What is said or how it is said makes a difference: role of the right fronto-parietal operculum in emotional prosody as revealed by repetitive TMS

Emotional signals in spoken language can be conveyed by semantic as well as prosodic cues. We investigated the role of the fronto-parietal operculum, a somatosensory area where the lips, tongue and jaw are represented, in the right hemisphere to detection of emotion in prosody vs. semantics. A total of 14 healthy volunteers participated in the present experiment, which involved transcranial magnetic stimulation (TMS) in combination with frameless stereotaxy. As predicted, compared with sham stimulation, TMS over the right fronto-parietal operculum differentially affected the reaction times for detection of emotional prosody vs. emotional semantics, showing that there is a dissociation at a neuroanatomical level. Detection of withdrawal emotions (fear and sadness) in prosody was delayed significantly by TMS. No effects of TMS were observed for approach emotions (happiness and anger). We propose that the right fronto-parietal operculum is not globally involved in emotion evaluation, but sensitive to specific forms of emotional discrimination and emotion types

The relation between cortisol and functional connectivity in people with and without stress-sensitive epilepsy

OBJECTIVE: The most common reported seizure-precipitant is stress. We recently showed a biologic basis for stress sensitivity of seizures: cortisol levels in people with stress-sensitive epilepsy correlated with focal interictal epileptiform discharges (IEDs) on electroencephalography (EEG). Here we aimed to determine whether the effect of cortisol on the epileptic brain is global or focal, and whether cortisol affects all brains or just those of stress-sensitive people. Because epilepsy is associated with changes in functional brain connectivity, we studied the relationship between cortisol and changes in global and focal (node-centered) functional connectivity measures for individuals with stress-sensitive and non-stress-sensitive epilepsy. METHODS: Seventeen people with epilepsy underwent long-term (>24 h) EEG recording. During the first 5 h after waking, saliva was collected every 15 min for cortisol measurements. Theta-band functional connectivity was assessed for every 15 min of the recording. We calculated the average phase-lag index (PLI) between all channels as a measure of global functional connectivity. We used network Strength, the averaged PLI per channel, as focal functional connectivity measure. We correlated cortisol, global, and focal functional connectivity (Strength) with IED frequency using linear mixed models. Analyses were split for people with and without stress-sensitivity of seizures. RESULTS: Cortisol was negatively correlated with global functional connectivity in people with stress-sensitive seizures (estimate -0.0020; P < .01), whereas not in those without stress-sensitivity (estimate -0.0003; P = .46). This relationship occurred irrespective of the presence of IEDs on a channel (channels without IEDs and stress-sensitivity: estimate -0.0019; P < .01, non-stress-sensitive -0.0003; P = .41). Global and focal functional connectivity were negatively correlated with IED frequency, irrespective of stress sensitivity of seizures or channel type. SIGNIFICANCE: People with stress-sensitive epilepsy have a whole-brain neuronal response to cortisol that is different from that of people with non-stress-sensitive epilepsy. This offers a basis for understanding seizure genesis in stress-sensitive epilepsy, which might require a different treatment approach

Resting-State Functional Connectivity and Network Analysis of Cerebellum with Respect to Crystallized IQ and Gender

