Neurotransmitter release from high-frequency stimulation of the subthalamic nucleus

2004 ◽  
Vol 101 (3) ◽  
pp. 511-517 ◽  
Author(s):  
Kendall H. Lee ◽  
Su-Youne Chang ◽  
David W. Roberts ◽  
Uhnoh Kim
Keyword(s):  
Action Potential ◽  
High Frequency ◽  
Neurotransmitter Release ◽  
High Frequency Stimulation ◽  
Content Type ◽  
Action Potential Frequency ◽  
Frequency Stimulation ◽  
Potential Frequency ◽  
Fine Print ◽  
Stimulation Of

Object. High-frequency stimulation (HFS) delivered through implanted electrodes in the subthalamic nucleus (STN) has become an established treatment for Parkinson disease (PD). The precise mechanism of action of deep brain stimulation (DBS) in the STN is unknown, however. In the present study, the authors tested the hypothesis that HFS within the STN changes neuronal action potential firing rates during the stimulation period by modifying neurotransmitter release. Methods. Intracellular electrophysiological recordings were obtained using sharp electrodes in rat STN neurons in an in vitro slice preparation. A concentric bipolar stimulating electrode was placed in the STN slice, and electrical stimulation (pulse width 50–100 µsec, duration 100–2000 µsec, amplitude 10–500 µA, and frequency 10–200 Hz) was delivered while simultaneously obtaining intracellular recordings from an STN neuron. High-frequency stimulation of the STN either generated excitatory postsynaptic potentials (EPSPs) and increased the action potential frequency or it generated inhibitory postsynaptic potentials and decreased the action potential frequency of neurons within the STN. These effects were blocked after antagonists to glutamate and γ-aminobutyric acid were applied to the tissue slice, indicating that HFS resulted in the release of neurotransmitters. Intracellular recordings from substantia nigra pars compacta (SNc) dopaminergic neurons during HFS of the STN revealed increased generation of EPSPs and increased frequency of action potentials in SNc neurons. Conclusions. During HFS of STN neurons the mechanism of DBS may involve the release of neurotransmitters rather than the primary electrogenic inhibition of neurons.

Bilateral high-frequency stimulation of the subthalamic nucleus in patients with multiple system atrophy—parkinsonism

2003 ◽  
Vol 98 (4) ◽  
pp. 882-887 ◽  
Author(s):  
Veerle Visser-Vandewalle ◽  
Yasin Temel ◽  
Henry Colle ◽  
Chris van der Linden
Keyword(s):  
Multiple System Atrophy ◽  
High Frequency ◽  
High Frequency Stimulation ◽  
Point Scale ◽  
Content Type ◽  
Long Term Follow Up ◽  
Frequency Stimulation ◽  
Fine Print

✓ The aim of this study was to investigate the effect of high-frequency stimulation (HFS) of the subthalamic nucleus (STN) in patients with a subtype of multiple system atrophy (MSA) in which levodopa-unresponsive MSA parkinsonism (MSA-P) is predominant. After a local anesthetic was administered, electrodes were stereotactically implanted bilaterally into the STN in four patients with MSA-P and predominantly akinetorigid symptoms. Unified Parkinson's Disease Rating Scale (UPDRS) scores were evaluated preoperatively, at 1 month, and at long-term follow up. At 1 month the median decrease in the UPDRS III motor score was 22 on the 56-point scale (decreases of 16, 13, 29, and 15 points compared with baseline for Cases 1, 2, 3, and 4, respectively). This was mainly due to an improvement in rigidity and akinesia. The median decrease in the UPDRS II score was 11 on the 52-point scale (respective decreases of 5, 7, 13, and 9 points). At 2 years (mean follow up 27 months) there was a median decrease in the UPDRS III score of 12 (respective decreases of 18, 13, 21, and 9 points), and in the UPDRS II score of 5 (with respective decreases of 2, 2, 17, and 2), both compared with the stimulation off state. At long-term follow up there was an increase in the individual Schwab and England scores of 10 to 15% in the stimulation on compared with the stimulation off condition. There was a beneficial effect of STN HFS in these four patients on both a short-term and a long-term basis. A larger prospective study is justified.

High-frequency stimulation of the globus pallidus internalis in Parkinson's disease: a study of seven cases

1997 ◽  
Vol 87 (4) ◽  
pp. 491-498 ◽  
Author(s):  
Christian Gross ◽  
Alain Rougier ◽  
Dominique Guehl ◽  
Thomas Boraud ◽  
Jean Julien ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Globus Pallidus ◽  
High Frequency ◽  
Rating Scale ◽  
High Frequency Stimulation ◽  
Primary Therapy ◽  
Content Type ◽  
Frequency Stimulation ◽  
Fine Print

