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Vascular cognitive impairment has been related to dysfunction of the central cholinergic system. Studies exploring the putative relationship between vascular cognitive impairment and cholinergic dysfunction have largely been aimed at symptomatic cholinergic treatment rather than focusing on etiological and pathological factors. The present study characterizes chronic responses of the cholinergic system to focal cerebral infarction. Two separate experiments investigated changes in receptor responsiveness versus changes in cell number after photothrombotic infarction of the frontal cortex in rat brain. First, we conducted pharmacological magnetic resonance imaging (phMRI) together with pilocarpine injection to assess relative cerebral blood volume (CBV) responses related to cholinergic muscarinic receptor activation. PhMRI was conducted at 1 and 3 weeks after photothrombotic infarction of either the left or right frontal cortex. Second, stereological assessment was performed on choline acetyltransferase (ChAT)-immunostained sections to determine cholinergic cell body count in several basal forebrain nuclei at 4 weeks after infarction. Significant reductions in relative CBV responses were observed both inside the ischemic area at 1 and 3 weeks, and in areas distant from the lesion at 3 weeks after right-sided frontal cortical infarction. In contrast, cholinergic cell number remained unchanged. These results demonstrate that cholinergic receptor responsiveness may be significantly altered following cerebral infarction, while projecting cholinergic cells are preserved.

In this study, we assessed whether peer education is an effective method of HIV/AIDS awareness, in terms of knowledge, misconception and behavior, among adolescents in the rural area of Nigeria. A comparative case series (n = 250), cross-sectional structured survey (n = 135) and focus group discussions (n = 80) were undertaken among adolescents. In both the case series and structured survey, a questionnaire was used which addresses the following issues: socio-demography, knowledge on transmission and prevention of HIV/AIDS, accessibility to different sources of HIV/AIDS information, stigmatization and sexual behavior. Binary logistic regression was applied to compare responses from the peer-educated and not peer-educated populations. The model was adjusted for confounders. We demonstrated increased knowledge and decreased misconception and sexual risk behavior in adolescents receiving peer education as compared to adolescents not receiving peer education. These differences are apparent both over time (2005-2007) and cross-sectional (2007). In conclusion, peer education in rural areas can be effective in HIV/AIDS prevention. Knowledge and behavior can be influenced positively.

The aim of this study was to compare the HIV/AIDS knowledge and accessibility to HIV/AIDS information between blind and sighted individuals in Nigeria. A cross-sectional survey was undertaken among rural and urban blind (57) and sighted (62) adolescents in 2006. A structured questionnaire was used to collect data about HIV/AIDS symptoms, transmission and prevention knowledge, as well as accessibility to sources of HIV/AIDS information. Binary logistic regression and chi-square statistics were applied to compare responses between the two populations. Blindness was found to be associated with diminished knowledge of HIV/AIDS transmission, prevention and symptoms. At the same time, the blind rely on different sources of HIV/AIDS information than sighted respondents. A lack of knowledge and limited accessibility to proper sources of information causes the blind disabled to be more vulnerable. It is necessary to supply them with proper information and increase their HIV/AIDS knowledge.

Many seizure-free patients consider withdrawal of antiepileptic drugs, both when seizure control is achieved by medication alone, or once they became seizure-free following epilepsy surgery. The risk of recurrence is consequently of very important prognostic value. However, estimations of recurrence risks are outdated for both populations. In addition, although many publications have reported predictors of seizure relapse, no comprehensive overview of prognostic factors is available.A systematic review of the databases of PubMed and EMBASE was conducted, identifying articles on antiepileptic drug withdrawal in patient cohorts. Recurrence risk meta-analyses were performed for both populations at one, two, three to four, and five or more years of follow-up. Within the selected articles, studies presenting multivariable analysis of predictors were identified; all studied predictors were listed, as well as all significant independent predictors. The quality of separate analyses of predictors was assessed.There was no significant difference of long-term cumulative recurrence risk between surgical and medication-only populations, with respectively 29% and 34% recurrences. In medication-only treated patients, 25 factors have been reported as significant independent predictors; 12 have been reported in surgical cohorts. The quality of most analyses of predictors was low to moderate. No predictor was consistently found among all analyses, and for most predictors, study results were contradictory.No consistent set of predictors could be identified because a large number of variables have been identified in the literature, many studies reported contradicting results, study populations varied considerably, and the quality of the original studies was often low. Meta-analysis of individual participant data is necessary, because it allows for (1) correction for differences in follow-up duration between subjects and studies, (2) a study of interaction effects, (3) calculation of more accurate estimates valid across several populations, and (4) the assessment of each predictor's effect size.

