Decoding Spontaneous Emotional States in the Human Brain.

Pattern classification of human brain activity provides unique insight into the neural underpinnings of diverse mental states. These multivariate tools have recently been used within the field of affective neuroscience to classify distributed patterns of brain activation evoked during emotion induction procedures. Here we assess whether neural models developed to discriminate among distinct emotion categories exhibit predictive validity in the absence of exteroceptive emotional stimulation. In two experiments, we show that spontaneous fluctuations in human resting-state brain activity can be decoded into categories of experience delineating unique emotional states that exhibit spatiotemporal coherence, covary with individual differences in mood and personality traits, and predict on-line, self-reported feelings. These findings validate objective, brain-based models of emotion and show how emotional states dynamically emerge from the activity of separable neural systems.

Dynamic classifiers for neonatal brain monitoring

Brain injury due to lack of oxygen or impaired blood flow around the time of birth, may cause long term neurological dysfunction or death in severe cases. The treatments need to be initiated as soon as possible and tailored according to the nature of the injury to achieve best outcomes. The Electroencephalogram (EEG) currently provides the best insight into neurological activities. However, its interpretation presents formidable challenge for the neurophsiologists. Moreover, such expertise is not widely available particularly around the clock in a typical busy Neonatal Intensive Care Unit (NICU). Therefore, an automated computerized system for detecting and grading the severity of brain injuries could be of great help for medical staff to diagnose and then initiate on-time treatments. In this study, automated systems for detection of neonatal seizures and grading the severity of Hypoxic-Ischemic Encephalopathy (HIE) using EEG and Heart Rate (HR) signals are presented. It is well known that there is a lot of contextual and temporal information present in the EEG and HR signals if examined at longer time scale. The systems developed in the past, exploited this information either at very early stage of the system without any intelligent block or at very later stage where presence of such information is much reduced. This work has particularly focused on the development of a system that can incorporate the contextual information at the middle (classifier) level. This is achieved by using dynamic classifiers that are able to process the sequences of feature vectors rather than only one feature vector at a time.

The Brain Drain : Myth and Reality - What it is and What Should be Done (Working Paper 13)

The brain drain debate has been marked by a considerable amount of confusion and frustration, largely because there has been relatively little hard data available, and that which exists has often been twisted into very different forms by those with competing policy agendas. The first goal of this paper is to pull together and summarize the available evidence regarding the size and nature of the outflows, thus establishing an empirical basis from which the issue can be addressed. The second goal is to address some of the major related policy issues. This begins with some general brain drain policy principles. The personal income tax cuts solution is then addressed with simulations of the effects on government revenues and the associated costs “per brain”, thus putting such discussions on a much firmer empirical footing. A number of alternative proposals are then suggested for various problem groups of brain drain workers.

Neurobiology and clinical implications of lucid dreaming

Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states.

Perturbations in Blood Phosphatidylcholine and Sphingomyelin Fatty Acid Composition in a Sample Population of Cigarette Smokers

Docosahexaenoic (DHA) and arachidonic acids (AA) are polyunsaturated fatty acids (PUFAs), major components of brain tissue and neural systems, and the precursors of a number of biologically active metabolites with functions in inflammation resolution, neuroprotection and other actions. As PUFAs are highly susceptible to peroxidation, we hypothesised whether cigarette smokers would present altered PUFAs levels in plasma and erythrocyte phospholipids. Adult males from Indian, Sri-Lankan or Bangladeshi genetic backgrounds who reported smoking between 20 and 60 cigarettes per week were recruited. The control group consisted of matched non-smokers. A blood sample was taken, plasma and erythrocyte total lipids were extracted, phospholipids were separated by thin layer chromatography, and the fatty acid content analysed by gas chromatography. In smokers, dihomo-gamma-linolenic acid, the AA precursor, was significantly reduced in plasma and erythrocyte phosphatidylcholine. AA and DHA were significantly reduced in erythrocyte sphingomyelin. Relatively short term smoking has affected the fatty acid composition of plasma and erythrocyte phospholipids with functions in neural tissue composition, cell signalling, cell growth, intracellular trafficking, neuroprotection and inflammation, in a relatively young population. As lipid peroxidation is pivotal in the pathogenesis of atherosclerosis and neurodegenerative diseases such as Alzheimer disease, early effects of smoking may be relevant for the development of such conditions.

A Palatable Hyperlipidic Diet Causes Obesity and Affects Brain Glucose Metabolism in Rats

Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H) or the alternation of chow (C) and an H diet (CH regimen) induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.

