INVESTIGATION ON NEURAL RESPONSES RELATED TO THE LOCALIZATION OF NATURAL SOUNDS

Spatial hearing allows the localization of sounds in complex acoustic environments. There is considerable evidence that this neural system rapidly adapts to changes in sensory inputs and behavioral goals. However, the mechanisms underlying this context-dependent coding are not well understood. In fact, previous studies on sound localization have mainly focused on the perception of simple artificial sounds, such as white-noise or pure tone bursts. In addition, previous research has generally investigated the localization of sounds in the frontal hemicircle while ignoring rear sources. However, their localization is evolutionary relevant and may show different neural coding, given the inherent lack of visual information. Here we present a pilot electroencephalography (EEG) study to identify robust indices of sound localization from participants listening to a short natural sound from eight source positions on the horizontal plane. We discuss a procedure to perform a within-subject classification of the perceived sound direction. Preliminary results suggest a pool of discriminative subject-specific temporal and topographical features correlated with the characteristics of the acoustic event. Our preliminary analysis has identified temporal and topographical features that are sensitive to spatial localization, leading to significant decoding of sounds direction for individual subjects. This pilot study adds to the literature a methodological approach that will lead to the objective classification of natural sounds location from EEG responses

Floquet-engineered nonlinearities and controllable pair-hopping processes: From optical Kerr cavities to correlated quantum matter

This work explores the possibility of creating and controlling unconventional nonlinearities by periodic driving, in a broad class of systems described by the nonlinear Schr\"odinger equation (NLSE). By means of a parent quantum many-body description, we demonstrate that such driven systems are well captured by an effective NLSE with emergent nonlinearities, which can be finely controlled by tuning the driving sequence. We first consider a general class of two-mode nonlinear systems - relevant to optical Kerr cavities, waveguides and Bose-Einstein condensates - where we find an emergent four-wave mixing nonlinearity, which originates from pair-hopping processes in the parent quantum picture. Tuning this drive-induced nonlinearity is shown to modify the phase-space topology, which can be detected through relative population and phase measurements. We then couple individual (two-mode) dimers in view of designing extended lattice models with unconventional nonlinearities and controllable pair-hopping processes. Following this general dimerization construction, we obtain an effective lattice model with drive-induced interactions, whose ground-state exhibits orbital order, chiral currents and emergent magnetic fluxes through the spontaneous breaking of time-reversal symmetry. We analyze these intriguing properties both in the weakly-interacting (mean-field) regime, captured by the effective NLSE, and in the strongly-correlated quantum regime. Our general approach opens a route for the engineering of unconventional optical nonlinearities in photonic devices and controllable drive-induced interactions in ultracold quantum matter.Comment: 33 pages, 21 figures, including Appendices. Extended version of arXiv:2203.0555

Size resolved aerosol respiratory doses in a Mediterranean urban area: From PM10 to ultrafine particles

In the framework of the 2017 "carbonaceous aerosol in Rome and Environs" (CARE) experiment, particle number size distributions have been continuously measured on February 2017 in downtown Rome. These data have been used to estimate, through MPPD model, size and time resolved particle mass, surface area and number doses deposited into the respiratory system. Dosimetry estimates are presented for PM10, PM2.5, PM1 and Ultrafine Particles (UFPs), in relation to the aerosol sources peculiar to the Mediterranean basin and to the atmospheric conditions. Particular emphasis is focused on UFPs and their fraction deposited on the olfactory bulb, in view of their possible translocation to the brain. The site of PM10 deposition within the respiratory system considerably changes, depending on the aerosol sources and then on its different size distributions. On making associations between health endpoints and aerosol mass concentrations, the relevant coarse and fine fractions would be more properly adopted, because they have different sources, different capability of penetrating deep into the respiratory system and different toxicological implications. The separation between them should be set at 1ʵm, rather than at 2.5ʵm, because the fine fraction is considerably less affected by the contribution of the natural sources. Mass dose is a suitable metric to describe coarse aerosol events but gives a poor representation of combustion aerosol. This fraction of particles, made of UFPs and of accumulation mode particles (mainly with size below 0.2ʵm), is of high health relevance. It elicited the highest oxidative activity in the CARE experiment and is properly described by the particle surface area and by the number metrics. Such metrics are even more relevant for the UFP doses deposited on the olfactory bulb, in consideration of the role recognized to oxidative stress in the progression of neurodegenerative diseases. Such metrics would be more appropriate, rather than PMx mass concentrations, to correlate neurodegenerative pathologies with aerosol pollution

