Relationship between oscillatory activity in the cortico-basal ganglia network and parkinsonism in MPTP-treated monkeys

Neurobiol Dis. 2014 Aug;68:156-66. doi: 10.1016/j.nbd.2014.04.004. Epub 2014 Apr 21.

Abstract

Parkinsonism is associated with changes in oscillatory activity patterns and increased synchronization of neurons in the basal ganglia and cortex in patients and animal models of Parkinson's disease, but the relationship between these changes and the severity of parkinsonian signs remains unclear. We examined this relationship by studying changes in local field potentials (LFPs) in the internal pallidal segment (GPi) and the subthalamic nucleus (STN), and in encephalographic signals (EEG) from the primary motor cortex (M1) in Rhesus monkeys which were rendered progressively parkinsonian by repeated systemic injections of small doses of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Observations during wakefulness and sleep (defined by EEG and video records) were analyzed separately. The severity of parkinsonism correlated with increases in spectral power at frequencies below 15.5Hz in M1 and GPi and reductions in spectral power at frequencies above 15.6Hz with little change in STN. The severity of parkinsonism also correlated with increases in the coherence between M1 EEG and basal ganglia LFPs in the low frequency band. Levodopa treatment reduced low-frequency activity and increased high-frequency activity in all three areas, but did not affect coherence. The state of arousal also affected LFP and EEG signals in all three structures, particularly in the STN. These results suggest that parkinsonism-associated changes in alpha and low-beta band oscillatory activity can be detected early in the parkinsonian state in M1 and GPi. Interestingly, oscillations detectable in STN LFP signals (including oscillations in the beta-band) do not appear to correlate strongly with the severity of mild-to-moderate parkinsonism in these animals. Levodopa-induced changes in oscillatory M1 EEG and basal ganglia LFP patterns do not necessarily represent a normalization of abnormalities caused by dopamine depletion.

Keywords: Basal ganglia; Local field potential; Motor cortex; Parkinson's disease; Sleep; Wakefulness.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Antiparkinson Agents / pharmacology
  • Antiparkinson Agents / therapeutic use
  • Basal Ganglia / pathology
  • Basal Ganglia / physiopathology*
  • Brain Waves / drug effects
  • Brain Waves / physiology*
  • Disease Models, Animal
  • Electroencephalography
  • Fourier Analysis
  • Globus Pallidus / physiopathology
  • Levodopa / pharmacology
  • Levodopa / therapeutic use
  • MPTP Poisoning / drug therapy
  • MPTP Poisoning / pathology*
  • Macaca mulatta
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Motor Cortex / physiopathology*
  • Neural Pathways / physiopathology*
  • Physical Stimulation
  • Sleep / physiology
  • Subthalamic Nucleus / physiopathology
  • Time Factors
  • Wakefulness / physiology

Substances

  • Antiparkinson Agents
  • Levodopa