Dataset Information

Altered visual contrast gain control is sensitive for idiopathic generalized epilepsies.

ABSTRACT: Visual hyperexcitability in the form of abnormal contrast gain control has been shown in photosensitive epilepsy and idiopathic generalized epilepsies. We assessed the accuracy and reliability of measures of visual contrast gain control in discerning individuals with idiopathic generalized epilepsies from healthy controls.Twenty-four adult patients with idiopathic generalized epilepsy and 32 neurotypical control subjects from two study sites participated in a prospective, cross-sectional study. We recorded steady-state visual evoked potentials to a wide range of contrasts of a flickering grating stimulus. The resultant response magnitude vs. contrast curves were fitted to a standard model of contrast response function, and the model parameters were used as input features to a linear classifier to separate patients from controls. Additionally we compared the relative contribution of model parameters towards the classification using a sparse feature-selection approach.Classification accuracy was 80% or better. Sensitivity and specificity both were 80-85%. Cross validation confirmed robust classifier performance generalizable across the data from the two samples. Patients' relative lack of gain control at high contrasts was the most important information distinguishing patients from controls.Individuals with idiopathic generalized epilepsy were distinguishable from the neurotypical with a high degree of accuracy and reliability by a reduction in gain control at high contrasts.Gain control is an essential neural operation that regulates neuronal sensitivity to stimuli and may represent a novel biomarker of hyperexcitability.

SUBMITTER: Won D

PROVIDER: S-EPMC5823846 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Altered visual contrast gain control is sensitive for idiopathic generalized epilepsies.

Won Daehan D Kim Wonsuk W Chaovalitwongse W Art WA Tsai Jeffrey J JJ

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 20161218 2

<h4>Objective</h4>Visual hyperexcitability in the form of abnormal contrast gain control has been shown in photosensitive epilepsy and idiopathic generalized epilepsies. We assessed the accuracy and reliability of measures of visual contrast gain control in discerning individuals with idiopathic generalized epilepsies from healthy controls.<h4>Methods</h4>Twenty-four adult patients with idiopathic generalized epilepsy and 32 neurotypical control subjects from two study sites participated in a pr ...[more]

PMID: 28056389

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Project description:Idiopathic generalized epilepsies account for 30% of all epilepsies. Despite a predominant genetic aetiology, the genetic factors predisposing to idiopathic generalized epilepsies remain elusive. Studies of structural genomic variations have revealed a significant excess of recurrent microdeletions at 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 in various neuropsychiatric disorders including autism, intellectual disability and schizophrenia. Microdeletions at 15q13.3 have recently been shown to constitute a strong genetic risk factor for common idiopathic generalized epilepsy syndromes, implicating that other recurrent microdeletions may also be involved in epileptogenesis. This study aimed to investigate the impact of five microdeletions at the genomic hotspot regions 1q21.1, 15q11.2, 16p11.2, 16p13.11 and 22q11.2 on the genetic risk to common idiopathic generalized epilepsy syndromes. The candidate microdeletions were assessed by high-density single nucleotide polymorphism arrays in 1234 patients with idiopathic generalized epilepsy from North-western Europe and 3022 controls from the German population. Microdeletions were validated by quantitative polymerase chain reaction and their breakpoints refined by array comparative genomic hybridization. In total, 22 patients with idiopathic generalized epilepsy (1.8%) carried one of the five novel microdeletions compared with nine controls (0.3%) (odds ratio = 6.1; 95% confidence interval 2.8-13.2; chi(2) = 26.7; 1 degree of freedom; P = 2.4 x 10(-7)). Microdeletions were observed at 1q21.1 [Idiopathic generalized epilepsy (IGE)/control: 1/1], 15q11.2 (IGE/control: 12/6), 16p11.2 IGE/control: 1/0, 16p13.11 (IGE/control: 6/2) and 22q11.2 (IGE/control: 2/0). Significant associations with IGEs were found for the microdeletions at 15q11.2 (odds ratio = 4.9; 95% confidence interval 1.8-13.2; P = 4.2 x 10(-4)) and 16p13.11 (odds ratio = 7.4; 95% confidence interval 1.3-74.7; P = 0.009). Including nine patients with idiopathic generalized epilepsy in this cohort with known 15q13.3 microdeletions (IGE/control: 9/0), parental transmission could be examined in 14 families. While 10 microdeletions were inherited (seven maternal and three paternal transmissions), four microdeletions occurred de novo at 15q13.3 (n = 1), 16p13.11 (n = 2) and 22q11.2 (n = 1). Eight of the transmitting parents were clinically unaffected, suggesting that the microdeletion itself is not sufficient to cause the epilepsy phenotype. Although the microdeletions investigated are individually rare (<1%) in patients with idiopathic generalized epilepsy, they collectively seem to account for a significant fraction of the genetic variance in common idiopathic generalized epilepsy syndromes. The present results indicate an involvement of microdeletions at 15q11.2 and 16p13.11 in epileptogenesis and strengthen the evidence that recurrent microdeletions at 15q11.2, 15q13.3 and 16p13.11 confer a pleiotropic susceptibility effect to a broad range of neuropsychiatric disorders.

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Dataset Information

Altered visual contrast gain control is sensitive for idiopathic generalized epilepsies.

Publications

Altered visual contrast gain control is sensitive for idiopathic generalized epilepsies.

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