Frequency-dependent effects of electrical stimulation in the globus pallidus of dystonia patients

2012 ◽  
Vol 108 (1) ◽  
pp. 5-17 ◽  
Author(s):  
Liu D. Liu ◽  
Ian A. Prescott ◽  
Jonathan O. Dostrovsky ◽  
Mojgan Hodaie ◽  
Andres M. Lozano ◽  
...  
Keyword(s):  
Globus Pallidus ◽  
High Frequency ◽  
Gaba Release ◽  
Neuronal Firing ◽  
High Frequency Stimulation ◽  
Low Frequencies ◽  
Clinical Benefits ◽  
Frequency Stimulation ◽  
Train Length ◽  
Additional Support

Deep brain stimulation (DBS) in the globus pallidus internus (GPi) has been shown to improve dystonia, a movement disorder of repetitive twisting movements and postures. DBS at frequencies above 60 Hz improves dystonia, but the mechanisms underlying this frequency dependence are unclear. In patients undergoing dual-microelectrode mapping of the GPi, microstimulation has been shown to reduce neuronal firing, presumably due to synaptic GABA release. This study examined the effects of different microstimulation frequencies (1–100 Hz) and train length (0.5–20 s), with and without prior high-frequency stimulation (HFS) on neuronal firing and evoked field potentials (fEPs) in 13 dystonia patients. Pre-HFS, the average firing decreased as stimulation frequency increased and was silenced above 50 Hz. The average fEP amplitudes increased up to frequencies of 20–30 Hz but then declined and at 50 Hz, were only at 75% of baseline. In some cases, short latency fiber volleys and antidromic-like spikes were observed and followed high frequencies. Post-HFS, overall firing was reduced compared with pre-HFS, and the fEP amplitudes were enhanced at low frequencies, providing evidence of inhibitory synaptic plasticity in the GPi. In a patient with DBS electrodes already implanted in the GPi, recordings from four neurons in the subthalamic nucleus showed almost complete inhibition of firing with clinically effective but not clinically ineffective stimulation parameters. These data provide additional support for the hypothesis of stimulation-evoked GABA release from afferent synaptic terminals and reduction of neuronal firing during DBS and additionally, implicate excitation of GPi axon fibers and neurons and enhancement of inhibitory synaptic transmission by high-frequency GPi DBS as additional putative mechanisms underlying the clinical benefits of DBS in dystonia.

scholarly journals Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation

2021 ◽  
Author(s):  
Leon A Steiner ◽  
Andrea A Kuehn ◽  
Joerg RP Geiger ◽  
Henrik Alle ◽  
Milos Popovic ◽  
...  
Keyword(s):  
Subthalamic Nucleus ◽  
High Frequency ◽  
Symptomatic Relief ◽  
Neuronal Firing ◽  
High Frequency Stimulation ◽  
Inhibitory Input ◽  
Frequency Specificity ◽  
Evoked Field Potentials ◽  
Frequency Stimulation ◽  
Synaptic Dynamics

Background: Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized. Objective: The objectives of this study were to (1) study local synaptic dynamics during high frequency extracellular stimulation of the subthalamic nucleus (STN), and (2) compare STN synaptic dynamics with those of the neighboring substantia nigra pars reticulata (SNr). Methods: Two microelectrodes were advanced into the STN and SNr of patients undergoing DBS surgery for PD. Neuronal firing and evoked field potentials (fEPs) were recorded with one microelectrode during stimulation from an adjacent microelectrode. Results: Excitatory and inhibitory fEPs could be discerned within the STN and their amplitudes predicted bidirectional effects on neuronal firing (p = .007). There were no differences between STN and SNr inhibitory fEP dynamics at low stimulation frequencies (p > .999). However, inhibitory neuronal responses were sustained over time in STN during high frequency stimulation, but not SNr (p < .001) where depression of inhibitory input was coupled with a return of neuronal firing (p = .003). Interpretation: Persistent inhibitory input to the STN suggests a local synaptic mechanism for the suppression of subthalamic firing during high frequency stimulation. Moreover, differences in the resiliency versus vulnerability of inhibitory inputs to the STN and SNr suggest a projection source- and frequency-specificity for this mechanism. The feasibility of targeting electrophysiologically-identified neural structures may provide insight into how DBS achieves frequency-specific modulation of neuronal projections.

scholarly journals Evoked transients of pH-sensitive fluorescent false neurotransmitter reveal dopamine hot spots in the globus pallidus

