title: Motor co-activation in siblings of patients with juvenile myoclonic epilepsy: an imaging endophenotype?
abstract: Juvenile myoclonic epilepsy is a heritable idiopathic generalized epilepsy syndrome, characterized by myoclonic jerks and frequently triggered by cognitive effort. Impairment of frontal lobe cognitive functions has been reported in patients with juvenile myoclonic epilepsy and their unaffected siblings. In a recent functional magnetic resonance imaging study we reported abnormal co-activation of the motor cortex and increased functional connectivity between the motor system and prefrontal cognitive networks during a working memory paradigm, providing an underlying mechanism for cognitively triggered jerks. In this study, we used the same task in 15 unaffected siblings (10 female; age range 18-65 years, median 40) of 11 of those patients with juvenile myoclonic epilepsy (six female; age range 22-54 years, median 35) and compared functional magnetic resonance imaging activations with 20 age- and gender-matched healthy control subjects (12 female; age range 23-46 years, median 30.5). Unaffected siblings showed abnormal primary motor cortex and supplementary motor area co-activation with increasing cognitive load, as well as increased task-related functional connectivity between motor and prefrontal cognitive networks, with a similar pattern to patients (P < 0.001 uncorrected; 20-voxel threshold extent). This finding in unaffected siblings suggests that altered motor system activation and functional connectivity is not medication- or seizure-related, but represents a potential underlying mechanism for impairment of frontal lobe functions in both patients and siblings, and so constitutes an endophenotype of juvenile myoclonic epilepsy.
authors.affiliation: 1 Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Britta
authors.initials: B
authors.lastname: Wandschneider
authors.affiliation: 1 Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK2 Imaging and Biophysics Department, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Centeno
authors.affiliation: 1 Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK3 Department of Neurology, Ludwig-Maximilians-Universität, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Vollmar
authors.affiliation: 1 Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Symms
authors.affiliation: 1 Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Thompson
authors.affiliation: 1 Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: John S
authors.initials: JS
authors.lastname: Duncan
authors.affiliation: 1 Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK m.koepp@ucl.ac.uk.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Koepp
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D058068:Endophenotypes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism*; D020190:Myoclonic Epilepsy, Juvenile / Q000175:diagnosis* / Q000378:metabolism* / Q000523:psychology; D009483:Neuropsychological Tests; D010775:Photic Stimulation / Q000379:methods; D011597:Psychomotor Performance / Q000502:physiology*; D035781:Siblings / Q000523:psychology; D055815:Young Adult
keywords: endophenotype; functional magnetic resonance imaging; genetic; juvenile myoclonic epilepsy; motor system