Cardiovascular Risk Factors and Family History of Major Thrombotic Events in Children with Migraine: A 12-Year Retrospective Single-Centre Study.

BACKGROUND: Migraine is one of the most frequent primary headaches in childhood. The role of thrombotic predisposition in its pathogenesis is debated. Our aim was to analyse the cardiovascular risk factors and family history of major thrombotic events in children with migraine. METHODS: A retrospective, single-centre study was performed over 12 years. Our headache centre record database was screened for migraine with aura (MA) and migraine without aura (MO) on the basis of the ICHD-II (until 2013) and III criteria. A control group of otherwise healthy children was recruited. Descriptive and multivariate analyses are provided; significance was set at p < 0.05. RESULTS: Migraine was diagnosed in 930 children (24.7% MA); 73.3% were 9-14 years old. Children with MA were older (p < 0.001). A family history of cerebral ischemic events at ≤50 years old was more commonly reported by children with MA than those with MO (p < 0.001) and those in the control group (p = 0.001). Children with MA showed a higher risk of a family history of cerebral ischemic events at ≤50 years old than children with MO (OR: 2.6) and those in the control group (OR: 3.1). When comparing the family history of DVT, we observed a significantly increased risk for MA vs. MO (OR: 2.9). CONCLUSION: A family history of cerebral ischemic events at ≤50 years old leads to an increased risk of MA. Further studies are needed to explore such an association.

Multimodal processing in face-to-face interactions: A bridging link between psycholinguistics and sensory neuroscience.

In face-to-face communication, humans are faced with multiple layers of discontinuous multimodal signals, such as head, face, hand gestures, speech and non-speech sounds, which need to be interpreted as coherent and unified communicative actions. This implies a fundamental computational challenge: optimally binding only signals belonging to the same communicative action while segregating signals that are not connected by the communicative content. How do we achieve such an extraordinary feat, reliably, and efficiently? To address this question, we need to further move the study of human communication beyond speech-centred perspectives and promote a multimodal approach combined with interdisciplinary cooperation. Accordingly, we seek to reconcile two explanatory frameworks recently proposed in psycholinguistics and sensory neuroscience into a neurocognitive model of multimodal face-to-face communication. First, we introduce a psycholinguistic framework that characterises face-to-face communication at three parallel processing levels: multiplex signals, multimodal gestalts and multilevel predictions. Second, we consider the recent proposal of a lateral neural visual pathway specifically dedicated to the dynamic aspects of social perception and reconceive it from a multimodal perspective ("lateral processing pathway"). Third, we reconcile the two frameworks into a neurocognitive model that proposes how multiplex signals, multimodal gestalts, and multilevel predictions may be implemented along the lateral processing pathway. Finally, we advocate a multimodal and multidisciplinary research approach, combining state-of-the-art imaging techniques, computational modelling and artificial intelligence for future empirical testing of our model.

Cross-modal integration and plasticity in the superior temporal cortex.

In congenitally deaf people, temporal regions typically believed to be primarily auditory enhance their response to nonauditory information. The neural mechanisms and functional principles underlying this phenomenon, as well as its impact on auditory recovery after sensory restoration, yet remain debated. In this chapter, we demonstrate that the cross-modal recruitment of temporal regions by visual inputs in congenitally deaf people follows organizational principles known to be present in the hearing brain. We propose that the functional and structural mechanisms allowing optimal convergence of multisensory information in the temporal cortex of hearing people also provide the neural scaffolding for feeding visual or tactile information into the deafened temporal areas. Innate in their nature, such anatomo-functional links between the auditory and other sensory systems would represent the common substrate of both early multisensory integration and expression of selective cross-modal plasticity in the superior temporal cortex.

Synesthesia in a congenitally blind individual.