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Jozsef Meszaros ◽  
Timothy Cheung ◽  
Maya M Erler ◽  
Un Jung Kang ◽  
Dalibor Sames ◽  
...  
Keyword(s):  
Globus Pallidus ◽  
Hot Spots ◽  
High Frequency ◽  
Dopamine Release ◽  
Electrochemical Analysis ◽  
Ph Sensitive ◽  
High Frequency Stimulation ◽  
Extracellular Milieu ◽  
Frequency Stimulation ◽  
Low Levels

Dopamine neurotransmission is suspected to play important physiological roles in multiple sparsely innervated brain nuclei, but there has not been a means to measure synaptic dopamine release in such regions. The globus pallidus externa (GPe) is a major locus in the basal ganglia that displays a sparse innervation of en passant dopamine axonal fibers. Due to the low levels of innervation that preclude electrochemical analysis, it is unknown if these axons engage in neurotransmission. To address this, we introduce an optical approach using a pH-sensitive fluorescent false neurotransmitter, FFN102, that exhibits increased fluorescence upon exocytosis from the acidic synaptic vesicle to the neutral extracellular milieu. In marked contrast to the striatum, FFN102 transients in the mouse GPe were spatially heterogeneous and smaller than in striatum with the exception of sparse hot spots. GPe transients were also significantly enhanced by high frequency stimulation. Our results support hot spots of dopamine release from substantia nigra axons.

scholarly journals Effects of High-Frequency Stimulation in the Internal Globus Pallidus on the Activity of Thalamic Neurons in the Awake Monkey

2003 ◽  
Vol 89 (2) ◽  
pp. 1150-1160 ◽  
Author(s):  
Marjorie E. Anderson ◽  
Nadia Postupna ◽  
Mark Ruffo
Keyword(s):  
Globus Pallidus ◽  
High Frequency ◽  
Internal Capsule ◽  
High Frequency Stimulation ◽  
Burst Frequency ◽  
Thalamic Neurons ◽  
Internal Globus Pallidus ◽  
Current Spread ◽  
Frequency Stimulation ◽  
Similar Intensity

The reduction in symptoms of Parkinson's disease produced by high-frequency stimulation (HFS) in the internal globus pallidus (GPi) has been proposed to be due to stimulus-induced inactivation of pallidal neurons and resulting disinhibition of thalamic neurons. We tested this in awake Macaca fascicularis by stimulating between pairs of electrodes inserted into GPi under electrophysiological control and recording the responses evoked in thalamic neurons. HFS produced a reduction, not an increase, in discharge frequency during the stimulus train in 77% of the responsive thalamic neurons. Only 16% of the responsive cells showed an increase in discharge during stimulation and, for some of these, stimulation at a similar intensity produced contralateral muscle contraction, a probable sign of current spread to the internal capsule. The few thalamic neurons studied during bursting had a reduction in burst frequency and duration during HFS. We conclude that high-frequency stimulation within GPi does not necessarily facilitate thalamic discharge, and it may act, instead, to interrupt abnormal patterns of thalamic discharge associated with parkinsonian symptoms.

scholarly journals Contrasting Changes in Cortical Activation Induced by Acute High-Frequency Stimulation within the Globus Pallidus in Parkinson's Disease

2008 ◽  
Vol 29 (2) ◽  
pp. 235-243 ◽  
Author(s):  
Pierre Payoux ◽  
Philippe Remy ◽  
Malika Miloudi ◽  
Jean-Luc Houeto ◽  
Claudio Stadler ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Globus Pallidus ◽  
High Frequency ◽  
Premotor Cortex ◽  
Synaptic Activity ◽  
Cortical Activation ◽  
High Frequency Stimulation ◽  
Clinical Effects ◽  
Frequency Stimulation

Continuous stimulation of the globus pallidus (GP) has been shown to be an effective treatment for Parkinson's disease (PD). We used the fact that the implanted quadripolar leads contain electrodes within the GPi and GPe to investigate the clinical effects of acute high-frequency stimulation applied in these nuclei and changes in regional cerebral blood flow (rCBF) as an index of synaptic activity. In five patients treated by chronic GP stimulation, we compared the effects on PD symptoms and the changes in rCBF at rest and during paced right-hand movements, with and without left GPe or GPi stimulation. Although improving contralateral rigidity and akinesia, left GPe stimulation decreased rCBF in the left cerebellum and lateral premotor cortex at rest and significantly increased it in the left primary sensorimotor cortex (SM1) during movement. In contrast, left ventral GPi stimulation, which improved rigidity and worsened akinesia, decreased rCBF in the left SM1, premotor area, anterior cingulum, and supplementary motor area but did not modify the movement-related activation. GPe stimulation seems to result in a reduced activity of motor-related areas and the facilitation of motor cortex activation during movement, the latter component being absent during GPi stimulation, and this may explain the observed worsening of akinesia.

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