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The cerebellum has long been conceptualized to control motor learning and motor coordination. However, increasing evidence suggests its roles in cognition and emotion behaviors. In particular, the cerebellum has been recognized as one of key brain regions affected in autism spectrum disorder (ASD). To better understand the contribution of the cerebellum in ASD pathogenesis, we here discuss recent behavioral, genetic, and molecular studies from the human and mouse models. In addition, we raise several questions that need to be investigated in future studies from the point view of cerebellar dysfunction, cerebro-cerebellar connectivity and ASD.

Background and purpose : The cerebellum has a pivotal role in regulating human behavior; yet whether this function is mediated only through contralateral cerebro-cerebellar pathways is under-investigated. Thus, we examined feed-backward and feed-forward ipsilateral and contralateral cerebro-cerebellar connections using a detereministic diffusion tensor imaging (DTI) algorithm, the robustness of which was also estimated using phantom DTI data. Materials and methods : Fifty-one healthy controls (22–60 years old; 15 males/36 females) were scanned in a 3T MRI scanner with a 30-direction DTI sequence. Multiple region-of-interest (ROI) method was applied for the reconstruction of the ipsilateral and contralateral (based on cerebellar seed ROI) fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC), occipito-ponto-cerebellar (OPC) and dentate-rubro-thalamo-cortical (DRTC) tract bilaterally using the Brainance DTI Suite. A realistic diffusion MR phantom was used to evaluate the fiber tracking methodology for 16 fibers containing crossing, kissing, splitting and bending configurations. Results Both contralateral and ipsilateral FPC, PPC, OPC and ipsilateral DRTC tracts were successfully reconstructed; the contralateral DRTC tract was not reconstructed in all subjects. Also, the TPC tract was not reproduced in several subjects mostly regarding the contralateral connection. Descriptive DTI measures (number of fibers, fractional anisotropy, radial and axial diffusivity) are presented for each tract. Regarding phantom data, Brainance DTI Suite returned a dataset of 16 fibers that almost perfectly matched the 16 ground truth fibers. Conclusions We identified ipsilateral and contralateral connections using a clinically applicable DTI sequence, a robust deterministic algorithm and an unbiased methodology, which can be applied in daily practice in different brain pathologies.

This paper reports the effects of gestational hypertension in the pulsatility index (PI) of umbilical artery (UA) and middle cerebral artery (MCA), cerebro-placental ratio (CPR), and associated adverse perinatal outcomes, after 20 to 40 weeks’ gestation in singleton pregnancy. A total of 280 pregnant women, divided equally into control and gestational hypertension groups, were recruited prospectively. Alpinion Medical System ECUBE 7 ultrasound equipment was used to measure the UA-PI, MCA-PI, and CPR within the two groups. Data were analyzed to correlate the results with the presence of adverse perinatal outcomes. In gestational hypertension group, the UA-PI, MCA-PI, and CPR were associated with adverse perinatal outcomes after adjustment for gestational age. The increase in risk for lower birth weight, higher incidence of elective Cesarean section delivery, and preterm birth were statistically significant for UA-PI, MCA-PI, and CPR. Study of pulsatility indices of placental and fetal circulation in singleton pregnancy developed gestational hypertension can provide important information regarding fetal well-being, yielding an opportunity to improve fetal outcome. Keywords: Cerebro-placental ratio, Doppler ultrasound, Gestational hypertension, Pulsatility index

The brain and kidney both uniquely are highly susceptible to vascular injury from shared vascular risk factors. However these are not sufficient to explain the complete extent of cerebrovascular disease especially small vessel disease in its myriad presentations that patients with chronic kidney disease manifest. They both require a large amount of blood supply to function optimally. Shared anatomical and physiological factors such as the presence of strain vessels, the local vascular autoregulation that control blood supply possible, results in the vulnerability of these organs to the vascular risk factors. Because it is a bidirectional system where each affects the other, it is best considered as a cerebro-renal unit.

Nutrients, hormones and the energy sensor AMP-activated protein kinase (AMPK) tightly regulate the intracel-lular levels of the metabolic intermediary malonyl-CoA, which is a precursor of fatty acid synthesis and a negative regulator of fatty acid oxidation. In the brain, the involvement of malonyl-CoA in the control of food intake and energy homeostasis has been known for decades. However, recent data uncover a new role in cognition and brain development. The sensing of malonyl-CoA by carnitine palmitoyltransferase 1 (CPT1) pro-teins regulates a variety of functions, such as the fate of neuronal stem cell precursors, the motility of lysosomes in developing axons, the trafficking of glutamate receptors to the neuron surface (necessary for proper synaptic function) and the metabolic coupling between astrocytes and neurons. We discuss the relevance of those recent findings evidencing how nutrients and metabolic disorders impact cognition. We also enumerate all nutritional and hormonal conditions that are known to regulate malonyl-CoA levels in the brain, reflect on protein malo-nylation as a new post-translational modification, and give a reasoned vision of the opportunities and challenges that future research in the field could address. info:eu-repo/semantics/publishedVersion

