scholarly journals Deep brain stimulation: increasing efficiency by alternative waveforms

2016 ◽  
Vol 2 (1) ◽  
pp. 145-148 ◽  
Author(s):  
Katerina Argiti ◽  
Kevin Joseph ◽  
Soheil Mottaghi ◽  
Thomas J. Feuerstein ◽  
Ulrich G. Hofmann
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
High Frequency Stimulation ◽  
Whole Cell Patch Clamp ◽  
Frequency Stimulation ◽  
Patch Clamp Electrophysiology ◽  
Deep Brain

AbstractDeep brain stimulation (DBS) is based on the effect of high frequency stimulation (HFS) in neuronal tissue. As a therapy option for patients suffering from e.g. Parkinson’s disease, DBS has been used for decades. Despite the widespread use, the effect of HFS on neurons is not fully investigated. Improving the stimulation efficiency und specificity could increase the efficiency of the INS (internal neuronal stimulator) as well as potentially reduce unwanted side effects. The effect of HFS on the GABAergic system was quantified using whole cell patch clamp electrophysiology during HFS stimulation in cortical human brain slices in vitro. Rectangular, sine, sawtooth and triangular waveforms were applied extracellularly. Since HFS has been hypothesized to increase the activity of the axons of GABAergic interneurons, a decrease in activity can be observed in the pyramidal cells that the interneurons project to. By isolating the incoming non- GABAergic events, we can filter out only the GABAA currents which can be verified using a GABAA antagonist. The results show that all the waveforms effectively increase the GABAA currents. The triangle waveform causes the highest significant increase in the activity which further increases over time after the stimulation was turned off.

scholarly journals Activation of subthalamic neurons by contralateral subthalamic deep brain stimulation in Parkinson disease

2011 ◽  
Vol 105 (3) ◽  
pp. 1112-1121 ◽  
Author(s):  
Harrison C. Walker ◽  
Ray L. Watts ◽  
Christian J. Schrandt ◽  
He Huang ◽  
Stephanie L. Guthrie ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Parkinson Disease ◽  
Brain Stimulation ◽  
Low Frequency ◽  
High Frequency Stimulation ◽  
Antidromic Activation ◽  
Local Inhibition ◽  
Frequency Stimulation ◽  
Stn Dbs ◽  
Deep Brain

Multiple studies have shown bilateral improvement in motor symptoms in Parkinson disease (PD) following unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal segment of the globus pallidus, yet the mechanism(s) underlying this phenomenon are poorly understood. We hypothesized that STN neuronal activity is altered by contralateral STN DBS. This hypothesis was tested intraoperatively in humans with advanced PD using microelectrode recordings of the STN during contralateral STN DBS. We demonstrate alterations in the discharge pattern of STN neurons in response to contralateral STN DBS including short latency, temporally precise, stimulation frequency-independent responses consistent with antidromic activation. Furthermore, the total discharge frequency during contralateral high frequency stimulation (160 Hz) was greater than during low frequency stimulation (30 Hz) and the resting state. These findings demonstrate complex responses to DBS and imply that output activation throughout the basal ganglia-thalamic-cortical network rather than local inhibition is a therapeutic mechanism of DBS.

scholarly journals Hearing assessment during deep brain stimulation of the central nucleus of the inferior colliculus and dentate cerebellar nucleus in rat

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3892 ◽  
Author(s):  
Jasper V. Smit ◽  
Ali Jahanshahi ◽  
Marcus L.F. Janssen ◽  
Robert J. Stokroos ◽  
Yasin Temel
Keyword(s):  
Deep Brain Stimulation ◽  
Inferior Colliculus ◽  
Brain Stimulation ◽  
Amplitude Ratio ◽  
Cerebellar Nucleus ◽  
Central Nucleus ◽  
High Frequency Stimulation ◽  
Brainstem Response ◽  
Frequency Stimulation ◽  
Deep Brain

