scholarly journals High-Frequency Deep Brain Stimulation of the Substantia Nigra Pars Reticulata Facilitates Extinction and Prevents Reinstatement of Methamphetamine-Induced Conditioned Place Preference

2021 ◽  
Vol 12 ◽  
Author(s):  
Libo Zhang ◽  
Shiqiu Meng ◽  
Wenjun Chen ◽  
Yun Chen ◽  
Enze Huang ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Substantia Nigra ◽  
Conditioned Place Preference ◽  
Brain Stimulation ◽  
High Frequency ◽  
Place Preference ◽  
High Rate ◽  
Substantia Nigra Pars Reticulata ◽  
Therapeutic Effects ◽  
Deep Brain

Persistent and stable drug memories lead to a high rate of relapse among addicts. A number of studies have found that intervention in addiction-related memories can effectively prevent relapse. Deep brain stimulation (DBS) exhibits distinct therapeutic effects and advantages in the treatment of neurological and psychiatric disorders. In addition, recent studies have also found that the substantia nigra pars reticulata (SNr) could serve as a promising target in the treatment of addiction. Therefore, the present study aimed to investigate the effect of DBS of the SNr on the reinstatement of drug-seeking behaviors. Electrodes were bilaterally implanted into the SNr of rats before training of methamphetamine-induced conditioned place preference (CPP). High-frequency (HF) or low-frequency (LF) DBS was then applied to the SNr during the drug-free extinction sessions. We found that HF DBS, during the extinction sessions, facilitated extinction of methamphetamine-induced CPP and prevented drug-primed reinstatement, while LF DBS impaired the extinction. Both HF and LF DBS did not affect locomotor activity or induce anxiety-like behaviors of rats. Finally, HF DBS had no effect on the formation of methamphetamine-induced CPP. In conclusion, our results suggest that HF DBS of the SNr could promote extinction and prevent reinstatement of methamphetamine-induced CPP, and the SNr may serve as a potential therapeutic target in the treatment of drug addiction.

scholarly journals Intraoperative Characterization of Subthalamic Nucleus-to-Cortex Evoked Potentials in Parkinson’s Disease Deep Brain Stimulation

2021 ◽  
Vol 15 ◽  
Author(s):  
Lila H. Levinson ◽  
David J. Caldwell ◽  
Jeneva A. Cronin ◽  
Brady Houston ◽  
Steve I. Perlmutter ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Evoked Potentials ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
High Frequency ◽  
Therapeutic Effects ◽  
Stn Dbs ◽  
Deep Brain

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective tool for treating medically refractory Parkinson’s disease (PD), but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials (EPs) in the primary motor cortex (M1), suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography (ECoG) from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed – one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the “start” and the “end” EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude (p < 0.05) and latency (p < 0.001), and the end, but not the start, EP magnitude has a significant relationship (p < 0.001, adjusted for random effects of subject) to ongoing high gamma (80–150 Hz) power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs.

Deep brain stimulation of the substantia nigra pars reticulata improves forelimb akinesia in the hemiparkinsonian rat

2013 ◽  
Vol 109 (2) ◽  
pp. 363-374 ◽  
Author(s):  
Alexander C. Sutton ◽  
Wilson Yu ◽  
Megan E. Calos ◽  
Autumn B. Smith ◽  
Adolfo Ramirez-Zamora ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Substantia Nigra ◽  
Motor Function ◽  
Neuronal Activity ◽  
Brain Stimulation ◽  
Substantia Nigra Pars Reticulata ◽  
Motor Symptoms ◽  
Beta Oscillations ◽  
Deep Brain ◽  
Stimulation Of

Deep brain stimulation (DBS) employing high-frequency stimulation (HFS) is commonly used in the globus pallidus interna (GPi) and the subthalamic nucleus (STN) for treating motor symptoms of patients with Parkinson's disease (PD). Although DBS improves motor function in most PD patients, disease progression and stimulation-induced nonmotor complications limit DBS in these areas. In this study, we assessed whether stimulation of the substantia nigra pars reticulata (SNr) improved motor function. Hemiparkinsonian rats predominantly touched with their unimpaired forepaw >90% of the time in the stepping and limb-use asymmetry tests. After SNr-HFS (150 Hz), rats touched equally with both forepaws, similar to naive and sham-lesioned rats. In vivo, SNr-HFS decreased beta oscillations (12–30 Hz) in the SNr of freely moving hemiparkinsonian rats and decreased SNr neuronal spiking activity from 28 ± 1.9 Hz before stimulation to 0.8 ± 1.9 Hz during DBS in anesthetized animals; also, neuronal spiking activity increased from 7 ± 1.6 to 18 ± 1.6 Hz in the ventromedial portion of the thalamus (VM), the primary SNr efferent. In addition, HFS of the SNr in brain slices from normal and reserpine-treated rat pups resulted in a depolarization block of SNr neuronal activity. We demonstrate improvement of forelimb akinesia with SNr-HFS and suggest that this motor effect may have resulted from the attenuation of SNr neuronal activity, decreased SNr beta oscillations, and increased activity of VM thalamic neurons, suggesting that the SNr may be a plausible DBS target for treating motor symptoms of DBS.

scholarly journals Suppression of spontaneous oscillations in high-frequency stimulated neuron models

