Improved Diagnosis in Children with Partial Epilepsy Using a Multivariable Prediction Model Based on EEG Network Characteristics

Background

Electroencephalogram (EEG) acquisition is routinely performed to support an epileptic origin of paroxysmal events in patients referred with a possible diagnosis of epilepsy. However, in children with partial epilepsies the interictal EEGs are often normal. We aimed to develop a multivariable diagnostic prediction model based on electroencephalogram functional network characteristics.

Methodology/Principal Findings

Routinely performed interictal EEG recordings at first presentation of 35 children diagnosed with partial epilepsies, and of 35 children in whom the diagnosis epilepsy was excluded (control group), were used to develop the prediction model. Children with partial epilepsy were individually matched on age and gender with children from the control group. Periods of resting-state EEG, free of abnormal slowing or epileptiform activity, were selected to construct functional networks of correlated activity. We calculated multiple network characteristics previously used in functional network epilepsy studies and used these measures to build a robust, decision tree based, prediction model. Based on epileptiform EEG activity only, EEG results supported the diagnosis of with a sensitivity and specificity of 0.77 and 0.91 respectively. In contrast, the prediction model had a sensitivity of 0.96 [95% confidence interval: 0.78–1.00] and specificity of 0.95 [95% confidence interval: 0.76–1.00] in correctly differentiating patients from controls. The overall discriminative power, quantified as the area under the receiver operating characteristic curve, was 0.89, defined as an excellent model performance. The need of a multivariable network analysis to improve diagnostic accuracy was emphasized by the lack of discriminatory power using single network characteristics or EEG''s power spectral density.

Conclusions/Significance

Diagnostic accuracy in children with partial epilepsy is substantially improved with a model combining functional network characteristics derived from multi-channel electroencephalogram recordings. Early and accurate diagnosis is important to start necessary treatment as soon as possible and inform patients and parents on possible risks and psychosocial aspects in relation to the diagnosis.     

Functional and Structural Neural Network Characterization of Serotonin Transporter Knockout Rats

Brain serotonin homeostasis is crucially maintained by the serotonin transporter (5-HTT), and its down-regulation has been linked to increased vulnerability for anxiety- and depression-related behavior. Studies in 5-HTT knockout (5-HTT^-/-) rodents have associated inherited reduced functional expression of 5-HTT with increased sensitivity to adverse as well as rewarding environmental stimuli, and in particular cocaine hyperresponsivity. 5-HTT down-regulation may affect normal neuronal wiring of implicated corticolimbic cerebral structures. To further our understanding of its contribution to potential alterations in basal functional and structural properties of neural network configurations, we applied resting-state functional MRI (fMRI), pharmacological MRI of cocaine-induced activation, and diffusion tensor imaging (DTI) in 5-HTT^-/- rats and wild-type controls (5-HTT^+/+). We found that baseline functional connectivity values and cocaine-induced neural activity within the corticolimbic network was not significantly altered in 5-HTT^-/- versus 5-HTT^+/+ rats. Similarly, DTI revealed mostly intact white matter structural integrity, except for a reduced fractional anisotropy in the genu of the corpus callosum of 5-HTT^-/- rats. At the macroscopic level, analyses of complex graphs constructed from either functional connectivity values or structural DTI-based tractography results revealed that key properties of brain network organization were essentially similar between 5-HTT^+/+ and 5-HTT^-/- rats. The individual tests for differences between 5-HTT^+/+ and 5-HTT^-/- rats were capable of detecting significant effects ranging from 5.8% (fractional anisotropy) to 26.1% (pharmacological MRI) and 29.3% (functional connectivity). Tentatively, lower fractional anisotropy in the genu of the corpus callosum could indicate a reduced capacity for information integration across hemispheres in 5-HTT^-/- rats. Overall, the comparison of 5-HTT^-/- and wild-type rats suggests mostly limited effects of 5-HTT genotype on MRI-based measures of brain morphology and function.     