Characterization of CDK5RAP2 as a novel regulator in the Hippo signaling pathway

CEP161 is a novel component of the Dictyostelium discoideum centrosome and is the ortholog of mammalian CDK5RAP2. Mutations in CDK5RAP2 are associated with autosomal recessive primary microcephaly (MCPH), a neurodevelopmental disorder characterized by reduced head circumference, a reduction in the size of the cerebral cortex and a mild to moderate mental retardation. Here we show that the amino acids 1-763 of the 1381 amino acids of CEP161 protein are sufficient for centrosomal targeting and centrosome association. AX2 cells over-expressing truncated and full length CEP161 proteins have defects in growth and development. Furthermore, we identified the kinase SvkA (severinkinase A) as its interaction partner which is the D. discoideum Hippo related kinase designated here as Hrk-svk. Hrk-svk is the direct homolog of human MST1. Both proteins co-localize at the centrosome. We further demonstrate that this interaction is also conserved in mammals. We were able to show that CDK5RAP2 interacts with MST1 and TAZ and it also down-regulates the transcript levels of TAZ in HEK293T cells. Taken together, our data on Dictyostelium CEP161 and human CDK5RAP2 supports the hypothesis that CDK5RAP2 as a novel regulator of Hippo signaling pathway. We propose that CDK5RAP2 mutations may lead to a decrease in the number of neurons and the subsequent reduction of brain size by regulating the hippo signaling pathway.

Scanning Laser Optical Tomography Resolves Structural Plasticity during Regeneration in an Insect Brain

Background: Optical Projection Tomography (OPT) is a microscopic technique that generates three dimensional images from whole mount samples the size of which exceeds the maximum focal depth of confocal laser scanning microscopes. As an advancement of conventional emission-OPT, Scanning Laser Optical Tomography (SLOTy) allows simultaneous detection of fluorescence and absorbance with high sensitivity. In the present study, we employ SLOTy in a paradigm of brain plasticity in an insect model system. Methodology: We visualize and quantify volumetric changes in sensory information procession centers in the adult locust, Locusta migratoria. Olfactory receptor neurons, which project from the antenna into the brain, are axotomized by crushing the antennal nerve or ablating the entire antenna. We follow the resulting degeneration and regeneration in the olfactory centers (antennal lobes and mushroom bodies) by measuring their size in reconstructed SLOTy images with respect to the untreated control side. Within three weeks post treatment antennal lobes with ablated antennae lose as much as 60% of their initial volume. In contrast, antennal lobes with crushed antennal nerves initially shrink as well, but regain size back to normal within three weeks. The combined application of transmission-and fluorescence projections of Neurobiotin labeled axotomized fibers confirms that recovery of normal size is restored by regenerated afferents. Remarkably, SLOTy images reveal that degeneration of olfactory receptor axons has a trans-synaptic effect on second order brain centers and leads to size reduction of the mushroom body calyx. Conclusions: This study demonstrates that SLOTy is a suitable method for rapid screening of volumetric plasticity in insect brains and suggests its application also to vertebrate preparations.

Increased CSF Aβ during the very early phase of cerebral Aβ deposition in mouse models

Abnormalities in brains of Alzheimer's disease (AD) patients are thought to start long before the first clinical symptoms emerge. The identification of affected individuals at this 'preclinical AD' stage relies on biomarkers such as decreased levels of the amyloid-β peptide (Aβ) in the cerebrospinal fluid (CSF) and positive amyloid positron emission tomography scans. However, there is little information on the longitudinal dynamics of CSF biomarkers, especially in the earliest disease stages when therapeutic interventions are likely most effective. To this end, we have studied CSF Aβ changes in three Aβ precursor protein transgenic mouse models, focusing our analysis on the initial Aβ deposition, which differs significantly among the models studied. Remarkably, while we confirmed the CSF Aβ decrease during the extended course of brain Aβ deposition, a 20-30% increase in CSF Aβ40 and Aβ42 was found around the time of the first Aβ plaque appearance in all models. The biphasic nature of this observed biomarker changes stresses the need for longitudinal biomarker studies in the clinical setting and the search for new 'preclinical AD' biomarkers at even earlier disease stages, by using both mice and human samples. Ultimately, our findings may open new perspectives in identifying subjects at risk for AD significantly earlier, and in improving the stratification of patients for preventive treatment strategies.

Neurobiology and clinical implications of lucid dreaming

Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states.

