title: Bilateral cerebellar activation in unilaterally challenged essential tremor.
abstract: BACKGROUND
  Essential tremor (ET) is one of the most common hyperkinetic movement disorders. Previous research into the pathophysiology of ET suggested underlying cerebellar abnormalities.
  
  
  OBJECTIVE
  In this study, we added electromyography as an index of tremor intensity to functional Magnetic Resonance Imaging (EMG-fMRI) to study a group of ET patients selected according to strict criteria to achieve maximal homogeneity. With this approach we expected to improve upon the localization of the bilateral cerebellar abnormalities found in earlier fMRI studies.
  
  
  METHODS
  We included 21 propranolol sensitive patients, who were not using other tremor medication, with a definite diagnosis of ET defined by the Tremor Investigation Group. Simultaneous EMG-fMRI recordings were performed while patients were off tremor medication. Patients performed unilateral right hand and arm extension, inducing tremor, alternated with relaxation (rest). Twenty-one healthy, age- and sex-matched participants mimicked tremor during right arm extension. EMG power variability at the individual tremor frequency as a measure of tremor intensity variability was used as a regressor, mathematically independent of the block regressor, in the general linear model used for fMRI analysis, to find specific tremor-related activations.
  
  
  RESULTS
  Block-related activations were found in the classical upper-limb motor network, both for ET patients and healthy participants in motor, premotor and supplementary motor areas. In ET patients, we found tremor-related activations bilaterally in the cerebellum: in left lobules V, VI, VIIb and IX and in right lobules V, VI, VIIIa and b, and in the brainstem. In healthy controls we found simulated tremor-related activations in right cerebellar lobule V.
  
  
  CONCLUSIONS
  Our results expand on previous findings of bilateral cerebellar involvement in ET. We have identified specific areas in the bilateral somatomotor regions of the cerebellum: lobules V, VI and VIII.
authors.affiliation: Department of Neurology, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands; Neuroimaging Center, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands. Electronic address: m.broersma@umcg.nl.
authors.forename: Marja
authors.initials: M
authors.lastname: Broersma
authors.affiliation: Department of Neurology, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands; Neuroimaging Center, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands. Electronic address: a.m.m.van.der.stouwe@umcg.nl.
authors.forename: Anna M M
authors.initials: AMM
authors.lastname: van der Stouwe
authors.affiliation: Department of Neurology and Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, the Netherlands; Brain Imaging Center, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, the Netherlands. Electronic address: a.w.buijink@amc.uva.nl.
authors.forename: Arthur W G
authors.initials: AWG
authors.lastname: Buijink
authors.affiliation: Department of Neurology, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands; Neuroimaging Center, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands. Electronic address: b.m.de.jong@umcg.nl.
authors.forename: Bauke M
authors.initials: BM
authors.lastname: de Jong
authors.affiliation: Brain Imaging Center, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, the Netherlands; Department of Radiology, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, the Netherlands. Electronic address: p.f.c.groot@amc.uva.nl.
authors.forename: Paul F C
authors.initials: PFC
authors.lastname: Groot
authors.affiliation: Department of Neurology and Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, the Netherlands. Electronic address: j.d.speelman@gmail.com.
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Speelman
authors.affiliation: Department of Neurology, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands; Neuroimaging Center, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands. Electronic address: m.a.j.de.koning-tijssen@umcg.nl.
authors.forename: Marina A J
authors.initials: MAJ
authors.lastname: Tijssen
authors.affiliation: Department of Neurology and Clinical Neurophysiology, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, the Netherlands; Brain Imaging Center, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, the Netherlands. Electronic address: a.f.vanrootselaar@amc.uva.nl.
authors.forename: Anne-Fleur
authors.initials: AF
authors.lastname: van Rootselaar
authors.affiliation: Department of Neurology, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands; Neuroimaging Center, University Medical Center Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands. Electronic address: n.m.maurits@umcg.nl.
authors.forename: Natasha M
authors.initials: NM
authors.lastname: Maurits
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001931:Brain Mapping / Q000379:methods; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology*; D004576:Electromyography; D020329:Essential Tremor / Q000175:diagnosis* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D055815:Young Adult
keywords: Cerebellum; EMG; Essential tremor; FMRI