Hemispherectomy is often followed by remarkable recovery of cognitive and motor functions. This reflects plastic capacities of the remaining hemisphere, involving large-scale structural and functional adaptations. Better understanding of these adaptations may (1) provide new insights in the neuronal configuration and rewiring that underlies sensorimotor outcome restoration, and (2) guide development of rehabilitation strategies to enhance recovery after hemispheric lesioning. We assessed brain structure and function in a hemispherectomy model. With MRI we mapped changes in white matter structural integrity and gray matter functional connectivity in eight hemispherectomized rats, compared with 12 controls. Behavioral testing involved sensorimotor performance scoring. Diffusion tensor imaging and resting-state functional magnetic resonance imaging were acquired 7 and 49 days post surgery. Hemispherectomy caused significant sensorimotor deficits that largely recovered within 2 weeks. During the recovery period, fractional anisotropy was maintained and white matter volume and axial diffusivity increased in the contralateral cerebral peduncle, suggestive of preserved or improved white matter integrity despite overall reduced white matter volume. This was accompanied by functional adaptations in the contralateral sensorimotor network. The observed white matter modifications and reorganization of functional network regions may provide handles for rehabilitation strategies improving functional recovery following large lesions.

There is a general need for high-quality, easily accessible, and comprehensive health-care information on epilepsy to better inform the general population about this highly stigmatized neurological disorder. The aim of this study was to evaluate the health literacy level of eight popular English-written websites that provide information on epilepsy in quantitative terms of readability. Educational epilepsy material on these websites, including 41 Wikipedia articles, were analyzed for their overall level of readability and the corresponding academic grade level needed to comprehend the published texts on the first reading. The Flesch Reading Ease (FRE) was used to assess ease of comprehension while the Gunning Fog Index, Coleman-Liau Index, Flesch-Kincaid Grade Level, Automated Readability Index, and Simple Measure of Gobbledygook scales estimated the corresponding academic grade level needed for comprehension. The average readability of websites yielded results indicative of a difficult-to-fairly-difficult readability level (FRE results: 44.0. ±. 8.2), with text readability corresponding to an 11th academic grade level (11.3. ±. 1.9). The average FRE score of the Wikipedia articles was indicative of a difficult readability level (25.6. ±. 9.5), with the other readability scales yielding results corresponding to a 14th grade level (14.3. ±. 1.7). Popular websites providing information on epilepsy, including Wikipedia, often demonstrate a low level of readability. This can be ameliorated by increasing access to clear and concise online information on epilepsy and health in general. Short "basic" summaries targeted to patients and nonmedical users should be added to articles published in specialist websites and Wikipedia to ease readability.

We aimed to relate the percentages of encountered epilepsy-related stigma in people with epilepsy with quantitative indicators of the quality of health systems and quality of life by country in Europe. The epilepsy-related stigma percentages were obtained from the largest population-based study in people with epilepsy available. We correlated percentages of people with perceived stigma per European country with data on the country's overall health system performance, health expenditure per capita in international dollars, and the Economist Intelligence Unit's quality-of-life index. Wefound a nonsignificant trend towards negative correlation between the epilepsy-related stigma percentage and the overall health system performance (r=-0.16; p= 0.57), the health expenditure per capita in international dollars (r = -0.24; p = 0.4), and the Economist Intelligence Unit's quality-of-life index (r = -0.33; p = 0.91). Living in a European country with a better health system performance and higher health expenditure per capita does not necessarily lead to a reduction in perceived epilepsy-related discrimination, unless the public health system invests on awareness programs to increase public knowledge and reduce stigma. (C) 2014 Elsevier Inc. All rights reserved.

In old and modern times and across cultures, recurrent seizures have been attributed to the lunar phase. It is unclear whether this relationship should be classified as a myth or whether a true connection exists between moon phases and seizures. We analyzed the worldwide aggregated search queries related to epilepsy health-seeking behavior between 2005 and 2012. Epilepsy-related Internet searches increased in periods with a high moon illumination. The overall association was weak (r=0.11, 95% confidence interval: 0.07 to 0.14) but seems to be higher than most control search queries not related to epilepsy. Increased sleep deprivation during periods of full moon might explain this positive association and warrants further study into epilepsy-related health-seeking behavior on the Internet, the lunar phase, and its contribution to nocturnal luminance.

