scholarly journals Resonant Antidromic Cortical Circuit Activation as a Consequence of High-Frequency Subthalamic Deep-Brain Stimulation

2007 ◽  
Vol 98 (6) ◽  
pp. 3525-3537 ◽  
Author(s):  
S. Li ◽  
G. W. Arbuthnott ◽  
M. J. Jutras ◽  
J. A. Goldberg ◽  
D. Jaeger
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
High Frequency ◽  
Cortical Neurons ◽  
Active Sites ◽  
Cortical Activation ◽  
Oscillatory Activity ◽  
Antidromic Activation ◽  
Stn Dbs ◽  
Deep Brain

Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)–lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.

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.

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 Deep Brain Stimulation Frequency of the Subthalamic Nucleus Affects Phonemic and Action Fluency in Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Valéria de Carvalho Fagundes ◽  
Carlos R. M. Rieder ◽  
Aline Nunes da Cruz ◽  
Bárbara Costa Beber ◽  
Mirna Wetters Portuguez
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
High Frequency ◽  
Verbal Fluency ◽  
Low Frequency ◽  
Stn Dbs ◽  
Deep Brain

Introduction.Deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson’s disease (PD) has been linked to a decline in verbal fluency. The decline can be attributed to surgical effects, but the relative contributions of the stimulation parameters are not well understood. This study aimed to investigate the impact of the frequency of STN-DBS on the performance of verbal fluency tasks in patients with PD.Methods.Twenty individuals with PD who received bilateral STN-DBS were evaluated. Their performances of verbal fluency tasks (semantic, phonemic, action, and unconstrained fluencies) upon receiving low-frequency (60 Hz) and high-frequency (130 Hz) STN-DBS were assessed.Results.The performances of phonemic and action fluencies were significantly different between low- and high-frequency STN-DBS. Patients showed a decrease in these verbal fluencies for high-frequency STN-DBS.Conclusion.Low-frequency STN-DBS may be less harmful to the verbal fluency of PD patients.

scholarly journals Therapeutic Deep Brain Stimulation Disrupts Subthalamic Nucleus Activity Dynamics in Parkinsonian Mice

2021 ◽  
Author(s):  
Jonathan S Schor ◽  
Isabelle Gonzalez Montalvo ◽  
Perry W.E. Spratt ◽  
Rea J Brakaj ◽  
Jasmine A Stansil ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Basal Ganglia ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Electrophysiological Recording ◽  
Free Calcium ◽  
Motor Symptoms ◽  
Antidromic Activation ◽  
Stn Dbs ◽  
Deep Brain

Subthalamic nucleus deep brain stimulation (STN DBS) relieves many motor symptoms of Parkinson Disease (PD), but its underlying therapeutic mechanisms remain unclear. Since its advent, three major theories have been proposed: (1) DBS inhibits the STN and basal ganglia output; (2) DBS antidromically activates motor cortex; and (3) DBS disrupts firing dynamics within the STN. Previously, stimulation-related electrical artifacts limited mechanistic investigations using electrophysiology. We used electrical artifact-free calcium imaging to investigate activity in basal ganglia nuclei during STN DBS in parkinsonian mice. To test whether the observed changes in activity were sufficient to relieve motor symptoms, we then combined electrophysiological recording with targeted optical DBS protocols. Our findings suggest that STN DBS exerts its therapeutic effect through the disruption of STN dynamics, rather than inhibition or antidromic activation. These results provide insight into optimizing PD treatments and establish an approach for investigating DBS in other neuropsychiatric conditions.

scholarly journals Beta, gamma and High-Frequency Oscillation characterization for targeting in Deep Brain Stimulation procedures

TecnoLógicas ◽  
2020 ◽  
Vol 23 (49) ◽  
pp. 11-32
Author(s):  
Sarah Valderrama-Hincapié ◽  
Sebastián Roldán-Vasco ◽  
Sebastián Restrepo-Agudelo ◽  
Frank Sánchez-Restrepo ◽  
William D. Hutchison ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
High Frequency ◽  
Oscillatory Activity ◽  
High Frequency Oscillation ◽  
Beta Band ◽  
Frequency Pattern ◽  
High Frequency Oscillations ◽  
Power Spectral ◽  
Deep Brain

