Resting-state connectivity and functional specialization in human medial parieto-occipital cortex

According to recent models of visuo-spatial processing, the medial parieto-occipital cortex is a crucial node of the dorsal visual stream. Evidence from neurophysiological studies in monkeys has indicated that the parieto-occipital sulcus (POS) contains three functionally and cytoarchitectonically distinct areas: the visual area V6 in the fundus of the POS, and the visuo-motor areas V6Av and V6Ad in a progressively dorsal and anterior location with respect to V6. Besides different topographical organization, cytoarchitectonics, and functional properties, these three monkey areas can also be distinguished based on their patterns of cortico-cortical connections. Thanks to wide-field retinotopic mapping, areas V6 and V6Av have been also mapped in the human brain. Here, using a combined approach of resting-state functional connectivity and task-evoked activity by fMRI, we identified a new region in the anterior POS showing a pattern of functional properties and cortical connections that suggests a homology with the monkey area V6Ad. In addition, we observed distinct patterns of cortical connections associated with the human V6 and V6Av which are remarkably consistent with those showed by the anatomical tracing studies in the corresponding monkey areas. Consistent with recent models on visuo-spatial processing, our findings demonstrate a gradient of functional specialization and cortical connections within the human POS, with more posterior regions primarily dedicated to the analysis of visual attributes useful for spatial navigation and more anterior regions primarily dedicated to analyses of spatial information relevant for goal-directed action

Concreteness and emotional valence of episodic future thinking (EFT) independently affect the dynamics of intertemporal decisions

During intertemporal decisions, the value of future rewards decreases as a function of the delay of its receipt (temporal discounting, TD). Since high discount rates have been associated with a series of problematic behaviours and clinical conditions, current research has focused on possible modulators of TD. Specifically, a reduction of individual discount rates has been shown during episodic future thinking (EFT), wherein time intervals are anchored to personal future events. However, it is not entirely clear whether this effect is mediated by a change in the representation of future events (i.e., from abstract to concrete) or by a positive-emotion modulation. Here, we investigated this issue by manipulating the valence of the EFT (i.e., using negative, neutral and positive episodic tags), and by collecting explicit and implicit measures of behaviour. The results showed a significant reduction of TD in all the three emotional conditions compared to the baseline, with differences among them, thus suggesting the existence of a cumulative effect of the concreteness and affective components of the EFT. The analyses of implicit measures additionally revealed that this effect was mediated by a simultaneous increase/decrease of attraction toward the delayed/immediate alternative. Finally, these effects appeared to be modulated by participants' baseline discounting preferences. These findings provide important insights on clinical applications in reward-related disorders

Interindividual variability in functional connectivity as long-term correlate of temporal discounting

During intertemporal choice (IT) future outcomes are usually devaluated as a function of the delay, a phenomenon known as temporal discounting (TD). Based on task-evoked activity, previous neuroimaging studies have described several networks associated with TD. However, given its relevance for several disorders, a critical challenge is to define a specific neural marker able to predict TD independently of task execution. To this aim, we used restingstate functional connectivity MRI (fcMRI) and measured TD during economic choices several months apart in 25 human subjects.We further explored the relationship between TD, impulsivity and decision uncertainty by collecting standard questionnaires on individual trait/ state differences. Our findings indicate that fcMRI within and between critical nodes of taskevoked neural networks associated with TD correlates with discounting behavior measured a long time afterwards, independently of impulsivity. Importantly, the nodes form an intrinsic circuit that might support all the mechanisms underlying TD, from the representation of subjective value to choice selection through modulatory effects of cognitive control and episodic prospection

Two-dimensional TiOx nanostructures on Au(111): a Scanning Tunneling Microscopy and Spectroscopy investigation

We investigated the growth of titanium oxide two-dimensional (2D) nanostructures on Au(111), produced by Ti evaporation and post-deposition oxidation. Scanning tunneling microscopy and spectroscopy (STM and STS) and low-energy electron diffraction (LEED) measurements characterized the morphological, structural and electronic properties of the observed structures. Five distinct TiOx phases were identified: the honeycomb and pinwheel phases appear as monolayer films wetting the gold surface, while nanocrystallites of the triangular, row and needle phases grow mainly over the honeycomb or pinwheel layers. Density Functional Theory (DFT) investigation of the honeycomb structure supports a (2 x 2) structural model based on a Ti-O bilayer having Ti2O3 stoichiometry. The pinwheel phase was observed to evolve, for increasing coverage, from single triangular crystallites to a well-ordered film forming a (4*sqrt(7) x 4*sqrt(7))R19.1° superstructure, which can be interpreted within a moire-like model. Structural characteristics of the other three phases were disclosed from the analysis of high-resolution STM measurements. STS measurements revealed a partial metallization of honeycomb and pinwheel and a semiconducting character of row and triangular phases

Adult Neural Stem Cell Regulation by Small Non-coding RNAs: Physiological Significance and Pathological Implications

