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Deep brain stimulation alleviates parkinsonian bradykinesia by regularizing pallidal activity.

Publication ,  Journal Article
Dorval, AD; Kuncel, AM; Birdno, MJ; Turner, DA; Grill, WM
Published in: J Neurophysiol
August 2010

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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Published In

J Neurophysiol

DOI

EISSN

1522-1598

Publication Date

August 2010

Volume

104

Issue

2

Start / End Page

911 / 921

Location

United States

Related Subject Headings

  • Thalamus
  • Parkinson Disease
  • Neurons
  • Neurology & Neurosurgery
  • Neural Pathways
  • Models, Neurological
  • Middle Aged
  • Membrane Potentials
  • Male
  • Hypokinesia
 

Citation

APA
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ICMJE
MLA
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Dorval, A. D., Kuncel, A. M., Birdno, M. J., Turner, D. A., & Grill, W. M. (2010). Deep brain stimulation alleviates parkinsonian bradykinesia by regularizing pallidal activity. J Neurophysiol, 104(2), 911–921. https://doi.org/10.1152/jn.00103.2010
Dorval, Alan D., Alexis M. Kuncel, Merrill J. Birdno, Dennis A. Turner, and Warren M. Grill. “Deep brain stimulation alleviates parkinsonian bradykinesia by regularizing pallidal activity.J Neurophysiol 104, no. 2 (August 2010): 911–21. https://doi.org/10.1152/jn.00103.2010.
Dorval AD, Kuncel AM, Birdno MJ, Turner DA, Grill WM. Deep brain stimulation alleviates parkinsonian bradykinesia by regularizing pallidal activity. J Neurophysiol. 2010 Aug;104(2):911–21.
Dorval, Alan D., et al. “Deep brain stimulation alleviates parkinsonian bradykinesia by regularizing pallidal activity.J Neurophysiol, vol. 104, no. 2, Aug. 2010, pp. 911–21. Pubmed, doi:10.1152/jn.00103.2010.
Dorval AD, Kuncel AM, Birdno MJ, Turner DA, Grill WM. Deep brain stimulation alleviates parkinsonian bradykinesia by regularizing pallidal activity. J Neurophysiol. 2010 Aug;104(2):911–921.

Published In

J Neurophysiol

DOI

EISSN

1522-1598

Publication Date

August 2010

Volume

104

Issue

2

Start / End Page

911 / 921

Location

United States

Related Subject Headings

  • Thalamus
  • Parkinson Disease
  • Neurons
  • Neurology & Neurosurgery
  • Neural Pathways
  • Models, Neurological
  • Middle Aged
  • Membrane Potentials
  • Male
  • Hypokinesia