Synesthesia represents an atypical merging of percepts, in which a given sensory experience (e.g., words, letters, music) triggers sensations in a different perceptual domain (e.g., color). According to recent estimates, the vast majority of the reported cases of synesthesia involve a visual experience. Purely non-visual synesthesia is extremely rare and to date there is no reported case of a congenitally blind synesthete. Moreover, it has been suggested that congenital blindness impairs the emergence of synesthesia-related phenomena such as multisensory integration and cross-modal correspondences between non-visual senses (e.g., sound-touch). Is visual experience necessary to develop synesthesia? Here we describe the case of a congenital blind man (CB) reporting a complex synesthetic experience, involving numbers, letters, months and days of the week. Each item is associated with a precise position in mental space and with a precise tactile texture. In one experiment we empirically verified the presence of number-texture and letter-texture synesthesia in CB, compared to non-synesthete controls, probing the consistency of item-texture associations across time and demonstrating that synesthesia can develop without vision. Our data fill an important void in the current knowledge on synesthesia and shed light on the mechanisms behind sensory crosstalk in the human mind.

Ecosystem services and justice of protected areas: the case of Circeo National Park, Italy.

Protected areas are key instruments for conserving biodiversity and landscapes. Yet, conservation initiatives are still often struggling to accommodate people's needs, provoking conflicts, and lacking support from local communities. Our study combines environmental justice and ecosystem services approaches to provide a critical understanding of trade-offs between people's interests and conservation goals in the case study of Circeo National Park (Italy). Applying a qualitative content analysis of different materials and using a survey of local residents, we focus on three main objectives: analysing the implementation of the ecosystem services framework in policy documents and exploring how different people value benefits from nature; investigating the decision-making process in terms of participation, information and communication strategies; and identifying how conservation policies generated different allocations of benefits, burdens and inequalities among social groups. The integrated approach applied in our study highlights ways to systematically uncover perceived injustices and identifies potential conflict lines. In the long run, this approach might help to increase the public acceptance of protected areas by fostering sustainability also in its often-overlooked social dimension.

Long-term clinical and serological follow-up of paediatric patients infected by SARS-CoV-2.

Studies concerning Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in paediatrics are limited to children mainly selected from hospitals, where patients with complications and co-morbidities are managed. We aimed to describe the course of the Coronavirus Disease 2019 (COVID-19) in a population of children enrolled by place of residence, from diagnosis to recovery, with a long-term clinical and serological follow-up. We identified patients aged <14 years old living in the Turin Health District 3 who had SARS-CoV-2 detected in at least one nasopharyngeal swab from 1st March to 1st June 2020. Epidemiological and clinical features of SARS-CoV-2 infection were collected by way of a telephone inquiry. Enrolled patients were tested for SARS-CoV-2 serology in order to provide evidence of seroconversion and persistence of specific antibodies some time after the infection. A total of 46 patients with SARS-CoV-2 infection/COVID-19 were identified. The main pattern of viral transmission was intra-family. Eleven children were totally asymptomatic. If symptoms appeared, the disease had a mild course. A single case of COVID-19-related respiratory insufficiency was registered. Among children who underwent serological evaluation, 84% had seroconversion. No significant differences in antibody development were found according to the age and the burden of the disease. Children tested farther from the primary infection had lower antibody index titre values than the others. In conclusion, COVID-19 has a good prognosis in paediatric age. Children are able to develop a valid immune response, although their index titres seem to decrease a long time after the disease.

Gastrointestinal involvement in paediatric COVID-19 - from pathogenesis to clinical management: A comprehensive review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is responsible for the first pandemic of the 21st century. As found in adults, signs and symptoms related to the disease mainly involve the respiratory tract in the paediatric population. However, a considerable number of children present with gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. The purpose of this review is an accurate description, from pathogenesis to clinical presentation, diagnosis and treatment, of COVID-19 effects on the gastrointestinal system at a paediatric age. SARS-CoV-2 can be identified in stool specimens of affected children by real-time polymerase chain reaction techniques. Positivity can last for several weeks after the end of the symptomatic phase. Gastrointestinal signs and symptoms are generally self-limited, can correlate with blood tests and imaging alterations, and may require supportive treatment such as hydration. However, they can precede severe disease manifestations such as the COVID-19-related multisystem inflammatory syndrome. Children belonging to risk categories such as those affected by celiac disease, inflammatory bowel disease, and hepatic disease seem to not have a more severe course than the others, even if they are undergoing immunosuppressant treatment. Medical follow-ups of patients with chronic diseases need to be revised during the pandemic period in order to postpone unnecessary tests, mainly endoscopic ones.

