Early and Bi-hemispheric seizure onset in a rat glioblastoma Multiforme model.

GBM is the most life-threatening neurological disease with annual incidence of âˆ¼ 5 cases per 100,000 people and a median survival of less than 15 months. Seizures are the first clinical symptoms in 40%-45% of patients with GBM and its epileptogenic mechanisms are poorly understood, largely due to the challenge to develop a clinically-relevant animal model and the unknown latent period. In this study, we used continuous video-EEG monitoring to detect the earliest interictal and ictal events in a CRISPR- IUE GBM rat model that shares pathological and clinical features with those observed in human patients. To our best knowledge, we showed for the first time that interictal epileptiform discharges emerged during early postnatal weeks and the first ictal event occurred during the fourth postnatal week. We also showed GBM animals showed independent bi-hemispheric epileptogenic events, suggesting a widespread circuitry dysregulation. Together, our work identified the temporal- and spatial frame of epileptogenic network in a highly clinically-relevant GBM animal model, paving ways for mechanistic studies at molecular, cellular and circuitry levels.

Posterior reversible encephalopathy syndrome as an underlying cause for encephalopathy in a sepsis patient in the intensive care unit: A case report.

Posterior reversible encephalopathy (PRES) is a clinical and radiological syndrome characterized by neurological findings and vasogenic edema in the posterior regions of the cerebral hemispheres. Sepsis and septic shock have recently been recognized as an etiological factor in PRES. In this case report, we are presenting a patient with intraabdominal sepsis and PRES followed in the intensive care unit with an unfavorable neurological outcome. Wider recognition of PRES as a cause of encephalopathy in sepsis patients is necessary.

Transcriptomic Landscape and Functional Characterization of Induced Pluripotent Stem Cell-Derived Cerebral Organoids in Schizophrenia.

Importance: Three-dimensional cerebral organoids generated from patient-derived induced pluripotent stem cells (iPSCs) may be used to interrogate cellular-molecular underpinnings of schizophrenia. Objective: To determine transcriptomic profiles and functional characteristics of cerebral organoids from patients with schizophrenia using gene expression studies, complemented with investigations of mitochondrial function through measurement of real-time oxygen consumption rate, and functional studies of neuronal firing with microelectrode arrays. Design, Setting, and Participants: This case-control study was conducted at Massachusetts General Hospital between 2017 and 2019. Transcriptomic profiling of iPSC-derived cerebral organoids from 8 patients with schizophrenia and 8 healthy control individuals was undertaken to identify cellular pathways that are aberrant in schizophrenia. Induced pluripotent stem cells and cerebral organoids were generated from patients who had been diagnosed as having schizophrenia and from heathy control individuals. Main Outcomes and Measures: Transcriptomic analysis of iPSC-derived cerebral organoids from patients with schizophrenia show differences in expression of genes involved in synaptic biology and neurodevelopment and are enriched for genes implicated in schizophrenia genome-wide association studies (GWAS). Results: The study included iPSC lines generated from 11 male and 5 female white participants, with a mean age of 38.8 years. RNA sequencing data from iPSC-derived cerebral organoids in schizophrenia showed differential expression of genes involved in synapses, in nervous system development, and in antigen processing. The differentially expressed genes were enriched for genes implicated in schizophrenia, with 23% of GWAS genes showing differential expression in schizophrenia and control organoids: 10 GWAS genes were upregulated in schizophrenia organoids while 15 GWAS genes were downregulated. Analysis of the gene expression profiles suggested dysregulation of genes involved in mitochondrial function and those involved in modulation of excitatory and inhibitory pathways. Studies of mitochondrial respiration showed lower basal consumption rate, adenosine triphosphate production, proton leak, and nonmitochondrial oxygen consumption in schizophrenia cerebral organoids, without any differences in the extracellular acidification rate. Microelectrode array studies of cerebral organoids showed no differences in baseline electrical activity in schizophrenia but revealed a diminished response to stimulation and depolarization. Conclusions and Relevance: Investigations of patient-derived cerebral organoids in schizophrenia revealed gene expression patterns suggesting dysregulation of a number of pathways in schizophrenia, delineated differences in mitochondrial function, and showed deficits in response to stimulation and depolarization in schizophrenia.

Automatic detection of the epileptogenic zone: An application of the fingerprint of epilepsy.

