Subjective mental time: the functional architecture of projecting the self to past and future.

Abstract Human experience takes place in the line of mental time (MT) created through 'self-projection' of oneself to different time-points in the past or future. Here we manipulated self-projection in MT not only with respect to one's life events but also with respect to one's faces from different past and future time-points. Behavioural and event-related functional magnetic resonance imaging activity showed three independent effects characterized by (i) similarity between past recollection and future imagination, (ii) facilitation of judgements related to the future as compared with the past, and (iii) facilitation of judgements related to time-points distant from the present. These effects were found with respect to faces and events, and also suggest that brain mechanisms of MT are independent of whether actual life episodes have to be re-experienced or pre-experienced, recruiting a common cerebral network including the anteromedial temporal, posterior parietal, inferior frontal, temporo-parietal and insular cortices. These behavioural and neural data suggest that self-projection in time is a fundamental aspect of MT, relying on neural structures encoding memory, mental imagery and self.

The brain tracks the energetic value in food images.

Do our brains implicitly track the energetic content of the foods we see? Using electrical neuroimaging of visual evoked potentials (VEPs) we show that the human brain can rapidly discern food's energetic value, vis à vis its fat content, solely from its visual presentation. Responses to images of high-energy and low-energy food differed over two distinct time periods. The first period, starting at approximately 165 ms post-stimulus onset, followed from modulations in VEP topography and by extension in the configuration of the underlying brain network. Statistical comparison of source estimations identified differences distributed across a wide network including both posterior occipital regions and temporo-parietal cortices typically associated with object processing, and also inferior frontal cortices typically associated with decision-making. During a successive processing stage (starting at approximately 300 ms), responses differed both topographically and in terms of strength, with source estimations differing predominantly within prefrontal cortical regions implicated in reward assessment and decision-making. These effects occur orthogonally to the task that is actually being performed and suggest that reward properties such as a food's energetic content are treated rapidly and in parallel by a distributed network of brain regions involved in object categorization, reward assessment, and decision-making.

Cell death and autophagy after severe hypoxic-ischemic encephalopathy in term newborns

Introduction: Various studies from hypoxic-ischemic animals haveinvestigated neuroprotection by targeting necrosis and apoptosis with inconclusive results. Three types of cell death have been described: apoptosis, necrosis and more recently, autophagic cell death. While autophagy is a physiological process of degradation of cellular components, excessive autophagy may be involved in cell death. Recent studies showed that inhibition of autophagy is neuroprotective in rodent neonatal models of cerebral ischemia. Furthermore, neonatal hypoxia-ischemia strongly increased neuronal autophagic flux which is linked to cell death in a rat model of perinatal asphyxia. Following our observations in animals, the aim of the present study was to characterize the different neuronal death phenotypes and to clarify whether autophagic cell death could be also involved in neuronal death in the human newborns after perinatal asphyxia. Methods: we selected retrospectively and anonymously all newborns who died in our unit of neonatology between 2004 and 2009, with the following criteria: gestational age >36 weeks, diagnosis of perinatal asphyxia (Apgar <5 at 5 minutes, arterial pH <7.0 at 1 hour of life and encephalopathy Sarnat III) and performed autopsy. The brain of 6 cases in asphyxia group and 6 control cases matching gestational age who died of pulmonary or other malformations were selected. On histological sections of thalamus, frontal cortex and hippocampus, different markers of apoptosis (caspase 3, TUNEL), autophagosomes (LC3-II) and lysosomes (LAMP1, Cathepsin D) were tested by immunohistochemistry. Results: Preliminary studies on markers of apoptosis (TUNEL, caspase 3) and of autophagy (Cathepsin D, LC3II, LAMP1) showed an expected increase of apoptosis, but also an increase of neuronal autophagic flux in the selected areas. The distribution seems to be region specific. Conclusion: This is the first time that autophagic flux linked with cell death is shown in brain of human babies, in association with hypoxicischemic encephalopathy. This work leads to a better understanding of the mechanisms associated with neuronal death following perinatal asphyxia and determines whether autophagy could be a promising therapeutic target.