Linking neural circuit activation at whole-brain level to neuronal activity at cellular level remains one of the major challenges in neuroscience research. We set up a novel functional neuroimaging approach to map global effects of locally induced activation of specific midbrain projection neurons using chemogenetics (Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-technology) combined with pharmacological magnetic resonance imaging (phMRI) in the rat mesocorticolimbic system. Chemogenetic activation of DREADD-targeted mesolimbic or mesocortical pathways, i.e. projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAcc) or medial prefrontal cortex (mPFC), respectively, induced significant blood oxygenation level-dependent (BOLD) responses in areas with DREADD expression, but also in remote defined neural circuitry without DREADD expression. The time-course of brain activation corresponded with the behavioral output measure, i.e. locomotor (hyper)activity, in the mesolimbic pathway-targeted group. Chemogenetic activation specifically increased neuronal activity, whereas functional connectivity assessed with resting state functional MRI (rs-fMRI) remained stable. Positive and negative BOLD responses distinctively reflected simultaneous ventral pallidum activation and substantia nigra pars reticulata deactivation, respectively, demonstrating the concept of mesocorticolimbic network activity with concurrent activation of the direct and indirect pathways following stimulation of specific midbrain projection neurons. The presented methodology provides straightforward and widely applicable opportunities to elucidate relationships between local neuronal activity and global network activity in a controllable manner, which will increase our understanding of the functioning and dysfunctioning of large-scale neuronal networks in health and disease.

Permanent focal brain damage can have critical effects on the function of nearby as well as remote brain regions. However, the effects of transient disturbances on global brain function are largely unknown. Our goal was to develop an experimental in vivo model to map the impact of transient functional brain impairment on large-scale neural networks in the absence of structural damage. We describe a new rat model of transient functional hemispheric disruption using unilateral focal anesthesia by intracarotid pentobarbital injection. The brain's functional status was assessed with resting-state fMRI (rs-fMRI) and electroencephalography (EEG). We performed network analysis to identify and quantify highly connected network hubs, i.e., “rich-club organization,” in pre- and postbarbital functional networks. Perfusion MRI data demonstrated that the catheterized carotid artery predominantly supplied the ipsilateral hemisphere, allowing for selective hemispheric brain silencing. The prebarbital baseline network displayed strong functional connectivity (FC) within and between hemispheres. Following pentobarbital injection, the disrupted hemisphere revealed increased intrahemispheric FC with concomitant decrease of interhemispheric connectivity. The bilateral functional network was characterized by a strong positive rich-club effect, which was not affected by ipsilateral disruption. Nevertheless, the rich-club value was significantly decreased in the ipsilateral hemisphere and to a lesser extent contralaterally. Loss of interhemispheric EEG synchronization supported the rs-fMRI findings. Our data support the concept that densely connected rich-club regions play a central role in global brain communication, and show that network hub configurations can be significantly affected by focal temporary functional hemispheric disruption without structural neuronal damage. Further studies with this rat model will provide essential additional insights into network reorganization patterns in response to transient functional brain disruption.

Permanent focal brain damage can have critical effects on the function of nearby as well as remote brain regions. However, the effects of transient disturbances on global brain function are largely unknown. Our goal was to develop an experimental in vivo model to map the impact of transient functional brain impairment on large-scale neural networks in the absence of structural damage.We describe a new rat model of transient functional hemispheric disruption using unilateral focal anesthesia by intracarotid pentobarbital injection. The brain’s functional status was assessed with resting-state fMRI (rs-fMRI) and EEG. We performed network analysis to identify and quantify highly connected network hubs, i.e. ‘rich-club organization’, in pre- and postbarbital functional networks.Perfusion MRI data demonstrated that the catheterized carotid artery predominantly supplied the ipsilateral hemisphere, allowing for selective hemispheric brain silencing. The prebarbital baseline network displayed strong functional connectivity within and between hemispheres. Following pentobarbital injection, the disrupted hemisphere revealed increased intrahemispheric functional connectivity with concomitant decrease of interhemispheric connectivity. The bilateral functional network was characterized by a strong positive rich-club effect, which was not affected by ipsilateral disruption. Nevertheless, the rich-club value was significantly decreased in the ipsilateral hemisphere and to a lesser extent contralaterally. Loss of interhemispheric EEG synchronization supported the rs-fMRI findings.Our data support the concept that densely connected rich-club regions play a central role in global brain communication, and show that network hub configurations can be significantly affected by focal temporary functional hemispheric disruption without structural neuronal damage. Further studies with this rat model will provide essential additional insights into network reorganization patterns in respon