Natalizumab in Multiple Sclerosis: Long-Term Management

Natalizumab is a monoclonal antibody highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Despite its effectiveness, there are growing concerns regarding the risk of progressive multifocal leukoencephalopathy (PML), a brain infection caused by John Cunningham virus (JCV), particularly after 24 doses and in patients who previously received immunosuppressive drugs. Long-term natalizumab treated, immunosuppressive-pretreated, and JCV antibody-positive patients are asked to rediscuss natalizumab continuation or withdrawal after 24 doses. Until now, there has not been a clear strategy that should be followed to avoid PML risk and in parallel reduce clinical and radiological rebound activity. In this review, we analyzed the results of clinical trials and case reports in relation to the following situations: natalizumab continuation, natalizumab discontinuation followed by full therapeutic suspension or switch to other first or second line MS treatments. Quitting all MS treatment after natalizumab increases MS activity occurrence. The results regarding the therapeutic switch are not homogeneous, so at the moment there are no established guidelines regarding natalizumab treatment after 24 administrations; the choice is currently based on the professional experience of the neurologist, and on patients’ clinical features and preferences

Neurology training and research in the Covid-19 pandemic: A survey of the Resident and Research Fellow Section of the European Academy of Neurology.

INTRODUCTION The COVID-19 (SARS-CoV2) outbreak has disrupted residency programs due to the university and hospital's priorities to face this emergency at all expenses. Most research projects and clinical trials were temporarily stopped or postponed. The Resident and Research Fellow Section (RRFS) of the European Academy of Neurology (EAN) has decided to assess the impact of the COVID-19 pandemic on neurology training. METHODS All EAN RRFS members were invited to fill out an online questionnaire of 40 items concerning their clinical involvement during the COVID-19 emergency, and the impact of the pandemic on their training. RESULTS Of the 227 RRFS members who completed the questionnaire, 222 were from Europe, and from those 111 were from Portugal, Italy or France. Responders highlighted that severe restrictions have been amended to face this pandemic, including reduction of inpatient beds, prohibition of in-person visits and limitation to hospitals access for patients' relatives. This was accompanied by an increase in email correspondence and phone calls with 50 % of countries allowing telemedicine to reach outpatients. Seventy-nine percent of the respondents felt that the pandemic will likely have a serious impact on their training and career. CONCLUSION The pandemic lead to a disruption of neurology activities, including medical training and research. The long-run impact of these changes remains unknown, but it will likely change the way neurology practice and training will be organized for future generations

Serotonin Heteroreceptor Complexes and Their Integration of Signals in Neurons and Astroglia—Relevance for Mental Diseases

The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor–receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical antipsychotic drugs not only based on blockade of 5-HT2AR and of D2R in higher doses but also based on blocking the allosteric enhancement of D2R protomer signaling by 5-HT2AR protomer activation. This research opens a new understanding of the integration of DA and 5-HT signals released from DA and 5-HT nerve terminal networks. The biological principle of forming 5-HT and other heteroreceptor complexes in the brain also help understand the mechanism of action for especially the 5-HT hallucinogens, including putative positive effects of e.g., psilocybin and the indicated prosocial and anti-stress actions of MDMA (ecstasy). The GalR1-GalR2 heterodimer and the putative GalR1-GalR2-5-HT1 heteroreceptor complexes are targets for Galanin N-terminal fragment Gal (1–15), a major modulator of emotional networks in models of mental disease. GPCR-receptor tyrosine kinase (RTK) heteroreceptor complexes can operate through transactivation of FGFR1 via allosteric mechanisms and indirect interactions over GPCR intracellular pathways involving protein kinase Src which produces tyrosine phosphorylation of the RTK. The exciting discovery was made that several antidepressant drugs such as TCAs and SSRIs as well as the fast-acting antidepressant drug ketamine can directly bind to the TrkB receptor and provide a novel mechanism for their antidepressant actions. Understanding the role of astrocytes and their allosteric receptor–receptor interactions in modulating forebrain glutamate synapses with impact on dorsal raphe-forebrain serotonin neurons is also of high relevance for research on major depressive disorder