Visual motion processing recruits regions selective for auditory motion in early deaf individuals.

In early deaf individuals, the auditory deprived temporal brain regions become engaged in visual processing. In our study we tested further the hypothesis that intrinsic functional specialization guides the expression of cross-modal responses in the deprived auditory cortex. We used functional MRI to characterize the brain response to horizontal, radial and stochastic visual motion in early deaf and hearing individuals matched for the use of oral or sign language. Visual motion showed enhanced response in the 'deaf' mid-lateral planum temporale, a region selective to auditory motion as demonstrated by a separate auditory motion localizer in hearing people. Moreover, multivariate pattern analysis revealed that this reorganized temporal region showed enhanced decoding of motion categories in the deaf group, while visual motion-selective region hMT+/V5 showed reduced decoding when compared to hearing people. Dynamic Causal Modelling revealed that the 'deaf' motion-selective temporal region shows a specific increase of its functional interactions with hMT+/V5 and is now part of a large-scale visual motion selective network. In addition, we observed preferential responses to radial, compared to horizontal, visual motion in the 'deaf' right superior temporal cortex region that also show preferential response to approaching/receding sounds in the hearing brain. Overall, our results suggest that the early experience of auditory deprivation interacts with intrinsic constraints and triggers a large-scale reallocation of computational load between auditory and visual brain regions that typically support the multisensory processing of motion information.

Hierarchical Brain Network for Face and Voice Integration of Emotion Expression.

The brain has separate specialized computational units to process faces and voices located in occipital and temporal cortices. However, humans seamlessly integrate signals from the faces and voices of others for optimal social interaction. How are emotional expressions, when delivered by different sensory modalities (faces and voices), integrated in the brain? In this study, we characterized the brains' response to faces, voices, and combined face-voice information (congruent, incongruent), which varied in expression (neutral, fearful). Using a whole-brain approach, we found that only the right posterior superior temporal sulcus (rpSTS) responded more to bimodal stimuli than to face or voice alone but only when the stimuli contained emotional expression. Face- and voice-selective regions of interest, extracted from independent functional localizers, similarly revealed multisensory integration in the face-selective rpSTS only; further, this was the only face-selective region that also responded significantly to voices. Dynamic causal modeling revealed that the rpSTS receives unidirectional information from the face-selective fusiform face area, and voice-selective temporal voice area, with emotional expression affecting the connection strength. Our study promotes a hierarchical model of face and voice integration, with convergence in the rpSTS, and that such integration depends on the (emotional) salience of the stimuli.

White matter connectivity between occipital and temporal regions involved in face and voice processing in hearing and early deaf individuals.

Neuroplasticity following sensory deprivation has long inspired neuroscience research in the quest of understanding how sensory experience and genetics interact in developing the brain functional and structural architecture. Many studies have shown that sensory deprivation can lead to cross-modal functional recruitment of sensory deprived cortices. Little is known however about how structural reorganization may support these functional changes. In this study, we examined early deaf, hearing signer and hearing non-signer individuals using diffusion MRI to evaluate the potential structural connectivity linked to the functional recruitment of the temporal voice area by face stimuli in deaf individuals. More specifically, we characterized the structural connectivity between occipital, fusiform and temporal regions typically supporting voice- and face-selective processing. Despite the extensive functional reorganization for face processing in the temporal cortex of the deaf, macroscopic properties of these connections did not differ across groups. However, both occipito- and fusiform-temporal connections showed significant microstructural changes between groups (fractional anisotropy reduction, radial diffusivity increase). We propose that the reorganization of temporal regions after early auditory deprivation builds on intrinsic and mainly preserved anatomical connectivity between functionally specific temporal and occipital regions.

Functional selectivity for face processing in the temporal voice area of early deaf individuals.

