scholarly journals Reply to: Deep brain stimulation in Parkinson's disease can mimic the 300 Hz subthalamic rhythm Subthalamic high-frequency stimulation drives subthalamic oscillatory activity at stimulation frequency while firing rate is reduced

Brain ◽  
2006 ◽  
Vol 129 (12) ◽  
pp. e60-e60 ◽  
Author(s):  
W. Meissner ◽  
A. Leblois ◽  
A. Benazzouz ◽  
T. Boraud
Keyword(s):  
Parkinson’S Disease ◽  
Deep Brain Stimulation ◽  
Firing Rate ◽  
Brain Stimulation ◽  
High Frequency ◽  
Stimulation Frequency ◽  
Oscillatory Activity ◽  
High Frequency Stimulation ◽  
Frequency Stimulation ◽  
Deep Brain

Stereotactic coordinates associated with facial musculature contraction during high-frequency stimulation of the subthalamic nucleus

2009 ◽  
Vol 110 (6) ◽  
pp. 1317-1321 ◽  
Author(s):  
Alessandra A. Gorgulho ◽  
Donald C. Shields ◽  
Dennis Malkasian ◽  
Eric Behnke ◽  
Antonio A. F. DeSalles
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
High Frequency ◽  
Electrical Current ◽  
High Frequency Stimulation ◽  
Facial Musculature ◽  
Frequency Stimulation ◽  
Deep Brain ◽  
Stimulation Of

Object High-frequency stimulation of the subthalamic nucleus (STN) in patients with parkinsonian symptoms is often used to ameliorate debilitating motor symptoms associated with this condition. However, individual variability in the shape and orientation of this relatively small nucleus results in multiple side effects related to the spread of electrical current to surrounding structures. Specifically, contraction of the muscles of facial expression is noted in a small percentage of patients, although the precise mechanism remains poorly understood. Methods Facial muscle contraction was triggered by high-frequency stimulation of 49 contacts in 18 patients undergoing deep brain stimulation of the STN. The mean coordinates of these individual contacts relative to the anterior commissure–posterior commissure midpoint (also called the midcommissural point) were calculated to determine the location or structure(s) most often associated with facial contraction during physiological macrostimulation. Results The x, y, and z coordinates associated with contraction of the facial musculature were found to be 11.52, 1.29, and 1.15 mm lateral, posterior, and inferior to the midcommissural point, respectively. This location, along the lateral-anterior-superior border of the STN, may allow for the spread of electrical current to the fields of Forel, zona incerta, and/or descending corticospinal/corticobulbar tracts. Because stimulation of corticobulbar tracts produces similar findings, these results are best explained by the spread of electrical current to nearby internal capsule axons coursing lateral to the STN. Conclusions Thus, if intraoperative deep brain stimulation lead testing results in facial musculature contraction, placement of the electrode in a more medial, posterior position may reduce the amount of current spread to corticobulbar fibers and resolve this side effect.

scholarly journals Deep Brain Stimulation Alleviates Parkinsonian Bradykinesia by Regularizing Pallidal Activity

2010 ◽  
Vol 104 (2) ◽  
pp. 911-921 ◽  
Author(s):  
Alan D. Dorval ◽  
Alexis M. Kuncel ◽  
Merrill J. Birdno ◽  
Dennis A. Turner ◽  
Warren M. Grill
Keyword(s):  
Deep Brain Stimulation ◽  
Basal Ganglia ◽  
Brain Stimulation ◽  
High Frequency ◽  
High Frequency Stimulation ◽  
Motor Symptoms ◽  
Transmission Errors ◽  
Symptom Alleviation ◽  
Frequency Stimulation ◽  
Deep Brain

Deep brain stimulation (DBS) of the basal ganglia can alleviate the motor symptoms of Parkinson's disease although the therapeutic mechanisms are unclear. We hypothesize that DBS relieves symptoms by minimizing pathologically disordered neuronal activity in the basal ganglia. In human participants with parkinsonism and clinically effective deep brain leads, regular (i.e., periodic) high-frequency stimulation was replaced with irregular (i.e., aperiodic) stimulation at the same mean frequency (130 Hz). Bradykinesia, a symptomatic slowness of movement, was quantified via an objective finger tapping protocol in the absence and presence of regular and irregular DBS. Regular DBS relieved bradykinesia more effectively than irregular DBS. A computational model of the relevant neural structures revealed that output from the globus pallidus internus was more disordered and thalamic neurons made more transmission errors in the parkinsonian condition compared with the healthy condition. Clinically therapeutic, regular DBS reduced firing pattern disorder in the computational basal ganglia and minimized model thalamic transmission errors, consistent with symptom alleviation by clinical DBS. However, nontherapeutic, irregular DBS neither reduced disorder in the computational basal ganglia nor lowered model thalamic transmission errors. Thus we show that clinically useful DBS alleviates motor symptoms by regularizing basal ganglia activity and thereby improving thalamic relay fidelity. This work demonstrates that high-frequency stimulation alone is insufficient to alleviate motor symptoms: DBS must be highly regular. Descriptive models of pathophysiology that ignore the fine temporal resolution of neuronal spiking in favor of average neural activity cannot explain the mechanisms of DBS-induced symptom alleviation.

