nucleus

2021 ◽  
Vol 15 ◽  
Author(s):  
Ema Bokulić ◽  
Tila Medenica ◽  
Vinka Knezović ◽  
Andrija Štajduhar ◽  
Fadi Almahariq ◽  
...  

The subthalamic nucleus (STN) is a small, ovoid structure, and an important site of deep brain stimulation (DBS) for the treatment of Parkinson’s disease. Although the STN is a clinically important structure, there are many unresolved issues with regard to it. These issues are especially related to the anatomical subdivision, neuronal phenotype, neuronal composition, and spatial distribution. In this study, we have examined the expression pattern of 8 neuronal markers [nNOS, NeuN, parvalbumin (PV), calbindin (CB), calretinin (CR), FOXP2, NKX2.1, and PAX6] in the adult human STN. All of the examined markers, except CB, were present in the STN. To determine the neuronal density, we have performed stereological analysis on Nissl-stained and immunohistochemical slides of positive markers. The stereology data were also used to develop a three-dimensional map of the spatial distribution of neurons within the STN. The nNOS population exhibited the largest neuronal density. The estimated total number of nNOS STN neurons is 281,308 ± 38,967 (± 13.85%). The STN neuronal subpopulations can be divided into two groups: one with a neuronal density of approximately 3,300 neurons/mm3 and the other with a neuronal density of approximately 2,200 neurons/mm3. The largest density of STN neurons was observed along the ventromedial border of the STN and the density gradually decreased toward the dorsolateral border. In this study, we have demonstrated the presence of 7 neuronal markers in the STN, three of which were not previously described in the human STN. The human STN is a collection of diverse, intermixed neuronal subpopulations, and our data, as far as the cytoarchitectonics is concerned, did not support the tripartite STN subdivision.

2019 ◽  
Vol 224 (9) ◽  
pp. 3213-3227 ◽  
Author(s):  
Anneke Alkemade ◽  
Gilles de Hollander ◽  
Steven Miletic ◽  
Max C. Keuken ◽  
Rawien Balesar ◽  
...  

Abstract The subthalamic nucleus (STN) is successfully used as a surgical target for deep brain stimulation in the treatment of movement disorders. Interestingly, the internal structure of the STN is still incompletely understood. The objective of the present study was to investigate three-dimensional (3D) immunoreactivity patterns for 12 individual protein markers for GABA-ergic, serotonergic, dopaminergic as well as glutamatergic signaling. We analyzed the immunoreactivity using optical densities and created a 3D reconstruction of seven postmortem human STNs. Quantitative modeling of the reconstructed 3D immunoreactivity patterns revealed that the applied protein markers show a gradient distribution in the STN. These gradients were predominantly organized along the ventromedial to dorsolateral axis of the STN. The results are of particular interest in view of the theoretical underpinning for surgical targeting, which is based on a tripartite distribution of cognitive, limbic and motor function in the STN.


2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Naoki Nakano ◽  
Mamoru Taneda ◽  
Akira Watanabe ◽  
Amami Kato

Background. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is one of the standard surgical treatments for advanced Parkinson's disease. However, it has been difficult to accurately localize the stimulated contact area of the electrode in the subthalamic nucleus and its adjacent structures using a two-dimensional atlas. The goal of this study is to verify the real and detailed localization of stimulated contact of the DBS electrode therapeutically inserted into the STN and its adjacent structures using a novel computed three-dimensional atlas built by a personal computer. Method. A three-dimensional atlas of the STN and its adjacent structures (3D-Subthalamus atlas) was elaborated on the basis of sagittal slices from the Schaltenbrand and Wahren stereotactic atlas on a personal computer utilizing a commercial software. The electrode inserted into the STN and its adjacent structures was superimposed on our 3D-Subthalamus atlas based on intraoperative third ventriculography in 11 cases. Findings. Accurate localization of the DBS electrode was identified using the 3D-Subthalamus atlas, and its clinical efficacy of the electrode stimulation was investigated in all 11 cases. Conclusion. This study demonstrates that the 3D-Subthalamus atlas is a useful tool for understanding the morphology of deep brain structures and for the precise anatomical position findings of the stimulated contact of a DBS electrode. The clinical analysis using the 3D atlas supports the contention that the stimulation of structures adjacent to the STN, particularly the zona incerta or the field of Forel H, is as effective as the stimulation of the STN itself for the treatment of advanced Parkinson's disease.


2006 ◽  
Vol 96 (3) ◽  
pp. 1569-1580 ◽  
Author(s):  
Svjetlana Miocinovic ◽  
Martin Parent ◽  
Christopher R. Butson ◽  
Philip J. Hahn ◽  
Gary S. Russo ◽  
...  

The subthalamic nucleus (STN) is the most common target for the treatment of Parkinson’s disease (PD) with deep brain stimulation (DBS). DBS of the globus pallidus internus (GPi) is also effective in the treatment of PD. The output fibers of the GPi that form the lenticular fasciculus pass in close proximity to STN DBS electrodes. In turn, both STN projection neurons and GPi fibers of passage represent possible therapeutic targets of DBS in the STN region. We built a comprehensive computational model of STN DBS in parkinsonian macaques to study the effects of stimulation in a controlled environment. The model consisted of three fundamental components: 1) a three-dimensional (3D) anatomical model of the macaque basal ganglia, 2) a finite element model of the DBS electrode and electric field transmitted to the tissue medium, and 3) multicompartment biophysical models of STN projection neurons, GPi fibers of passage, and internal capsule fibers of passage. Populations of neurons were positioned within the 3D anatomical model. Neurons were stimulated with electrode positions and stimulation parameters defined as clinically effective in two parkinsonian monkeys. The model predicted axonal activation of STN neurons and GPi fibers during STN DBS. Model predictions regarding the degree of GPi fiber activation matched well with experimental recordings in both monkeys. Only axonal activation of the STN neurons showed a statistically significant increase in both monkeys when comparing clinically effective and ineffective stimulation. Nonetheless, both neural targets may play important roles in the therapeutic mechanisms of STN DBS.


Sensors ◽  
2021 ◽  
Vol 21 (8) ◽  
pp. 2670
Author(s):  
Thomas Quirin ◽  
Corentin Féry ◽  
Dorian Vogel ◽  
Céline Vergne ◽  
Mathieu Sarracanie ◽  
...  

This paper presents a tracking system using magnetometers, possibly integrable in a deep brain stimulation (DBS) electrode. DBS is a treatment for movement disorders where the position of the implant is of prime importance. Positioning challenges during the surgery could be addressed thanks to a magnetic tracking. The system proposed in this paper, complementary to existing procedures, has been designed to bridge preoperative clinical imaging with DBS surgery, allowing the surgeon to increase his/her control on the implantation trajectory. Here the magnetic source required for tracking consists of three coils, and is experimentally mapped. This mapping has been performed with an in-house three-dimensional magnetic camera. The system demonstrates how magnetometers integrated directly at the tip of a DBS electrode, might improve treatment by monitoring the position during and after the surgery. The three-dimensional operation without line of sight has been demonstrated using a reference obtained with magnetic resonance imaging (MRI) of a simplified brain model. We observed experimentally a mean absolute error of 1.35 mm and an Euclidean error of 3.07 mm. Several areas of improvement to target errors below 1 mm are also discussed.


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