Brain systems supporting face and voice processing both contribute to the extraction of important information for social interaction (e.g., person identity). How does the brain reorganize when one of these channels is absent? Here, we explore this question by combining behavioral and multimodal neuroimaging measures (magneto-encephalography and functional imaging) in a group of early deaf humans. We show enhanced selective neural response for faces and for individual face coding in a specific region of the auditory cortex that is typically specialized for voice perception in hearing individuals. In this region, selectivity to face signals emerges early in the visual processing hierarchy, shortly after typical face-selective responses in the ventral visual pathway. Functional and effective connectivity analyses suggest reorganization in long-range connections from early visual areas to the face-selective temporal area in individuals with early and profound deafness. Altogether, these observations demonstrate that regions that typically specialize for voice processing in the hearing brain preferentially reorganize for face processing in born-deaf people. Our results support the idea that cross-modal plasticity in the case of early sensory deprivation relates to the original functional specialization of the reorganized brain regions.

Clinical utility of magnetic resonance imaging in first-episode psychosis.

BackgroundThere is no consensus as to whether magnetic resonance imaging (MRI) should be used as part of the initial clinical evaluation of patients with first-episode psychosis (FEP).Aims(a) To assess the logistical feasibility of routine MRI; (b) to define the clinical significance of radiological abnormalities in patients with FEP.MethodRadiological reports from MRI scans of two FEP samples were reviewed; one comprised 108 patients and 98 healthy controls recruited to a research study and the other comprised 241 patients scanned at initial clinical presentation plus 66 healthy controls.ResultsIn the great majority of patients, MRI was logistically feasible. Radiological abnormalities were reported in 6% of the research sample and in 15% of the clinical sample (odds ratio (OR)=3.1, 95% CI 1.26-7.57, χ2(1) = 6.63, P = 0.01). None of the findings necessitated a change in clinical management.ConclusionsRates of neuroradiological abnormalities in FEP are likely to be underestimated in research samples that often exclude patients with organic abnormalities. However, the majority of findings do not require intervention.

Mother and Infant Body Mass Index, Breast Milk Leptin and Their Serum Leptin Values.

PURPOSE: This study investigates correlations between mother and infant Body Mass Index (BMI), their serum leptin values and breast milk leptin concentration in early infancy. SUBJECTS AND METHODS: We determined serum leptin values in 58 healthy infants and leptin values in their mothers' breast milk, using radioimmunoassay (RIA). Infant and maternal anthropometrics were measured. RESULTS: Median leptin concentration was 3.9 ng/mL (interquartile range (IQR): 2.75) in infant serum, 4.27 ng/mL (IQR: 5.62) in maternal serum and 0.89 ng/mL (IQR: 1.32) in breast milk. Median maternal BMI and weight were 24 kg/m² (IQR: 4.41) and 64 kg (IQR: 15). Median infant BMI was 15.80 kg/cm² (IQR: 4.02), while average weight was 5.130 kg (IQR: 1.627). Infants serum leptin values positively correlated with infants' BMI (p = 0.001; r = 0.213) and breast milk leptin (p = 0.03; r = 0.285). Maternal serum leptin values positively correlated with maternal BMI (p = 0.000, r = 0.449) and breast milk leptin ones (p = 0.026; r = 0.322). CONCLUSION: Breast milk leptin and maternal BMI could influence infant serum leptin values. Further studies are needed to better elucidate the role of genetics and environment on infant leptin production and risk of obesity later in life.

Does neuroanatomy account for superior temporal dysfunction in early psychosis? A multimodal MRI investigation.

