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Motor hyperactivation during cognitive tasks: An endophenotype of juvenile myoclonic epilepsy
Author(s) -
Caciagli Lorenzo,
Wandschneider Britta,
Centeno Maria,
Vollmar Christian,
Vos Sjoerd B.,
Trimmel Karin,
Long Lili,
Xiao Fenglai,
Lowe Alexander J.,
Sidhu Meneka K.,
Thompson Pamela J.,
Winston Gavin P.,
Duncan John S.,
Koepp Matthias J.
Publication year - 2020
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.16575
Subject(s) - endophenotype , juvenile myoclonic epilepsy , psychology , neuroscience , functional magnetic resonance imaging , cognition , epilepsy , idiopathic generalized epilepsy , audiology , epilepsy syndromes , medicine
Objective Juvenile myoclonic epilepsy (JME) is the most common genetic generalized epilepsy syndrome. Myoclonus may relate to motor system hyperexcitability and can be provoked by cognitive activities. To aid genetic mapping in complex neuropsychiatric disorders, recent research has utilized imaging intermediate phenotypes (endophenotypes). Here, we aimed to (a) characterize activation profiles of the motor system during different cognitive tasks in patients with JME and their unaffected siblings, and (b) validate those as endophenotypes of JME. Methods This prospective cross‐sectional investigation included 32 patients with JME, 12 unaffected siblings, and 26 controls, comparable for age, sex, handedness, language laterality, neuropsychological performance, and anxiety and depression scores. We investigated patterns of motor system activation during episodic memory encoding and verb generation functional magnetic resonance imaging (fMRI) tasks. Results During both tasks, patients and unaffected siblings showed increased activation of motor system areas compared to controls. Effects were more prominent during memory encoding, which entailed hand motion via joystick responses. Subgroup analyses identified stronger activation of the motor cortex in JME patients with ongoing seizures compared to seizure‐free patients. Receiver‐operating characteristic curves, based on measures of motor activation, accurately discriminated both patients with JME and their siblings from healthy controls (area under the curve: 0.75 and 0.77, for JME and a combined patient‐sibling group against controls, respectively; P < .005). Significance Motor system hyperactivation represents a cognitive, domain‐independent endophenotype of JME. We propose measures of motor system activation as quantitative traits for future genetic imaging studies in this syndrome.