title: Cerebellum-dependent associative learning deficits in primary dystonia are normalized by rTMS and practice.
abstract: Eyeblink classical conditioning (EBCC) is a cerebellum-dependent paradigm of associative motor learning, and abnormal EBCC is a neurophysiological indicator of cerebellar dysfunction. We have previously demonstrated impaired EBCC in patients with primary dystonia, but it remains uncertain if this represents actual cerebellar pathology or reflects a functional cerebellar disruption. We examined this further by: (1) studying acquisition and retention of EBCC in a second session in eight patients with cervical dystonia (CD) who had a first session 7-10 days earlier; and (2) by investigating the potential of continuous theta burst stimulation (cTBS) over the right cerebellar hemisphere to modify a first-ever EBCC session in 11 patients with CD. EBCC data of eight healthy controls previously studied were used for additional between-group comparisons. We observed an improvement of EBCC in a second session in patients with CD, which is in contrast to patients with proven cerebellar pathology who do not show further improvement of EBCC in additional sessions. We also found that cerebellar cTBS paradoxically normalized EBCC in patients with CD, while we previously showed that it disrupts EBCC in healthy volunteers. Combined, these two experiments are in keeping with a functional and reversible disruption of the cerebellum in dystonia, a phenomenon that is probably secondary to either cerebellar compensation or to cerebellar recruitment in the abnormal sensorimotor network.
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, UCL, Queen Square, London WC1N 3BG, UK.
authors.forename: B S
authors.initials: BS
authors.lastname: Hoffland
authors.forename: P
authors.initials: P
authors.lastname: Kassavetis
authors.forename: M
authors.initials: M
authors.lastname: Bologna
authors.forename: J T H
authors.initials: JT
authors.lastname: Teo
authors.forename: K P
authors.initials: KP
authors.lastname: Bhatia
authors.forename: J C
authors.initials: JC
authors.lastname: Rothwell
authors.forename: M J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: B P
authors.initials: BP
authors.lastname: van de Warrenburg
mesh_terms: D000368:Aged; D001245:Association Learning; D001767:Blinking; D016022:Case-Control Studies; D002531:Cerebellum / Q000503:physiopathology*; D003214:Conditioning, Classical; D004421:Dystonia / Q000151:congenital; D005260:Female; D006801:Humans; D007859:Learning Disabilities / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013826:Theta Rhythm; D014103:Torticollis / Q000151:congenital* / Q000175:diagnosis / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation
keywords: cerebellum; dystonia; eyeblink classical conditioning; theta burst stimulation