The web of laughter: frontal and limbic projections of the anterior cingulate cortex revealed by cortico-cortical evoked potential from sites eliciting laughter

According to an evolutionist approach, laughter is a multifaceted behaviour affecting social, emotional, motor and speech functions. Albeit previous studies have suggested that high-frequency electrical stimulation (HF-ES) of the pregenual anterior cingulate cortex ( pACC) may induce bursts of laughter—suggesting a crucial contribution of this region to the cortical con- trol of this behaviour—the complex nature of laughter implies that outward connections from the pACC may reach and affect a complex network of fron- tal and limbic regions. Here, we studied the effective connectivity of the pACC by analysing the cortico-cortical evoked potentials elicited by single-pulse electrical stimulation of pACC sites whose HF-ES elicited laugh- ter in 12 patients. Once these regions were identified, we studied their clinical response to HF-ES, to reveal the specific functional target of pACC representation of laughter. Results reveal that the neural representation of laughter in the pACC interacts with several frontal and limbic regions, including cingulate, orbitofrontal, medial prefrontal and anterior insular regions—involved in interoception, emotion, social reward and motor be- haviour. These results offer neuroscientific support to the evolutionist approach to laughter, providing a possible mechanistic explanation of the interplay between this behaviour and emotion regulation, speech production and social interactions. This article is part of the theme issue ‘Cracking the laugh code: laughter through the lens of biology, psychology, and neuroscience’

Language lateralization mapping (reversibly) masked by non-dominant focal epilepsy: a case report

Language lateralization in patients with focal epilepsy frequently diverges from the left-lateralized pattern that prevails in healthy right-handed people, but the mechanistic explanations are still a matter of debate. Here, we debate the complex interaction between focal epilepsy, language lateralization, and functional neuroimaging techniques by introducing the case of a right-handed patient with unaware focal seizures preceded by aphasia, in whom video-EEG and PET examination suggested the presence of focal cortical dysplasia in the right superior temporal gyrus, despite a normal structural MRI. The functional MRI for language was inconclusive, and the neuropsychological evaluation showed mild deficits in language functions. A bilateral stereo-EEG was proposed confirming the right superior temporal gyrus origin of seizures, revealing how ictal aphasia emerged only once seizures propagated to the left superior temporal gyrus and confirming, by cortical mapping, the left lateralization of the posterior language region. Stereo-EEG-guided radiofrequency thermocoagulations of the (right) focal cortical dysplasia not only reduced seizure frequency but led to the normalization of the neuropsychological assessment and the “restoring” of a classical left-lateralized functional MRI pattern of language. This representative case demonstrates that epileptiform activity in the superior temporal gyrus can interfere with the functioning of the contralateral homologous cortex and its associated network. In the case of presurgical evaluation in patients with epilepsy, this interference effect must be carefully taken into consideration. The multimodal language lateralization assessment reported for this patient further suggests the sensitivity of different explorations to this interference effect. Finally, the neuropsychological and functional MRI changes after thermocoagulations provide unique cues on the network pathophysiology of focal cortical dysplasia and the role of diverse techniques in indexing language lateralization in complex scenarios

Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness

An in–vivo validation of ESI methods with focal sources

Electrophysiological source imaging (ESI) aims at reconstructing the precise origin of brain activity from measurements of the electric field on the scalp. Across laboratories/research centers/hospitals, ESI is performed with different methods, partly due to the ill-posedness of the underlying mathematical problem. However, it is difficult to find systematic comparisons involving a wide variety of methods. Further, existing comparisons rarely take into account the variability of the results with respect to the input parameters. Finally, comparisons are typically performed using either synthetic data, or in-vivo data where the ground-truth is only roughly known. We use an in-vivo high-density EEG dataset recorded during intracranial single pulse electrical stimulation, in which the true sources are substantially dipolar and their locations are precisely known. We compare ten different ESI methods, using their implementation in the MNE-Python package: MNE, dSPM, LORETA, sLORETA, eLORETA, LCMV beamformers, irMxNE, Gamma Map, SESAME and dipole fitting. We perform comparisons under multiple choices of input parameters, to assess the accuracy of the best reconstruction, as well as the impact of such parameters on the localization performance. Best reconstructions often fall within 1 cm from the true source, with most accurate methods hitting an average localization error of 1.2 cm and outperforming least accurate ones erring by 2.5 cm. As expected, dipolar and sparsity-promoting methods tend to outperform distributed methods. For several distributed methods, the best regularization parameter turned out to be the one in principle associated with low SNR, despite the high SNR of the available dataset. Depth weighting played no role for two out of the six methods implementing it. Sensitivity to input parameters varied widely between methods. While one would expect high variability being associated with low localization error at the best solution, this is not always the case, with some methods producing highly variable results and high localization error, and other methods producing stable results with low localization error. In particular, recent dipolar and sparsity-promoting methods provide significantly better results than older distributed methods. As we repeated the tests with “conventional” (32 channels) and dense (64, 128, 256 channels) EEG recordings, we observed little impact of the number of channels on localization accuracy; however, for distributed methods denser montages provide smaller spatial dispersion. Overall findings confirm that EEG is a reliable technique for localization of point sources and therefore reinforce the importance that ESI may have in the clinical context, especially when applied to identify the surgical target in potential candidates for epilepsy surgery