Background The cerebellum has a crucial role in mood regulation. While cerebellar grey matter (GM) alterations have been previously reported in bipolar disorder (BD), cerebro-cerebellar white matter (WM) connectivity alterations and cerebellar GM profiles have not been characterised in the context of predominant polarity (PP) and onset polarity (OP) subphenotypes of BD patients which is the aim of the present study. Methods Forty-two euthymic BD patients stratified for PP and OP and 42 healthy controls (HC) were included in this quantitative neuroimaging study to evaluate cerebellar GM patterns and cerebro-cerebellar WM connections. Diffusion tensor tractography was used to characterise afferent and efferent cerebro-cerebellar tract integrity. False discovery rate corrections were applied in post-hoc comparisons. Results BD patients exhibited higher fractional anisotropy (FA) in fronto-ponto-cerebellar tracts bilaterally compared to HC. Subphenotype-specific FA profiles were identified within the BD cohort. Regarding PP subgroups, we found FA changes in a) left contralateral fronto-ponto-cerebellar tract (depressive-PP > HC) and b) contralateral/ipsilateral fronto-ponto-cerebellar tracts bilaterally (manic-PP > HC). Regarding OP subgroups, we observed FA changes in a) left/right contralateral fronto-ponto-cerebellar tracts (depressive-OP > HC) and b) all fronto-ponto-cerebellar, most parieto-ponto-cerebellar and right contralateral occipito-ponto-cerebellar tracts (manic-OP>HC). In general, greater and more widespread cerebro-cerebellar changes were observed in manic-OP patients than in depressive-OP patients compared to HC. Manic-OP showed higher FA compared to depressive-OP patients in several afferent WM tracts. No GM differences were identified between BD and HC and across BD subgroups. Conclusions Our findings highlight fronto-ponto-cerebellar connectivity alterations in euthymic BD. Polarity-related subphenotypes have distinctive cerebro-cerebellar WM signatures with potential clinical and pathobiological implications.

Introduction Numerous structural studies have already reported volumetric reduction in cerebellum with aging. However, there are still limited studies particularly focusing on analysis of the cerebellar resting state FC in old adults. Even so, the least related studies were unable to include some important cerebellar lobules due to limited cerebellum segmentation methods. Objective The purpose of this study is to explore cognitive function in relation to cerebellar lobular morphometry and cortico-cerebellar connectivity changes in old adults' lifespan by incorporating previously undetected cerebellar lobules. Methods This study includes a sample of 264 old adults subdivided into five cognitively normal age groups (G1 through G5). Cerebellum Segmentation (CERES) software was used to obtain morphometric measures and brain masks of all the 24 cerebellar lobules. We then defined individual lobules as seed regions and mapped the whole-brain to get functional connectivity maps. To analyze age group differences in cortico-cerebellar connectivity and cerebellar lobular volume, we used one way ANOVA and post hoc analysis was performed for multiple comparisons using Bonferroni method. Results Our results report cerebellar lobular volumetric reduction, disrupted intra-cerebellar connectivity and significant differences in cortico-cerebellar resting state FC across age groups. In addition, our results show that disrupted FC between left Crus-II and right ACC relates to well emotion regulation and cognitive decline and is associated with poor performance on TMT-B and logical memory tests in older adults. Conclusion Overall, our findings confirm that as humans get older and older, the cerebellar lobular volumes as well as the cortico-cerebellar functional connectivity are affected and hence reduces cognition.

The aim of this study was to investigate the relationship between the cerebro-umbilical ratio (CUR), measured at 30-34 weeks, and adverse intrapartum and perinatal outcomes.This was a retrospective cross-sectional cohort study of women delivering at the Mater Mothers' Hospital in Brisbane, Australia. Fetal Doppler indices for 1224 singleton pregnancies were correlated with maternal demographics and intrapartum and perinatal outcomes. Only women who attempted vaginal delivery were included in the study.Infants delivered by emergency cesarean section for fetal compromise had the lowest median CUR, 1.65 (IQR 1.17-2.12), compared to any other delivery group. The proportion of infants with a CUR ≤1 who required emergency cesarean section for fetal compromise was 33.3% compared to 9.3% of infants with a CUR1 (adjusted OR 6.92 (95% CI 2.04-25.75), p0.001). However, the detection rate of CUR ≤1 as a predictor for emergency cesarean delivery for fetal compromise was poor (18.9%). Detection rates increased in cohorts of infants born within two weeks of the scan or with birth weights10th centile or5th centile. Additionally, a CUR ≤1 was associated with lower median birth weight, higher rates of admission to the neonatal critical care unit and increased neonatal mortality.This study suggests that a CUR ≤1, measured at 30-34 weeks, is associated with a greater risk of emergency cesarean delivery for fetal compromise and a number of other adverse perinatal outcomes. The association was strongest in low birth weight babies.

Previous studies have suggested cerebro-cerebellar circuitry in working memory. The present fMRI study aims to distinguish differential cerebro-cerebellar activation patterns in verbal and visual working memory, and employs a quantitative analysis to deterimine lateralization of the activation patterns observed. Consistent with Chen and Desmond (2005a,b) predictions, verbal working memory activated a cerebro-cerebellar circuitry that comprised left-lateralized language-related brain regions including the inferior frontal and posterior parietal areas, and subcortically, right-lateralized superior (lobule VI) and inferior cerebellar (lobule VIIIA/VIIB) areas. In contrast, a distributed network of bilateral inferior frontal and inferior temporal areas, and bilateral superior (lobule VI) and inferior (lobule VIIB) cerebellar areas, was recruited during visual working memory. Results of the study verified that a distinct cross cerebro-cerebellar circuitry underlies verbal working memory. However, a neural circuitry involving specialized brain areas in bilateral neocortical and bilateral cerebellar hemispheres subserving visual working memory is observed. Findings are discussed in the light of current models of working memory and data from related neuroimaging studies. MOE (Min. of Education, S’pore) Accepted version

Neuroimaging studies have shown continued structural and functional development in neural circuitry underlying social and emotional behaviour during adolescence. This article explores adolescent neurocognitive development in two domains: sensitivity to social rejection and Theory of Mind (ToM). Adolescents often report hypersensitivity to social rejection. The studies presented here suggest that this is accompanied by reduced responses in brain regions involved in emotion regulation. Studies on social rejection in adolescents with autism spectrum conditions will also be discussed. ToM is another social cognitive domain which undergoes neurocognitive development between adolescence and adulthood. ToM refers to the ability to understand others’ thoughts and intentions. Neuroimaging data suggest that the ability to integrate emotional information into ToM decisions continues to develop between adolescence and adulthood. In sum, these studies demonstrate ongoing development of social and emotional cognition during adolescence at both behavioural and neural levels, providing a neurocognitive framework for understanding adolescent behaviour.