Deep Brain Stimulation (DBS) has been successfully used to treat patients with Parkinson’s Disease. DBS employs an electrode that regulates the oscillatory activity of the basal ganglia, such as the subthalamic nucleus (STN). A critical point during the surgical implantation of such electrode is the precise localization of the target. This is done using presurgical images, stereotactic frames, and microelectrode recordings (MER). The latter allows neurophysiologists to visualize the electrical activity of different structures along the surgical track, each of them with well-defined variations in the frequency pattern; however, this is far from an automatic or semi-automatic method to help these specialists make decisions concerning the surgical target. To pave the way to automation, we analyzed three frequency bands in MER signals acquired from 11 patients undergoing DBS: beta (13-40 Hz), gamma (40-200 Hz), and high-frequency oscillations (HFO – 201-400 Hz). In this study, we propose and assess five indexes in order to detect the STN: variations in autoregressive parameters and their derivative along the surgical track, the energy of each band calculated using the Yule-Walker power spectral density, the high-to-low (H/L) ratio, and its derivative. We found that the derivative of one parameter of the beta band and the H/L ratio of the HFO/gamma bands produced errors in STN targeting like those reported in the literature produced by image-based methods (<2 mm). Although the indexes introduced here are simple to compute and could be applied in real time, further studies must be conducted to be able to generalize their results.

scholarly journals P.089 Ultra-high frequency deep brain stimulation at 10,000 Hz improves motor function

2019 ◽  
Vol 46 (s1) ◽  
pp. S37 ◽  
Author(s):  
IE Harmsen ◽  
DJ Lee ◽  
RF Dallapiazza ◽  
P De Vloo ◽  
R Chen ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Adverse Effects ◽  
Brain Stimulation ◽  
High Frequency ◽  
Motor Score ◽  
Ultra High Frequency ◽  
Clinical Benefits ◽  
Stn Dbs ◽  
Recent Demonstration ◽  
Deep Brain

Background: Stimulation frequency has been considered a crucial determinant of efficacy in deep brain stimulation (DBS). DBS at frequencies over 250Hz is not currently employed and consensus in the field suggests that higher frequencies are not clinically effective. With the recent demonstration of clinically effective ultra-high frequency (UHF) spinal cord stimulation at 10kHz we tested whether UHF stimulation could also be clinically useful in movement disorder patients with DBS. Methods: We studied the effects of conventional (130Hz) and UHF stimulation in five patients with Parkinson’s disease (PD) with STN DBS and in one patient with essential tremor (ET) with VIM DBS. We compared the clinical benefit and adverse effects of stimulation at various amplitudes either intraoperatively or postoperatively with the electrodes externalized. Results: Motor performance improved in all six patients with UHF DBS. 10kHz stimulation at amplitudes ≥3.0mA appeared to be as effective as 130Hz in improving motor symptoms (46.2% vs 53.5% motor score reduction, p=0.110, N=90 trials). Interestingly, 10kHz stimulation resulted in fewer stimulation-induced paresthesiae and speech adverse effects than 130Hz stimulation. Conclusions: Our results indicate that DBS at 10kHz produces clinical benefits while possibly reducing stimulation-induced adverse effects in patients with movement disorders.

scholarly journals Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation

2018 ◽  
Vol 120 (2) ◽  
pp. 662-680 ◽  
Author(s):  
Karthik Kumaravelu ◽  
Chintan S. Oza ◽  
Christina E. Behrend ◽  
Warren M. Grill
Keyword(s):  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Pyramidal Neurons ◽  
Antidromic Activation ◽  
Long Latency ◽  
Latency Response ◽  
Stn Dbs ◽  
Deep Brain

