1,721,148 research outputs found
The deployment of visual attention in autism spectrum disorders
Full text linkAutism spectrum disorder (ASD) is a pervasive neurodevelopmental condition that affects almost 1% of the population. One of the main challenges in the current ASD research is to define the early neurocognitive impairments that provide critical foundations for the core deficits in social and communication abilities. In particular, early attentional dysfunctions may play a critical role in the emergence of ASD. In this doctoral thesis I present six studies that give significant new insights into the nature of altered visual attention in individuals with ASD and their possible neural underpinnings.
In the first study we show that individuals with ASD are impaired in enlarging (i.e., “zooming-out”) the attentional focus size relative to the control group and this deficit can impact the rapid orienting toward a cued location in the visual field. The second and the third studies show how parents without any history of ASD but with elevated autistic traits can transmit to their infants subtle deficit in visual attention (at the expense of both orienting and zooming mechanism) that may impact children’s future socio-communicative abilities. In the fourth and the fifth studies we employed transcranial magnetic stimulation and dense-array electroencephalography, respectively, with typical adults participants and we show that a network of frontal (mainly FEF and IFG) and parietal (mainly IPS/SPL) brain areas are fundamental in regulating the size of the attentional focus. In the last study, we evaluated the spatial profile of the attentional focus in individuals with ASD and results show that the inhibitory ring outside the focus of attention – fundamental to attenuate processing of irrelevant information – is significantly weakened relative to the control group.
Overall, these findings show the importance of attentional impairments in the core manifestations of ASD and in its developmental course. Defining attentional abnormalities and their neural correlates is extremely important (i) to improve the early detection of the disorder and, (ii) to implement timely prevention programs to reduce the incidence of ASD.Il disturbo dello spettro autistico (DSA) è un disturbo neuroevolutivo pervasivo che colpisce quasi l'1% della popolazione. Una delle principali sfide nell'attuale ricerca sul DSA è definire i deficit neurocognitivi precoci che costituiscono le fondamenta dei disturbi "chiave" nelle abilità sociali e comunicative. In particolare, precoci disfuzioni attentive potrebbero giocare un ruolo decisivo nell'emergere del DSA. Nella presente tesi di dottorato presento sei studi che contribuiscono significativamente alla comprensione delle alterazioni dell'attenzione visiva nei DSA e le loro possibili basi neurali.
Nel primo studio, mostriamo che gli individui affetti da DSA sono compromessi nell'abilità di allargare ("zoom-out") la dimensione del fuoco attentivo e che questo problema può avere un impatto negativo nell'orientamento rapido verso una posizione segnalata nel campo visivo. Il secondo e terzo studio mostrano come genitori senza alcuna storia clinica di DSA ma con elevati tratti autistici possano trasmettere ai loro infanti sottili alterazioni nell'attenzione visiva (a carico sia del meccanismo di orientamento che di quello di zoom) che possono avere conseguenze negative sul futuro sviluppo delle abilità socio-comunicative dei loro figli. Nel quarto e quinto studio, abbiamo utilizzato la stimolazione magnetica transcranica e l'elettroencefalografia ad alta densità, rispettivamente, in partecipanti adulti a sviluppo tipico e mostriamo che un network di aree frontali (principalmente FEF e IFG) e parietali (principalmente IPS/SPL) sono fondamentali nella regolazione della dimensione del fuoco attentivo. Nell'ultimo studio, abbiamo valutato il profilo spaziale del fuoco attentivo in individui con DSA e mostriamo come l'anulo inibitorio circostante al fuoco attentivo – fondamentale per attenuare il processamento d'informazioni irrilevanti – è significativamente più debole nel DSA rispetto al gruppo di controllo.
Complessivamente, queste evidenze mostrano l'importanza dei deficit attentivi nelle manifestazioni chiave del DSA e nel suo decorso evolutivo. Definire le anomalie dell'attenzione e i corrispondenti correlati neurali è estremamente importante (i) per migliorare la diagnosi precoce del disturbo e (ii) per implementare tempestivi programmi preventivi mirati a ridurre l'incidenza dei DSA
Rational design of gold(III)-dithiocarbamato peptidomimetics for the targeted anticancer chemotherapy
No full textCancer cells are known to overexpress specific biomarkers and receptors needed for tumor growth; therefore, targeted chemotherapies aim at blocking cancer cell proliferation by targeting such molecules. In this regard, membrane peptide transporters (PEPTs) were proved to be upregulated in several tumors and, owing to their capability to promote the cellular uptake of potentially all physiologically occurring di- and tripeptides, they can also internalize peptide-like chemotherapeutics resembling the main structural features of small peptides (i.e. peptidomimetics). Thus, they represent an excellent target for the site-specific delivery of pharmacologically active substrates acting as “Trojan horses” [1].