Early life stress, in the form of MD (24 h at pnd 9), interferes with brain developmental trajectories modifying both behavioral and neurobiochemical parameters. MD has been reported to enhance neuroendocrine responses to stress, to affect emotional behavior and to impair cognitive function. More recently, changes in body weight gain, metabolic parameters and immunological responding have also been described. Present data give support to the fact that neuronal degeneration and/or astrocyte proliferation are present in specific brain regions, mainly hippocampus, prefrontal cortex and hypothalamus, which are particularly vulnerable to the effects of neonatal stress. The MD animal model arises as a valuable tool for the investigation of the brain processes occurring at the narrow time window comprised between pnd 9 and 10 that are critical for the establishment of brain circuitries critical for the regulation of behavior, metabolism and energy homeostasis. In the present review we will discuss three possible mechanisms that might be crucial for the effects of MD, namely, the rapid increase in glucocorticoids, the lack of the neonatal leptin surge, and the enhanced endocannabinoid signaling during the specific critical period of MD. A better understanding of the mechanisms underlying the detrimental consequences of MD is a concern for public health and may provide new insights into mental health prevention strategies and into novel therapeutic approaches in neuropsychiatry. Sin financiación 8.580 JCR (2015) Q1, 3/51 Behavioral Sciences, 16/256 Neurosciences UEM

Fil: Hardeland, Rüdiger. University of Goettingen. Johann Friedrich Blumenbach Institute of Zoology and Anthropology; Alemania Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Brown, Gregory M. University of Toronto. Faculty of Medicine. Department of Psychiatry; Canada Fil: Pandi Perumal, Seithikurippu R. Clinical & Translational Research Institute. New York University Medical Center. Department of Population Health. Division of Health and Behavior. Center for Healthful Behavior Change; Estados Unidos Abstract: Melatonin is known to possess several properties of value for healthy aging, as a direct and indirect antioxidant, protectant and modulator of mitochondrial function, antiexcitotoxic agent, enhancer of circadian amplitudes, immune modulator and neuroprotectant. It is levels tend to decrease in the course of senescence and are more strongly reduced in several neurodegenerative disorders, especially Alzheimer’s disease, and in diseases related to insulin resistance such as diabetes type 2. Although the role of melatonin in aging and age-related diseases has been repeatedly discussed, the newly emerged concept of inflammaging, that is, the contribution of low-grade inflammation to senescence progression has not yet been the focus of melatonin research. This review addresses the multiple protective actions of melatonin and its kynuramine metabolites that are relevant to the attenuation of inflammatory responses and progression of inflammaging in the brain, i.e. avoidance of excitotoxicity, reduction of free radical formation by support of mitochondrial electron flux, prevention of NADPH oxidase activation and suppression of inducible nitric oxide synthase, as well as downregulation of proinflammatory cytokines. The experimental evidence is primarily discussed on the basis of aging and senescence-accelerated animals, actions in the immune system, and the relationship between melatonin and sirtuins, having properties of aging suppressors. Sirtuins act either as accessory components or downstream factors of circadian oscillators, which are also under control by melatonin. Inflammaging is assumed to strongly contribute to neurodegeneration of the circadian master clock observed in advanced senescence and, even more, in Alzheimer’s disease, a change that affects countless physiological functions.

It has been demonstrated that motor learning is supported by the cerebellum and the cerebro-cerebellar interaction. Response inhibition involves motor responses and the higher-order inhibition that controls the motor responses. In this functional MRI study, we measured the cerebro-cerebellar interaction during response inhibition in two separate days of task performance, and detected the changes in the interaction following performance improvement. Behaviorally, performance improved in the second day, compared to the first day. The psycho-physiological interaction (PPI) analysis revealed the interaction decrease from the right inferior frontal cortex (rIFC) to the cerebellum (lobule VII or VI). It was also revealed that the interaction increased from the same cerebellar region to the primary motor area. These results suggest the involvement of the cerebellum in response inhibition, and raise the possibility that the performance improvement was supported by the changes in the cerebro-cerebellar interaction.

Introduction and aim Although psychosocial factors (PSF) including work-related stress and low quality of life at work are emerging cardiovascular risk factors, PSF burden remains poorly investigated after acute cerebro- or cardiovascular event (CVE). Methods INEV@L, an ongoing prospective multidisciplinary study, included 156 patients aged Results Among the 156 patients included, 121(78%) had acute MI and 35(22%) stroke. Median (IQR) age was 53(48–58) years, and 18% were women, 56% smokers and had high PSW [15(10–20)], but a low QLW [85(75–95)]. Patients with a higher score to PSW, had similar risk factors including age (P = 0.450), women (0.542), hypertension (P = 0.791), smoking (P = 0.384), diabetes (P = 0.193), obesity (P = 0.995) than patients with a lower score. Although high PSW patients showed a trend toward lower education level (P = 0.067), marital status, and socio-economic categories were similar for both groups. Elevated perceived disease severity was more common (49 vs. 19%) in stressed patients. Patients with high PSW are more anxious (78 vs. 25%, P Conclusion These preliminary data from a prospective pilot study shows a high PSF burden in patients hospitalized for acute CVE. If confirmed at a larger scale, our data could identify new opportunities for secondary preventive strategies.