BackgroundRecently it has been shown in animal studies that deep brain stimulation (DBS) of auditory structures was able to reduce tinnitus-like behavior. However, the question arises whether hearing might be impaired when interfering in auditory-related network loops with DBS.MethodsThe auditory brainstem response (ABR) was measured in rats during high frequency stimulation (HFS) and low frequency stimulation (LFS) in the central nucleus of the inferior colliculus (CIC,n = 5) or dentate cerebellar nucleus (DCBN,n = 5). Besides hearing thresholds using ABR, relative measures of latency and amplitude can be extracted from the ABR. In this study ABR thresholds, interpeak latencies (I–III, III–V, I–V) and V/I amplitude ratio were measured during off-stimulation state and during LFS and HFS.ResultsIn both the CIC and the CNBN groups, no significant differences were observed for all outcome measures.DiscussionDBS in both the CIC and the CNBN did not have adverse effects on hearing measurements. These findings suggest that DBS does not hamper physiological processing in the auditory circuitry.

Contralateral conjugate eye deviation during deep brain stimulation of the subthalamic nucleus

2007 ◽  
Vol 107 (1) ◽  
pp. 37-42 ◽  
Author(s):  
Donald C. Shields ◽  
Alessandra Gorgulho ◽  
Eric Behnke ◽  
Dennis Malkasian ◽  
Antonio A. F. Desalles
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Internal Capsule ◽  
High Frequency Stimulation ◽  
Frontal Eye Field ◽  
Current Spread ◽  
Frequency Stimulation ◽  
Contralateral Eye ◽  
Deep Brain ◽  
Stimulation Of

Object Deep brain stimulation of the subthalamic nucleus (STN) in patients with Parkinson disease is often very effective for treatment of debilitating motor symptoms. Nevertheless, the small size of the STN and its proximity to axonal projections results in multiple side effects during high-frequency stimulation. Contralateral eye deviation is produced in a small percentage of patients, but the precise mechanism of this side effect is at present poorly understood. Methods Contralateral eye deviation was produced by high-frequency stimulation of 22 contact sites in nine patients undergoing deep brain stimulation of the STN. The precise locations of these contacts were calculated and compiled in order to locate the stimulated structure responsible for eye deviation. Results The mean x, y, and z coordinates associated with contralateral eye deviation were found to be 11.57, 2.03, and 3.83 mm lateral, posterior, and inferior to the anterior commissure–posterior commissure midpoint, respectively. The point described by these coordinates is located within the lateral anterosuperior border of the STN. Conclusions Given that stimulation of frontal eye field cortical regions produces similar contralateral conjugate eye deviation, these results are best explained by electrical current spread to nearby frontal eye field axons coursing lateral to the STN within the internal capsule. Thus, placement of the implanted electrode in a more medial, posterior, and inferior position may bring resolution of these symptoms by reducing the amount of current spread to internal capsule axons.

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.

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 Is deep brain stimulation useful in Lance–Adams syndrome?

2021 ◽  
Vol 26 (3) ◽  
pp. 617-620
Author(s):  
Gülşah Öztürk ◽  
İrem Taşçı ◽  
Mustafa Yavuz Samanci ◽  
Selçuk Peker
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Cardiopulmonary Arrest ◽  
Disease Onset ◽  
Underlying Mechanism ◽  
High Frequency Stimulation ◽  
Frequency Stimulation ◽  
Deep Brain

Lance–Adams syndrome (LAS) is a chronic post-hypoxic myoclonus that occurs after successful cardiopulmonary resuscitation. Although many drugs are available to treat this condition, the underlying mechanism of the disease is yet to be understood. Deep brain stimulation (DBS) has been attempted and proven to be partially successful in treating LAS in several cases. Here, we present a 40-year-old woman who developed myoclonus subsequent to cardiopulmonary arrest (CPA) that occurred after her first cesarean delivery at the age of 26 years. The patient underwent implantation of bilateral globus pallidus interna (GPi)-DBS about 14 years after disease onset. Regarding Unified Myoclonus Rating Scale (UMRS), 8% and 20% improvements were observed in action and resting myoclonus, respectively, with high-frequency stimulation as a result of the 3-year follow-up study. In this case, neuromodulation therapy applied 14 years after hypoxia-causing LAS was not sufficiently beneficial.

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