Pregnant Mothers with Resolved Anxiety Disorders and Their Offspring Have Reduced Heart Rate Variability: Implications for the Health of Children

Objective

Active anxiety disorders have lasting detrimental effects on pregnant mothers and their offspring but it is unknown if historical, non-active, maternal anxiety disorders have similar effects. Anxiety-related conditions, such as reduced autonomic cardiac control, indicated by reduced heart rate variability (HRV) could persist despite disorder resolution, with long-term health implications for mothers and children. The objective in this study is to test the hypotheses that pregnant mothers with a history of, but not current anxiety and their children have low HRV, predicting anxiety-like offspring temperaments.

Methods

The participants in this case-control study consist of 56 women during their first trimester and their offspring (15 male, 29 female). Women had a history of an anxiety disorder (n=22) or no psychopathology (n=34) determined using the Mini-International Neuropsychiatric Interview. The main outcome measures were indices of autonomic cardiac control including root mean square of successive differences (RMSSD) and high frequency (HF) variability. Children’s fearfulness was also assessed using the Laboratory Temperament Assessment Battery (Lab-TAB)-Locomotor Version.

Results

HRV was lower in women and children in the past anxiety group compared to controls. HRV measures for mothers and children were positively correlated in the anxiety group only. In all children, low HRV measures at 2-4 months were associated with a higher chance of fearful behavior at 9-10 months.

Conclusions

Pregnant women with previous but not current anxiety and their children have low HRV. Children with low HRV tend to show more fearfulness. These findings have implications for identifying children at risk of anxiety disorders and point to possible underlying mechanisms of child psychopathology.     

Sensitive fluorescence in situ hybridization signal detection in maize using directly labeled probes produced by high concentration DNA polymerase nick translation

The signal produced by fluorescence in situ hybridization (FISH) often is inconsistent among cells and sensitivity is low. Small DNA targets on the chromatin are difficult to detect. We report here an improved nick translation procedure for Texas red and Alexa Fluor 488 direct labeling of FISH probes. Brighter probes can be obtained by adding excess DNA polymerase I. Using such probes, a 30?kb yeast transgene, and the rp1, rp3 and zein multigene clusters were clearly detected.     

Proteomic analysis in the model organism Daphnia has the potential to unravel molecular pathways involved in phenotypic changes in response to changing environmental conditions

Hydrobiologia - The crustacean genus Daphnia holds a key position in aquatic ecosystems rendering it an important model organism in environmental research. Its enormous sensitivity to environmental...     

The status and conservation of the Cape Gannet Morus capensis

The Cape Gannet Morus capensis is one of several seabird species endemic to the Benguela upwelling ecosystem (BUS) but whose population has recently decreased, leading to an unfavourable IUCN Red List assessment. Application of ‘JARA’ (‘Just Another Red-List Assessment,’ a Bayesian state-space tool used for IUCN Red List assessments) to updated information on the areas occupied by Cape Gannets and the nest densities of breeding birds at their six colonies, suggested that the species should be classified as Vulnerable. However, the rate of decrease of Cape Gannets in their most-recent generation exceeded that of the previous generation, primarily as a result of large decreases at Bird Island, Lambert’s Bay, and Malgas Island, off South Africa’s west coast (the western part of their range). Since the 1960s, there has been an ongoing redistribution of the species from northwest to southeast around southern Africa, and ～70% of the population now occurs on the south coast of South Africa, at Bird Island in Algoa Bay, on the eastern border of the BUS. Recruitment rather than adult survival may be limiting the present population; however, information on the seabird’s demographic parameters and mortality in fisheries is lacking for colonies in the northern part of the BUS. Presently, major threats to Cape Gannet include: substantially decreased availability of their preferred prey in the west; heavy mortalities of eggs, chicks and fledglings at and around colonies, inflicted by Cape Fur Seals Arctocephalus pusillus and other seabirds; substantial disturbance at colonies caused by Cape Fur Seals attacking adult gannets ashore; oiling; and disease.