title: Short-latency afferent inhibition in patients with Parkinson's disease and freezing of gait.
abstract: Freezing of gait (FOG) is one of the most common gait disturbances in patients with Parkinson's disease (PD). Recently, a PET study has documented that PD patients with FOG display cholinergic deficits selectively driven by nucleus basalis of Meynert (nbM)-neocortical denervation and not by peduncolopontine nucleus (PPN)-thalamic degeneration. Short-latency afferent inhibition (SAI) is a neurophysiological technique that allows evaluating major cholinergic sources in the central nervous system in vivo. We sought to determine whether central cholinergic circuits, evaluated by means of SAI testing, are impaired in patients with PD with FOG (FOG+) as compared to those without (FOG-). SAI and neuropsychological data were collected in 14 FOG+ and 10 FOG-. SAI was also performed in 11 healthy control subjects. Demographic, clinical, and cognitive data were compared by using non-parametric tests. Parametric tests were used to compare electrophysiological results among groups. FOG+ and FOG- had similar SAI without significant differences with controls (p = 0.207). None of the PD patients had SAI values outside the normal range (>72 %). FOG+ presented poorer executive and visuospatial performances as compared to FOG-. Despite the presence of cognitive deficits, SAI failed to detect any significant decrease of cholinergic activity in FOG+. However, nbM-related cholinergic dysfunction cannot be ruled out. In fact, integrity or even increased activation of PPN-related cholinergic circuits may mask an eventual nbM dysfunction thus resulting in normal SAI findings. Indeed, selective PPN cholinergic neurons sparing maybe a distinctive features of FOG. Alternatively or complementary, FOG pathophysiology is underpinned by non-cholinergic neurotransmitters dysfunction.
authors.affiliation: Department of Medicine and Surgery, Center for Neurodegenerative Diseases (CEMAND), University of Salerno, 84131, Salerno, Italy. maripici@libero.it.|Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital and Division of Neurology, University of Toronto, Toronto, ON, Canada. maripici@libero.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Picillo
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy. rafdubbioso@gmail.com.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Dubbioso
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy. rosaiodice@libero.it.
authors.forename: Rosa
authors.initials: R
authors.lastname: Iodice
authors.affiliation: Neurological and Stroke Unit, CTO Hospital, AORN Ospedale dei Colli, Naples, Italy. aleiavarone@libero.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Iavarone
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy. chiara.pisciotta@gmail.com.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pisciotta
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy. ema.spina@libero.it.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Spina
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy. lusantor@unina.it.
authors.forename: Lucio
authors.initials: L
authors.lastname: Santoro
authors.affiliation: Department of Medicine and Surgery, Center for Neurodegenerative Diseases (CEMAND), University of Salerno, 84131, Salerno, Italy. pbarone@unisa.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Barone
authors.affiliation: Department of Medicine and Surgery, Center for Neurodegenerative Diseases (CEMAND), University of Salerno, 84131, Salerno, Italy. marianna.amboni@libero.it.|IDC Hermitage-Capodimonte, Naples, Italy. marianna.amboni@libero.it.
authors.forename: Marianna
authors.initials: M
authors.lastname: Amboni
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, University Federico II of Naples, Via Sergio Pansini, 5, 80131, Naples, Italy. fiore.manganelli@unina.it.
authors.forename: Fiore
authors.initials: F
authors.lastname: Manganelli
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology*; D000368:Aged; D004558:Electric Stimulation / Q000379:methods; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D005385:Fingers / Q000503:physiopathology; D005684:Gait / Q000502:physiology*; D020233:Gait Disorders, Neurologic / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000503:physiopathology* / Q000523:psychology; D013003:Somatosensory Cortex / Q000503:physiopathology; D013995:Time; D050781:Transcranial Magnetic Stimulation / Q000379:methods
keywords: Cholinergic activity; Cognition; Freezing; Gait; PPN; Parkinson's disease; SAI; TMS