Stress is the most often reported seizure-precipitant in epilepsy. As most evidence for the relation between stress and epilepsy is derived from human self-reports, observational studies including a larger part of the population could provide additional proof. A stressor often reported to increase seizure frequency in children with epilepsy in the Netherlands is the national celebration of Saint Nicholas' eve (December 5) and the weeks before; this is the main period of festivities for children in this country. To study the relation between stress and epilepsy, we analyzed epilepsy information-seeking behavior on the Internet, an indirect measure of seizure frequency, around this national children's celebration.Google Trends was used to extract relative search percentages for 'epilepsy' on Google in the Netherlands, the United States, and the United Kingdom between 2004 and 2013. Relative search percentages during the Saint Nicholas period were compared with baseline.Epilepsy searches increased by 14% in the Saint Nicholas period compared with baseline (p0.001). This effect was not found for searches performed in the same period in the United States or the United Kingdom, countries where this holiday is not celebrated.The increase in epilepsy information-seeking behavior in the Saint Nicholas period is possibly caused by an increased occurrence of epileptic seizures. This underscores the potential of health information-seeking behavior on the Internet to answer clinically relevant research questions and provides circumstantial evidence for a relation between stress and the occurrence of epileptic seizures.

Recent literature shows that diffusion tensor properties can be estimated more accurately with diffusion kurtosis imaging (DKI) than with diffusion tensor imaging (DTI). Furthermore, the additional non-Gaussian diffusion features from DKI can be sensitive markers for tissue characterization. Despite these benefits, DKI is more susceptible to data artifacts than DTI due to its increased model complexity, higher acquisition demands, and longer scanning times. To increase the reliability of diffusion tensor and kurtosis estimates, we propose a robust estimation procedure for DKI.We have developed a robust and linear estimation framework, coined REKINDLE (Robust Extraction of Kurtosis INDices with Linear Estimation), consisting of an iteratively reweighted linear least squares approach. Simulations are performed, in which REKINDLE is evaluated and compared with the widely used RESTORE (Robust EStimation of Tensors by Outlier REjection) method.Simulations demonstrate that in the presence of outliers, REKINDLE can estimate diffusion and kurtosis indices reliably and with a 10-fold reduction in computation time compared with RESTORE.We have presented and evaluated REKINDLE, a linear and robust estimation framework for DKI. While REKINDLE has been developed for DKI, it is by design also applicable to DTI and other diffusion models that can be linearized.

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. © 2013 van Diessen et al.

Reducing the burden of epilepsy in low- and middle-income countries requires understanding of the cultural aspects of epilepsy. This cross-sectional study among individuals attending a clinic in an urban setting in Paramaribo, Suriname aimed to obtain information on the knowledge of and attitudes towards epilepsy and epilepsy treatment, comparing people with epilepsy (PWE) to those without epilepsy. This study also explored the help-seeking behavior and experience of having epilepsy in PWE. While the results of interviews with 49 PWE and 33 controls compared favorably to studies conducted in similar countries, a significant minority of PWE still rely on traditional remedies. Prejudices regarding social roles, schooling, and occupational choices of PWE also remain prevalent. Currently, the major source of information for both groups is the media, but there could be opportunities for the local epilepsy association to play a larger role. These findings, despite some selection bias, could be useful in bringing conventional medical treatment strategies to more PWE in Suriname, as well as empower patient organizations in designing stigma-reducing interventions.

OBJECTIVE: It remains unclear to what extent brain networks are altered at an early stage of epilepsy, which may be important to improve our understanding on the course of network alterations and their association with recurrent seizures and cognitive deficits.METHODS: 89 Drug-naïve children with newly diagnosed focal or generalized epilepsies and 179 controls were included. Brain networks were based on interictal electroencephalography recordings obtained at first consultation. Conventional network metrics and minimum spanning tree (MST) metrics were computed to characterize topological network differences, such integration and segregation and a hub measures (betweenness centrality).RESULTS: Network alterations between groups were only identified by MST metrics and most pronounced in the delta band, in which a loss of network integration and a significant lower betweenness centrality was found in children with focal epilepsies compared to healthy controls (pCONCLUSIONS: Interictal network alterations - only identifiable with the MST method - are already present at an early stage of focal epilepsy.SIGNIFICANCE: We argue that these alterations are subtle at the early stage and aggravate later as a result of persisting seizures.