BACKGROUND: The successful delineation of the epileptogenic zone in epilepsy monitoring is crucial for achieving seizure freedom after epilepsy surgery. NEW METHOD: We aim to improve epileptogenic zone localization by utilizing a computer-assisted tool for the automated grading of the seizure activity recorded in various locations for 20 patients undergoing stereo electroencephalography. Their epileptic seizures were processed to extract two potential biomarkers. The concentration of these biomarkers from within each patient's implantation were then graded to identify their epileptogenic zone and were compared to the clinical assessment. RESULTS: Our technique was capable of ranking the clinically defined epileptogenic zone with high accuracy, above 95%, with a true to false positive ratio of 1:1.52, and was effective with both temporal and extra-temporal onset epilepsies. COMPARISON WITH EXISTING METHOD: We compared our method to two other groups performing localization using similar biomarkers. Our classification metrics, sensitivity and precision together were comparable to both groups and our overall accuracy from a larger population was also higher then both. CONCLUSIONS: Our method is highly accurate, automated and non-parametric providing clinicians another tool that can be used to help identify the epileptogenic zone in patients undergoing the stereo electroencephalography procedure for epilepsy monitoring.

Senescence-associated-ß-galactosidase staining following traumatic brain injury in the mouse cerebrum.

Primary and secondary traumatic brain injury (TBI) can cause tissue damage by inducing cell death pathways including apoptosis, necroptosis, and autophagy. However, similar pathways can also lead to senescence. Senescent cells secrete senescence-associated secretory phenotype proteins following persistent DNA damage response signaling, leading to cell disorders. TBI initially activates the cell cycle followed by the subsequent triggering of senescence. This study aims to clarify how the mRNA and protein expression of different markers of cell cycle and senescence are modulated and switched over time after TBI. We performed senescence-associated-ß-galactosidase (SA-ß-gal) staining, immunohistochemical analysis, and real-time PCR to examine the time-dependent changes in expression levels of proteins and mRNA, related to cell cycle and cellular senescence markers, in the cerebrum during the initial 14 days after TBI using a mouse model of controlled cortical impact (CCI). Within the area adjacent to the cerebral contusion after TBI, the protein and/or mRNA expression levels of cell cycle markers were increased significantly until 4 days after injury and senescence markers were significantly increased at 4, 7, and 14 days after injury. Our findings suggested that TBI initially activated the cell cycle in neurons, astrocytes, and microglia within the area adjacent to the hemicerebrum contusion in TBI, whereas after 4 days, such cells could undergo senescence in a cell-type-dependent manner.

Tinnitus: una patología cerebral / Tinnitus: a brain pathology

RESUMEN El tinnitus es un síntoma caracterizado por la percepción de un sonido en ausencia de un estímulo externo. Si bien su fisiopatología puede involucrar una alteración a nivel del funcionamiento del oído interno, la percepción de éste y el grado de molestias asociadas dependen de modificaciones de redes cerebrales cognitivas y emocionales. En la presente revisión, se abordan los cambios que existen a nivel coclear, de tronco encefálico, tálamo y la extensa red cerebral que dan cuenta del tinnitus, discutiendo como esta nueva conceptualización tiene importantes implicancias clínicas, permitiendo una mejor comprensión de los síntomas asociados al tinnitus, sus comorbilidades, y el desarrollo de nuevas estrategias terapéuticas.

ABSTRACT Tinnitus is a symptom characterized by the perception of a sound without an external stimulus. Although the pathophysiology of tinnitus initially involves an alteration of the inner ear function, the perception of it and the degree of distress associated with it depends on changes in cognitive and emotional brain networks. In this article, we review the changes that exist at the cochlea, brainstem, thalamus and a widespread cerebral networks that account for tinnitus, discussing how this new conceptualization has significant clinical implications and allows a better understanding of the symptoms associated with tinnitus, its co-morbidities, and how this view has allowed the development of new therapies.

Microglia and amyloid precursor protein coordinate control of transient Candida cerebritis with memory deficits.

Bloodborne infections with Candida albicans are an increasingly recognized complication of modern medicine. Here, we present a mouse model of low-grade candidemia to determine the effect of disseminated infection on cerebral function and relevant immune determinants. We show that intravenous injection of 25,000 C. albicans cells causes a highly localized cerebritis marked by the accumulation of activated microglial and astroglial cells around yeast aggregates, forming fungal-induced glial granulomas. Amyloid precursor protein accumulates within the periphery of these granulomas, while cleaved amyloid beta (Aß) peptides accumulate around the yeast cells. CNS-localized C. albicans further activate the transcription factor NF-κB and induce production of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor (TNF), and Aß peptides enhance both phagocytic and antifungal activity from BV-2 cells. Mice infected with C. albicans display mild memory impairment that resolves with fungal clearance. Our results warrant additional studies to understand the effect of chronic cerebritis on cognitive and immune function.