BACKGROUND: Neuroimaging studies of ultra-high risk (UHR) and first-episode psychosis (FEP) have revealed widespread alterations in brain structure and function. Recent evidence suggests there is an intrinsic relationship between these 2 types of alterations; however, there is very little research linking these 2 modalities in the early stages of psychosis. METHODS: To test the hypothesis that functional alteration in UHR and FEP articipants would be associated with corresponding structural alteration, we examined brain function and structure in these participants as well as in a group of healthy controls using multimodal MRI. The data were analyzed using statistical parametric mapping. RESULTS: We included 24 participants in the FEP group, 18 in the UHR group and 21 in the control group. Patients in the FEP group showed a reduction in functional activation in the left superior temporal gyrus relative to controls, and the UHR group showed intermediate values. The same region showed a corresponding reduction in grey matter volume in the FEP group relative to controls. However, while the difference in grey matter volume remained significant after including functional activation as a covariate of no interest, the reduction in functional activation was no longer evident after including grey matter volume as a covariate of no interest. LIMITATIONS: Our sample size was relatively small. All participants in the FEP group and 2 in the UHR group had received antipsychotic medication, which may have impacted neurofunction and/or neuroanatomy. CONCLUSION: Our results suggest that superior temporal dysfunction in early psychosis is accounted for by a corresponding alteration in grey matter volume. This finding has important implications for the interpretation of functional alteration in early psychosis.

Auditory verbal hallucinations and brain dysconnectivity in the perisylvian language network: a multimodal investigation.

Neuroimaging studies of schizophrenia have indicated that the development of auditory verbal hallucinations (AVHs) is associated with altered structural and functional connectivity within the perisylvian language network. However, these studies focussed mainly on either structural or functional alterations in patients with chronic schizophrenia. Therefore, they were unable to examine the relationship between the 2 types of measures and could not establish whether the observed alterations would be expressed in the early stage of the illness. We used diffusion tensor imaging and functional magnetic resonance imaging to examine white matter integrity and functional connectivity within the left perisylvian language network of 46 individuals with an at risk mental state for psychosis or a first episode of the illness, including 28 who had developed AVH group and 18 who had not (nonauditory verbal hallucination [nAVH] group), and 22 healthy controls. Inferences were made at P < .05 (corrected). The nAVH group relative to healthy controls showed a reduction of both white matter integrity and functional connectivity as well as a disruption of the normal structure-function relationship along the fronto-temporal pathway. For all measures, the AVH group showed intermediate values between healthy controls and the nAVH group. These findings seem to suggest that, in the early stage of the disorder, a significant impairment of fronto-temporal connectivity is evident in patients who do not experience AVHs. This is consistent with the hypothesis that, whilst mild disruption of connectivity might still enable the emergence of AVHs, more severe alterations may prevent the occurrence of the hallucinatory experience.

Serum reference values for leptin in healthy infants.

OBJECTIVE: Reports on leptin concentrations in pediatric populations lack reference values for infants in the first months of life. Our study was conducted on healthy full-term infants between 2002 and 2012 to determine serum leptin reference values in subjects less than 18 months old. METHODS: Routine outpatient blood tests for serum leptin were performed on 317 infants using a radioimmunoassay method. The median and 10th-90th percentiles were calculated to obtain reference values using quantile regression. Values established in this study were compared with another independent cohort of 110 infants. RESULTS: The median (IQR) serum leptin concentration in the infants was 2.37 (3.26) ng/ml (n = 317). The median leptin concentration was 2.81 (3.49) ng/ml (n = 202) in infants younger than 6 months of age, 1.44 (2.27) ng/ml (n = 59) in infants between 6-12 months of age and 1.77 (2.05) ng/ml (n = 56) in infants between 12-18 months of age. We obtained leptin reference values based on age by estimating the lower and upper percentiles. In the entire cohort, the median (IQR) leptin concentration was 2.22 (3.11) ng/ml in males (n = 168) and 2.60 (3.32) ng/ml in females (n = 149). According to the type of feeding median serum leptin concentration was higher in breast-fed infants (n = 188) than in formula-fed infants (n = 129) (2.63 (3.34) ng/ml vs. 2.12 (2.77) ng/ml; p<0.05). CONCLUSIONS: Our data revealed no gender difference in leptin concentration in early infancy. After 6 months of life, leptin concentrations decreased slightly. We used a large cohort to confirm that breast-fed infants had significantly higher serum leptin levels than formula-fed infants during the first 6 months of life, although this difference disappeared later in life. In this study, we defined the leptin reference range in healthy infants in the first 18 months of life according to the Clinical and Laboratory Standards Institute (CLSI).