ResumenLa técnica híbrida PET/CT ha experimentado un notable desarrollo en los últimos años, y sus indicaciones se han extendido más allá del área oncológica. El radiotrazador más utilizado es la F18-fluorodeoxiglucosa (F18-FDG), aunque una serie de nuevos radiofármacos han sido sintetizados mostrando alto rendimiento diagnóstico en ciertas patologías especificas. El presente artículo describe brevemente la utilidad clínica actual del PET/CT y los diferentes radiotrazadores disponibles, tanto en el área oncológica como no oncológica.SummaryPET/CT hybrid image has undergone an important development in last years, and its indications spread beyond oncological area. F18-FDG is the most used radiotracer, but several others new tracers have been synthesized, showing high diagnosis accuracy in some specific situations. The present paper describes briefly the current clinical utility of PET/CT and the different radiotracers available for oncological and non oncological conditions.

ResumoObjetivoInvestigar os efeitos da música motivacional durante 5km de corrida.MétodoTreze corredores amadores foram submetidos a dois condições experimentais aleatórias durante 5km de corrida. Análises de espectroscopia funcional de infravermelho foram usadas previamente em uma tentativa de investigar as características motivacionais da música e sua ativação no córtex pré‐frontal. Durante o exercício proposto, avaliações psicofisiológicas (desempenho; percepção subjetiva de esforço e frequência cardíaca) foram usadas durante cada uma das 12.5 voltas (400 metros).ResultadosAs músicas escolhidas foram capazes de ativar a área do córtex pré‐frontal (diferenças positivas superiores a 0.5ua.μM). A música motivacional aumentou parâmetros relacionados com o desempenho (condição controle – 27.02±0.35min vs. música motivacional – 25.31±0.31min; melhorou em 6.33%). Maior tamanho do efeito foi identificado durante as primeiras voltas (Cohen's d) (0.99 – 1.ɑ volta; 0.62 – 2.ɑ volta; 0.55 – 3.ɑ volta; 0.61 – 4.ɑ volta). A frequência cardíaca foi superior para a condição música motivacional, considerada uma resposta advinda ao maior trabalho físico realizado.ConclusãoA música foi capaz de ativar a região do córtex pré‐frontal e alterar parâmetros psicofisiológicos e de desempenho.AbstractObjectiveInvestigate the psychophysiological effects of motivational music for 5km run.MethodsThirteen amateur runners were subjected to two random experimental conditions during 5km run. Functional infrared spectroscopy analyses were previously used to investigate the motivational qualities of music and its activation in the prefrontal cortex. During the proposed exercise, psychophysiological changes (performance, subjective perception of effort and heart rate) were used for each of the 12.5 laps (400 meters).ResultsThe chosen songs were able to activate the prefrontal cortex area (over 0.5ua.μM positive differences). Motivational music increased performance related parameters (Control ‐ 27.02±0.35min vs motivational music ‐ 25.31±0.31min; improved in 6.33%). Larger size effect was identified during the early laps (Cohen's d) (0.99 ‐ 1st lap; 0.62 ‐ 2nd lap; 0.55 ‐ 3rd lap; 0.61 ‐ 4th lap). Heart rate was higher for motivational music condition, considered a derivative response of greater physical work done.ConclusionThe music was able to activate the prefrontal cortex area and alter psychophysiological and performance parameters.

Summary Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). Its autoimmune origin has been recently challenged by a substantially different mechanism termed chronic cerebrospinal venous insufficiency (CCSVI), which has attracted worldwide attention in the scientific community, in the media and among MS patients. According to this hypothesis, a congestion of cerebrovenous outflow induces an increased intracranial pressure and a disintegration of the blood–brain barrier in perivenular regions promoting local iron deposition and activation of pro-inflammatory factors, ultimately leading to MS. After the initial report of a perfect association between CCSVI and MS, different independent groups were not able to replicate these results, casting doubts on the credibility of the CCSVI concept in MS. In spite of this, interventional procedures like venous angioplasty named the “liberation” treatment have been claimed as a cure of MS or at least as a major improvement of MS symptoms. As a result, an increasing number of MS patients are undergoing endovascular treatment, in spite of a lack of an evidenced-based benefit and recent reports of serious adverse events. This review represents a critical appraisal of the CCSVI hypothesis, discusses its basis, the diagnostic criteria and its relationship with MS.

The study was undertaken to evaluate changes in the activity of adenosine deaminase (ADA) in brains of rats infected by Trypanosoma evansi. Each rat was intraperitoneally infected with 10(6) trypomastigotes either suspended in fresh (group A; n = 13) and cryopreserved blood (group B; n = 13). Thirteen animals were used as control (group C). ADA activity was estimated in the cerebellum, cerebral cortex, striatum and hippocampus. No differences (P0.05) in ADA activity were observed in the cerebellum between infected and non-infected animals. Significant (P0.05) reductions in ADA activity occurred in cerebral cortex in acutely (day 4 post-infection; PI) and chronically (day 20 PI) infected rats. ADA activity was significantly (P0.05) decreased in the hippocampus in acutely infected rats, but significantly (P0.05) increased in the chronically infected rats. Significant (P0.05) reductions in ADA activity occurred in the striatum of chronically infected rats. Parasites could be found in peripheral blood and brain tissue through microscopic examination and PCR assay, respectively, in acutely and chronically infected rats. The reduction of ADA activity in the brain was associated with high levels of parasitemia and anemia in acute infections. Alterations in ADA activity of the brain in T. evansi-infected rats may have implications for pathogenesis of the disease.