The pathophysiology of CADASIL: studies in a Scottish cohort

Since identification that mutations in NOTCH3 are responsible for cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) in the early 1990s, there has been extensive characterisation of the clinical and radiological features of the disease. However therapeutic interventions remain elusive, partly due to a limited understanding of the vascular pathophysiology and how it leads to the development of strokes, cognitive decline and disability. The apparent rarity and heterogenous natural history of CADASIL potentially make conducting any longitudinal or therapeutic trials difficult. The role of disease biomarkers is therefore of some interest. This thesis focuses on vascular function in CADASIL and how it may relate to clinical and radiological markers of disease. Establishing the prevalence of CADASIL in the West of Scotland was important to assess the impact of the disease, and how feasible a trial would be. A mutation prevalence of 10.7 per 100,000 was demonstrated, suggesting significant under diagnosis of the disease across much of Scotland. Cerebral hypoperfusion is thought to be important in CADASIL, and it has been shown that vascular abnormalities precede the development of brain pathology in mouse models. Investigation of vascular function in patients, both in the brain and systemically, requires less invasive measures. Arterial spin labelling magnetic resonance imaging (MRI) and transcranial Doppler ultrasound (TCD) can both be used to obtain non-invasive and quantifiable indices of vascular function. Monitoring patients with MRI whilst they receive different concentrations of inspired oxygen and carbon dioxide can provide information on brain function, and I reviewed the practicalities of this technique in order to guide the design of the studies in this thesis. 22 CADASIL patients were recruited to a longitudinal study. Testing included peripheral vascular assessment, assessment of disability, neurological dysfunction, mood and cognition. A CO2 reactivity challenge during both TCD and arterial spin labelling MRI, and detailed MRI sequences were obtained. I was able to demonstrate that vasoreactivity was associated with the number of lacunes and brain atrophy, as were carotid intima-media thickness, vessel stiffness, and age. Patients with greater disability, higher depressive symptoms and poorer processing speed showed a tendency to worse cerebral vasoreactivity but numbers were small. This observation suggests vasoreactivity may have potential as a therapeutic target, or a biomarker. I then wished to establish if arterial spin labelling MRI was useful for assessing change in cerebral blood flow in CADASIL patients. Cortical grey matter showed the highest blood flow, mean (SD), 55 (10) ml/100g/min and blood flow was significantly lower within hyperintensities (19 (4) ml/100g/min; p <0.001). Over one year, blood flow in both grey matter (mean -7 (10) %; p = 0.028) and deep white matter (-8 (13) %; p = 0.036) declined significantly. Cerebrovascular reactivity did not change over one year. I then investigated whether baseline vascular markers were able to predict change in radiological or neuropsychological measures of disease. Changes in brain volume, lacunes, microbleeds and normalised subcortical hyperintensity volume (increase of 0.8%) were shown over one year. Baseline vascular parameters were not able to predict these changes, or those in neuropsychological testing. NOTCH3 is found throughout the body and a systemic vasculopathy has been seen particularly affecting resistance vessels. Gluteal biopsies were obtained from 20 CADASIL patients, and ex vivo myography investigated the response to vasoactive agents. Evidence of impairment in both vasodilation and vasoconstriction was shown. The addition of antioxidants improved endothelium-dependent relaxation, indicating a role for oxidative stress in CADASIL pathology. Myography measures were not related to in vivo measures in the sub-group of patients who had taken part in both studies. The small vessels affected in CADASIL are unable to be imaged by conventional MR imaging so I aimed to establish which vessels might be responsible for lacunes with use of a microangiographic template overlaid onto brain images registered to a standard brain template. This showed most lacunes are small and associated with tertiary arterioles. On the basis of this thesis, it is concluded that vascular dysfunction plays an important role in the pathophysiology of CADASIL, and further assessment of vascular measures in longitudinal studies is needed. Arterial spin labelling MRI should be used as it is a reliable, non-invasive modality that can measure change over one year. Furthermore conventional cardiovascular risk factor prevention should be undertaken in CADASIL patients to delay the deleterious effects of the disease.

