Early, severe and bilateral loss of LTP and LTD-like plasticity in motor cortex (M1) in de novo Parkinson's disease

Clin Neurophysiol. 2012 Apr;123(4):822-8. doi: 10.1016/j.clinph.2011.06.034. Epub 2011 Sep 23.

Abstract

Objective: To test the plasticity of bilateral motor cortices (M1) in treatment-naïve (de novo) Parkinson's disease (PD) patients and its response to single dose of L-DOPA.

Methods: Twenty-one de novo PD patients with only unilateral motor symptoms were recruited to eliminate the effects of advanced disease and chronic treatment and were tested with intermittent (n=10) and continuous theta burst stimulation (iTBS and cTBS) (n=11) protocols to induce LTP and LTD-like plasticity on both M1 cortices. They were compared with two groups of 10 each, age-matched, healthy volunteers (HV). Severity of motor signs and effectiveness of TBS were measured bilaterally in the untreated state and after a uniform dose of L-DOPA in all patients.

Results: iTBS and cTBS induced significant LTP and LTD- like plasticity in M1 of HV. In de novo patients, there was no plasticity in both M1. Acute L-DOPA challenge did not improve plasticity in either M1 cortices, though motor signs of PD improved. There was no correlation of motor signs with M1 plasticity.

Conclusion: The early, severe and bilateral loss of plasticity in M1 in de novo PD patients is a primary disease-related cortical dysfunction. The contrasting L-DOPA response of motor signs and M1 plasticity could arise from differences in neural circuits mediating them or differing effects of acute dopamine replacement on circuits recruited by specific plasticity-induction techniques, particularly in treatment naïve PD.

Significance: M1 plasticity defect occurs early in PD and might affect motor learning. Acute vs. chronic dopamine replacement could have different effects on plasticity in PD or in the networks recruited by a specific plasticity induction technique.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / therapeutic use
  • Dopamine Agents / administration & dosage
  • Dopamine Agents / therapeutic use
  • Electroencephalography
  • Evoked Potentials, Motor / physiology
  • Female
  • Functional Laterality / physiology
  • Humans
  • Levodopa / administration & dosage
  • Levodopa / therapeutic use
  • Linear Models
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Male
  • Middle Aged
  • Motor Cortex / drug effects
  • Motor Cortex / physiopathology*
  • Motor Skills / physiology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Parkinson Disease / drug therapy
  • Parkinson Disease / physiopathology*
  • Rest / physiology
  • Theta Rhythm / physiology
  • Transcranial Magnetic Stimulation

Substances

  • Antiparkinson Agents
  • Dopamine Agents
  • Levodopa