title: Impaired intracortical transmission in G2019S leucine rich-repeat kinase Parkinson patients.
abstract: A mutation in leucine-rich repeat kinase 2 is the most common cause of hereditary Parkinson's disease (PD), yet the neural mechanisms and the circuitry potentially involved are poorly understood.
  
  
  
  We used different transcranial magnetic stimulation protocols to explore in the primary motor cortex the activity of intracortical circuits and cortical plasticity (long-term potentiation) in patients with the G2019S leucine-rich repeat kinase 2 gene mutation when compared with idiopathic PD patients and age-matched healthy subjects. Paired pulse transcranial magnetic stimulation was used to investigate short intracortical inhibition and facilitation and short afferent inhibition. Intermittent theta burst stimulation, a form of repetitive transcranial magnetic stimulation, was used to test long-term potentiation-like cortical plasticity. Leucine-rich repeat kinase 2 and idiopathic PD were tested both in ON and in OFF l-dopa therapy.
  
  
  
  When compared with idiopathic PD and healthy subjects, leucine-rich repeat kinase 2 PD patients showed a remarkable reduction of short intracortical inhibition in both ON and in OFF l-dopa therapy. This reduction was paralleled by an increase of intracortical facilitation in OFF l-dopa therapy. Leucine-rich repeat kinase 2 PD showed abnormal long-term potentiation-like cortical plasticity in ON l-dopa therapy.
  
  
  
  The motor cortex in leucine-rich repeat kinase 2 mutated PD patients is strongly disinhibited and hyperexcitable. These abnormalities could be a result of an impairment of inhibitory (gamma-Aminobutyric acid) transmission eventually related to altered neurotransmitter release. © 2017 International Parkinson and Movement Disorder Society.
authors.affiliation: Non-Invasive Brain Stimulation Unit, Neurologia Clinica e Comportamentale, Fondazione Santa Lucia, Rome, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Ponzo
authors.affiliation: Non-Invasive Brain Stimulation Unit, Neurologia Clinica e Comportamentale, Fondazione Santa Lucia, Rome, Italy.|Tor Vergata University, Department of Systems Medicine, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Lorenzo
authors.affiliation: Neurology Unit, Ospedale Sant'Eugenio, Rome, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Brusa
authors.affiliation: Non-Invasive Brain Stimulation Unit, Neurologia Clinica e Comportamentale, Fondazione Santa Lucia, Rome, Italy.|Tor Vergata University, Department of Systems Medicine, Rome, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Schirinzi
authors.affiliation: Department of Medical, Surgical and Neurological Science, University of Siena, Siena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Battistini
authors.affiliation: Department of Medical, Surgical and Neurological Science, University of Siena, Siena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ricci
authors.affiliation: Laboratory of Neuroimmunology Fondazione Santa Lucia, Rome, Italy.
authors.forename: Manolo
authors.initials: M
authors.lastname: Sambucci
authors.affiliation: Non-Invasive Brain Stimulation Unit, Neurologia Clinica e Comportamentale, Fondazione Santa Lucia, Rome, Italy.|Tor Vergata University, Department of Systems Medicine, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: Non-Invasive Brain Stimulation Unit, Neurologia Clinica e Comportamentale, Fondazione Santa Lucia, Rome, Italy.|Stroke Unit, Department of Neuroscience, Policlinico Tor Vergata, Rome, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Koch
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics; D007980:Levodopa / Q000627:therapeutic use; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009435:Synaptic Transmission; D050781:Transcranial Magnetic Stimulation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D005680:gamma-Aminobutyric Acid; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: LRRK2; Parkinson disease; TMS; cortical plasticity; levodopa