The potential of the adult brain to reorganize after ischemic injury is critical for functional recovery and provides a significant target for therapeutic strategies to promote brain repair. Despite the accumulating evidence of brain plasticity, the interaction and significance of morphological and physiological modifications in post-stroke brain tissue remain mostly unclear. Neuroimaging techniques such as functional MRI (fMRI) and diffusion tensor imaging (DTI) enable in vivo assessment of the spatial and temporal pattern of functional and structural changes inside and outside ischemic lesion areas. This can contribute to the elucidation of critical aspects in post-stroke brain remodeling. Task/stimulus-related fMRI, resting-state fMRI, or pharmacological MRI enables direct or indirect measurement of neuronal activation, functional connectivity, or neurotransmitter system responses, respectively. DTI allows estimation of the structural integrity and connectivity of white matter tracts. Together, these MRI methods provide an unprecedented means to (a) measure longitudinal changes in tissue structure and function close by and remote from ischemic lesion areas, (b) evaluate the organizational profile of neural networks after stroke, and (c) identify degenerative and restorative processes that affect post-stroke functional outcome. Besides, the availability of MRI in clinical institutions as well as research laboratories provides an optimal basis for translational research on stroke recovery. This review gives an overview of the current status and perspectives of fMRI and DTI applications to study brain reorganization in experimental stroke models.

Purpose: High rates of poor knowledge of, and negative attitudes towards people with epilepsy (PWE) are generally found among school teachers. Their first aid epilepsy management skills are poor. It remains unknown if this is different among trainee teachers and whether educational intervention might reduce these rates. We examined the effect of health education on the knowledge, attitudes, and first aid management of epilepsy on trainee teachers in Nigeria. Methods: Baseline data and socio-demographic determinants were collected from 226 randomly selected trainee teachers, at the Federal College of Education, Lagos, Nigeria, with self-administered questionnaires. They received a health intervention comprising an hour and half epilepsy lecture followed by a discussion. Baseline knowledge of, and attitudes towards PWE and their first aid epilepsy management skills were compared to post-interventional follow-up data collected twelve weeks later with similar questionnaires. Results: At baseline the majority (61.9%) and largest proportion (44.2%) of respondents had negative attitudes and poor knowledge of epilepsy, respectively. The knowledge of, and attitudes towards epilepsy, and the first aid management skill increased in most respondents, post-intervention. The proportion of respondents with poor knowledge and negative attitudes dropped by 15.5% (p

The majority of patients with epilepsy report that seizures are sometimes triggered or provoked. Stress is the most frequently self-reported seizure-precipitant. The mechanisms underlying stress-sensitivity of seizures are currently unresolved. We hypothesized that stress-sensitivity of seizures relates to alteration of the stress response, which could affect neuronal excitability and hence trigger seizures. To study this, children with epilepsy between 6 and 17 years of age and healthy controls, with similar age, sex and intelligence, were exposed to a standardized acute psychosocial stressor (the Trier Social Stress Test for Children), during which salivary cortisol and sympathetic parameters were measured. Beforehand, the relation between stress and seizures in children with epilepsy was assessed by (i) a retrospective questionnaire; and (ii) a prospective 6-week diary on stress and seizure occurrence. Sixty-four children with epilepsy and 40 control subjects were included in the study. Of all children with epilepsy, 49% reported that seizures were precipitated by acute stress. Diary analysis showed a positive association between acute stress and seizures in 62% of children who experienced at least one seizure during the diary period. The acute social stress test was completed by 56 children with epilepsy and 37 control subjects. Children with sensitivity of seizures for acute stress, either determined by the questionnaire or by the prospective diary, showed a blunted cortisol response to stress compared with patients without acute stress-precipitated seizures and healthy controls (questionnaire-based F = 2.74, P = 0.018; diary-based F = 4.40, P = 0.007). No baseline differences in cortisol were observed, nor differences in sympathetic stress response. The relation between acute stress-sensitivity of seizures and the cortisol response to stress remained significant in multivariable analysis (β = -0.30, P = 0.03). Other variables associated with the acute stress response were the number of anti-epileptic drugs (β = -0.27, P = 0.05) and sleep quality (β = 0.30, P = 0.03). In conclusion, we show that children with acute stress-sensitive seizures have a decreased cortisol response to stress. These results support our hypothesis that stress-sensitivity of seizures is associated with alterations of the stress response, thereby providing a first step in unravelling the mechanisms behind the seizure-precipitating effects of stress. Increased knowledge of the relation between stress and seizures in childhood epilepsy might benefit our understanding of the fundamental processes underlying epilepsy and ictogenesis in general, and provide valuable clues to direct the development of new therapeutic strategies for epilepsy.