Table_1_Language lateralization mapping (reversibly) masked by non-dominant focal epilepsy: a case report.DOCX

Language lateralization in patients with focal epilepsy frequently diverges from the left-lateralized pattern that prevails in healthy right-handed people, but the mechanistic explanations are still a matter of debate. Here, we debate the complex interaction between focal epilepsy, language lateralization, and functional neuroimaging techniques by introducing the case of a right-handed patient with unaware focal seizures preceded by aphasia, in whom video-EEG and PET examination suggested the presence of focal cortical dysplasia in the right superior temporal gyrus, despite a normal structural MRI. The functional MRI for language was inconclusive, and the neuropsychological evaluation showed mild deficits in language functions. A bilateral stereo-EEG was proposed confirming the right superior temporal gyrus origin of seizures, revealing how ictal aphasia emerged only once seizures propagated to the left superior temporal gyrus and confirming, by cortical mapping, the left lateralization of the posterior language region. Stereo-EEG-guided radiofrequency thermocoagulations of the (right) focal cortical dysplasia not only reduced seizure frequency but led to the normalization of the neuropsychological assessment and the “restoring” of a classical left-lateralized functional MRI pattern of language. This representative case demonstrates that epileptiform activity in the superior temporal gyrus can interfere with the functioning of the contralateral homologous cortex and its associated network. In the case of presurgical evaluation in patients with epilepsy, this interference effect must be carefully taken into consideration. The multimodal language lateralization assessment reported for this patient further suggests the sensitivity of different explorations to this interference effect. Finally, the neuropsychological and functional MRI changes after thermocoagulations provide unique cues on the network pathophysiology of focal cortical dysplasia and the role of diverse techniques in indexing language lateralization in complex scenarios.</p

Monitoring the Establishment of VOC Gamma in Minas Gerais, Brazil: A Retrospective Epidemiological and Genomic Surveillance Study

Since its first identification in Brazil, the variant of concern (VOC) Gamma has been associated with increased infection and transmission rates, hospitalizations, and deaths. Minas Gerais (MG), the second-largest populated Brazilian state with more than 20 million inhabitants, observed a peak of cases and deaths in March&ndash;April 2021. We conducted a surveillance study in 1240 COVID-19-positive samples from 305 municipalities distributed across MG&rsquo;s 28 Regional Health Units (RHU) between 1 March to 27 April 2021. The most common variant was the VOC Gamma (71.2%), followed by the variant of interest (VOI) zeta (12.4%) and VOC alpha (9.6%). Although the predominance of Gamma was found in most of the RHUs, clusters of Zeta and Alpha variants were observed. One Alpha-clustered RHU has a history of high human mobility from countries with Alpha predominance. Other less frequent lineages, such as P.4, P.5, and P.7, were also identified. With our genomic characterization approach, we estimated the introduction of Gamma on 7 January 2021, at RHU Belo Horizonte. Differences in mortality between the Zeta, Gamma and Alpha variants were not observed. We reinforce the importance of vaccination programs to prevent severe cases and deaths during transmission peaks

Unsung Hero Robert C. Gallo

Awarding the Nobel prize in physiology or medicine to Francoise Barré-Sinoussi and Luc Montagnier for the discovery of HIV-1, the causative agent of AIDS, is timely given the harm that the virus continues to inflict on the people of the world. While these awardees fully deserve the award, it is equally important to recognize the contributions of Robert C. Gallo. Gallo definitively proved HIV-1 as the cause of AIDS through the successful isolation and long-term cultivation of HIV-1 and developed a diagnostic kit that prevented new infections and saved thousands of lives. These contributions, together with Gallo's earlier discovery of interleukin-2 (fundamental for growing HIV-1 in vitro) and of HTLV-1, the first human pathogenic retrovirus, warrant equal recognition

Indicatori ambientali nello studio EpiAir2: I dati di qualit\ue0 dell'aria per la sorveglianza epidemiologica