International audience; Pregnant rats were daily whole-body exposed or sham-exposed to a Wi-Fi signal in a free-running reverberation chamber at 0, 0.08, 0.4, and 4 W/kg for 2 h during the last 2 weeks of gestation (5 days/week). Following this in utero exposure, the pups were divided into two groups and 1 group continued exposure for 5 weeks after birth. Several brain areas were examined for gliosis and apoptotic cells. Comparison among sham and exposed groups revealed no significant differences, suggesting that in utero and post-natal exposure to Wi-Fi did not damage the brains of the young rats.

Background and purpose Although diffusion characteristics of white matter (WM) and its aging effects have been well described in the literature, diffusion characteristics of grey matter (GM), especially the cortical GM, have not been fully evaluated. In the present study, we used the fluid-inversion prepared diffusion imaging (FLIPD) technique to determine if there are age-related water diffusivity changes in GM. Materials and methods 120 healthy volunteers were recruited for our study. They were divided into three age groups: group one (20–39 years old), group two (40–59 years old) and group three (60 years or older). All patients were evaluated with MRI using FLIPD at 3.0 T. Apparent diffusion coefficient (ADC) values of the frontal GM, cingulate cortex and thalami were determined bilaterally by region-of-interest analysis. Results Group three had significantly higher ADC values in both thalami and the left frontal GM compared to group two or group one. No ADC value difference was found among the three groups in the right frontal GM and bilateral cingulate cortex. There was a significant positive correlation between individual ADC values and age in both thalami and left frontal GM. For the cingulate cortex and the right frontal GM, ADC values did not correlate significantly with advancing age. Conclusion Statistically significant age-related diffusion changes were observed in both thalami and the left frontal cortex. The data reported here may serve as a reference for future studies.

Contributions of cerebro-cerebellar function to executive verbal working memory were examined using event-related functional magnetic resonance imaging (fMRI) while 16 subjects completed two versions of the Sternberg task. In both versions subjects were presented with two or six target letters during the encoding phase, which were held in memory during the maintenance phase. A single probe letter was presented during the retrieval phase. In the “match condition”, subjects decided whether the probe matched the target letters. In the “executive condition”, subjects created a new probe by counting two alphabetical letters forward (e.g., f → h) and decided whether the new probe matched the target letters. Neural activity during the match and executive conditions was compared during each phase of the task. There were four main findings. First, cerebro-cerebellar activity increased as a function of executive load. Second, the dorsal cerebellar dentate co-activated with the supplementary motor area (SMA) during encoding. This likely represented the formation of an articulatory (motor) trajectory. Third, the ventral cerebellar dentate co-activated with anterior prefrontal regions Brodmann Area (BA) 9/46 and the pre-SMA during retrieval. This likely represented the manipulation of information and formation of a response. A functional dissociation between the dorsal “motor” dentate and “cognitive” ventral dentate agrees with neuroanatomical tract tracing studies that have demonstrated separate neural pathways involving each region of the dentate: the dorsal dentate projects to frontal motor areas (including the SMA), and the ventral dentate projects to frontal cognitive areas (including BA 9/46 and the pre-SMA). Finally, activity during the maintenance phase in BA 9, anterior insula, pre-SMA and ventral dentate predicted subsequent accuracy of response to the probe during the retrieval phase. This finding underscored the significant contribution of the pre-SMA/ventral dentate pathway – observed several seconds prior to any motor response to the probe – to executive verbal working memory.

AIM: To evaluate if the intima-media thickening (IMT) and asymptomatic carotid plaque (ACP), as expression of carotid preclinical atherosclerosis (pre-ATS), can provide further information on the global cardiovascular risk (GCVR). METHODS: We studied 454 asymptomatic subjects, with a cluster of risk factors (RF), and evaluated the incidence of a first cardiovascular (CV) event in a five-year follow-up. The subjects at admission were subdivided in three groups of risk. RESULTS: Events occurred in 38% of subjects at high risk, in 13% and 6% of subjects at intermediate and low risk (p

Objective To determine the regional effects of age and sex on the metabolic ratios obtained in the medial temporal lobe, the posteromedial region, and the frontal lobe at 1.5 T single-voxel magnetic resonance spectroscopy. Material and methods We used single-voxel magnetic resonance spectroscopy to study the areas of the brain most affected in neurodegenerative disease (the left frontal lobe, the left medial temporal lobe, and the posteromedial region) in 31 healthy subjects older than 55 years of age (group 1) and in 20 healthy subjects under 30 years of age (group 2). We calculated the following ratios for each voxel: N-acetyl-aspartate/creatine-phosphocreatine (NAA/Cr), N-acetylaspartate/ choline (NAA/Cho), N-acetyl-aspartate /myoinositol (NAA/mI), choline/ creatine-phosphocreatine (Cho/Cr), and myoinositol (mI/Cr). We compared the metabolic ratios in each region in each group and the correlation between age and the ratios within age ranges. Finally, we analyzed the differences in the metabolic ratios between groups and between sexes. Results In group 1, we found negative correlations between age and Cho/Cr in the frontal region and NAA/mI in the temporal region. In group 2, we found negative correlations between age and mI/Cr and NAA/Cho in the temporal region as well as a positive correlation between age and NAA/mI in the temporal region. In the frontal lobe and the posteromedial region, NAA/ Cr, NAA/Cho, and NAA/mI were lower in group 1 (P ≤ 0.003). No differences between groups were seen in Cho/Cr or mI/Cr. The values of the ratios differed regionally in all cases (P Conclusions When using single-voxel magnetic resonance spectroscopy, especially in patients with neurodegenerative disease, variations due to region, age, and sex should always be taken into account.