Accordingly, we have been designing gold(III)-peptidedithiocarbamato derivatives which could combine both the antitumor properties and reduced side-effects of the previously reported gold(III) analogues [2] with an enhanced bioavailability and tumor selectivity due to the peptide-mediated cellular internalization provided by PEPTs. Selected derivatives showed promising cytotoxic activity toward several human tumor cell lines in vitro and no cross-resistance with the reference anticancer drug cisplatin [3]. Remarkably, their chemotherapeutic properties were confirmed in vivo by inducing up to 85% and 65% reduction of breast and prostate cancer, respectively, together with negligible (or even no) organ and acute toxicity (LD50 ca. 30 mg kg-1), thus allowing the filing of an international patent for their use in cancer chemotherapy [4] as well as providing a solid starting point for them to enter Phase I clinical trials soon
The Midas touch in cancer chemotherapy: from platinum- to gold-dothiocarbamato complexes
No full textThe unquestionable therapeutic success of the anticancer drug cisplatin and its second- and third-generation analogues has triggered, in the past forty years, the development of several metal-based potential chemotherapeutic agents, most of which have failed to enter clinical trials. In this context, during the last decade, our research group has been making quite an effort to design a number of metal-dithiocarbamato derivatives that were expected, at least in principle, to resemble the main features of cisplatin together with higher activity, improved selectivity and bioavailability, and lower side-effects. Among all, gold(iii) complexes have shown outstanding in vitro and in vivo antitumour properties and reduced or no systemic and renal toxicity, compared to the reference drug. Here, we summarize the results achieved to date, focusing on the mechanistic studies and the potential future developments opened up by our research work
Beta oscillations in vision: a (preconscious) neural mechanism for the dorsal visual stream?
Full text linkNeural oscillations in alpha (8-12 Hz) and beta (13-30 Hz) frequency bands are thought to reflect feedback/reentrant loops and large-scale cortical interactions. In the last decades a main effort has been made in linking perception with alpha-band oscillations, with converging evidence showing that alpha oscillations have a key role in the temporal and featural binding of visual input, configuring the alpha rhythm a key determinant of conscious visual experience. Less attention has been historically dedicated to link beta oscillations and visual processing. Nonetheless, increasing studies report that task conditions that require to segregate/integrate stimuli in space, to disentangle local/global shapes, to spatially reorganize visual inputs, and to achieve motion perception or form-motion integration, rely on the activity of beta oscillations, with a main hub in parietal areas. In the present review, we summarize the evidence linking oscillations within the beta band and visual perception. We propose that beta oscillations represent a neural code that supports the functionality of the magnocellular-dorsal (M-D) visual pathway, serving as a fast primary neural code to exert top-down influences on the slower parvocellular-ventral visual pathway activity. Such M-D-related beta activity is proposed to act mainly pre-consciously, providing the spatial coordinates of vision and guiding the conscious extraction of objects identity that are achieved with slower alpha rhythms in ventral areas. Finally, within this new theoretical framework, we discuss the potential role of M-D-related beta oscillations in visuo-spatial attention, oculo-motor behavior and reading (dis)abilities
Using coordination chemistry to design new medicines
No full textThe rich diversity of coordination chemistry provides exciting prospects for the design of novel therapeutic agents with unique mechanisms of action. Central to such discovery is the understanding of both the kinetics and thermodynamics of reactions of metal complexes under conditions of biological relevance, and consideration of the roles of both the metal and its ligands in recognition processes. Examples from our recent work are reported here and discussed. Xylylbicyclam is a potent anti-HIV agent and is in clinical use as a stem-cell-mobilizing drug (AMD3100, "Mozobil"). Its target is the 7-helix membrane receptor CXCR4. Specific metallomacrocycle configurations can be recognized by proteins via metal coordination to specific amino acid side-chains, H-bonding and hydrophobic interactions, allowing optimisation of drug design. Photoactivation of octahedral cis and trans diam(m)ino diazido Pt(IV) complexes can lead to unusual redox and substitution reactions. Such activated complexes can kill cancer cells by novel mechanisms of action, providing a basis for a novel form of photochemotherapy. Substitution and redox reactions and the anticancer activity of Ru(II) arene complexes of the type [(η6-arene)Ru(X)(YZ)] are highly dependent on the nature of the arene, and monodentate (X) and chelated (YZ) ligands. Understanding of the factors which control such reactions has led to the rational design of analogous osmium anticancer complexes
Insights into the reactivity of gold(III)-dithiocarbamato anticancer agents toward model biomolecules from multinuclear NMR spectroscopy
No full textThe neural origins of visual crowding as revealed by event-related potentials and oscillatory dynamics
No full textAlpha-band sensory entrainment alters the duration of temporal windows in visual perception
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