Special issue of Epilepsia dedicated to the 31stInternational Epilepsy Congress Istanbul, Turkey 5th–9th September, 2015
Many environmental stimuli present a quasi-rhythmic structure at different timescales that the brain needs to decompose and integrate. Cortical oscillations have been proposed as instruments of sensory de-multiplexing, i.e., the parallel processing of different frequency streams in sensory signals. Yet their causal role in such a process has never been demonstrated. Here, we used a neural microcircuit model to address whether coupled theta–gamma oscillations, as observed in human auditory cortex, could underpin the multiscale sensory analysis of speech. We show that, in continuous speech, theta oscillations can flexibly track the syllabic rhythm and temporally organize the phoneme-level response of gamma neurons into a code that enables syllable identification. The tracking of slow speech fluctuations by theta oscillations, and its coupling to gamma-spiking activity both appeared as critical features for accurate speech encoding. These results demonstrate that cortical oscillations can be a key instrument of speech de-multiplexing, parsing, and encoding.
The contribution of modifiable risk factors to the increasing global and regional burden of stroke is unclear, but knowledge about this contribution is crucial for informing stroke prevention strategies. We used data from the Global Burden of Disease Study 2013 (GBD 2013) to estimate the population-attributable fraction (PAF) of stroke-related disability-adjusted life-years (DALYs) associated with potentially modifiable environmental, occupational, behavioural, physiological, and metabolic risk factors in different age and sex groups worldwide and in high-income countries and low-income and middle-income countries, from 1990 to 2013.
We used data on stroke-related DALYs, risk factors, and PAF from the GBD 2013 Study to estimate the burden of stroke by age and sex (with corresponding 95% uncertainty intervals [UI]) in 188 countries, as measured with stroke-related DALYs in 1990 and 2013. We evaluated attributable DALYs for 17 risk factors (air pollution and environmental, dietary, physical activity, tobacco smoke, and physiological) and six clusters of risk factors by use of three inputs: risk factor exposure, relative risks, and the theoretical minimum risk exposure level. For most risk factors, we synthesised data for exposure with a Bayesian meta-regression method (DisMod-MR) or spatial-temporal Gaussian process regression. We based relative risks on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks, such as high body-mass index (BMI), through other risks, such as high systolic blood pressure (SBP) and high total cholesterol.
Globally, 90·5% (95% UI 88·5–92·2) of the stroke burden (as measured in DALYs) was attributable to the modifiable risk factors analysed, including 74·2% (95% UI 70·7–76·7) due to behavioural factors (smoking, poor diet, and low physical activity). Clusters of metabolic factors (high SBP, high BMI, high fasting plasma glucose, high total cholesterol, and low glomerular filtration rate; 72·4%, 95% UI 70·2–73·5) and environmental factors (air pollution and lead exposure; 33·4%, 95% UI 32·4–34·3) were the second and third largest contributors to DALYs. Globally, 29·2% (95% UI 28·2–29·6) of the burden of stroke was attributed to air pollution. Although globally there were no significant differences between sexes in the proportion of stroke burden due to behavioural, environmental, and metabolic risk clusters, in the low-income and middle-income countries, the PAF of behavioural risk clusters in males was greater than in females. The PAF of all risk factors increased from 1990 to 2013 (except for second-hand smoking and household air pollution from solid fuels) and varied significantly between countries.
Our results suggest that more than 90% of the stroke burden is attributable to modifiable risk factors, and achieving control of behavioural and metabolic risk factors could avert more than three-quarters of the global stroke burden. Air pollution has emerged as a significant contributor to global stroke burden, especially in low-income and middle-income countries, and therefore reducing exposure to air pollution should be one of the main priorities to reduce stroke burden in these countries.
Bill & Melinda Gates Foundation, American Heart Association, US National Heart, Lung, and Blood Institute, Columbia University, Health Research Council of New Zealand, Brain Research New Zealand Centre of Research Excellence, and National Science Challenge, Ministry of Business, Innovation and Employment of New Zealand.