314 cases of combined cerebro-cranial trauma and posttraumatic intracranial hematomas were identified of which ethanol was detected in 114 hematomas. The other investigative group was 103 hospitalized patients who had hematomas evacuated during neurosurgical procedures. In 62 of these cases ethanol was detected. Blood and urine samples were also collected and the alcohol concentration was determined in all specimens by GC and ADH. The ethanol elimination rate for autopsy and operative intracranial hematomas was approximately 0.07–0.08‰/h(±0.034‰/h). The elimination rate of ethanol from blood (β60) was about two or three times greater as that from hematomas. Because of the different water content of intracranial hematomas from blood, it was necessary to adjust the ethanol concentration for water content. On the basis of the corrected ethanol concentrations and the elimination rates for both tissues it was possible to estimate the ethanol concentration at the time of injury. Intracranial hematomas are tissues of possible value in the determination of alcohol intoxication especially in alcoholism. Ethanol can be found in hematomas even after 72 h from head injury.

Brain-machine interfaces (BMIs) have the potential to improve the quality of life for individuals with disabilities. We engaged in the development of neural mind-reading techniques for cognitive BMIs to provide a readout of decision processes. We trained 2 monkeys on go/no-go tasks, and monitored the activity of groups of neurons in their mid-brain superior colliculus (SC). We designed a virtual decision function (VDF) reflecting the continuous progress of binary decisions on a single-trial basis, and applied it to the ensemble activity of SC neurons. Post hoc analyses using the VDF predicted the cue location as well as the monkey's motor choice (go or no-go) soon after the presentation of the cue. These results suggest that our neural mind-reading techniques have the potential to provide rapid real-time control of communication support devices.

Functional near-infrared spectroscopy (NIRS) and functional magnetic resonance imaging (fMRI) are non-invasive methods for acquiring hemodynamic signals from the brain with the primary benefit of anatomical specificity of signals. Recently, there has been a surge of studies with NIRS and fMRI for the implementation of a brain-computer interface (BCI), for the acquisition, decoding and regulation of hemodynamic signals in the brain, and to investigate their behavioural consequences. Both NIRS and fMRI rely on the measurement of the task-induced blood oxygen level-dependent response. In this review, we consider fundamental principles, recent developments, applications and future directions and challenges of NIRS-based and fMRI-based BCIs.

Brain overgrowth in early developmental stages of children with autism is well documented. This paper explores the possibility that increases in propagation delays of stimuli and the signals triggered by them, resulting from this overgrowth, may be conducive to the development of poorly structured cortical maps, which may in turn be associated with autistic characteristics. We use a framework based on Self-Organizing Maps (SOMs). Unlike the conventional SOM model that assumes that all neurons in the neighborhood of the neuron closest to a stimulus instantaneously react to it and adjust their weights, we propose a more biologically realistic model that acknowledges delays inherent in the propagation of signals. We show that propagation delays can significantly affect the performance of SOMs. Coverage of stimuli is negatively affected by either an increase in the dilution factor (a parameter in the proposed model that controls the adjustment of responses to overlapping stimuli), or a decrease in propagation speed. For large dilution factors the topological structure of the maps is also compromised. We also demonstrate the model's robustness to different input stimuli layouts and distributions.

Mercury (Hg) has been shown to have immunotoxic effects and to influence the severity of infection. However, the impact of infection on the normal Hg homeostasis in different target organs involved in the disease process has not been studied. In this study, Hg was measured through inductively coupled plasma-mass spectrometry (ICP-MS) in the intestine, serum, liver, and brain on days 3, 6, and 9 of coxsackievirus B3 (CVB3) infection in female Balb/c mice. The severity of the infection was assessed from clinical signs of disease and the number of virus particles in infected organs. CVB3 and gene expression of metallothionein 1 (MT1) was measured by reverse transcription-polymerase chain reaction (RT-PCR). Gene expression of MT1 increased and peaked on day 3 in the brain (93%, p

While neural net models have been developed to a high degree of sophistication, they have some drawbacks at a more integrative, ''architectural'' level of analysis. We describe a ''hybrid'' cognitive architecture that is implementable in neuronal nets, and which has uniform brainlike features, including activation-passing and highly distributed ''codelets,'' implementable as small-scale neural nets. Empirically, this cognitive architecture accounts qualitatively for the data described by Baars' Global Workspace Theory (GWT), and Franklin's LIDA architecture, including state-of-the-art models of conscious contents in action-planning, Baddeley-style Working Memory, and working models of episodic and semantic longterm memory. These terms are defined both conceptually and empirically for the current theoretical domain. The resulting architecture meets four desirable goals for a unified theory of cognition: practical workability, autonomous agency, a plausible role for conscious cognition, and translatability into plausible neural terms. It also generates testable predictions, both empirical and computational.

Borsheim E, Bui Q-UT, Wolfe RR. Plasma amino acid concentrations during late rehabilitation in patients with traumatic brain injury. Objectives To investigate whether the basal plasma amino acid concentrations in patients with traumatic brain injury (TBI) have returned to levels found in healthy controls at about 17 months postinjury and to determine the effect of intake of a mixture of essential amino acids (EAA) on plasma amino acid concentrations in TBI versus healthy controls. Design Peripheral venous amino acid concentrations in subjects with TBI were compared with concentrations in healthy controls both at rest and for 1 hour after intake of 7g of EAA. Setting Postacute brain injury rehabilitation center. Participants Six men with TBI (age ± standard deviation, 27±6y; months postinjury, 17±4) and 6 healthy men (age, 43±7y). Intervention Intake of a drink consisting of 7g of EAA. Main Outcome Measures Individual and total plasma amino acid concentrations. Results Total amino acid concentration was about 12% lower in TBI versus controls ( P =.022). Valine was reduced by 33% in the TBI group versus controls ( P =.003), whereas the other EAA did not differ between groups. After intake of the EAA drink, plasma non-EAA increased to a significantly higher level in controls versus TBI subjects ( P =.017). Conclusions Plasma total amino acid concentration is still reduced 17 months postinjury in patients with TBI versus healthy controls, mainly because of a lower valine level. This may be of importance for both brain and muscle metabolic functions, and warrant further study. Further, ingested EAA are apparently not as readily converted to non-EAA in TBI patients as in healthy controls, suggesting that in recovery from TBI, certain non-EAA may become provisionally essential.