Post-switching beta synchronization reveals concomitant sensory reafferences and active inhibition processes

It is known that post-movement beta synchronization (PMBS) is involved both in active inhibition and in sensory reafferences processes. The aim of this study was examine the temporal and spatial dynamics of the PMBS involved during multi-limb coordination task. We investigated post-switching beta synchronization (assigned PMBS) using time-frequency and source estimations analyzes. Participants (n = 17) initiated an auditory-paced bimanual tapping. After a 1500 ms preparatory period, an imperative stimulus required to either selectively stop the left while maintaining the right unimanual tapping (Switch condition: SWIT) or to continue the bimanual tapping (Continue condition: CONT). PMBS significantly increased in SWIT compared to CONT with maximal difference within right central region in broad-band 14âeuro"30 Hz and within left central region in restricted-band 22âeuro"26 Hz. Source estimations localized these effects within right pre-frontal cortex and left parietal cortex, respectively. A negative correlation showed that participants with a low percentage of errors in SWIT had a large PMBS amplitude within right parietal and frontal cortices. This study shows for the first time simultaneous PMBS with distinct functions in different brain regions and frequency ranges. The left parietal PMBS restricted to 22âeuro"26 Hz could reflect the sensory reafferences of the right hand tapping disrupted by the switching. In contrast, the right pre-frontal PMBS in a broad-band 14âeuro"30 Hz is likely reflecting the active inhibition of the left hand stopped. Finally, correlations between behavioral performance and the magnitude of the PMBS suggest that beta oscillations can be viewed as a marker of successful active inhibition.

Mutations in DNAH5 account for only 15% of a non-preselected cohort of patients with primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is characterised by recurrent infections of the upper respiratory airways (nose, bronchi, and frontal sinuses) and randomisation of left-right body asymmetry. To date, PCD is mainly described with autosomal recessive inheritance and mutations have been found in five genes: the dynein arm protein subunits DNAI1, DNAH5 and DNAH11, the kinase TXNDC3, and the X-linked retinitis pigmentosa GTPase regulator RPGR. METHODS: We screened 89 unrelated individuals with PCD for mutations in the coding and splice site regions of the gene DNAH5 by denaturing high performance liquid chromatography (DHPLC) and sequencing. Patients were mainly of European origin and were recruited without any phenotypic preselection. RESULTS: We identified 18 novel (nonsense, splicing, small deletion and missense) and six previously described mutations. Interestingly, these DNAH5 mutations were mainly associated with outer + inner dyneins arm ultrastructural defects (50%). CONCLUSION: Overall, mutations on both alleles of DNAH5 were identified in 15% of our clinically heterogeneous cohort of patients. Although genetic alterations remain to be identified in most patients, DNAH5 is to date the main PCD gene.

Childhood epilepsy with neuropsychological regression and continuous spike waves during sleep: epilepsy surgery in a young adult.

We describe the case of a man with a history of complex partial seizures and severe language, cognitive and behavioural regression during early childhood (3.5 years), who underwent epilepsy surgery at the age of 25 years. His early epilepsy had clinical and electroencephalogram features of the syndromes of epilepsy with continuous spike waves during sleep and acquired epileptic aphasia (Landau-Kleffner syndrome), which we considered initially to be of idiopathic origin. Seizures recurred at 19 years and presurgical investigations at 25 years showed a lateral frontal epileptic focus with spread to Broca's area and the frontal orbital regions. Histopathology revealed a focal cortical dysplasia, not visible on magnetic resonance imaging. The prolonged but reversible early regression and the residual neuropsychological disorders during adulthood were probably the result of an active left frontal epilepsy, which interfered with language and behaviour during development. Our findings raise the question of the role of focal cortical dysplasia as an aetiology in the syndromes of epilepsy with continuous spike waves during sleep and acquired epileptic aphasia.

New prognostic factors and calculators for outcome prediction in patients with recurrent glioblastoma: A pooled analysis of EORTC Brain Tumour Group phase I and II clinical trials.

