title: Enhanced long-term potentiation-like plasticity of the trigeminal blink reflex circuit in blepharospasm.
abstract: Benign essential blepharospasm (BEB) is a focal cranial dystonia affecting eye closure. Here, we tested the hypothesis that BEB is associated with abnormal plasticity of the neuronal circuits mediating reflex blinks. In patients with BEB and healthy age-matched controls, we used the conditioning protocol introduced by Mao and Evinger (2001) to induce long-term potentiation (LTP)-like plasticity in trigeminal wide dynamic range neurons of the blink reflex circuit. High-frequency trains of electrical stimuli were repeatedly given over the right supraorbital nerve (SO) and timed to coincide with the R2 response elicited by a preceding SO stimulus. High-frequency stimulation (HFS) resulted in a long-lasting and input-specific potentiation of the R2 response in both groups, yet the facilitation of the R2 response was markedly increased in patients relative to controls. Botulinum toxin (BTX) injections in both orbicularis oculi muscles normalized the previously enhanced LTP-like plasticity of the R2 response. The increased responsiveness to HFS provides first-time evidence that LTP-like plasticity is increased in the trigeminal reflex circuit of patients affected by BEB. The results also show that the enhanced modifiability is not fixed in BEB, because BTX injections can transiently restore normal LTP-like plasticity. We propose that an abnormal corneal input induced by excessive blinking exacerbates increased LTP-like plasticity in BEB. BTX treatment removes the latter and restores plasticity toward normal values. Our results support the concept that maladaptive reorganization contributes to the pathophysiology of focal dystonias.
authors.affiliation: Department of Neurosciences, University of Messina, 98125 Messina, Italy. angelo.quartarone@unime.it
authors.forename: Angelo
authors.initials: A
authors.lastname: Quartarone
authors.forename: Antonino
authors.initials: A
authors.lastname: Sant'Angelo
authors.forename: Fortunato
authors.initials: F
authors.lastname: Battaglia
authors.forename: Sergio
authors.initials: S
authors.lastname: Bagnato
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Rizzo
authors.forename: Francesca
authors.initials: F
authors.lastname: Morgante
authors.forename: John C
authors.initials: JC
authors.lastname: Rothwell
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
authors.forename: Paolo
authors.initials: P
authors.lastname: Girlanda
mesh_terms: D000368:Aged; D001764:Blepharospasm / Q000188:drug therapy / Q000503:physiopathology*; D001767:Blinking / Q000502:physiology*; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use; D004558:Electric Stimulation; D004576:Electromyography; D005260:Female; D006801:Humans; D017774:Long-Term Potentiation; D008297:Male; D008875:Middle Aged; D009465:Neuromuscular Agents / Q000627:therapeutic use; D012021:Reflex, Abnormal / Q000502:physiology*; D014276:Trigeminal Nerve / Q000503:physiopathology*
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A