Spatio-temporal dynamics of cortical drive to human subthalamic nucleus neurons in Parkinson's disease

Neurobiol Dis. 2018 Apr:112:49-62. doi: 10.1016/j.nbd.2018.01.001. Epub 2018 Jan 4.

Abstract

Pathological synchronisation of beta frequency (12-35Hz) oscillations between the subthalamic nucleus (STN) and cerebral cortex is thought to contribute to motor impairment in Parkinson's disease (PD). For this cortico-subthalamic oscillatory drive to be mechanistically important, it must influence the firing of STN neurons and, consequently, their downstream targets. Here, we examined the dynamics of synchronisation between STN LFPs and units with multiple cortical areas, measured using frontal ECoG, midline EEG and lateral EEG, during rest and movement. STN neurons lagged cortical signals recorded over midline (over premotor cortices) and frontal (over prefrontal cortices) with stable time delays, consistent with strong corticosubthalamic drive, and many neurons maintained these dynamics during movement. In contrast, most STN neurons desynchronised from lateral EEG signals (over primary motor cortices) during movement and those that did not had altered phase relations to the cortical signals. The strength of synchronisation between STN units and midline EEG in the high beta range (25-35Hz) correlated positively with the severity of akinetic-rigid motor symptoms across patients. Together, these results suggest that sustained synchronisation of STN neurons to premotor-cortical beta oscillations play an important role in disrupting the normal coding of movement in PD.

Keywords: Beta oscillations; Motor cortex; Neuronal synchronisation; Parkinson's disease; Subthalamic nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Beta Rhythm / drug effects
  • Beta Rhythm / physiology*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Deep Brain Stimulation / methods
  • Dopamine Agonists / pharmacology
  • Dopamine Agonists / therapeutic use
  • Electroencephalography / drug effects
  • Electroencephalography / methods
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurons / drug effects
  • Neurons / physiology*
  • Parkinson Disease / physiopathology*
  • Parkinson Disease / therapy
  • Subthalamic Nucleus / drug effects
  • Subthalamic Nucleus / physiology*
  • Time Factors

Substances

  • Dopamine Agonists