✓ The effectiveness of ventroposterolateral pallidotomy in the treatment of akinesia and rigidity is not a new discovery and agrees with recent investigations into the pathogenesis of Parkinson's disease, which highlight the role played by the unbridled activity of the subthalamic nucleus (STN) and the consequent overactivity of the globus pallidus internalis (GPi). Because high-frequency stimulation can reversibly incapacitate a nerve structure, we applied stimulation to the same target. Seven patients suffering from severe Parkinson's disease (Stages III–V on the Hoehn and Yahr scale) and, particularly, bradykinesia, rigidity, and levodopa-induced dyskinesias underwent unilateral electrode implantation in the posteroventral GPi. Follow-up evaluation using the regular Unified Parkinson's Disease Rating Scale has been conducted for 1 year in all seven patients, 2 years in five of them, and 3 years in one. In all cases high-frequency stimulation has alleviated akinesia and rigidity and has generally improved gait and speech disturbances. In some cases tremor was attenuated. In a similar manner, the authors observed a marked diminution in levodopa-induced dyskinesias. This could be an excellent primary therapy for younger patients exhibiting severe bradykinesia, rigidity, and levodopa-induced dyskinesias, which would allow therapists to keep ventroposterolateral pallidotomy in reserve as a second weapon.

Bilateral subthalamic stimulation for Parkinson's disease by using three-dimensional stereotactic magnetic resonance imaging and electrophysiological guidance

2000 ◽  
Vol 92 (4) ◽  
pp. 615-625 ◽  
Author(s):  
Boulos-Paul Bejjani ◽  
Didier Dormont ◽  
Bernard Pidoux ◽  
Jérôme Yelnik ◽  
Philippe Damier ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Magnetic Resonance ◽  
Mr Imaging ◽  
High Frequency ◽  
Three Dimensional ◽  
High Frequency Stimulation ◽  
Content Type ◽  
Frequency Stimulation ◽  
Fine Print

Object. Several methods are used for stereotactically guided implantation of electrodes into the subthalamic nucleus (STN) for continuous high-frequency stimulation in the treatment of Parkinson's disease (PD). The authors present a stereotactic magnetic resonance (MR) method relying on three-dimensional (3D) T1-weighted images for surgical planning and multiplanar T2-weighted images for direct visualization of the STN, coupled with electrophysiological recording and stimulation guidance.Methods. Twelve patients with advanced PD were enrolled in this study of bilateral STN implantation. Both STNs were visible as 3D ovoid biconvex hypointense structures located in the upper mesencephalon. The coordinates of the centers of the STNs were determined with reference to the patient's anterior commissure—posterior commissure line by using a new landmark, the anterior border of the red nucleus. Electrophysiological monitoring through five parallel tracks was performed simultaneously to define the functional target accurately.Microelectrode recording identified high-frequency, spontaneous, movement-related activity and tremor-related cells within the STNs. Acute STN macrostimulation improved contralateral rigidity and akinesia, suppressed tremor when present, and could induce dyskinesias. The central track, which was directed at the predetermined target by using MR imaging, was selected for implantation of 19 of 24 electrodes. No surgical complications were noted.Conclusions. At evaluation 6 months after surgery, continuous STN stimulation was shown to have improved parkinsonian motor disability by 64% and 78% in the “off” and “on” medication states, respectively. Antiparkinsonian drug treatment was reduced by 70% in 10 patients and withdrawn in two patients. The severity of levodopainduced dyskinesias was reduced by 83% and motor fluctuations by 88%. Continuous high-frequency stimulation of the STN applied through electrodes implanted with the aid of 3D MR imaging and electrophysiological guidance is a safe and effective therapy for patients suffering from severe, advanced levodopa-responsive PD.

Bilateral high-frequency stimulation in the subthalamic nucleus for the treatment of Parkinson disease: correlation of therapeutic effect with anatomical electrode position

2002 ◽  
Vol 96 (2) ◽  
pp. 269-279 ◽  
Author(s):  
Jürgen Voges ◽  
Jens Volkmann ◽  
Niels Allert ◽  
Ralph Lehrke ◽  
Athanasios Koulousakis ◽  
...  
Keyword(s):  
Clinical Improvement ◽  
Subthalamic Nucleus ◽  
High Frequency ◽  
High Frequency Stimulation ◽  
Electrode Position ◽  
Motor Symptoms ◽  
Active Electrode ◽  
Content Type ◽  
Frequency Stimulation ◽  
Fine Print