The protective mechanism underlying total flavones of Dracocephalum (TFD) effects on rat cerebral ischemia reperfusion injury.

Previously, total flavones of Dracocephalum (TFD), derived from Dracocephalum, were found to exert protective effects in cerebral ischemia reperfusion injury (CIRI) in middle cerebral artery occlusion (MCAO) rat model. However, the mechanisms underlying these observed effects of TFD on MCAO-induced rats still remain to be determined. Therefore, the aim of this study was to examine whether TFD alleviated MCAO through mechanisms involving anti-inflammatory and anti-apoptotic using MCAO rats. The following parameters were measured: (1) percentage (%) area of brain infarction; (2) serum levels of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and (3) expression protein levels of caspase-3 and AMP-activated protein kinase (AMPK). Results showed that MCAO significantly increased the % area of brain infarction, while TFD administration in these animals markedly reduced % area of brain infarction. A significant elevation on serum levels of TNF-α and IL-6 was noted with MCAO which was markedly reduced by TFD. In addition, MCAO produced a significant rise in protein expression levels of caspase-3 and AMPK. In contrast, TFD markedly lowered protein expression levels of caspase-3 and AMPK. Data suggest that the protective effects of TFD in MCAO model animals may involve inhibition of inflammatory mediator release associated with apoptosis through down regulation of AMPK signaling pathway.

Reorganization of cerebro-cerebellar circuit in patients with left hemispheric gliomas involving language network: A combined structural and resting-state functional MRI study.

The role of cerebellum and cerebro-cerebellar system in neural plasticity induced by cerebral gliomas involving language network has long been ignored. Moreover, whether or not the process of reorganization is different in glioma patients with different growth kinetics remains largely unknown. To address this issue, we utilized preoperative structural and resting-state functional MRI data of 78 patients with left cerebral gliomas involving language network areas, including 46 patients with low-grade glioma (LGG, WHO grade II), 32 with high-grade glioma (HGG, WHO grade III/IV), and 44 healthy controls. Spontaneous brain activity, resting-state functional connectivity and gray matter volume alterations of the cerebellum were examined. We found that both LGG and HGG patients exhibited bidirectional alteration of brain activity in language-related cerebellar areas. Brain activity in areas with increased alteration was significantly correlated with the language and MMSE scores. Structurally, LGG patients exhibited greater gray matter volume in regions with increased brain activity, suggesting a structure-function coupled alteration in cerebellum. Furthermore, we observed that cerebellar regions with decreased brain activity exhibited increased functional connectivity with contralesional cerebro-cerebellar system in LGG patients. Together, our findings provide empirical evidence for a vital role of cerebellum and cerebro-cerebellar circuit in neural plasticity following lesional damage to cerebral language network. Moreover, we highlight the possible different reorganizational mechanisms of brain functional connectivity underlying different levels of behavioral impairments in LGG and HGG patients.

The PKA-C3 catalytic subunit is required in two pairs of interneurons for successful mating of Drosophila.

Protein kinase A (PKA) has been shown to play a role in a plethora of cellular processes ranging from development to memory formation. Its activity is mediated by the catalytic subunits whereby many species express several paralogs. Drosophila encodes three catalytic subunits (PKA-C1-3) and whereas PKA-C1 has been well studied, the functions of the other two subunits were unknown. PKA-C3 is the orthologue of mammalian PRKX/Pkare and they are structurally more closely related to each other than to other catalytic subunits within their species. PRKX is expressed in the nervous system in mice but its function is also unknown. We now show that the loss of PKA-C3 in Drosophila causes copulation defects, though the flies are active and show no defects in other courtship behaviours. This phenotype is specifically due to the loss of PKA-C3 because PKA-C1 cannot replace PKA-C3. PKA-C3 is expressed in two pairs of interneurons that send projections to the ventro-lateral protocerebrum and the mushroom bodies and that synapse onto motor neurons in the ventral nerve cord. Rescue experiments show that expression of PKA-C3 in these interneurons is sufficient for copulation, suggesting a role in relaying information from the sensory system to motor neurons to initiate copulation.