BACKGROUND: Prognostic models have been developed to predict survival of patients with newly diagnosed glioblastoma (GBM). To improve predictions, models should be updated with information at the recurrence. We performed a pooled analysis of European Organization for Research and Treatment of Cancer (EORTC) trials on recurrent glioblastoma to validate existing clinical prognostic factors, identify new markers, and derive new predictions for overall survival (OS) and progression free survival (PFS).¦METHODS: Data from 300 patients with recurrent GBM recruited in eight phase I or II trials conducted by the EORTC Brain Tumour Group were used to evaluate patient's age, sex, World Health Organisation (WHO) performance status (PS), presence of neurological deficits, disease history, use of steroids or anti-epileptics and disease characteristics to predict PFS and OS. Prognostic calculators were developed in patients initially treated by chemoradiation with temozolomide.¦RESULTS: Poor PS and more than one target lesion had a significant negative prognostic impact for both PFS and OS. Patients with large tumours measured by the maximum diameter of the largest lesion (⩾42mm) and treated with steroids at baseline had shorter OS. Tumours with predominant frontal location had better survival. Age and sex did not show independent prognostic values for PFS or OS.¦CONCLUSIONS: This analysis confirms performance status but not age as a major prognostic factor for PFS and OS in recurrent GBM. Patients with multiple and large lesions have an increased risk of death. With these data prognostic calculators with confidence intervals for both medians and fixed time probabilities of survival were derived.

Le Briançonnais, terrain exotique dans les Alpes ?

New reconstructions of the Western Alps from late Early Jurassic till early Tertiary are proposed. These reconstructions use deep lithospheric data gathered through recent seismic surveys and tomographic studies carried out in the Alps. The present day position, under the Po plain, of the southern limit of the European plate (fig. 1), allows to define the former geometry of the Brianconnais peninsula. The Brianconnais domain is regarded as an exotic terrane formerly belonging to the European margin until Late Jurassic, then transported eastward during the drift of Iberia (fig. 5). Therefore, on a present day Western Alps cross section, a duplication of the European continental margin can be recognized (fig. 10). Stratigraphic and sedimentological data along a zone linking the Pyrenean fracture zone to the Brianconnais, can be related to a rifting event starting in Oxfordian time. This event is responsible for the Late Jurassic till mid-Cretaceous drift of Iberia opening, first the northern Atlantic, then the Gulf of Biscay. Simultaneously, the drift of the Brianconnais will open the Valais ocean and close the Piemontese ocean. The resulting oblique collision zone between the Brianconnais and the Apulian margin generates HP/LT metamorphism starting in Early Cretaceous. The eastward drift of the Brianconnais peninsula will eventually bring it in front of a more northerly segment of the former European margin. The thrusting of the Brianconnais unto that margin takes place in early Tertiary (fig. 9), following the subduction of the Valais ocean. The present nappe pile results not only from continent/continent frontal collision, but also from important lateral displacement of terranes, the most important one being the Brianconnais. The dilemma of `'en echelon'' oceanic domains in the Alps is an outcome of these translations. A solution is found when considering the opening of a Cretaceous Valais ocean across the European margin, running out eastward into the Piemontese ocean, where the drift is taken up along a former transform fault and compensated by subduction under the Apulian margin (fig. 8). In the Western Alps we are then dealing with two oceans, the Piemontese and the Valaisan and a duplicated European margin. In the Eastern Alps the single Piemontese ocean is cut by newly created oceanic crust. All these elements will be incorporated into the Penninic structural domain which does not represent a former unique paleogeographic area, it is a composite accretionary domain squeezed between Europe and Apulia.

Decreased pyramidal neuron size in Brodmann areas 44 and 45 in patients with autism.

Autism is a neurodevelopmental disorder characterized by deficits in social interaction and social communication, as well as by the presence of repetitive and stereotyped behaviors and interests. Brodmann areas 44 and 45 in the inferior frontal cortex, which are involved in language processing, imitation function, and sociality processing networks, have been implicated in this complex disorder. Using a stereologic approach, this study aims to explore the presence of neuropathological differences in areas 44 and 45 in patients with autism compared to age- and hemisphere-matched controls. Based on previous evidence in the fusiform gyrus, we expected to find a decrease in the number and size of pyramidal neurons as well as an increase in volume of layers III, V, and VI in patients with autism. We observed significantly smaller pyramidal neurons in patients with autism compared to controls, although there was no difference in pyramidal neuron numbers or layer volumes. The reduced pyramidal neuron size suggests that a certain degree of dysfunction of areas 44 and 45 plays a role in the pathology of autism. Our results also support previous studies that have shown specific cellular neuropathology in autism with regionally specific reduction in neuron size, and provide further evidence for the possible involvement of the mirror neuron system, as well as impairment of neuronal networks relevant to communication and social behaviors, in this disorder.

