Effective Deep Brain Stimulation Suppresses Low-Frequency Network Oscillations in the Basal Ganglia by Regularizing Neural Firing Patterns
Open Access
- 7 November 2012
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 32 (45), 15657-15668
- https://doi.org/10.1523/jneurosci.2824-12.2012
Abstract
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson's disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90 Hz) improve motor symptoms, while low frequencies (<50 Hz) are either ineffective or exacerbate symptoms. The neuronal basis for these frequency-dependent effects of DBS is unclear. The effects of different frequencies of STN-DBS on behavior and single-unit neuronal activity in the basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high-frequency DBS reversed motor symptoms, and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high-frequency DBS, but not low-frequency DBS, reduced pathological low-frequency oscillations (∼9 Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low-frequency band to the stimulation frequency during high-frequency DBS, but not during low-frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high-frequency DBS is more effective than low-frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low-frequency network oscillations with a regularized pattern of neuronal firing.Keywords
This publication has 45 references indexed in Scilit:
- A quantitative comparison of basal ganglia neuronal activities of normal and Parkinson's disease model ratsNeuroscience Letters, 2011
- Relative contributions of local cell and passing fiber activation and silencing to changes in thalamic fidelity during deep brain stimulation and lesioning: a computational modeling studyJournal of Computational Neuroscience, 2011
- Subthalamic nucleus high‐frequency stimulation generates a concomitant synaptic excitation–inhibition in substantia nigra pars reticulataThe Journal of Physiology, 2011
- Dynamic Stereotypic Responses of Basal Ganglia Neurons to Subthalamic Nucleus High-Frequency Stimulation in the Parkinsonian PrimateFrontiers in Systems Neuroscience, 2011
- Network perspectives on the mechanisms of deep brain stimulationNeurobiology of Disease, 2010
- Deep Brain Stimulation Reduces Neuronal Entropy in the MPTP-Primate Model of Parkinson's DiseaseJournal of Neurophysiology, 2008
- Effects of low-frequency stimulation of the subthalamic nucleus on movement in Parkinson's diseaseExperimental Neurology, 2008
- Mechanisms of Deep Brain Stimulation in Movement Disorders as Revealed by Changes in Stimulus FrequencyNeurotherapeutics, 2008
- Impact of High-Frequency Stimulation Parameters on the Pattern of Discharge of Subthalamic NeuronsJournal of Neurophysiology, 2005
- Tremor at rest episodes in unilaterally 6-OHDA-induced substantia nigra lesioned rats: EEG-EMG and behaviorNeuropharmacology, 1986