Hemispherectomy in treatment of seizures: current perspectives of the indications, techniques and complications: literature review

Introducción: A hemisferectomía es un procedimiento valioso en el tratamiento de trastornos convulsivos causados por desordenes hemisféricos unilaterales. El hemisferectomía anatómica se ha utilizado para este fin desde 1938, sin embargo, se abandonó este procedimiento después de informes de complicaciones postoperatorias causadas por hemosiderosis superficial, ependimitis e hidrocefalia obstructiva. Así que, se ha mostrado en la literatura modificaciones en las indicaciones y técnicas de hemisferectomía anatómica cuya finalidad es la de reducir la incidencia de esta complicación sin dejar de lograr control de las convulsiones. Sobre la base de la literatura, la hemisferectomía mejora la calidad de vida de los pacientes que tiene la indicación para realizar este procedimiento, ya que permite reducir la frecuencia de las convulsiones, si tónica o átona, tónico-clónicas Objetivo: El objetivo de esta revisión de la literatura es discutir los detalles técnicos, modalidades, riesgos, complicaciones, resultados y de pronóstico de hemisferectomía basado en la revisión crítica de la literatura. Casuística y Métodos: Se realizó la consulta bibliográfica, utilizando la base de datos MEDLINE, LILACS, SciELO, que utiliza el lenguaje como criterios de selección, la elección de los artículos recientes preferiblemente en portugués, español o inglés. Conclusión: Según las referencias, hemisferectomía es un procedimiento con buen resultado para las personas con convulsiones derivadas cuando está indicado para casos seleccionados y la tasa de éxito no es proporcional a la extensión de la resección del tejido neuronal. A mayor resección puede o no reducir la frecuencia de las crisis, sin embargo, la incidencia de la morbilidad puede ser mayor.

Background: The hemispherectomy is a valuable procedure in the management of seizure disorders caused by unilateral hemispheric disease. The anatomical hemispherectomy has been used for this purpose since 1938, however, it was abandoned after reports of postoperative complications caused by superficial hemosiderosis, ependymitis and obstructive hydrocephalus. So that, it has been showed modifications in the techniques of hemispherectomy whose the purpose is reduce the incidence of this complications while still achieving seizure control. Based on literature, the hemispherectomy improves the quality of life of patients that has the indication to perform this procedure because it allows reducing the frequency of seizures, whether tonic or atonic, tonic-clonic. Aim: The aim of this literature review is discuss the indications, technical details, modalities, risks, complications, results as well de prognosis of callosotomy based on critical literature review and the authors experience. Casuistry and Methods: It was performed bibliographical consultation, using the databases MEDLINE, LILACS, SciELO, utilizing language as selection criteria, choosing preferably recent articles in Portuguese, Spanish or English. Conclusion: According to references, the functional hemispherectomy has a good outocome for those with seizures arisin when indicated to selected cases and the success rate is not proportional to the extent of neuronal tissue resection. So that, a greater resection cannot necessarily reduce the seizure frequency, however the morbidity may also be larger.

Effects of vanillin on potassium bromate-induced neurotoxicity in adult mice: impact on behavior, oxidative stress, genes expression, inflammation and fatty acid composition.

CONTEXT: Vanillin is known to possess important antioxidant activity. OBJECTIVE: The current study was conducted to establish the therapeutic efficiency of vanillin against potassium bromate (KBrO3)-induced depression-like behavior and oxidative stress in mice. MATERIAL AND METHODS: Mice were exposed during 15 days either to potassium bromate (KBrO3), KBrO3+ vanillin or to only vanillin. RESULTS: Our results revealed a significant modification in the fatty acid composition of the KBrO3-treated mice. In addition, KBrO3 induced a significant reduction in enzymatic activities and gene expressions, Na+ -K+ and Mg2+-ATPases, acetylcholinesterase and butylcholinesterase activities. The gene expression of tumor necrosis factor-α, interleukin-1ß, interleukin-6 and COX2, significantly increased in the cerebrum of KBrO3-treated group. Histopathological observations were consistent with these effects. Co-treatment with vanillin significantly attenuated KBrO3-induced oxidative stress and inflammation. CONCLUSION: This work suggests that vanillin mitigates KBrO3-induced depression, and that this neuroprotective effect proceeds through anti-oxidant and anti-inflammatory activities.

Stereotactic probability and variability of speech arrest and anomia sites during stimulation mapping of the language dominant hemisphere.