OBIETTIVO: costruzione di indicatori ambientali di inquinamento aerodiffuso per finalit\ue0 di sorveglianza epidemiologica in 25 citt\ue0 italiane per il progetto EpiAir2 (2006-2010) e presentazione dei dati di dieci anni di sorveglianza in 10 citt\ue0 italiane (2001-2010). DISEGNO: sono stati raccolti dati di particolato (nelle frazioni PM10 e PM2.5 ), biossido di azoto (NO2 ) e ozono (O3 ), considerati fattori di rischio per la salute. I datimeteorologici considerati come confondenti nell\u2019analisi dell\u2019effetto degli inquinanti sono stati: temperatura, umidit\ue0 relativa (e la variabile derivata \u201ctemperatura apparente\u201d) e pressione barometrica. I criteri per la selezione delle stazioni dimonitoraggio e imetodi di calcolo per la costruzione di indicatori ambientali a partire dalle serie giornaliere disponibili sono stati scelti in continuit\ue0 con la precedente edizione di EpiAir. Per tutte le citt\ue0, \ue8 stata verificata l\u2019omogeneit\ue0 dei dati selezionati nel rappresentare l\u2019esposizione delle popolazioni. SETTING E PARTECIPANTI: il progetto EpiAir2 coinvolge per gli anni 2006-2010 le citt\ue0 diMilano,Mestre-Venezia,Torino, Bologna, Firenze, Pisa, Roma,Taranto,Cagliari e Palermo, gi\ue0 presenti nello studio EpiAir. A questo elenco vanno aggiunte le citt\ue0 di Treviso, Trieste, Padova, Rovigo, Piacenza, Parma, Ferrara, Reggio Emilia, Modena, Genova, Rimini, Ancona, Bari, Napoli e Brindisi. RISULTATI: nel periodo considerato \ue8 stato osservato un decremento delle concentrazioni di particolato nella maggior parte delle citt\ue0 in analisi, mentre non si pu\uf2 giungere a conclusioni cos\uec nette per NO2 e ozono. L\u2019analisi dell\u2019andamento temporale degli indicatori ha evidenziato valori medi annuali di PM10 superiori ai 40 \u3bcg/m3 in alcune citt\ue0 della Pianura Padana, e valori medi annuali di NO2 costantemente superiori ai 40 \u3bcg/m3 nelle citt\ue0 di Trieste, Milano, Padova, Torino, Modena, Bologna, Roma e Napoli. CONCLUSIONE: l\u2019ampliamento del progetto EpiAir, con l\u2019inclusione di ulteriori 13 citt\ue0, ha permesso di evidenziare peculiarit\ue0 legate alle differenti aree geografiche in studio e numerose situazioni di criticit\ue0 con superamenti dei valori di concentrazione limite fissati dalla legislazione corrente. I risultati dello studio EpiAir2 confermano la necessit\ue0 di un sistema di sorveglianza dell\u2019inquinamento aerodiffuso nei centri urbani e industriali al fine di ottenere stime affidabili dell\u2019esposizione della popolazione residente e di monitorarne l\u2019andamento nel tempo

Impatto a breve termine dell'inquinamento dell'aria nelle citt\ue0 coperte dalla sorveglianza epidemiologica EpiAir2