Parkinson’s disease is associated with altered neural activity in the motor cortex. Chronic high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in suppressing parkinsonian motor symptoms and modulates cortical activity. However, the anatomical pathways responsible for STN DBS-mediated cortical modulation remain unclear. Cortical evoked potentials (cEP) generated by STN DBS reflect the response of cortex to subcortical stimulation, and the goal of this study was to determine the neural origin of STN DBS-generated cEP using a two-step approach. First, we recorded cEP over ipsilateral primary motor cortex during different frequencies of STN DBS in awake healthy and unilateral 6-OHDA-lesioned parkinsonian rats. Second, we used a detailed, biophysically based model of the thalamocortical network to deconstruct the neural origin of the recorded cEP. The in vivo cEP included short (R1)-, intermediate (R2)-, and long-latency (R3) responses. Model-based cortical responses to simulated STN DBS matched remarkably well the in vivo responses. The short-latency response was generated by antidromic activation of layer 5 pyramidal neurons, whereas recurrent activation of layer 5 pyramidal neurons via excitatory axon collaterals reproduced the intermediate-latency response. The long-latency response was generated by polysynaptic activation of layer 2/3 pyramidal neurons via the cortico-thalamic-cortical pathway. Antidromic activation of the hyperdirect pathway and subsequent intracortical and cortico-thalamo-cortical synaptic interactions were sufficient to generate cortical potential evoked by STN DBS, and orthodromic activation through basal ganglia-thalamus-cortex pathways was not required. These results demonstrate the utility of cEP to determine the neural elements activated by STN DBS that might modulate cortical activity and contribute to the suppression of parkinsonian symptoms. NEW & NOTEWORTHY Subthalamic nucleus (STN) deep brain stimulation (DBS) is increasingly used to treat Parkinson’s disease (PD). Cortical potentials evoked by STN DBS in patients with PD exhibit consistent short-latency (1–3 ms), intermediate-latency (5–15 ms), and long-latency (18–25 ms) responses. The short-latency response occurs as a result of antidromic activation of the hyperdirect pathway comprising corticosubthalamic axons. However, the neural origins of intermediate- and long-latency responses remain elusive, and the dominant view is that these are produced through the orthodromic pathway (basal ganglia-thalamus-cortex). By combining in vivo electrophysiology with computational modeling, we demonstrate that antidromic activation of the cortico-thalamic-cortical pathway is sufficient to generate the intermediate- and long-latency cortical responses to STN DBS.

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.

scholarly journals Deep Brain Stimulation of the Posterior Insula in Chronic Pain: A Theoretical Framework

2021 ◽  
Vol 11 (5) ◽  
pp. 639
Author(s):  
David Bergeron ◽  
Sami Obaid ◽  
Marie-Pierre Fournier-Gosselin ◽  
Alain Bouthillier ◽  
Dang Khoa Nguyen
Keyword(s):  
Chronic Pain ◽  
Electrical Stimulation ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
High Frequency ◽  
Brain Lesion ◽  
Low Frequency ◽  
Posterior Insula ◽  
Deep Brain ◽  
Stimulation Of

Introduction: To date, clinical trials of deep brain stimulation (DBS) for refractory chronic pain have yielded unsatisfying results. Recent evidence suggests that the posterior insula may represent a promising DBS target for this indication. Methods: We present a narrative review highlighting the theoretical basis of posterior insula DBS in patients with chronic pain. Results: Neuroanatomical studies identified the posterior insula as an important cortical relay center for pain and interoception. Intracranial neuronal recordings showed that the earliest response to painful laser stimulation occurs in the posterior insula. The posterior insula is one of the only regions in the brain whose low-frequency electrical stimulation can elicit painful sensations. Most chronic pain syndromes, such as fibromyalgia, had abnormal functional connectivity of the posterior insula on functional imaging. Finally, preliminary results indicated that high-frequency electrical stimulation of the posterior insula can acutely increase pain thresholds. Conclusion: In light of the converging evidence from neuroanatomical, brain lesion, neuroimaging, and intracranial recording and stimulation as well as non-invasive stimulation studies, it appears that the insula is a critical hub for central integration and processing of painful stimuli, whose high-frequency electrical stimulation has the potential to relieve patients from the sensory and affective burden of chronic pain.

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