OBJECTIVE Functional mapping using direct cortical stimulation is the gold standard for the prevention of postoperative morbidity during resective surgery in dominant-hemisphere perisylvian regions. Its role is necessitated by the significant interindividual variability that has been observed for essential language sites. The aim in this study was to determine the statistical probability distribution of eliciting aphasic errors for any given stereotactically based cortical position in a patient cohort and to quantify the variability at each cortical site. METHODS Patients undergoing awake craniotomy for dominant-hemisphere primary brain tumor resection between 1999 and 2014 at the authors' institution were included in this study, which included counting and picture-naming tasks during dense speech mapping via cortical stimulation. Positive and negative stimulation sites were collected using an intraoperative frameless stereotactic neuronavigation system and were converted to Montreal Neurological Institute coordinates. Data were iteratively resampled to create mean and standard deviation probability maps for speech arrest and anomia. Patients were divided into groups with a "classic" or an "atypical" location of speech function, based on the resultant probability maps. Patient and clinical factors were then assessed for their association with an atypical location of speech sites by univariate and multivariate analysis. RESULTS Across 102 patients undergoing speech mapping, the overall probabilities of speech arrest and anomia were 0.51 and 0.33, respectively. Speech arrest was most likely to occur with stimulation of the posterior inferior frontal gyrus (maximum probability from individual bin = 0.025), and variance was highest in the dorsal premotor cortex and the posterior superior temporal gyrus. In contrast, stimulation within the posterior perisylvian cortex resulted in the maximum mean probability of anomia (maximum probability = 0.012), with large variance in the regions surrounding the posterior superior temporal gyrus, including the posterior middle temporal, angular, and supramarginal gyri. Patients with atypical speech localization were far more likely to have tumors in canonical Broca's or Wernicke's areas (OR 7.21, 95% CI 1.67-31.09, p < 0.01) or to have multilobar tumors (OR 12.58, 95% CI 2.22-71.42, p < 0.01), than were patients with classic speech localization. CONCLUSIONS This study provides statistical probability distribution maps for aphasic errors during cortical stimulation mapping in a patient cohort. Thus, the authors provide an expected probability of inducing speech arrest and anomia from specific 10-mm2 cortical bins in an individual patient. In addition, they highlight key regions of interindividual mapping variability that should be considered preoperatively. They believe these results will aid surgeons in their preoperative planning of eloquent cortex resection.

Alteration of the Intra- and Cross- Hemisphere Posterior Default Mode Network in Frontal Lobe Glioma Patients.

Patients with frontal lobe gliomas often experience neurocognitive dysfunctions before surgery, which affects the default mode network (DMN) to different degrees. This study quantitatively analyzed this effect from the perspective of cerebral hemispheric functional connectivity (FC). We collected resting-state fMRI data from 20 frontal lobe glioma patients before treatment and 20 healthy controls. All of the patients and controls were right-handed. After pre-processing the images, FC maps were built from the seed defined in the left or right posterior cingulate cortex (PCC) to the target regions determined in the left or right temporal-parietal junction (TPJ), respectively. The intra- and cross-group statistical calculations of FC strength were compared. The conclusions were as follows: (1) the intra-hemisphere FC strength values between the PCC and TPJ on the left and right were decreased in patients compared with controls; and (2) the correlation coefficients between the FC pairs in the patients were increased compared with the corresponding controls. When all of the patients were grouped by their tumor's hemispheric location, (3) the FC of the subgroups showed that the dominant hemisphere was vulnerable to glioma, and (4) the FC in the dominant hemisphere showed a significant correlation with WHO grade.

Bateria Montreal de Avaliação da Comunicação - versão portuguesa: efeito da idade e escolaridade / Montreal Communication Evaluation Battery - Portuguese version: age and education effects

RESUMO Objetivos: Verificar o efeito das variáveis idade e escolaridade no desempenho de adultos saudáveis na Bateria Montreal de Avaliação da Comunicação, versão portuguesa (MAC-PT). Métodos: A amostra foi composta por 90 indivíduos portugueses, falantes do Portugês Europeu, distribuídos em 9 grupos de acordo com a escolaridade (4 a 9; 10 a 13; e mais de 13 anos de ensino formal) e com a idade (19 a 40; 41 a 64; e 65 a 80 anos). Para análise de comparação entre grupos, utilizou-se o testetwo-way ANOVA, com post-hoc Bonferroni (p≤0,05). Resultados: Verificou-se que o desempenho dos indivíduos foi influenciado pela variável idade nas tarefas pragmático-inferencial, discursiva e prosódica. Já a escolaridade influenciou o desempenho em todos os processamentos avaliados pela MAC-PT. Conclusão: As variáveis idade e escolaridade influenciaram o desempenho comunicativo e devem ser consideradas no processo de avaliação de pacientes neurológicos.

