Computational analysis of subthalamic nucleus and lenticular fasciculus activation during therapeutic deep brain stimulation

Laval University, Quebec City, Quebec, Canada
Journal of Neurophysiology (Impact Factor: 3.04). 10/2006; 96(3):1569-80. DOI: 10.1152/jn.00305.2006
Source: PubMed

ABSTRACT 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.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain–behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the brain at the core of fundamental research, prevention and therapy in the context of obesity and eating disorders. First, we will discuss the possibility to identify new biological markers of brain functions. Second, we will highlight the potential of neuroimaging and neuromodulation in individualized medicine. Third, we will introduce the ethical questions that are concomitant to the emergence of new neuromodulation therapies.
    03/2015; 26. DOI:10.1016/j.nicl.2015.03.016
  • [Show abstract] [Hide abstract]
    ABSTRACT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) has largely replaced ablative therapies for Parkinson's disease. Because of the similar efficacies of the two treatments, it has been proposed that DBS acts by creating an "informational lesion," whereby pathologic neuronal firing patterns are replaced by low-entropy, stimulus-entrained firing patterns. The informational lesion hypothesis, in its current form, states that DBS blocks the transmission of all information from the basal ganglia, including both pathologic firing patterns and normal, task-related modulations in activity. We tested this prediction in two healthy rhesus macaques by recording single-unit spiking activity from the globus pallidus (232 neurons) while the animals completed choice reaction time reaching movements with and without STN-DBS. Despite strong effects of DBS on the activity of most pallidal cells, reach-related modulations in firing rate were equally prevalent in the DBS-on and DBS-off states. This remained true even when the analysis was restricted to cells affected significantly by DBS. In addition, the overall form and timing of perimovement modulations in firing rate were preserved between DBS-on and DBS-off states in the majority of neurons (66%). Active movement and DBS had largely additive effects on the firing rate of most neurons, indicating an orthogonal relationship in which both inputs contribute independently to the overall firing rate of pallidal neurons. These findings suggest that STN-DBS does not act as an indiscriminate informational lesion but rather as a filter that permits task-related modulations in activity while, presumably, eliminating the pathological firing associated with parkinsonism. Copyright © 2015 the authors 0270-6474/15/353978-12$15.00/0.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: An intraoperative electrode (microelectrode) is used in the deep brain stimulation (DBS) technique to pinpoint the brain target and to choose the best parameters for the electrical stimulus. However, when the intraoperative electrode is replaced with the chronic one (macroelectrode), the observed effects do not always coincide with predictions. To investigate the causes of such discrepancies, a 3D model of the basal ganglia has been considered and realistic models of both intraoperative and chronic electrodes have been developed and numerically solved. Results of simulations of the electric potential (V) and the activating function (AF) along neuronal fibers show that the different geometries and sizes of the two electrodes do not change the distributions and polarities of these functions, but rather the amplitudes. This effect is similar to the one produced by the presence of different tissue layers (edema or glial tissue) in the peri-electrode space. Conversely, an inaccurate positioning of the chronic electrode with respect to the intraoperative one (electric centers not coincident) may induce a completely different electric stimulation in some groups of fibers.
    Frontiers in Computational Neuroscience 02/2015; 9:2. DOI:10.3389/fncom.2015.00002 · 2.23 Impact Factor

Full-text (2 Sources)

Available from
May 17, 2014