During the last years, it has been established that the prefrontal and posterior parietal brain lobes, which are mostly related to intelligence, have many connections to cerebellum. However, there is a limited research investigating cerebellum's relationship with cognitive processes. In this study, the network of cerebellum was analyzed in order to investigate its overall organization in individuals with low and high crystallized Intelligence Quotient (IQ). Functional magnetic resonance imaging (fMRI) data were selected from 136 subjects in resting-state from the Human Connectome Project (HCP) database and were further separated into two IQ groups composed of 69 low-IQ and 67 high-IQ subjects. Cerebellum was parcellated into 28 lobules/ROIs (per subject) using a standard cerebellum anatomical atlas. Thereafter, correlation matrices were constructed by computing Pearson's correlation coefficients between the average BOLD time-series for each pair of ROIs inside the cerebellum. By computing conventional graph metrics, small-world network properties were verified using the weighted clustering coefficient and the characteristic path length for estimating the trade-off between segregation and integration. In addition, a connectivity metric was computed for extracting the average cost per network. The concept of the Minimum Spanning Tree (MST) was adopted and implemented in order to avoid methodological biases in graph comparisons and retain only the strongest connections per network. Subsequently, six global and three local metrics were calculated in order to retrieve useful features concerning the characteristics of each MST. Moreover, the local metrics of degree and betweenness centrality were used to detect hubs, i.e., nodes with high importance. The computed set of metrics gave rise to extensive statistical analysis in order to examine differences between low and high-IQ groups, as well as between all possible gender-based group combinations. Our results reveal that both male and female networks have small-world properties with differences in females (especially in higher IQ females) indicative of higher neural efficiency in cerebellum. There is a trend toward the same direction in men, but without significant differences. Finally, three lobules showed maximum correlation with the median response time in low-IQ individuals, implying that there is an increased effort dedicated locally by this population in cognitive tasks

Epidemiology of Epilepsy in Nigeria: A Community-Based Study From 3 Sites

BACKGROUND: We determined the prevalence, incidence, and risk factors for epilepsy in Nigeria. METHODS: We conducted a door-to-door survey to identify cases of epilepsy in 3 regions. We estimated age-standardized prevalence adjusted for nonresponse and sensitivity and the 1-year retrospective incidence for active epilepsy. To assess potential risk factors, we conducted a case-control study by collecting sociodemographic and risk factor data. We estimated odds ratios using logistic regression analysis and corresponding population attributable fractions (PAFs). RESULTS: We screened 42,427 persons (age ≥6 years), of whom 254 had confirmed active epilepsy. The pooled prevalence of active epilepsy per 1,000 was 9.8 (95% confidence interval [CI] 8.6-11.1), 17.7 (14.2-20.6) in Gwandu, 4.8 (3.4-6.6) in Afikpo, and 3.3 (2.0-5.1) in Ijebu-Jesa. The pooled incidence per 100,000 was 101.3 (95% CI 57.9-167.6), 201.2 (105.0-358.9) in Gwandu, 27.6 (3.3-128.0) in Afikpo, and 23.9 (3.2-157.0) in Ijebu-Jesa. Children's significant risk factors included febrile seizures, meningitis, poor perinatal care, open defecation, measles, and family history in first-degree relatives. In adults, head injury, poor perinatal care, febrile seizures, family history in second-degree relatives, and consanguinity were significant. Gwandu had more significant risk factors. The PAF for the important factors in children was 74.0% (71.0%-76.0%) and in adults was 79.0% (75.0%-81.0%). CONCLUSION: This work suggests varied epidemiologic numbers, which may be explained by differences in risk factors and population structure in the different regions. These variations should differentially determine and drive prevention and health care responses

Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols

Purpose: There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed. Methods: Narrative review and presentation of PBM parameters are based on current evidence and expert opinion. Results: PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780–830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2–3 J (J/cm2), and no more than 6 J/cm2 on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations. Conclusion: PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.National Institutes of Health (U.S.) (NIH grant R01AI050875

Low level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 1: mechanisms of action, dosimetric, and safety considerations