ABSTRACT Purpose: To verify age and education effects on communication performance of healthy adults in the Montreal Communication Evaluation Battery, Portuguese version (MAC-PT). Methods: The sample comprised 90 healthy adults from Portugal, European Portuguese speakers, divided into nine groups according to educational level (4-9, 10-13, and >13 years of formal schooling) and age (19-40, 41-64, and 65-80 years). The influence of age and education was assessed by comparing mean scores between groups, using a two-way analysis of variance followed by Bonferroni post hoc tests (p ≤0.05). Results: The results showed that participants' performance was influenced by age in pragmatic-inferential, discursive, and prosodic tasks. Education had the greatest influence on the performance in all processes evaluated by the MAC-PT. Conclusion: Age and education seem to influence the communicative performance and should be considered in the assessment of neurological patients.

Tinnitus neural mechanisms and structural changes in the brain: the contribution of neuroimaging research

Introduction Tinnitus is an abnormal perception of sound in the absence of an external stimulus. Chronic tinnitus usually has a high impact in many aspects of patients' lives, such as emotional stress, sleep disturbance, concentration difficulties, and so on. These strong reactions are usually attributed to central nervous system involvement. Neuroimaging has revealed the implication of brain structures in the auditory system. Objective This systematic review points out neuroimaging studies that contribute to identifying the structures involved in the pathophysiological mechanism of generation and persistence of various forms of tinnitus. Data Synthesis Functional imaging research reveals that tinnitus perception is associated with the involvement of the nonauditory brain areas, including the front parietal area; the limbic system, which consists of the anterior cingulate cortex, anterior insula, and amygdala; and the hippocampal and parahippocampal area. Conclusion The neuroimaging research confirms the involvement of the mechanisms of memory and cognition in the persistence of perception, anxiety, distress, and suffering associated with tinnitus.

Have You Ever Seen the Impact of Crossing Fiber in DTI?: Demonstration of the Corticospinal Tract Pathway.

OBJECTIVE: The identification of the corticospinal tract (CST) pathway with a deterministic fiber tracking approach is limited because of crossing fibers, especially for the hand fibers of the CST due to the crossing superior longitudinal fasciculus (SLF). We examined a patient with congenital bilateral perisylvian syndrome (CBPS) who did not have the SLF, in order to visualize CST hand fibers that were not affected by crossing fibers. METHODS: A 10-year-old girl without the SLF due to CBPS and three normal healthy subjects participated in this study. We used a deterministic fiber tracking algorithm, and the regions of interest (ROIs) were drawn in the posterior limb of internal capsule (PLIC) and the primary motor cortex. The apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative anisotropy (RA), and volume ratio (VR) were measured based on the extracted fiber tracts. RESULTS: The ADC values were not different between the normal subjects and the patient with CBPS. The FA, RA, and VR values of the normal subjects were similar, but were relatively higher than those of the patient with CBPS. CONCLUSION: Our results clearly show the impact of the crossing fiber for the hand motor fibers of the CST pathway with deterministic tracking algorithms in diffusion tensor tractography.

Experiencias globales de la fortificación de la harina con ácido fólico para disminuir los defectos del tubo neural / Global experiences with folic acid fortification of flour to reduce neural tube defects

Los defectos del tubo neural son defectos congénitos del cerebro y la médula espinal que pueden provocar discapacidad permanente o muerte en los bebés afectados. Se estima que globalmente hay 320.000 defectos del tubo neural cada año. De estos, aproximadamente tres cuartos se pueden prevenir si la mujer tiene un buen estado de folato en el periodo alrededor de la concepción. La fortificación masiva de alimentos aporta ácido fólico a la dieta de mujeres en el periodo peri-concepcional. De los 81 países que requieren la fortificación de harina de trigo o maíz, 77 obligan la adición de ácido fólico. Se ha documentado en varios países que la fortificación obligatoria y masiva de harina con ácido fólico aumenta niveles séricos de folatos y reduce defectos del tubo neural. Una meta-análisis ha estimado en 46% la reducción promedio en defectos del tubo neural a raíz de la fortificación masiva de harina con ácido fólico. La espina bífida es uno de los defectos del tubo neural que se puede prevenir con ácido fólico; el costo:beneficio de prevenir la espina bífida es favorable y se ha estimado entre 1:12 y 1:48. A pesar de estos éxitos, se estima que solamente 15% de los defectos del tubo neural que se pudieran prevenir con ácido fólico se están previniendo con fortificación masiva de harina. Existen lineamientos y experiencias globales para guiar aquellos países interesados en fortificar la harina con ácido fólico para reducir defectos del tubo neural(AU)