We previously reported [Cardenas, V.A., Studholme, C., Meyerhoff, D.J., Song, E., Weiner, M.W., 2005. Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes. Psychiatry Res. 138, 115–130] that non-treatment-seeking, active heavy drinkers (HD) demonstrated smaller regional neocortical gray matter volumes compared to light drinking controls; however, the potential effects of chronic cigarette smoking on regional brain volumes were not addressed. The goal of this retrospective analysis was to determine if chronic smoking affected brain structure in the non-treatment-seeking heavy drinking sample from our earlier report (i.e., Cardenas et al., 2005). Regional volumetric comparisons were made among age-matched smoking HD (n = 17), non-smoking HD (n = 16), and non-smoking light drinkers (nsLD; n = 20) from our original sample. Quantitative volumetric measures of neocortical gray matter (GM), white matter (WM), subcortical structures, and cerebral spinal fluid (CSF) were derived from high-resolution magnetic resonance imaging. Smoking HD demonstrated smaller volumes than nsLD in the frontal, parietal, temporal GM, and for total neocortical GM. Smoking HD also demonstrated smaller temporal and total GM volumes than non-smoking HD. Non-smoking HD and nsLD did not differ significantly on GM volumes. Further, the three groups did not differ on lobar WM, subcortical structures or regional CSF volumes. These retrospective analyses indicate neocortical GM volume reductions in non-treatment-seeking smoking HD, but not in non-smoking HD, which are consistent with our studies in recently detoxified treatment-seeking alcohol-dependent samples. © 2006 Elsevier Ireland Ltd. All rights reserved.

Subtle neurological disturbances have been described in organophosphorus intoxication. Experimental studies have reported neuronal necrosis, particularly in animals experiencing seizures. The objective of the present work was to investigate if in rats (without seizures) exposed to an organophosphate agent, morphological changes occur in specific regions of the brain. The animals received 2.5 or 5.0 mg/kg methamidophos once a week for 2 months and were decapitated after 2 months 7 days of drug administration. We observed atrophy of the molecular layer of the parietal cortex without neuronal loss in specific cerebral regions. This would be due to atrophy or loss of neuronal ramifications but without neuronal loss.

Trabajo de revisión de 75 páginas de extensión, publicado enInternatinal Review of Cytology sobre los tanicitos hipotalámicos. Este trabajo reune y pone al día las aportaciones realizadas en este campo en los últimos diez años, contiene una gran cantidad de datos originales de nuestro grupo que no habían sido publicados con anterioridad. En sus diversos apartados revisa 1) la ontogenia, marcadores celulares y linajede los tanicitos; 2) los subtipos de tanicitos, su localización,morfología, caracteres citoquímicos, ultraestructura, particularidadesfuncionales y control nervioso de su funcionamiento; 3) las propiedades debarrera que han de realizar; 4) la función de transporte entre el líquidocefalorraquídeo y los espacios porta; 5) la síntesis por parte de estascélulas de compuestos biológicamente activos, especialmente su papel en elcontrol de la liberación de hormona liberadora de gonadotropinas (GnRH);6) la posibilidad de que los tanicitos sean células stem del sistemanervioso. En casi todos los apartados mencionados se efectúan aportacionesoriginales que, en conjunto, han supuesto una visión de estas células máscompleja, actual y novedosa. Así por ejemplo, se profundiza en el análisisdel papel de estas células en el control de la liberación de GnRHaportando los resultados de un experimento de eliminación de tanicitos yse demuestra que estas células proliferan de forma muy notable encircunstancias de lesión excitotóxica en el hipotálamo mediobasal. Estapublicación es el resultado del trabajo conjunto del Instituto deHistología y Patología de la Universidad Austral de Chile, liderado por elProfesor Esteban M. Rodríguez, y nuestra unidad de Anatomía de laUniversidad de Salamanca., Tanycytes are bipolar cells bridging the cerebrospinal fluid (CSF) to the portal capillaries and may link the CSF to neuroendocrine events. During the perinatal period a subpopulation of radial glial cells differentiates into tanycytes, a cell lineage sharing some properties with astrocytes and the radial glia, but displayingunique and distinct morphological, molecular, and functional characteristics. Four populations of tanycytes, a1,2 and b1,2, can be distinguished. These subtypes express differentially important functional molecules, such as glucose and glutamate transporters; a series of receptors for neuropeptide and peripheral hormones; secretory molecules such as transforming growth factors, prostaglandin E2, and the specific protein P85; and proteins of the endocytic pathways. This results in functional differences between the four subtypes of tanycytes. Thus, a1,2 tanycytes do not have barrier properties, whereas b1,2tanycytes do. Different types of tanycytes use different mechanisms to internalize and transport cargo molecules; compounds internalized via a clathrin?dependent endocytosis would only enter tanycytes from the CSF. There are also differences in the neuron tanycyte relationships; b1,2 tanycytes are innervated by peptidergic and aminergic neurons, but a1,2 tanycytes are not. Important aspects of the neuron b1 tanycyte relationships have been elucidated. Tanycytes can participatein the release of gonadotropin?releasing hormone (GnRH) to the portal blood by expressing estrogen receptors, absorbing molecules from the CSF, and providingsignal(s) to the GnRH neurons. Removal of tanycytes prevents the pulse of GnRHrelease into the portal blood, the peak of luteinizing hormone, and ovulation. The discovery in tanycytes of new functional molecules is opening a new field of research. Thus, thyroxine deiodinase type II, an enzyme generating triiodothyronine (T3) from thyroxine, appears to be exclusively expressed by tanycytes, suggesting that these cells are the main source of brain T3. Glucose transporter?2 (GLUT?2), a low?affinity transporter of glucose and fructose, andATP?sensitive Kþ channels are expressed by tanycytes, uggesting that they may sense CSF glucose concentrations.