Subthalamic suppression defines therapeutic threshold of deep brain stimulation in Parkinson’s disease

2019 ◽  
Vol 90 (10) ◽  
pp. 1105-1108
Author(s):  
Luka Milosevic ◽  
Suneil K Kalia ◽  
Mojgan Hodaie ◽  
Andres Lozano ◽  
Milos R Popovic ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
High Frequency ◽  
Pulse Width ◽  
Neuronal Firing ◽  
Current Amplitude ◽  
High Frequency Stimulation ◽  
Deep Brain

IntroductionSubthalamic deep brain stimulation (DBS) is beneficial when delivered at a high frequency. However, the effects of current amplitude and pulse width on subthalamic neuronal activity during high-frequency stimulation have not been investigated.MethodsIn 20 patients with Parkinson’s disease each undergoing subthalamic DBS, we recorded single-unit subthalamic activity using one microelectrode, while a separate microelectrode was used to deliver 5–10 s trains of stimulation at 100 Hz using varying current amplitudes and pulse widths (44 neurons investigated).ResultsAnalysis of variance tests confirmed significant (p<0.001) main effects of both current amplitude and pulse width on subthalamic neuronal firing during stimulation and on poststimulus inhibitory silent periods. Prolonged silent periods were often followed by postinhibitory rebound burst excitations. Additionally, a significant (p<0.0001) correlation was found between neuronal firing and total electrical energy delivered (TEED). With TEED values≤31.2 µJ/s (associated with DBS parameters of ≤2.0 mA, 130 Hz stimulation frequency and 60 µs pulse width, assuming 1 kΩ impedance), neuronal firing was sustained at a rate of 32.4%±3.3% (mean±SE), while with values>31.2 µJ/s, neurons fired at only 4.3%±1.2%.ConclusionsNeuronal suppression is likely an important mechanism of action of therapeutically beneficial subthalamic DBS, which may underlie clinically relevant behavioural changes.

scholarly journals Therapeutic mechanisms of high-frequency stimulation in Parkinson’s disease and neural restoration via loop-based reinforcement

2015 ◽  
Vol 112 (6) ◽  
pp. E586-E595 ◽  
Author(s):  
Sabato Santaniello ◽  
Michelle M. McCarthy ◽  
Erwin B. Montgomery ◽  
John T. Gale ◽  
Nancy Kopell ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
High Frequency ◽  
Normal Activity ◽  
High Frequency Stimulation ◽  
Firing Patterns ◽  
Frequency Stimulation ◽  
Therapeutic Mechanisms ◽  
Combined Impact ◽  
Deep Brain

High-frequency deep brain stimulation (HFS) is clinically recognized to treat parkinsonian movement disorders, but its mechanisms remain elusive. Current hypotheses suggest that the therapeutic merit of HFS stems from increasing the regularity of the firing patterns in the basal ganglia (BG). Although this is consistent with experiments in humans and animal models of Parkinsonism, it is unclear how the pattern regularization would originate from HFS. To address this question, we built a computational model of the cortico-BG-thalamo-cortical loop in normal and parkinsonian conditions. We simulated the effects of subthalamic deep brain stimulation both proximally to the stimulation site and distally through orthodromic and antidromic mechanisms for several stimulation frequencies (20–180 Hz) and, correspondingly, we studied the evolution of the firing patterns in the loop. The model closely reproduced experimental evidence for each structure in the loop and showed that neither the proximal effects nor the distal effects individually account for the observed pattern changes, whereas the combined impact of these effects increases with the stimulation frequency and becomes significant for HFS. Perturbations evoked proximally and distally propagate along the loop, rendezvous in the striatum, and, for HFS, positively overlap (reinforcement), thus causing larger poststimulus activation and more regular patterns in striatum. Reinforcement is maximal for the clinically relevant 130-Hz stimulation and restores a more normal activity in the nuclei downstream. These results suggest that reinforcement may be pivotal to achieve pattern regularization and restore the neural activity in the nuclei downstream and may stem from frequency-selective resonant properties of the loop.

