scholarly journals Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy

2011 ◽  
Vol 1 (5) ◽  
pp. e5-e5 ◽  
Author(s):  
M-L Welter ◽  
◽  
P Burbaud ◽  
S Fernandez-Vidal ◽  
E Bardinet ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Neuronal Activity ◽  
High Frequency ◽  
High Frequency Stimulation ◽  
Frequency Stimulation

Enhanced Ih Depresses Rat Entopeduncular Nucleus Neuronal Activity From High-Frequency Stimulation or Raised Ke+

2008 ◽  
Vol 99 (5) ◽  
pp. 2203-2219 ◽  
Author(s):  
D. S. Shin ◽  
P. L. Carlen
Keyword(s):  
Neuronal Activity ◽  
High Frequency ◽  
Neurological Diseases ◽  
Input Resistance ◽  
High Frequency Stimulation ◽  
Channel Activity ◽  
Entopeduncular Nucleus ◽  
Inhibitory Effects ◽  
Frequency Stimulation ◽  
Spontaneous Action

High-frequency stimulation (HFS) is used to treat a variety of neurological diseases, yet its underlying therapeutic action is not fully elucidated. Previously, we reported that HFS-induced elevation in [K+]e or bath perfusion of raised Ke+ depressed rat entopeduncular nucleus (EP) neuronal activity via an enhancement of an ionic conductance leading to marked depolarization. Herein, we show that the hyperpolarization-activated ( Ih) channel mediates the HFS- or K+-induced depression of EP neuronal activity. The perfusion of an Ih channel inhibitor, 50 μM ZD7288 or 2 mM CsCl, increased input resistance by 23.5 ± 7% (ZD7288) or 35 ± 10% (CsCl), hyperpolarized cells by 3.4 ± 1.7 mV (ZD7288) or 2.3 ± 0.9 mV (CsCl), and decreased spontaneous action potential (AP) frequency by 51.5 ± 12.5% (ZD7288) or 80 ± 13.5% (CsCl). The Ih sag was absent with either treatment, suggesting a block of Ih channel activity. Inhibition of the Ih channel prior to HFS or 6 mM K+ perfusion not only prevented the previously observed decrease in AP frequency, but increased neuronal activity. Under voltage-clamp conditions, Ih currents were enhanced in the presence of 6 mM K+. Calcium is also involved in the depression of EP neuronal activity, since its removal during raised Ke+ application prevented this attenuation and blocked the Ih sag. We conclude that the enhancement of Ih channel activity initiates the HFS- and K+-induced depression of EP neuronal activity. This mechanism could underlie the inhibitory effects of HFS used in deep brain stimulation in output basal ganglia nuclei.

Subthalamic Stimulation and Neuronal Activity in the Substantia Nigra in Parkinson's Disease

2007 ◽  
Vol 97 (6) ◽  
pp. 4017-4022 ◽  
Author(s):  
D. Maltête ◽  
N. Jodoin ◽  
C. Karachi ◽  
J. L. Houeto ◽  
S. Navarro ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Firing Rate ◽  
Neuronal Activity ◽  
High Frequency ◽  
High Frequency Stimulation ◽  
Motor Disability ◽  
Frequency Stimulation ◽  
The Mean

High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for severe forms of Parkinson's disease (PD). To study the effects of high-frequency STN stimulation on one of the main output pathways of the basal ganglia, single-unit recordings of the neuronal activity of the substantia nigra pars reticulata (SNr) were performed before, during, and after the application of STN electrical stimulation in eight PD patients. During STN stimulation at 14 Hz, no change in either the mean firing rate or the discharge pattern of SNr neurons was observed. STN stimulation at 140 Hz decreased the mean firing rate by 64% and the mean duration of bursting mode activity of SNr neurons by 70%. The SNr residual neuronal activity during 140-Hz STN stimulation was driven by the STN stimulation. How the decrease in rate and modification of firing pattern of SNr-evoked neural activity, during high-frequency STN stimulation, contribute to the improvement of parkinsonian motor disability remains to be elucidated.

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.

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