Objective To quantify the use of question marks in titles of published studies. Design and setting Literature review. Participants All Pubmed publications between 1 January 2013 and 31 December 2013 with an available abstract. Papers were classified as being clinical when the search terms clin*, med* or patient* were found anywhere in the paper’s title, abstract or the journal’s name. Other papers were considered controls. As a verification, clinical journals were compared to non-clinical journals in two different approaches. Also, 50 highest impact journals were explored for publisher group dependent differences. Main outcome measure Total number of question marks in titles. Results A total of 368,362 papers were classified as clinical and 596,889 as controls. Clinical papers had question marks in 3.9% (95% confidence interval 3.8–4.0%) of titles and other papers in 2.3% (confidence interval 2.3–2.3%; p Conclusion We found more question marks in titles of clinical papers than in other papers. This could suggest that clinicians often have a question-driven approach to research and scientists in more fundamental research a hypothesis-driven approach. An alternative explanation is that clinicians like catchy titles. Publishing groups might have pro- and anti-question mark policies.

Normal brain functioning is presumed to depend upon interacting regions within large-scale neuronal networks. Increasing evidence exists that interictal network alterations in focal epilepsy are associated with cognitive and behavioral deficits. Nevertheless, the reported network alterations are inconclusive and prone to low statistical power due to small sample sizes as well as modest effect sizes. We therefore systematically reviewed the existing literature and conducted a meta-analysis to characterize the changes in whole-brain interictal focal epilepsy networks at sufficient power levels. We focused on the two most commonly used metrics in whole-brain networks: average path length and average clustering coefficient. Twelve studies were included that reported whole-brain network average path length and average clustering coefficient characteristics in patients and controls. The overall group difference, quantified as the standardized mean average path length difference between epilepsy and control groups, corresponded to a significantly increased average path length of 0.29 (95% confidence interval (CI): 0.12 to 0.45, p = 0.0007) in the epilepsy group. This suggests a less integrated interictal whole-brain network. Similarly, a significantly increased standardized mean average clustering coefficient of 0.35 (CI: 0.05 to 0.65, p = 0.02) was found in the epilepsy group in comparison with controls, pointing towards a more segregated interictal network. Sub-analyses revealed similar results for functional and structural networks in terms of effect size and directionality for both metrics. In addition, we found individual network studies to be prone to low power due to the relatively small group differences in average path length and average clustering coefficient in combination with small sample sizes. The pooled network characteristics support the hypothesis that focal epilepsy has widespread detrimental effects, that is, reduced integration and increased segregation, on whole brain interictal network organization, which may relate to the co-morbid cognitive and behavioral impairments often reported in patients with focal epilepsy.

Contains fulltext : 125449.pdf (Publisher’s version ) (Open Access) 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.

Millions of people worldwide use the internet daily as a source of health information. Wikipedia is a popular free online encyclopaedia used by patients and physicians to search for health-related information. Our aim was to evaluate information-seeking behaviour of English-speaking internet users searching Wikipedia for articles related to epilepsy and epileptic seizures. Using Wiki Trends, which provides quantitative information on daily viewing of articles, data on global search queries for Wikipedia articles related to epilepsy and seizures were analysed. The daily Wikipedia article views on syncope, psychogenic non-epileptic seizures, migraine, and multiple sclerosis served as comparative data. The period of analysis covered was from January 2008 to December 2014. Overall, the Wikipedia article "epilepsy and driving" was found to be more frequently visited than the articles "epilepsy and employment" or "epilepsy in children". Since January 2008, the Wikipedia article "multiple sclerosis" was more often visited compared to the articles "epilepsy", "syncope", "psychogenic non-epileptic seizures" or "migraine"; the article "epilepsy" ranked 3,779 and was less frequently visited than "multiple sclerosis", ranked at 571, in traffic on Wikipedia. The highest peak in search volume for the article "epilepsy" coincided with the news of a celebrity having seizures. Fears and worries about epileptic seizures, their impact on driving and employment, and news about celebrities with epilepsy might be major determinants in searching Wikipedia for information.