title: Early, severe and bilateral loss of LTP and LTD-like plasticity in motor cortex (M1) in de novo Parkinson's disease.
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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Comprehensive Care Centre for Movement Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala 695 011, India. ashakishore99@gmail.com
authors.forename: Asha
authors.initials: A
authors.lastname: Kishore
authors.forename: Thomas
authors.initials: T
authors.lastname: Joseph
authors.forename: Balu
authors.initials: B
authors.lastname: Velayudhan
authors.forename: Traian
authors.initials: T
authors.lastname: Popa
authors.forename: Sabine
authors.initials: S
authors.lastname: Meunier
mesh_terms: D000328:Adult; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015259:Dopamine Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004569:Electroencephalography; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use; D016014:Linear Models; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects / Q000503:physiopathology*; D009048:Motor Skills / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology*; D012146:Rest / Q000502:physiology; D013826:Theta Rhythm / Q000502:physiology; D050781:Transcranial Magnetic Stimulation
chemical_list: D000978:Antiparkinson Agents; D015259:Dopamine Agents; D007980:Levodopa