Deep Brain Stimulation Alleviates Parkinsonian Bradykinesia by Regularizing Pallidal Activity
- 1 August 2010
- journal article
- clinical trial
- Published by American Physiological Society in Journal of Neurophysiology
- Vol. 104 (2), 911-921
- https://doi.org/10.1152/jn.00103.2010
Abstract
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.Keywords
This publication has 49 references indexed in Scilit:
- Tremor varies as a function of the temporal regularity of deep brain stimulationNeuroReport, 2008
- Mechanisms of Deep Brain Stimulation in Movement Disorders as Revealed by Changes in Stimulus FrequencyNeurotherapeutics, 2008
- Pulse-to-Pulse Changes in the Frequency of Deep Brain Stimulation Affect Tremor and Modeled Neuronal ActivityJournal of Neurophysiology, 2007
- Selective Attenuation of Afferent Synaptic Transmission as a Mechanism of Thalamic Deep Brain Stimulation-Induced Tremor ArrestJournal of Neuroscience, 2006
- Effects of stimulation of the subthalamic area on oscillatory pallidal activity in Parkinson's diseaseExperimental Neurology, 2004
- Complex Locking Rather Than Complete Cessation of Neuronal Activity in the Globus Pallidus of a 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Primate in Response to Pallidal MicrostimulationJournal of Neuroscience, 2004
- Effects of High-Frequency Stimulation in the Internal Globus Pallidus on the Activity of Thalamic Neurons in the Awake MonkeyJournal of Neurophysiology, 2003
- High-Frequency Stimulation Produces a Transient Blockade of Voltage-Gated Currents in Subthalamic NeuronsJournal of Neurophysiology, 2001
- High frequency stimulation of the internal Globus Pallidus (GPi) simultaneously improves parkinsonian symptoms and reduces the firing frequency of GPi neurons in the MPTP-treated monkeyNeuroscience Letters, 1996
- The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonismJournal of Neurophysiology, 1994