Pharmacoresistant epilepsy is a chronic neurological condition in which a basal brain hyperexcitability results in paroxysmal hypersynchronous neuronal discharges. Human temporal lobe epilepsy has been associated with dysfunction or loss of the potassium-chloride cotransporter KCC2 in a subset of pyramidal cells in the subiculum, a key structure generating epileptic activities. KCC2 regulates intraneuronal chloride and extracellular potassium levels by extruding both ions. Absence of effective KCC2 may alter the dynamics of chloride and potassium levels during repeated activation of GABAergic synapses due to interneuron activity. In turn, such GABAergic stress may itself affect Cl− regulation. Such changes in ionic homeostasis may switch GABAergic signaling from inhibitory to excitatory in affected pyramidal cells and also increase neuronal excitability. Possibly these changes contribute to periodic bursting in pyramidal cells, an essential component in the onset of ictal epileptic events. We tested this hypothesis with a computational model of a subicular network with realistic connectivity. The pyramidal cell model explicitly incorporated the cotransporter KCC2 and its effects on the internal/external chloride and potassium levels. Our network model suggested the loss of KCC2 in a critical number of pyramidal cells increased external potassium and intracellular chloride concentrations leading to seizure-like field potential oscillations. These oscillations included transient discharges leading to ictal-like field events with frequency spectra as in vitro. Restoration of KCC2 function suppressed seizure activity and thus may present a useful therapeutic option. These simulations therefore suggest that reduced KCC2 cotransporter activity alone may underlie the generation of ictal discharges.
he 19th Annual Meeting of the Organization for Human Brain Mapping was held June 16-20, 2013 at the Washington State Convention Center in Seattle, WA, USA. OHBM draws attendance between 2500-3000 attendees each year. Membership in the organization is growing and the meeting continues to be one of the most significant neuroimaging conferences for those in the field. The OHBM meeting boasts a combination of exciting scientific programs and social events, all tailored to the city the meeting is being held. Unique, innovative and full of surprises, Seattle is a diverse city with a laid-back approach to life. To experience Seattle is to experience the quiet confidence and balanced urban and natural lifestyles. Seattle is a world-class metropolis with a fast-paced city life within wild, beautiful natural surroundings.
Abstracts of the 12th European Congress on Epileptology
Research on comparative efficаcy and tolerability of monotherapy with Depakine chronosphere, drugs of Carbamazepine group with ex- tended release and oxcarbazepine in symptomatic and cryptogenic focal epilepsy has been conducted at Svt. Luka’s Institute of Child Neurol- ogy and Epilepsy (ICNE) (Moscow). This retrospective study covers a random sample of patients treated in ICNE in the period from Decem- ber 1, 2013 to September 1, 2014. The study included 131 patients aged 1 to 18 years with symptomatic and cryptogenic focal epilepsy receiving treatment with one of the study drugs in monotherapy: group 1 - monotherapy with Depakine chronosphere (n = 56); group 2 - monotherapy with drugs of carbamazepine group with extended release (n = 55); group 3 - monotherapy with oxcarbazepine (trileptal) (n = 20).The obtained results allow us to conclude that the effectiveness of Depakin chronosphere, carbamazepine with extended release and oxcar- bazepine in monotherapy of symptomatic and cryptogenic focal epilepsy was comparable (statistically significant differences in efficacy were not found). However, carbamazepine was awarded the highest frequency of seizures aggravation.Drugs showed approximately same tolerability (statistically significant differences in tolerability were not found). However, withdrawal of the drug due to side effects was the rarest in Depakine (3.5 %), and withdrawal due to intolerance was higher in carbamazepine and oxcarbazepine (5 and 10 % respectively).Depakinum and oxcarbazepine had the best results in the blocking of pathological activity on the electroencephalogram, whereas carbam- azepine was clearly inferior to them. In this regard, complete clinical-electroencephalographic remission (lasting 12 months or more) was achieved under treatment of Depakine chromosphere in 21.5 % of cases, oxcarbazepine - 20 %, and carbamazepine - only 11 %. Holding on therapy for 12 months was similar in all study drugs.Considering that the objective of epilepsy treatment is to achieve complete control over seizures, or at least substantially reduce and weaken them in the absence of significant side effects that disturb the patient’s quality of life, it can be concluded that the best treatment results were obtained in group of depakine chronosphere therapy.
One of the key advances in genome assembly that has led to a significant improvement in contig lengths has been improved algorithms for utilization of paired reads (mate-pairs). While in most assemblers, mate-pair information is used in a post-processing step, the recently proposed Paired de Bruijn Graph (PDBG) approach incorporates the mate-pair information directly in the assembly graph structure. However, the PDBG approach faces difficulties when the variation in the insert sizes is high. To address this problem, we first transform mate-pairs into edge-pair histograms that allow one to better estimate the distance between edges in the assembly graph that represent regions linked by multiple mate-pairs. Further, we combine the ideas of mate-pair transformation and PDBGs to construct new data structures for genome assembly: pathsets and pathset graphs.