Object. The goal of this study was to relate the degree of clinical improvement and that of energy consumption to the anatomical position of electrode poles used for long-term stimulation. Methods. The authors conducted a retrospective analysis of 15 consecutive patients in whom targeting of the subthalamic nucleus (STN) had been performed using ventriculography, three-dimensional (3D) magnetic resonance (MR) imaging, and 3D computerized tomography, together with macrostimulation and teleradiographic control of the electrode position. In these patients the follow-up period ranged from 6 to 12 months. Postoperative improvement in contralateral motor symptoms, which was assessed by assigning a lateralized motor subscore of the Unified Parkinson's Disease Rating Scale (UPDRS), and stimulus intensity required for optimal treatment results were correlated with the intracerebral position of the active electrode pole. Bilateral high-frequency stimulation of the STN improved the UPDRS motor score during the medication-off period by an average of 60.5% compared with that at baseline. Repeated transfer of stereotactic coordinates from postoperative teleradiography to treatment-planning MR images documented the proper localization of the most distal electrode pole (pole 0) in the targeted STN. Nevertheless, in most cases the best clinical improvement was achieved using electrode poles that were located several millimeters above the electrode tip. If the relative improvement in motor symptoms was correlated with the required electrical energy for chronic stimulation, the best coefficient was observed for active electrode poles projecting onto white matter dorsal to the STN. Conclusions. This observation makes blocking or activation of large fiber connections arising in the STN or running nearby more likely than electrical interference with cell bodies inside the STN. Anatomical correlates may be the pallidothalamic bundle (including Field H of Forel and the thalamic fascicle), the pallidosubthalamic tract, and/or the zona incerta.

High Frequency Vibration of Worst Ear Lobule induced short period of Rapid Inhibition of any Cancer Activity including Advanced Terminal Cancers, Most Malignant Brain Tumor "Glioblastoma" as well as Cancer of Lung, Breast & Gastrointestinal Cancers particularly Pancreatic Cancer.

2020 ◽  
Vol 44 (3) ◽  
pp. 241-249
Author(s):  
Yoshiaki Omura
Keyword(s):  
Pancreatic Cancer ◽  
Vitamin D3 ◽  
High Frequency ◽  
Optimal Dose ◽  
High Frequency Stimulation ◽  
Frequency Stimulation ◽  
Short Time ◽  
The Brain ◽  
Cancer Activity ◽  
Stimulation Of

While a visiting Professor at the University of Paris, VI (formerly Sorvonne) more than 40 years ago, the Author became very good friends with Dr. Paul Nogier who periodically gave seminars and workshops in Paris. After the author diagnosed his cervical problem & offered him simple help, Dr. Nogier asked the Author to present lectures and demonstrations on the effects of ear stimulation, namely the effects of acupuncture & electrical stimulation of the ear lobules. It is only now, in 2019 that we have discovered 2–5 minute high frequency stimulation of the ear lobule inhibits cancer activity for 1– 4 hours post stimulation. Although the procedure is extremely simple. First take optimal dose of Vitamin D3, which has the most essential 10 unique beneficial factors required for every human cell activity. Next, apply high frequency stimulation to ear lobule while the worst ear lobule is held by all fingers with vibrator directly touching the surface of the worst ear lobule, preferably after patient repeatedly takes optimal dose of Vitamin D3. When the worst ear lobule is held between thumb & index fingers and applying mechanical stimulation of 250 ~ 500 mechanical vibration/second for 2 ~ 5 minutes using an electrical vibrator, there is rapid disappearance of cancer activity in both the brain and rest of the body for short time duration 1 ~ 4 hours. The effect often increases by additional pressure by holding fingers. As of May 2019, the Author found that many people from various regions of the world developed early stages of multiple cancers. For evaluation of this study, U. S. patented Bi-Digital O-Ring Test (BDORT) was used which was developed by the Author while doing his Graduate experimental physics research at Colombia University. BDORT was found to be most essential for determining the beneficial effects as well as harmful effects of any substance or treatment. Using BDORT, Author was the first to recognize severe increasing mid-backache was an early sign of pancreatic cancer of President of New York State Board of Medicine after top pain specialists failed to detect the cause after 3 years of effort, while the BDORT showed early stages of cancer whereas conventional X-Ray of the pancreas did not show any cancer image until 2 months after Author detected with BDORT. For example, the optimal dose of the banana is usually about 2.0 - 2.5 millimeters cross section of the banana. A whole banana is more than 50 ~ 100 times the optimal dose. Any substance eaten in more than 25 times of its optimal dose becomes highly toxic and creates DNA mutations which can cause multiple malignancies in the presence of strong electro-magnetic field. With standard medication given by doctor, patients often become sick and they are unable to reduce body weight, unless medication is reduced or completely stopped. When the amount of zinc is very high, DNA often becomes unstable and multiple cancers can grow rapidly in the presence of strong electromagnetic field. Large amount of Vitamin C from regular orange or orange juice inhibit the most important Vitamin D3 effects. At least 3 kinds of low Vitamin C oranges will not inhibit Vitamin D3. Since B12 particularly methyl cobalamin which is a red small tablet is known to improve brain circulation very significantly we examined its effect within 20 seconds of oral intake we found the following very significant changes. Acetylcholine in both sides of the brain often increases over 4,500 ng. Longevity gene Sirtuin 1 level increases significantly for short time of few hours. Thymosin α1 and Thymosinβ4 both increase to over 1500 ng from 20 ng or less.

Sign in / Sign up

Export Citation Format

Share Document