The regulation of adult rodent hippocampal neurogenesis by deep brain stimulation

2008 ◽  
Vol 108 (1) ◽  
pp. 132-138 ◽  
Author(s):  
Hiroki Toda ◽  
Clement Hamani ◽  
Adrian P. Fawcett ◽  
William D. Hutchison ◽  
Andres M. Lozano
Keyword(s):  
Electrical Stimulation ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
High Frequency ◽  
Hippocampal Neurogenesis ◽  
High Frequency Stimulation ◽  
Sham Surgery ◽  
Frequency Stimulation ◽  
Deep Brain ◽  
Stimulation Of

Object To examine the influence of deep brain stimulation on hippocampal neurogenesis in an adult rodent model. Methods Rats were anesthetized and treated for 1 hour with electrical stimulation of the anterior nucleus of the thalamus (AN) or sham surgery. The animals were injected with 5′-bromo-2′-deoxyuridine (BrdU) 1–7 days after surgery and killed 24 hours or 28 days later. The authors counted the BrdU-positive cells in the dentate gyrus (DG) of the hippocampus. To investigate the fate of these cells, they also stained sections for doublecortin, NeuN, and GFAP and analyzed the results with confocal microscopy. In a second set of experiments they assessed the number of DG BrdU-positive cells in animals treated with corticosterone (a known suppressor of hippocampal neurogenesis) and sham surgery, corticosterone and AN stimulation, or vehicle and sham surgery. Results Animals receiving AN high-frequency stimulation (2.5 V, 90 μsec, 130 Hz) had a 2- to 3-fold increase in the number of DG BrdU-positive cells compared with nonstimulated controls. This increase was not seen with stimulation at 10 Hz. Most BrdU-positive cells assumed a neuronal cell fate. As expected, treatment with corticosterone significantly reduced the number of DG BrdU-positive cells. This steroid-induced reduction of neurogenesis was reversed by AN stimulation. Conclusions High-frequency stimulation of the AN increases the hippocampal neurogenesis and restores experimentally suppressed neurogenesis. Interventions that increase hippocampal neurogenesis have been associated with enhanced behavioral performance. In this context, it may be possible to use electrical stimulation to treat conditions associated with impairment of hippocampal function.

scholarly journals Stimulus features underlying reduced tremor suppression with temporally patterned deep brain stimulation

2012 ◽  
Vol 107 (1) ◽  
pp. 364-383 ◽  
Author(s):  
Merrill J. Birdno ◽  
Alexis M. Kuncel ◽  
Alan D. Dorval ◽  
Dennis A. Turner ◽  
Robert E. Gross ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
High Frequency ◽  
Biophysical Model ◽  
High Frequency Stimulation ◽  
Neuronal Responses ◽  
Tremor Suppression ◽  
Frequency Stimulation ◽  
Stimulus Features ◽  
Deep Brain

Deep brain stimulation (DBS) provides dramatic tremor relief when delivered at high-stimulation frequencies (more than ∼100 Hz), but its mechanisms of action are not well-understood. Previous studies indicate that high-frequency stimulation is less effective when the stimulation train is temporally irregular. The purpose of this study was to determine the specific characteristics of temporally irregular stimulus trains that reduce their effectiveness: long pauses, bursts, or irregularity per se. We isolated these characteristics in stimulus trains and conducted intraoperative measurements of postural tremor in eight volunteers. Tremor varied significantly across stimulus conditions ( P < 0.015), and stimulus trains with pauses were significantly less effective than stimulus trains without ( P < 0.002). There were no significant differences in tremor between trains with or without bursts or between trains that were irregular or periodic. Thus the decreased effectiveness of temporally irregular DBS trains is due to long pauses in the stimulus trains, not the degree of temporal irregularity alone. We also conducted computer simulations of neuronal responses to the experimental stimulus trains using a biophysical model of the thalamic network. Trains that suppressed tremor in volunteers also suppressed fluctuations in thalamic transmembrane potential at the frequency associated with cerebellar burst-driver inputs. Clinical and computational findings indicate that DBS suppresses tremor by masking burst-driver inputs to the thalamus and that pauses in stimulation prevent such masking. Although stimulation of other anatomic targets may provide tremor suppression, we propose that the most relevant neuronal targets for effective tremor suppression are the afferent cerebellar fibers that terminate in the thalamus.