The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update

Gluten-related disorders have recently been reclassified with an emerging scientific literature supporting the concept of non-celiac gluten sensitivity (NCGS). New research has specifically addressed prevalence, immune mechanisms, the recognition of non-immunoglobulin E (non-IgE) wheat allergy and overlap of NCGS with irritable bowel syndrome (IBS)-type symptoms. This review article will provide clinicians with an update that directly impacts on the management of a subgroup of their IBS patients whose symptoms are triggered by wheat ingestion

First Results of the “Carbonaceous Aerosol in Rome and Environs (CARE)” Experiment: Beyond Current Standards for PM10

In February 2017 the “Carbonaceous Aerosol in Rome and Environs (CARE)” experiment was carried out in downtown Rome to address the following specific questions: what is the color, size, composition, and toxicity of the carbonaceous aerosol in the Mediterranean urban background area of Rome? The motivation of this experiment is the lack of understanding of what aerosol types are responsible for the severe risks to human health posed by particulate matter (PM) pollution, and how carbonaceous aerosols influence radiative balance. Physicochemical properties of the carbonaceous aerosol were characterised, and relevant toxicological variables assessed. The aerosol characterisation includes: (i) measurements with high time resolution (min to 1–2 h) at a fixed location of black carbon (eBC), elemental carbon (EC), organic carbon (OC), particle number size distribution (0.008–10 μ m), major non refractory PM1 components, elemental composition, wavelength-dependent optical properties, and atmospheric turbulence; (ii) 24-h measurements of PM10 and PM2.5 mass concentration, water soluble OC and brown carbon (BrC), and levoglucosan; (iii) mobile measurements of eBC and size distribution around the study area, with computational fluid dynamics modeling; (iv) characterisation of road dust emissions and their EC and OC content. The toxicological assessment includes: (i) preliminary evaluation of the potential impact of ultrafine particles on lung epithelia cells (cultured at the air liquid interface and directly exposed to particles); (ii) assessment of the oxidative stress induced by carbonaceous aerosols; (iii) assessment of particle size dependent number doses deposited in different regions of the human body; (iv) PAHs biomonitoring (from the participants into the mobile measurements). The first experimental results of the CARE experiment are presented in this paper. The objective here is to provide baseline levels of carbonaceous aerosols for Rome, and to address future research directions. First, we found that BC and EC mass concentration in Rome are larger than those measured in similar urban areas across Europe (the urban background mass concentration of eBC in Rome in winter being on average 2.6 ± 2.5 μ g · m − 3 , mean eBC at the peak level hour being 5.2 (95% CI = 5.0–5.5) μ g · m − 3 ). Then, we discussed significant variations of carbonaceous aerosol properties occurring with time scales of minutes, and questioned on the data averaging period used in current air quality standard for PM 10 (24-h). Third, we showed that the oxidative potential induced by aerosol depends on particle size and composition, the effects of toxicity being higher with lower mass concentrations and smaller particle size. Albeit this is a preliminary analysis, findings reinforce the need for an urgent update of existing air quality standards for PM 10 and PM 2.5 with regard to particle composition and size distribution, and data averaging period. Our results reinforce existing concerns about the toxicity of carbonaceous aerosols, support the existing evidence indicating that particle size distribution and composition may play a role in the generation of this toxicity, and remark the need to consider a shorter averaging period (<1 h) in these new standards