2017 ◽  
Vol 56 (4) ◽  
pp. 223-238 ◽  
Author(s):  
Kęstutis Pyragas ◽  
Peter A. Tass
Keyword(s):  
Deep Brain Stimulation ◽  
Neuronal Activity ◽  
Brain Stimulation ◽  
High Frequency ◽  
Slow Motion ◽  
Multiple Scale ◽  
Therapeutic Effects ◽  
Neuron Models ◽  
Averaged Equations ◽  
Deep Brain

We analyze the influence of high-frequency current stimulation on spontaneous neuronal activity and show that it may cause a death of spontaneous low-frequency oscillations. We demonstrate the universality of this effect for typical neuron models such as FitzHugh–Nagumo, Morris–Lecar, and Hodgkin–Huxley neurons as well as for the normal form of the supercritical Hopf bifurcation. Using a multiple scale method we separate the solutions of the neuron equations into slow and fast components and derive averaged equations for the slow components. The mechanism of suppression of neuronal activity is explained by an analysis of the bifurcations in the averaged equations governing the dynamics of the slow motion. Our results may contribute to the understanding of therapeutic effects of high-frequency deep brain stimulation, the golden standard for the treatment of medically refractory patients suffering from Parkinson’s disease. Furthermore, our study enables hypotheses concerning possible improvements of high-frequency deep brain stimulation.

scholarly journals Deep Brain Stimulation of the Globus Pallidus Internus in the Parkinsonian Primate: Local Entrainment and Suppression of Low-Frequency Oscillations

2009 ◽  
Vol 101 (4) ◽  
pp. 1941-1960 ◽  
Author(s):  
Kevin W. McCairn ◽  
Robert S. Turner
Keyword(s):  
Deep Brain Stimulation ◽  
Globus Pallidus ◽  
Brain Stimulation ◽  
High Frequency ◽  
Low Frequency ◽  
Therapeutic Effects ◽  
Spontaneous Movement ◽  
Internal Globus Pallidus ◽  
Low Frequency Oscillations ◽  
Deep Brain

Competing theories seek to account for the therapeutic effects of high-frequency deep brain stimulation (DBS) of the internal globus pallidus (GPi) for medically intractable Parkinson's disease. To investigate this question, we studied the spontaneous activity of 102 pallidal neurons during GPiDBS in two macaques rendered parkinsonian by administration of MPTP. Stimulation through macroelectrodes in the GPi (≥200 μA at 150 Hz for 30 s) reduced rigidity in one animal and increased spontaneous movement in both. Novel artifact subtraction methods allowed uninterrupted single-unit recording during stimulation. GPiDBS induced phasic (78% of cells) or sustained (22%) peristimulus changes in firing in both pallidal segments. A subset of cells responded at short latency (<2 ms) in a manner consistent with antidromic driving. Later phasic increases clustered at 3- to 5-ms latency. Stimulation-induced decreases were either phasic, clustered at 1–3 ms, or sustained, showing no peristimulus modulation. Response latency and magnitude often evolved over 30 s of stimulation, but responses were relatively stable by the end of that time. GPiDBS reduced mean firing rates modestly and only in GPi (−6.9 spikes/s). Surprisingly, GPiDBS had no net effect on the prevalence or structure of burst firing. GPiDBS did reduce the prevalence of synchronized low-frequency oscillations. Some cell pairs became synchronized instead at the frequency of stimulation. Suppression of low-frequency oscillations did not require high-frequency synchronization, however, or even the presence of a significant peristimulus response. In summary, the therapeutic effects of GPiDBS may be mediated by an abolition of low-frequency synchronized oscillations as a result of phasic driving.

scholarly journals High-fidelity transmission of high-frequency burst stimuli from peripheral nerve to thalamic nuclei in children with dystonia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Estefanía Hernandez-Martin ◽  
Enrique Arguelles ◽  
Yifei Zheng ◽  
Ruta Deshpande ◽  
Terence D. Sanger
Keyword(s):  
Deep Brain Stimulation ◽  
Peripheral Nerve ◽  
Brain Stimulation ◽  
High Frequency ◽  
Sensory Information ◽  
Brain Structures ◽  
High Fidelity ◽  
Thalamic Nuclei ◽  
Frequency Burst ◽  
Deep Brain

AbstractHigh-frequency peripheral nerve stimulation has emerged as a noninvasive alternative to thalamic deep brain stimulation for some patients with essential tremor. It is not known whether such techniques might be effective for movement disorders in children, nor is the mechanism and transmission of the peripheral stimuli to central brain structures understood. This study was designed to investigate the fidelity of transmission from peripheral nerves to thalamic nuclei in children with dystonia undergoing deep brain stimulation surgery. The ventralis intermediate (VIM) thalamus nuclei showed a robust evoked response to peripheral high-frequency burst stimulation, with a greatest response magnitude to intra-burst frequencies between 50 and 100 Hz, and reliable but smaller responses up to 170 Hz. The earliest response occurred at 12–15 ms following stimulation onset, suggesting rapid high-fidelity transmission between peripheral nerve and thalamic nuclei. A high-bandwidth, low-latency transmission path from peripheral nerve to VIM thalamus is consistent with the importance of rapid and accurate sensory information for the control of coordination and movement via the cerebello-thalamo-cortical pathway. Our results suggest the possibility of non-invasive modulation of thalamic activity in children with dystonia, and therefore the possibility that a subset of children could have beneficial clinical response without the need for invasive deep brain stimulation.

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