title: Impaired consciousness in patients with absence seizures investigated by functional MRI, EEG, and behavioural measures: a cross-sectional study.
abstract: BACKGROUND
  The neural underpinnings of impaired consciousness and of the variable severity of behavioural deficits from one absence seizure to the next are not well understood. We aimed to measure functional MRI (fMRI) and electroencephalography (EEG) changes in absence seizures with impaired task performance compared with seizures in which performance was spared.
  
  
  METHODS
  In this cross-sectional study done at the Yale School of Medicine, CT, USA, we recruited patients from 59 paediatric neurology practices in the USA. We did simultaneous EEG, fMRI, and behavioural testing in patients aged 6-19 years with childhood or juvenile absence epilepsy, and with an EEG with typical 3-4 Hz bilateral spike-wave discharges and normal background. The main outcomes were fMRI and EEG amplitudes in seizures with impaired versus spared behavioural responses analysed by t test. We also examined the timing of fMRI and EEG changes in seizures with impaired behavioural responses compared with seizures with spared responses.
  
  
  RESULTS
  93 patients were enrolled between Jan 1, 2005, and Sept 1, 2013; we recorded 1032 seizures in 39 patients. fMRI changes during seizures occurred sequentially in three functional brain networks. In the default mode network, fMRI amplitude was 0·57% (SD 0·26) for seizures with impaired and 0·40% (0·16) for seizures with spared behavioural responses (mean difference 0·17%, 95% CI 0·11-0·23; p<0·0001). In the task-positive network, fMRI amplitude was 0·53% (SD 0·29) for seizures with impaired and 0·39% (0·15) for seizures with spared behavioral responses (mean difference 0·14%, 95% CI 0·08-0·21; p<0·0001). In the sensorimotor-thalamic network, fMRI amplitude was 0·41% (0·25) for seizures with impaired and 0·34% (0·14) for seizures with spared behavioural responses (mean difference 0·07%, 95% CI 0·01-0·13; p=0·02). Mean fractional EEG power in the frontal leads was 50·4 (SD 15·2) for seizures with impaired and 24·8 (6·5) for seizures with spared behavioural responses (mean difference 25·6, 95% CI 21·0-30·3); middle leads 35·4 (6·5) for seizures with impaired, 13·3 (3·4) for seizures with spared behavioural responses (mean difference 22·1, 95% CI 20·0-24·1); posterior leads 41·6 (5·3) for seizures with impaired, 24·6 (8·6) for seizures with spared behavioural responses (mean difference 17·0, 95% CI 14·4-19·7); p<0·0001 for all comparisons. Mean seizure duration was longer for seizures with impaired behaviour at 7·9 s (SD 6·6), compared with 3·8 s (3·0) for seizures with spared behaviour (mean difference 4·1 s, 95% CI 3·0-5·3; p<0·0001). However, larger amplitude fMRI and EEG signals occurred at the outset or even preceding seizures with behavioural impairment.
  
  
  CONCLUSIONS
  Impaired consciousness in absence seizures is related to the intensity of physiological changes in established networks affecting widespread regions of the brain. Increased EEG and fMRI amplitude occurs at the onset of seizures associated with behavioural impairment. These finding suggest that a vulnerable state might exist at the initiation of some absence seizures leading them to have more severe physiological changes and altered consciousness than other absence seizures.
  
  
  BACKGROUND
  National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Science, the Loughridge Williams Foundation, and the Betsy and Jonathan Blattmachr Family.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Guo
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Kim
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Michiro
authors.initials: M
authors.lastname: Negishi
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Jhun
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Jun Hwan
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Feeney
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Rodriguez-Fernandez
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Hetal
authors.initials: H
authors.lastname: Mistry
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Crunelli
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Crowley
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Mayes
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Constable
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA. Electronic address: hal.blumenfeld@yale.edu.
authors.forename: Hal
authors.initials: H
authors.lastname: Blumenfeld
mesh_terms: D000293:Adolescent; D002648:Child; D003244:Consciousness Disorders / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000502:physiology*; D055815:Young Adult