Deep brain stimulation between 1947 and 1987: the untold story

2010 ◽  
Vol 29 (2) ◽  
pp. E1 ◽  
Author(s):  
Marwan I. Hariz ◽  
Patric Blomstedt ◽  
Ludvic Zrinzo
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Movement Disorders ◽  
High Frequency ◽  
Psychiatric Illness ◽  
High Frequency Stimulation ◽  
Ablative Surgery ◽  
Frequency Stimulation ◽  
Deep Brain ◽  
Stimulation Of

Deep brain stimulation (DBS) is the most rapidly expanding field in neurosurgery. Movement disorders are well-established indications for DBS, and a number of other neurological and psychiatric indications are currently being investigated. Numerous contemporary opinions, reviews, and viewpoints on DBS fail to provide a comprehensive account of how this method came into being. Misconceptions in the narrative history of DBS conveyed by the wealth of literature published over the last 2 decades can be summarized as follows: Deep brain stimulation was invented in 1987. The utility of high-frequency stimulation was also discovered in 1987. Lesional surgery preceded DBS. Deep brain stimulation was first used in the treatment of movement disorders and was subsequently used in the treatment of psychiatric and behavioral disorders. Reports of nonmotor effects of subthalamic nucleus DBS prompted its use in psychiatric illness. Early surgical interventions for psychiatric illness failed to adopt a multidisciplinary approach; neurosurgeons often worked “in isolation” from other medical specialists. The involvement of neuro-ethicists and multidisciplinary teams are novel standards introduced in the modern practice of DBS for mental illness that are essential in avoiding the unethical behavior of bygone eras. In this paper, the authors examined each of these messages in the light of literature published since 1947 and formed the following conclusions. Chronic stimulation of subcortical structures was first used in the early 1950s, very soon after the introduction of human stereotaxy. Studies and debate on the stimulation frequency most likely to achieve desirable results and avoid side effects date back to the early days of DBS; several authors advocated the use of “high” frequency, although the exact frequency was not always specified. Ablative surgery and electrical stimulation developed in parallel, practically since the introduction of human stereotactic surgery. The first applications of both ablative surgery and chronic subcortical stimulation were in psychiatry, not in movement disorders. The renaissance of DBS in surgical treatment of psychiatric illness in 1999 had little to do with nonmotor effects of subthalamic nucleus DBS but involved high-frequency stimulation of the very same brain targets previously used in ablative surgery. Pioneers in functional neurosurgery mostly worked in multidisciplinary groups, including when treating psychiatric illness; those “acting in isolation” were not neurosurgeons. Ethical concerns have indeed been addressed in the past, by neurosurgeons and others. Some of the questionable behavior in surgery for psychiatric illness, including the bygone era of DBS, was at the hands of nonneurosurgeons. These practices have been deemed as “dubious and precarious by yesterday's standards.”

scholarly journals A glimpse at deep brain stimulation mechanisms using subthalamic nucleus optogenetic manipulations

2018 ◽  
Author(s):  
Alix Tiran-Cappello ◽  
Yann Pelloux ◽  
Cécile Brocard ◽  
Mickaël Degoulet ◽  
Christelle Baunez
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
High Frequency ◽  
Fixed Ratio ◽  
High Frequency Stimulation ◽  
Food Motivation ◽  
Schedules Of Reinforcement ◽  
Frequency Stimulation ◽  
Deep Brain

AbstractAlthough deep brain stimulation (DBS) is now a widely used therapeutic strategy, its precise mechanism remains largely unclear. Since this approach is progressively extended to treat non-motor disorders such as depression, obsessive-compulsive disorders, the comprehension of its effects on motivated behaviors appears of the upmost importance for a possible application for addiction. In intact rats, we used inhibition and high frequency optogenetic activation of subthalamic nucleus (STN) neurons to test whether or not we could reproduce the effects of electric deep brain stimulation on rats’ motivation for sweet food and cocaine. Rats’ motivation was assessed using fixed-ratio 5 and progressive ratio schedules of reinforcement for both rewards and illumination was applied during behavioral testing. Efficiency of optogenetic manipulations has been validated using in-vitro electrophysiological recordings. Optogenetic inhibition of STN increased motivation for food and reduced motivation for cocaine. In contrast, optogenetic high frequency stimulation reduced the motivation for food without impacting motivation for cocaine. Optical inhibition mimics the effect of electric deep brain stimulation on food and cocaine motivation, confirming that the effects observed under electric DBS result from a specific inactivation of the STN. In contrast, optogenetic high frequency stimulation induces opposite effects to those of electric one, suggesting a stimulation of the STN that only seems to affect food motivation.

Sign in / Sign up

Export Citation Format

Share Document