The management of asymptomatic carotid stenosis remains unclear in terms of screening as well as of treatment. The degree of carotid stenosis is not enough to clarify the debate. It seems useful to search among severe carotid stenosis parameters indicating higher ipsilateral stroke risk. Duplex ultrasound and transcranial Doppler offer this opportunity with a diagnostic battery allowing to evaluate hemodynamical risk (degree of stenosis, common carotid flow, MCA signal, cerebral vasoreactivity), thrombo-embolic risk (echostructure of the stenosis, micro-embolic signals, HITS) and progression of the stenosis.

Understanding of oligodendrocyte precursor cells and their role in the generation of oligodendrocytes in developing and adult rodents has been considered, particularly much less is known about aged-rodent oligodendrocyte precursor cells and their cell lineage. In this present study, we have developed oligodendrocyte cultures from the 30-month-old rat brain and examined whether oligodendrocyte precursor cells can proliferate in vitro. Adult oligodendrocyte precursor cells (O1−, O4+) and oligodendrocytes (O1+, O4+) are present in the cultures of the 30-month-old rat brain. They are also capable of proliferating and differentiating in the cultures. These capabilities increased four- to fivefold, when the aged rats are treated with Ninjin-Youei-To for 3 months in comparison with those of control aged rats. These results suggest that Ninjin-Youei-To has a potential mitotic effect on oligodendrocyte precursor cells in aged-rat brains and may be expected to have a therapeutic effect on brain aging.

RESUME L’hemorragie cerebrale n’est pas la forme la plus frequente des accidents vasculaires cerebraux, mais elle en est la plus grave. Son incidence a notablement diminue grâce a une meilleure prise en charge des hypertensions arterielles qui en sont la cause la plus frequente. Le diagnostic a ete transforme par les examens neuroradiologiques modernes, le traitement optimal d’urgence, medical et/ou chirurgical, reste encore l’objet de controverses. Le choix doit prendre en compte l’etat clinique, le volume de l’hemorragie et sa localisation, l’âge du patient. La prise en charge d’urgence en milieu specialise a contribue a ameliorer le pronostic global ; la place et l’interet du traitement chirurgical devraient beneficier d’etudes prospectives pour definir les meilleurs candidats a ce type de traitement. Le probleme est tout different pour l’hemorragie meningee liee a la rupture d’une malformation vasculaire cerebrale ou un traitement rapide est necessaire, qu’il soit chirurgical ou par embolisation.

Development of some immune-mediated disorders may depend on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. To explore neuropsychologic mechanisms in relation to the abnormal endocrine reactivity in patients with systemic lupus erythematosus (SLE) and chronic hepatitis C (CHC) we used the corticotropin releasing hormone (CRH) test, the Minnesota Multiphasic Personality Inventory (MMPI), and the Edinburgh Inventory of Manual Preference Inventory (EIMP). Compared to controls, the adrenocorticotrophic hormone (ACTH) response to CRH was reduced in CHC, while SLE presented reduced baseline dehydroepiandrosterone sulfate levels; higher neurotic scores were found in SLE and higher behavior deviant scores in CHC. Peak ACTH levels were a significant factor for the MMPI profile variability, while the manual preference score was a significant factor for the ACTH response. Personality and manual preference contribute to neuroendocrine abnormalities. Different behavioral and neuroimmunoendocrine models emerge for these disorders.

Cerebellar atrophy occurring in patients with chronic epilepsy is considered either to be a sequel of cumulative seizure-mediated cell loss or a side effect of phenytoin treatment but there is little neuropathological data regarding the distribution of this cerebellar damage. We aimed to address if there is any relationship between the localisation of the cortical pathology in symptomatic epilepsy and the pattern of neocerebellar atrophy. A quantitative neuropathological post mortem analysis of the lobular distribution of hemispheric cerebellar atrophy in 16 patients with chronic epilepsy and four controls was carried out. Cerebellar atrophy, as measured by significant reductions in hemispheric linear Purkinje cell densities was confirmed in the epilepsy patients (P = 0.015) and even where the cerebellum appeared macroscopically normal, Purkinje cell loss was evident (P = 0.062). Two distinct patterns of atrophy were observed, predominantly involving either the anterior or posterior cerebellar lobes. Posterior lobe atrophy was more often associated with old fronto-temporal contusions and may be post traumatic in aetiology rather than a result of excitotoxic damage mediated via cerebro cerebellar pathways. As the majority of patients showing either pattern of atrophy had received phenytoin treatment, we concluded that it is unlikely that this drug acts alone in inducing the Purkinje cell loss.

The venous extracranial abnormalities in multiple sclerosis (MS) provide a new perspective in the treatment. The primary endpoint of our study was to evaluate the occurrence of venous obstructions in the extracranial venous pathway and the secondary endpoint to assess the effect of angioplasty on