title: Altered thalamocortical functional connectivity in idiopathic generalized epilepsy.
abstract: OBJECTIVE
  Aberrant thalamocortical network has been hypothesized to play a crucial role in the fundamental pathogenesis underlying idiopathic generalized epilepsy (IGE). We aimed to investigate alterations of thalamocortical functional network in patients with IGE using thalamic seed-based functional connectivity (FC) analysis, and their relationships with frontal cognitive functions and clinical characteristics.
  
  
  METHODS
  Forty-nine IGE patients (31 with juvenile myoclonic epilepsy, 17 with IGE with generalized tonic-clonic seizures only, one with juvenile absence epilepsy) and 42 control subjects were prospectively recruited. Voxel-based morphometry (VBM) was first performed to detect thalamic region of gray matter (GM) reduction in patients compared to controls. Between-group comparison of thalamocortical FC was then carried out using resting-state functional magnetic resonance imaging (MRI) analysis seeding at thalamic region of volume difference. In addition, thalamocortical FC was correlated with frontal cognitive performance and clinical variables.
  
  
  RESULTS
  Neuropsychological assessment revealed that patients with IGE had poorer performance than controls on most of the frontal cognitive functions. VBM detected a reduction in GM in the anteromedial thalamus in patients relative to controls. FC analysis seeding at the anteromedial thalamus revealed a reduction of thalamocortical FC in the bilateral medial prefrontal cortex and precuneus/posterior cingulate cortex in patients with IGE compared to controls. Thalamocortical FC strength of bilateral medial prefrontal cortex correlated negatively with disease duration, but did not correlate with seizure frequency or frontal cognitive functions in patients with IGE.
  
  
  CONCLUSIONS
  Our results indicate that IGE is associated with decreased thalamocortical FC between anteromedial thalamus and medial prefrontal cortex and precuneus/posterior cingulate cortex. Our finding of greater reduction of medial prefrontal FC in relation to increasing disease duration suggests that thalamoprefrontal network abnormality, the proposed pathophysiologic mechanism underlying IGE, may be the consequence of the long-standing burden of the disease.
authors.affiliation: Department of Neurology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Jung Bin
authors.initials: JB
authors.lastname: Kim
authors.forename: Sang-Il
authors.initials: SI
authors.lastname: Suh
authors.forename: Woo-Keun
authors.initials: WK
authors.lastname: Seo
authors.forename: Kyungmi
authors.initials: K
authors.lastname: Oh
authors.forename: Seong-Beom
authors.initials: SB
authors.lastname: Koh
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D003430:Cross-Sectional Studies; D004829:Epilepsy, Generalized / Q000175:diagnosis* / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009434:Neural Pathways / Q000473:pathology / Q000502:physiology; D011446:Prospective Studies; D013788:Thalamus / Q000473:pathology* / Q000502:physiology*; D055815:Young Adult
keywords: Frontal cognitive dysfunction; Idiopathic generalized epilepsy; Resting-state functional connectivity; Thalamocortical network