OBIETTIVO: stimare l\u2019impatto a breve termine dell\u2019inquinamento atmosferico sulla popolazione adulta di 23 citt\ue0 italiane nel periodo 2006-2009 nell\u2019ambito del progetto EpiAir2. DISEGNO, MATERIALI E METODI: per ogni citt\ue0 inclusa nello studio \ue8 stato calcolato l\u2019impatto dell\u2019effetto a breve termine dell\u2019inquinamento atmosferico sulla mortalit\ue0. In particolare, sono stati calcolati i decessi attribuibili a concentrazioni delle polveri (PM10 e PM2.5) superiori a soglie differenti definite dalla legislazione europea o nell\u2019ambito delle linee guida dell\u2019Organizzazione mondiale della sanit\ue0 (per il PM10: 20 e 40 \u3bcg/m3, riduzione del 20% ad arrivare a 20 \u3bcg/m3 e superamento del limite di 35 giorni con concentrazioni medie di 50 \u3bcg/m3; per il PM2.5: 10, 18 e 25 \u3bcg/m3, riduzione del 20% ad arrivare a 18 \u3bcg/m3). La stima di impatto \ue8 stata ottenuta combinando la stima di effetto delle polveri, il livello di mortalit\ue0 osservato e i livelli di concentrazione degli inquinanti misurati dalle reti di monitoraggio urbane. Per quanto riguarda le stime di effetto, sono state utilizzate le distribuzioni a posteriori specifiche per citt\ue0 risultanti da una metanalisi bayesiana. L\u2019incertezza sulle stime di impatto \ue8 stata calcolata con metodi Monte Carlo. RISULTATI: nell\u2019insieme delle 23 citt\ue0 valutate nel presente studio il numero di decessi attribuibili agli effetti a breve termine delle concentrazioni di PM10 superiori a 20 \u3bcg/m3 e di PM2.5 superiori a 10 \u3bcg/m3 nel periodo 2006-2009 \ue8 risultato rispettivamente pari allo 0,9% (assumendo indipendenza tra citt\ue0 l\u2019intervallo di credibilit\ue0 all\u201980% \ue8 0,4-1,4) e allo 0,8% (ICr80% 0,2-1,3) della mortalit\ue0 naturale. L\u2019impatto delle concentrazioni di polveri PM10 e PM2.5 \ue8 risultato concentrato nelle citt\ue0 della Pianura Padana, della Piana fiorentina, e nelle grandi realt\ue0 metropolitane di Roma, Napoli e Palermo: per il PM10 la percentuale sui decessi \ue8 risultata 1,0% (ICr80% 0,4-1,5) contro 0,4% (ICr80% 0,2-0,7) nelle altre citt\ue0 analizzate. Se i livelli di concentrazione delle polveri fossero stati inferiori del 20%, complessivamente l\u2019impatto si sarebbe ridotto del 42% per il PM10 e del 51% per il PM2.5. CONCLUSIONI: i livelli di inquinamento osservati nel periodo in studio sono stati responsabili di un numero importante di decessi nelle citt\ue0 analizzate. Politiche di contenimento basate sulla diminuzione percentuale delle concentrazioni annuali di polveri interesserebbero tutte le citt\ue0 coperte dallo studio e potrebbero ridurre in modo importante l\u2019impatto dell\u2019inquinamento sulla salute

Le politiche per la promozione della mobilit\ue0 sostenibile e la riduzione dell'inquinamento atmosferico causato dal traffico veicolare nelle citt\ue0 partecipanti allo studio EpiAir2

OBIETTIVO: fornire un quadro sintetico delle politiche di mobilit\ue0 adottate negli ultimi anni (2006-2010) dalle amministrazioni di alcuni Comuni italiani attraverso la rilevazione degli interventi sulla mobilit\ue0 urbana e relativa efficacia. DISEGNO E SETTING: i dati presentati si riferiscono alle quindici citt\ue0 inizialmente partecipanti al progetto EpiAir2: Torino, Milano, Venezia, Bologna, Firenze, Pisa, Roma, Taranto, Palermo, Cagliari, Trieste, Genova, Ancona, Napoli, Bari. RISULTATI: da questa indagine emergono debolezze e punti di forza delle citt\ue0 italiane nell\u2019affrontare il tema della mobilit\ue0 sostenibile. Le modifiche della consistenza del parco circolante sono state accompagnate da un suo rinnovamento con conseguente riduzione dei veicoli rispondenti agli standard emissivi pi\uf9 vecchi, seppur con differenze marcate tra le varie citt\ue0. Tra le debolezze pi\uf9 rilevanti nella gestione locale della mobilit\ue0 urbana \ue8 da segnalare in primo luogo lo sviluppo ridotto di metropolitane e di sistemi tranviari e il ritardo nell\u2019ammodernamento delle reti ferroviarie suburbane, che pongono le citt\ue0 italiane in una posizione evidentemente svantaggiata rispetto ad altre realt\ue0 urbane europee analoghe. Per quanto riguarda gli altri aspetti della mobilit\ue0 urbana (offerta/domanda di trasporto pubblico, ZTL, zone pedonali, km di piste ciclabili, servizi di car sharing e bike sharing), si segnala una situazione estremamente disomogenea tra le varie citt\ue0 italiane. CONCLUSIONI: le disomogeneit\ue0 tra le diverse realt\ue0 sono in parte spiegabili con le peculiarit\ue0 strutturali e culturali locali, oltre che da una diversa attenzione \u201cstorica\u201d alle problematiche ambientali e a un\u2019estemporaneit\ue0 delle scelte effettuate dalle rispettive amministrazioni. Pur in presenza di molte iniziative settoriali, pare sia mancata una strategia nazionale che, pur rispettosa del livello di autonomia locale, abbia fornito linee di indirizzo per affrontare in maniera adeguata e coordinata il tema della mobilit\ue0 sostenibile e dell\u2019inquinamento atmosferico da traffico veicolare