Purpose: There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved, may expand the applications for PBM in the management of other complications associated with HNC treatment. This article (part 1) describes PBM mechanisms of action, dosimetry, and safety aspects and, in doing so, provides a basis for a companion paper (part 2) which describes the potential breadth of potential applications of PBM in the management of side-effects of (chemo)radiation therapy in patients being treated for HNC and proposes PBM parameters. Methods: This study is a narrative non-systematic review. Results: We review PBM mechanisms of action and dosimetric considerations. Virtually, all conditions modulated by PBM (e.g., ulceration, inflammation, lymphedema, pain, fibrosis, neurological and muscular injury) are thought to be involved in the pathogenesis of (chemo)radiation therapy-induced complications in patients treated for HNC. The impact of PBM on tumor behavior and tumor response to treatment has been insufficiently studied. In vitro studies assessing the effect of PBM on tumor cells report conflicting results, perhaps attributable to inconsistencies of PBM power and dose. Nonetheless, the biological bases for the broad clinical activities ascribed to PBM have also been noted to be similar to those activities and pathways associated with negative tumor behaviors and impeded response to treatment. While there are no anecdotal descriptions of poor tumor outcomes in patients treated with PBM, confirming its neutrality with respect to cancer responsiveness is a critical priority. Conclusion: Based on its therapeutic effects, PBM may have utility in a broad range of oral, oropharyngeal, facial, and neck complications of HNC treatment. Although evidence suggests that PBM using LLLT is safe in HNC patients, more research is imperative and vigilance remains warranted to detect any potential adverse effects of PBM on cancer treatment outcomes and survival.National Institutes of Health (U.S.) (grant R01AI050875

Comprehensive diagnostics of acute myeloid leukemia by whole transcriptome RNA sequencing

Acute myeloid leukemia (AML) is caused by genetic aberrations that also govern the prognosis of patients and guide risk-adapted and targeted therapy. Genetic aberrations in AML are structurally diverse and currently detected by different diagnostic assays. This study sought to establish whole transcriptome RNA sequencing as single, comprehensive, and flexible platform for AML diagnostics. We developed HAMLET (Human AML Expedited Transcriptomics) as bioinformatics pipeline for simultaneous detection of fusion genes, small variants, tandem duplications, and gene expression with all information assembled in an annotated, user-friendly output file. Whole transcriptome RNA sequencing was performed on 100 AML cases and HAMLET results were validated by reference assays and targeted resequencing. The data showed that HAMLET accurately detected all fusion genes and overexpression of EVI1 irrespective of 3q26 aberrations. In addition, small variants in 13 genes that are often mutated in AML were called with 99.2% sensitivity and 100% specificity, and tandem duplications in FLT3 and KMT2A were detected by a novel algorithm based on soft-clipped reads with 100% sensitivity and 97.1% specificity. In conclusion, HAMLET has the potential to provide accurate comprehensive diagnostic information relevant for AML classification, risk assessment and targeted therapy on a single technology platform

Accounting for the complex hierarchical topology of EEG phase-based functional connectivity in network binarisation

Research into binary network analysis of brain function faces a methodological challenge in selecting an appropriate threshold to binarise edge weights. For EEG phase-based functional connectivity, we test the hypothesis that such binarisation should take into account the complex hierarchical structure found in functional connectivity. We explore the density range suitable for such structure and provide a comparison of state-of-the-art binarisation techniques, the recently proposed Cluster-Span Threshold (CST), minimum spanning trees, efficiency-cost optimisation and union of shortest path graphs, with arbitrary proportional thresholds and weighted networks. We test these techniques on weighted complex hierarchy models by contrasting model realisations with small parametric differences. We also test the robustness of these techniques to random and targeted topological attacks.We find that the CST performs consistenty well in state-of-the-art modelling of EEG network topology, robustness to topological network attacks, and in three real datasets, agreeing with our hypothesis of hierarchical complexity. This provides interesting new evidence into the relevance of considering a large number of edges in EEG functional connectivity research to provide informational density in the topology.Comment: Accepted for publication in PLOS One, 27th September 201

Seizure prediction : ready for a new era

Acknowledgements: The authors acknowledge colleagues in the international seizure prediction group for valuable discussions. L.K. acknowledges funding support from the National Health and Medical Research Council (APP1130468) and the James S. McDonnell Foundation (220020419) and acknowledges the contribution of Dean R. Freestone at the University of Melbourne, Australia, to the creation of Fig. 3.Peer reviewedPostprin