Transjugular liver biopsy: prospective evaluation of the angle formed between the hepatic veins and the vena cava main axis and modification of a semi-automated biopsy device in cases of an unfavorable angle.

In cases of transjugular liver biopsies, the venous angle formed between the chosen hepatic vein and the vena cava main axis in a frontal plane can be large, leading to technical difficulties. In a prospective study including 139 consecutive patients who underwent transjugular liver biopsy using the Quick-Core biopsy set, the mean venous angle was equal to 49.6 degrees. For 21.1% of the patients, two attempts at hepatic venous catheterization failed because the venous angle was too large, with a mean of 69.7 degrees. In all of these patients, manual reshaping of the distal curvature of the stiffening metallic cannula, by forming a new mean angle equal to 48 degrees , allowed successful completion of the procedure in less than 10 min.

Brain dysfunctions, psychopathologies, and body image distortions

The major features in eating disorders are a preoccupation with food and its consumption and body dissatisfaction. Diagnostic manuals provide clusters of criteria according to which affected individuals can be categorized into one or other group of eating disorder. Yet, when considering the high proportion of comorbidities and ignoring the content of the symptoms (food, body), the major features seem to yield obsessional-compulsive, addictive, and impulsive qualities. In the present article, we review studies from the neuroscientific literature (mainly lesion studies) on eating disorder, obsessive-compulsive disorder, impulse control disorder, and addiction to investigate the possibility of a wider phenotype that can be related to a common brain network. The literature localizes this network to the right frontal lobe and its connectivities. This network, when dysfunctional, might result in a behavior that favors the preoccupation with particular thoughts, behaviors, anxieties, and uncontrollable urges that are accompanied by little scope for ongoing behavioral adjustments (e.g., impulse control). We reason that this network may turn out to be equally involved in understudied mental conditions of dysfunctional body processing such as muscle dysmorphia, body dysmorphic disorder (including esthetic surgery), and xelomelia. We finally consider previous notions of a wider phenotype approach to current diagnostic practice (using DSM), such as the possibility of a model with a reduced number of diagnostic categories and primary and secondary factors, and to etiological models of mental health conditions.

Deontological and altruistic guilt: evidence for distinct neurobiological substrates.

The feeling of guilt is a complex mental state underlying several human behaviors in both private and social life. From a psychological and evolutionary viewpoint, guilt is an emotional and cognitive function, characterized by prosocial sentiments, entailing specific moral believes, which can be predominantly driven by inner values (deontological guilt) or by more interpersonal situations (altruistic guilt). The aim of this study was to investigate whether there is a distinct neurobiological substrate for these two expressions of guilt in healthy individuals. We first run two behavioral studies, recruiting a sample of 72 healthy volunteers, to validate a set of stimuli selectively evoking deontological and altruistic guilt, or basic control emotions (i.e., anger and sadness). Similar stimuli were reproduced in a event-related functional magnetic resonance imaging (fMRI) paradigm, to investigate the neural correlates of the same emotions, in a new sample of 22 healthy volunteers. We show that guilty emotions, compared to anger and sadness, activate specific brain areas (i.e., cingulate gyrus and medial frontal cortex) and that different neuronal networks are involved in each specific kind of guilt, with the insula selectively responding to deontological guilt stimuli. This study provides evidence for the existence of distinct neural circuits involved in different guilty feelings. This complex emotion might account for normal individual attitudes and deviant social behaviors. Moreover, an abnormal processing of specific guilt feelings might account for some psychopathological manifestation, such as obsessive-compulsive disorder and depression.

Accuracy of indirect estimation of power output from uphill performance in cycling.