The adult neurogenic niches are complex multicellular systems, receiving regulatory input from a multitude of intracellular, juxtacrine, and paracrine signals and biological pathways. Within the niches, adult neural stem cells (aNSCs) generate astrocytic and neuronal progeny, with the latter predominating in physiological conditions. The new neurons generated from this neurogenic process are functionally linked to memory, cognition, and mood regulation, while much less is known about the functional contribution of aNSC-derived newborn astrocytes and adult-born oligodendrocytes. Accumulating evidence suggests that the deregulation of aNSCs and their progeny can impact, or can be impacted by, aging and several brain pathologies, including neurodevelopmental and mood disorders, neurodegenerative diseases, and also by insults, such as epileptic seizures, stroke, or traumatic brain injury. Hence, understanding the regulatory underpinnings of aNSC activation, differentiation, and fate commitment could help identify novel therapeutic avenues for a series of pathological conditions. Over the last two decades, small non-coding RNAs (sncRNAs) have emerged as key regulators of NSC fate determination in the adult neurogenic niches. In this review, we synthesize prior knowledge on how sncRNAs, such as microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs), may impact NSC fate determination in the adult brain and we critically assess the functional significance of these events. We discuss the concepts that emerge from these examples and how they could be used to provide a framework for considering aNSC (de)regulation in the pathogenesis and treatment of neurological diseases

Elastic and vibrational properties of alpha and beta-PbO

The structure, electronic and dynamic properties of the two layered alpha (litharge) and beta (massicot) phases of PbO have been studied by density functional methods. The role of London dispersion interactions as leading component of the total interaction energy between layers has been addressed by using the Grimme's approach, in which new parameters for Pb and O atoms have been developed. Both gradient corrected and hybrid functionals have been adopted using Gaussian-type basis sets of polarized triple zeta quality for O atoms and small core pseudo-potential for the Pb atoms. Basis set superposition error (BSSE) has been accounted for by the Boys-Bernardi correction to compute the interlayer separation. Cross check with calculations adopting plane waves that are BSSE free have also been performed for both structures and vibrational frequencies. With the new set of proposed Grimme's type parameters structures and dynamical parameters for both PbO phases are in good agreement with experimental data.Comment: 8 pages, 5 figure

Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group

Background: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood-brain barrier has demonstrated preclinical activity in glioma models. Patients and methods: Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m2 over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points. Results: Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3-18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3-12.3), with a 1-year survival rate of 31.6% (95% CI 17.7-46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination. Conclusions: No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administratio

A self-sustaining endocytic-based loop promotes breast cancer plasticity leading to aggressiveness and pro-metastatic behavior

The subversion of endocytic routes leads to malignant transformation and has been implicated in human cancers. However, there is scarce evidence for genetic alterations of endocytic proteins as causative in high incidence human cancers. Here, we report that Epsin 3 (EPN3) is an oncogene with prognostic and therapeutic relevance in breast cancer. Mechanistically, EPN3 drives breast tumorigenesis by increasing E-cadherin endocytosis, followed by the activation of a \u3b2-catenin/TCF4-dependent partial epithelial-to-mesenchymal transition (EMT), followed by the establishment of a TGF\u3b2-dependent autocrine loop that sustains EMT. EPN3-induced partial EMT is instrumental for the transition from in situ to invasive breast carcinoma, and, accordingly, high EPN3 levels are detected at the invasive front of human breast cancers and independently predict metastatic rather than loco-regional recurrence. Thus, we uncover an endocytic-based mechanism able to generate TGF\u3b2-dependent regulatory loops conferring cellular plasticity and invasive behavior

The Human Homologue of Macaque Area V6A

In macaque monkeys, V6A is a visuomotor area located in the anterior bank of the POs, dorsal and anterior to retinotopically-organized extrastriate area V6 (Galletti et al 1996). Unlike V6, V6A represents both contra- and ipsilateral visual fields and is broadly retinotopically organized (Galletti et al 1999b). The contralateral lower visual field is over-represented in V6A. The central 20°-30° of the visual field are mainly represented dorsally (V6Ad) and the periphery ventrally (V6Av), at the border with V6. Both sectors of area V6A contain arm movement-related cells, active during spatially-directed reaching movements (Gamberini et al., 2011). In humans, we previously mapped the retinotopic organization of area V6 (Pitzalis et al., 2006). Here, using phase-encoded fMRI, cortical surface-based analysis and wide-field retinotopic mapping, we define a new cortical region that borders V6 anteriorly and shows a clear over-representation of the contralateral lower visual field and of the periphery. As with macaque V6A, the eccentricity increases moving ventrally within the area. The new region contains a non-mirror-image representation of the visual field. Functional mapping reveals that, as in macaque V6A, the new region, but not the nearby area V6, responds during finger pointing and reaching movements. Based on similarity in position, retinotopic properties, functional organization and relationship with the neighbouring extrastriate visual areas, we propose that the new cortical region is the human homologue of macaque area V6A