Neural tube defects are congenital anomalies of the brain and spine that can lead to permanent disability or death in affected babies. There are an estimated 320,000 neural tube defects annually throughout the world. Of these, approximately three-fourths are preventable if women have sufficient folate status in the peri-conceptional period. Mass food fortification contributes folic acid to women's diets in the peri-conceptional period. Of 81 countries that mandate wheat flour or maize flour fortification, 77 require the addition of folic acid. It has been documented in several countries that mandatory mass fortification of flour with folic acid increases blood folate levels and reduces neural tube defects. A metaanalysis estimated a 46% average reduction in neural tube defects due to folic-acid fortification of flour. The cost:benefit ratio of preventing spina bifida, a type of neural tube defect that can be prevented with folic acid, is favorable and estimated to be between 1:12 and 1:48. Despite these successes, it is estimated that only 15% of those neural tube defects that can be prevented by folic acid are being prevented through mass fortification of flour. There are international guidelines and experiences that interested countries can draw upon to fortify flour with folic acid to reduce neural tube defects(AU)

Impaired pre-attentive auditory processing in fibromyalgia: A mismatch negativity (MMN) study.

OBJECTIVE: Fibromyalgia (FM) patients often show deficits in cognitive functions such as attention and working memory. We assumed that pre-attentive information processing, a crucial element in human perception and cognition, would be altered in FM patients. Thus, the objective of this study was to determine whether FM patients exhibit alterations in pre-attentive processing as assessed by auditory mismatch negativity (MMN). METHODS: Auditory evoked magnetic fields were recorded in FM patients (n=18) and healthy control subjects (n=21) during a duration-deviant auditory oddball paradigm. The magnetic mismatch negativity (MMNm) was obtained by subtracting responses to standard tones from responses to deviant tones. Pressure pain thresholds over the thenar and trapezius muscles were determined using an algometer. RESULTS: MMNm peak amplitudes in right hemispheres were attenuated, and the directional asymmetry coefficient of the MMNm amplitude was lower in FM patients, indicating a more leftward asymmetry than in healthy control subjects. Smaller right MMNm amplitude was associated with lower pressure pain thresholds of thenar muscles in FM patients. CONCLUSIONS: Our results suggested that pre-attentive processing of auditory information is impaired in FM patients. SIGNIFICANCE: This study provided neurophysiological evidence of impaired pre-attentive sensory change detection in FM.

Executive-affective connectivity in smokers viewing anti-smoking images: an fMRI study.

Despite knowledge of the harmful consequences of smoking on health, tobacco users continue to smoke. Neuroimaging studies have begun to provide insight into the mechanisms underlying this response. Regions involved in executive control and affective processing/persuasion are activated when viewing the negative value of smoking, but these systems can interact in ways that promote or hinder its impact on behavior. The goal of this functional magnetic resonance imaging (fMRI) study was to examine the dynamics between these systems during the processing of images designed to elicit a negative emotional response regarding tobacco smoking in a group of current smokers. Thirty chronic smokers passively viewed aversive smoking-related, aversive nonsmoking-related and neutral images presented in a block design while being scanned. Functional connectivity analyses showed that the left inferior frontal gyrus (IFG) is negatively associated to activity in medial frontal, cingulate, limbic, subcortical and parietal regions in chronic smokers during the processing of aversive smoking-related material, a pattern that was significantly greater when stimuli were drug-related compared with when they were nondrug-related. Our results suggest that individuals with tobacco dependence present different patterns of functional connectivity depending on whether the aversive stimuli are smoking- or nonsmoking-related. Activity in the left inferior frontal gyrus may act to down-regulate corresponding activity in regions key to an affective and persuasive response during the processing of anti-smoking material. This mechanism may reduce the extent to which "feeling bad" brings about a change in behavior.