PURPOSE: To use measurement by cycling power meters (Pmes) to evaluate the accuracy of commonly used models for estimating uphill cycling power (Pest). Experiments were designed to explore the influence of wind speed and steepness of climb on accuracy of Pest. The authors hypothesized that the random error in Pest would be largely influenced by the windy conditions, the bias would be diminished in steeper climbs, and windy conditions would induce larger bias in Pest. METHODS: Sixteen well-trained cyclists performed 15 uphill-cycling trials (range: length 1.3-6.3 km, slope 4.4-10.7%) in a random order. Trials included different riding position in a group (lead or follow) and different wind speeds. Pmes was quantified using a power meter, and Pest was calculated with a methodology used by journalists reporting on the Tour de France. RESULTS: Overall, the difference between Pmes and Pest was -0.95% (95%CI: -10.4%, +8.5%) for all trials and 0.24% (-6.1%, +6.6%) in conditions without wind (<2 m/s). The relationship between percent slope and the error between Pest and Pmes were considered trivial. CONCLUSIONS: Aerodynamic drag (affected by wind velocity and orientation, frontal area, drafting, and speed) is the most confounding factor. The mean estimated values are close to the power-output values measured by power meters, but the random error is between ±6% and ±10%. Moreover, at the power outputs (>400 W) produced by professional riders, this error is likely to be higher. This observation calls into question the validity of releasing individual values without reporting the range of random errors.

Familial frontotemporal dementia with ubiquitin inclusion bodies and without motor neuron disease.

Frontotemporal dementia (FTD) is the second most common degenerative dementia after Alzheimer's disease and its Lewy body variant. Clinical pathology can be subdivided in three main neuropathological subtypes: frontal lobe dementia, Pick's disease and FTD with motor neuron disease (MND), all characterised by distinct histological features. Until recently the presence of ubiquitin-positive intraneuronal inclusions in the dentate gyrus, and the temporal and frontal cortex was usually associated with the MND type. Such inclusions were also observed in a few sporadic cases of FTD without or with parkinsonism (FTDP) in the absence of MND. We present here clinical, neuropathological and immunohistochemical data about a Swiss FTD family with FTDP-like features but without MND. Spongiosis and mild gliosis were observed in the grey matter. No neurofibrillary tangles, Pick bodies, Lewy bodies, senile plaques or prion-positive signals were present. However, ubiquitin-positive intracytoplasmic inclusions were detected in various structures but predominantly in the dentate gyrus. These observations support the existence of a familial form of FTDP with ubiquitin-positive intracytoplasmic inclusions (Swiss FTDP family).

Temporal dynamics of auditory what and where processing in humans

Recent evidence suggests the human auditory system is organized,like the visual system, into a ventral 'what' pathway, devoted toidentifying objects and a dorsal 'where' pathway devoted to thelocalization of objects in space w1x. Several brain regions have beenidentified in these two different pathways, but until now little isknown about the temporal dynamics of these regions. We investigatedthis issue using 128-channel auditory evoked potentials(AEPs).Stimuli were stationary sounds created by varying interaural timedifferences and environmental real recorded sounds. Stimuli ofeach condition (localization, recognition) were presented throughearphones in a blocked design, while subjects determined theirposition or meaning, respectively.AEPs were analyzed in terms of their topographical scalp potentialdistributions (segmentation maps) and underlying neuronalgenerators (source estimation) w2x.Fourteen scalp potential distributions (maps) best explained theentire data set.Ten maps were nonspecific (associated with auditory stimulationin general), two were specific for sound localization and two werespecific for sound recognition (P-values ranging from 0.02 to0.045).Condition-specific maps appeared at two distinct time periods:;200 ms and ;375-550 ms post-stimulus.The brain sources associated with the maps specific for soundlocalization were mainly situated in the inferior frontal cortices,confirming previous findings w3x. The sources associated withsound recognition were predominantly located in the temporal cortices,with a weaker activation in the frontal cortex.The data show that sound localization and sound recognitionengage different brain networks that are apparent at two distincttime periods.References1. Maeder et al. Neuroimage 2001.2. Michel et al. Brain Research Review 2001.3. Ducommun et al. Neuroimage 2002.