Fabrication and Pseudo-Analog Characteristics of Ta2O5 -Based ReRAM Cell

Memristori on yksi elektroniikan peruskomponenteista vastuksen, kondensaattorin ja kelan lisäksi. Se on passiivinen komponentti, jonka teorian kehitti Leon Chua vuonna 1971. Kesti kuitenkin yli kolmekymmentä vuotta ennen kuin teoria pystyttiin yhdistämään kokeellisiin tuloksiin. Vuonna 2008 Hewlett Packard julkaisi artikkelin, jossa he väittivät valmistaneensa ensimmäisen toimivan memristorin. Memristori eli muistivastus on resistiivinen komponentti, jonka vastusarvoa pystytään muuttamaan. Nimens mukaisesti memristori kykenee myös säilyttämään vastusarvonsa ilman jatkuvaa virtaa ja jännitettä. Tyypillisesti memristorilla on vähintään kaksi vastusarvoa, joista kumpikin pystytään valitsemaan syöttämällä komponentille jännitettä tai virtaa. Tämän vuoksi memristoreita kutsutaankin usein resistiivisiksi kytkimiksi. Resistiivisiä kytkimiä tutkitaan nykyään paljon erityisesti niiden mahdollistaman muistiteknologian takia. Resistiivisistä kytkimistä rakennettua muistia kutsutaan ReRAM-muistiksi (lyhenne sanoista resistive random access memory). ReRAM-muisti on Flash-muistin tapaan haihtumaton muisti, jota voidaan sähköisesti ohjelmoida tai tyhjentää. Flash-muistia käytetään tällä hetkellä esimerkiksi muistitikuissa. ReRAM-muisti mahdollistaa kuitenkin nopeamman ja vähävirtaiseman toiminnan Flashiin verrattuna, joten se on tulevaisuudessa varteenotettava kilpailija markkinoilla. ReRAM-muisti mahdollistaa myös useammin bitin tallentamisen yhteen muistisoluun binäärisen (”0” tai ”1”) toiminnan sijaan. Tyypillisesti ReRAM-muistisolulla on kaksi rajoittavaa vastusarvoa, mutta näiden kahden tilan välille pystytään mahdollisesti ohjelmoimaan useampia tiloja. Muistisoluja voidaan kutsua analogisiksi, jos tilojen määrää ei ole rajoitettu. Analogisilla muistisoluilla olisi mahdollista rakentaa tehokkaasti esimerkiksi neuroverkkoja. Neuroverkoilla pyritään mallintamaan aivojen toimintaa ja suorittamaan tehtäviä, jotka ovat tyypillisesti vaikeita perinteisille tietokoneohjelmille. Neuroverkkoja käytetään esimerkiksi puheentunnistuksessa tai tekoälytoteutuksissa. Tässä diplomityössä tarkastellaan Ta2O5 -perustuvan ReRAM-muistisolun analogista toimintaa pitäen mielessä soveltuvuus neuroverkkoihin. ReRAM-muistisolun valmistus ja mittaustulokset käydään läpi. Muistisolun toiminta on harvoin täysin analogista, koska kahden rajoittavan vastusarvon välillä on usein rajattu määrä tiloja. Tämän vuoksi toimintaa kutsutaan pseudoanalogiseksi. Mittaustulokset osoittavat, että yksittäinen ReRAM-muistisolu kykenee binääriseen toimintaan hyvin. Joiltain osin yksittäinen solu kykenee tallentamaan useampia tiloja, mutta vastusarvoissa on peräkkäisten ohjelmointisyklien välillä suurta vaihtelevuutta, joka hankaloittaa tulkintaa. Valmistettu ReRAM-muistisolu ei sellaisenaan kykene toimimaan pseudoanalogisena muistina, vaan se vaati rinnalleen virtaa rajoittavan komponentin. Myös valmistusprosessin kehittäminen vähentäisi yksittäisen solun toiminnassa esiintyvää varianssia, jolloin sen toiminta muistuttaisi enemmän pseudoanalogista muistia.

The “handwriting brain”: a motor/linguistic network with specialized “writing-specific” areas?

International audience

Error analyses reveal contrasting deficits in “theory of mind”: neuropsychological evidence from a 3-option false belief task

Perspective taking is a crucial ability that guides our social interactions. In this study, we show how the specific patterns of errors of brain-damaged patients in perspective taking tasks can help us further understand the factors contributing to perspective taking abilities. Previous work (e.g., Samson, Apperly, Chiavarino, & Humphreys, 2004; Samson, Apperly, Kathirgamanathan, & Humphreys, 2005) distinguished two components of perspective taking: the ability to inhibit our own perspective and the ability to infer someone else’s perspective. We assessed these components using a new nonverbal false belief task which provided different response options to detect three types of response strategies that participants might be using: a complete and spared belief reasoning strategy, a reality-based response selection strategy in which participants respond from their own perspective, and a simplified mentalising strategy in which participants avoid responding from their own perspective but rely on inaccurate cues to infer the other person’s belief. One patient, with a self-perspective inhibition deficit, almost always used the reality-based response strategy; in contrast, the other patient, with a deficit in taking other perspectives, tended to use the simplified mentalising strategy without necessarily transposing her own perspective. We discuss the extent to which the pattern of performance of both patients could relate to their executive function deficit and how it can inform us on the cognitive and neural components involved in belief reasoning.

Maladaptive defense mechanisms are associated with decoupling of testosterone from sexual desire in women of reproductive age

O presente artigo contém uma errata, disponível em: http://www.tandfonline.com/doi/full/10.1080/15294145.2015.1108503