An empirical comparison of different approaches for combining multimodal neuroimaging data with support vector machine.

In the pursuit of clinical utility, neuroimaging researchers of psychiatric and neurological illness are increasingly using analyses, such as support vector machine, that allow inference at the single-subject level. Recent studies employing single-modality data, however, suggest that classification accuracies must be improved for such utility to be realized. One possible solution is to integrate different data types to provide a single combined output classification; either by generating a single decision function based on an integrated kernel matrix, or, by creating an ensemble of multiple single modality classifiers and integrating their predictions. Here, we describe four integrative approaches: (1) an un-weighted sum of kernels, (2) multi-kernel learning, (3) prediction averaging, and (4) majority voting, and compare their ability to enhance classification accuracy relative to the best single-modality classification accuracy. We achieve this by integrating structural, functional, and diffusion tensor magnetic resonance imaging data, in order to compare ultra-high risk (n = 19), first episode psychosis (n = 19) and healthy control subjects (n = 23). Our results show that (i) whilst integration can enhance classification accuracy by up to 13%, the frequency of such instances may be limited, (ii) where classification can be enhanced, simple methods may yield greater increases relative to more computationally complex alternatives, and, (iii) the potential for classification enhancement is highly influenced by the specific diagnostic comparison under consideration. In conclusion, our findings suggest that for moderately sized clinical neuroimaging datasets, combining different imaging modalities in a data-driven manner is no "magic bullet" for increasing classification accuracy. However, it remains possible that this conclusion is dependent on the use of neuroimaging modalities that had little, or no, complementary information to offer one another, and that the integration of more diverse types of data would have produced greater classification enhancement. We suggest that future studies ideally examine a greater variety of data types (e.g., genetic, cognitive, and neuroimaging) in order to identify the data types and combinations optimally suited to the classification of early stage psychosis.

The effects of psychotherapy on brain function: a systematic and critical review.

Over the past two decades, the development of neuroimaging techniques has allowed the non-invasive investigation of neuroplastic changes associated with psychotherapeutic treatment. The aim of the present article is to present a systematic and critical review of longitudinal studies addressing the impact of psychotherapy on the brain published to date. After summarizing the results reported in the literature for each psychiatric disorder separately (i.e. obsessive-compulsive disorder, panic disorder, unipolar major depressive disorder, posttraumatic stress disorder, specific phobia, schizophrenia), we discuss the results focusing on three questions of interest: (i) whether neurobiological changes which follow psychotherapy occur in regions that showed significant neurofunctional alteration pre-treatment; (ii) whether these neurobiological changes are similar, or different, to those observed following pharmacological treatment; and (iii) whether neurobiological changes could be used as an objective means of monitoring the progress and outcome of psychotherapy. The evidence reviewed indicates that (i) depending on the disorder under investigation, psychotherapy results in either a normalisation of abnormal patterns of activity, the recruitment of additional areas which did not show altered activation prior to treatment, or a combination of the two; (ii) the effects of psychotherapy on brain function are comparable to those of medication for some but not all disorders; and (iii) there is preliminary evidence that neurobiological changes are associated with the progress and outcome of psychotherapy. It is hoped that a better understanding of the impact of psychotherapy on brain function will eventually inform the development of new biologically informed treatments and allow clinicians to make more effective treatment decisions.

Is there a future for sensory substitution outside academic laboratories?

Sensory substitution devices (SSDs) have been developed with the ultimate purpose of supporting sensory deprived individuals in their daily activities. However, more than forty years after their first appearance in the scientific literature, SSDs still remain more common in research laboratories than in the daily life of people with sensory deprivation. Here, we seek to identify the reasons behind the limited diffusion of SSDs among the blind community by discussing the ergonomic, neurocognitive and psychosocial issues potentially associated with the use of these systems. We stress that these issues should be considered together when developing future devices or improving existing ones. We provide some examples of how to achieve this by adopting a multidisciplinary and participatory approach. These efforts would contribute not solely to address fundamental theoretical research questions, but also to better understand the everyday needs of blind people and eventually promote the use of SSDs outside laboratories.