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Link to original content: https://pubmed.ncbi.nlm.nih.gov/27839650
Impaired consciousness in patients with absence seizures investigated by functional MRI, EEG, and behavioural measures: a cross-sectional study - PubMed Skip to main page content
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. 2016 Dec;15(13):1336-1345.
doi: 10.1016/S1474-4422(16)30295-2.

Impaired consciousness in patients with absence seizures investigated by functional MRI, EEG, and behavioural measures: a cross-sectional study

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Impaired consciousness in patients with absence seizures investigated by functional MRI, EEG, and behavioural measures: a cross-sectional study

Jennifer N Guo et al. Lancet Neurol. 2016 Dec.

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.

Findings: 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.

Interpretation: 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.

Funding: 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.

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Figures

Figure 1
Figure 1. Study profile
Patients were screened for eligibility by telephone (see Methods). Eligible patients underwent EEG-fMRI or high-density EEG without fMRI to obtain data during seizures.
Figure 2
Figure 2
Behavioral performance on two tasks during seizures. (A) Timecourse of behavioural performance on the repetitive tapping task (RTT) and continuous performance task (CPT). Gray indicates seizure periods, normalized to mean seizure duration (8 seconds). Data are plotted in two-second time bins, and dotted lines indicate standard error of the mean (SEM) for each bin. (B) Bimodal distribution of task performance (% targets with correct response) for individual seizures with the two tasks.
Figure 3
Figure 3
Sequential involvement of known large-scale networks during seizures. (A) Axial brain slices with parcellation of functional MRI activity into three distinct networks during seizures using k-means clustering. These networks encompass the default-mode network (DMN), task-positive network (TPN), and primary sensorimotor-thalamic network (SMT). (B) The three networks on whole brain surface renderings. (C) Distinct timecourses of fMRI signals for each of the three networks as a percent change of total signal (0 s = seizure onset). n = 810 seizures in 34 patients. Anterior insula/frontal operculum (AI/FO); Ventral medial prefrontal cortex (vmPFC); Inferior parietal lobule (IPL); Supplementary motor area (SMA).
Figure 4
Figure 4
Larger fMRI signals in all three networks during seizures with impaired task performance. (A-C) Axial brain t-maps with fMRI signals for seizures with spared performance in the default-mode network (A, DMN), task-positive network (B, TPN), and primary sensorimotor-thalamic network (C, SMT). (D-F) Corresponding t-maps for seizures with impaired performance. Hot colors indicate brain regions with significant fMRI changes in the same direction as the network-specific HRFs. Cool colors indicate changes in the opposite direction. (G) Mean fMRI percent change across seizures in each network. n = 93 spared seizures in 17 patients, and 112 impaired seizures in 22 patients.
Figure 5
Figure 5
Greater EEG amplitude in widespread brain regions during seizures with impaired task performance. (A-B) Head maps of 256 channel high-density EEG power in the 2·5-4 Hz frequency range, representing the wave components of spike-wave discharges for seizures with spared (A) or impaired (B) task performance. (C) Mean fractional EEG power in the 2·5-4 Hz frequency range for seizures with spared versus impaired performance. (D-E) Maps of EEG power in the 10-125 Hz frequency range (spike components of spike-wave discharges) for spared (D) and impaired (E) seizures. (F) Mean fractional EEG power in the 10-125 Hz frequency range for seizures with spared versus impaired performance. Color scale bars are EEG power during seizures divided by baseline power prior to seizures (fractional power). The top color bar is for panels (A) and (B), and bottom bar is for (D) and (E). Regions used for analysis in (C) and (F) (Frontal, Middle, Posterior) are shown by yellow dashed lines in (A). * p < 0·0001. Error bars are SEM. n = 30 spared seizures in 5 patients, and 26 impaired seizures in 8 patients.
Figure 6
Figure 6
Greater fMRI and EEG amplitude from the outset or preceding seizures with impaired behavior. (A-C) Timecourse of percent fMRI signal changes in the default mode (A), task positive (B), and sensorimotor-thalamic (C) networks for seizures with spared (green) and impaired (purple) task performance. (D-E) Timecourse of EEG amplitude fractional change (seizure divided by baseline) over time for low (2·5-4 Hz, D) and high (10-125 Hz, E) frequency ranges representing waves and spikes of seizures. (* p < 0 05). Timecourses are aligned to seizure onset (time = 0s) showing mean and SEM of signals. Data for (A-C) are from the same patients and seizures as Figure 3, and data for (D-E) are from the same patients and seizures as Figure 4. Dotted vertical lines indicate seizure onset (black) or offset (green and purple for seizures associated with spared or impaired performance, respectively).

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