Tactile sensory processing deficits in genetic mouse models of autism spectrum disorder.

Altered sensory processing is a common feature in autism spectrum disorder (ASD), as recognized in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Although altered responses to tactile stimuli are observed in over 60% of individuals with ASD, the neurobiological basis of this phenomenon is poorly understood. ASD has a strong genetic component and genetic mouse models can provide valuable insights into the mechanisms underlying tactile abnormalities in ASD. This review critically addresses recent findings regarding tactile processing deficits found in mouse models of ASD, with a focus on behavioral, anatomical, and functional alterations. Particular attention was given to cellular and circuit-level functional alterations, both in the peripheral and central nervous systems, with the objective of highlighting possible convergence mechanisms across models. By elucidating the impact of mutations in ASD candidate genes on somatosensory circuits and correlating them with behavioral phenotypes, this review significantly advances our understanding of tactile deficits in ASD. Such insights not only broaden our comprehension but also pave the way for future therapeutic interventions.

The Shank3-InsG3680(+/+) mouse model of autism spectrum disorder displays auditory avoidance in a novel behavioral test.

Introduction: Autism spectrum disorder (ASD) is characterized by deficits in communication and social interaction, restricted interests, repetitive behaviors, and sensory alterations, with auditory hypersensitivity being one of the most commonly reported sensory-perceptual abnormalities. Several candidate genes for involvement in this disorder have emerged from patient studies, including SHANK3, a gene that encodes a protein (SHANK3) in the postsynaptic density of excitatory synapses. Previous work has shown that mutant mice carrying a human ASD mutation in the Shank3 gene (InsG3680) exhibit repetitive behaviors and social interaction deficits, indicating important construct and face validity for this genotype as an animal model of ASD. Methods: To further address whether these mice also present auditory sensory-perceptual alterations, we developed a novel behavioral test in which mice can choose between different soundscapes. Results: Our results reveal that, in comparison to wild-type mice, Shank3 mutants display a strong behavioral preference toward silent regions of the arena. Discussion: These data suggest that Shank3- mutant mice might express an auditory hypersensitivity phenotype, further adding to the face validity of this genotype as an animal model of ASD.

Ultrasensitive dopamine detection with graphene aptasensor multitransistor arrays.

Detecting physiological levels of neurotransmitters in biological samples can advance our understanding of brain disorders and lead to improved diagnostics and therapeutics. However, neurotransmitter sensors for real-world applications must reliably detect low concentrations of target analytes from small volume working samples. Herein, a platform for robust and ultrasensitive detection of dopamine, an essential neurotransmitter that underlies several brain disorders, based on graphene multitransistor arrays (gMTAs) functionalized with a selective DNA aptamer is presented. High-yield scalable methodologies optimized at the wafer level were employed to integrate multiple graphene transistors on small-size chips (4.5 × 4.5 mm). The multiple sensor array configuration permits independent and simultaneous replicate measurements of the same sample that produce robust average data, reducing sources of measurement variability. This procedure allowed sensitive and reproducible dopamine detection in ultra-low concentrations from small volume samples across physiological buffers and high ionic strength complex biological samples. The obtained limit-of-detection was 1 aM (10-18) with dynamic detection ranges spanning 10 orders of magnitude up to 100 µM (10-8), and a 22 mV/decade peak sensitivity in artificial cerebral spinal fluid. Dopamine detection in dopamine-depleted brain homogenates spiked with dopamine was also possible with a LOD of 1 aM, overcoming sensitivity losses typically observed in ion-sensitive sensors in complex biological samples. Furthermore, we show that our gMTAs platform can detect minimal changes in dopamine concentrations in small working volume samples (2 µL) of cerebral spinal fluid samples obtained from a mouse model of Parkinson's Disease. The platform presented in this work can lead the way to graphene-based neurotransmitter sensors suitable for real-world academic and pre-clinical pharmaceutical research as well as clinical diagnosis.

Chronic stress causes striatal disinhibition mediated by SOM-interneurons in male mice.

Chronic stress (CS) is associated with a number of neuropsychiatric disorders, and it may also contribute to or exacerbate motor function. However, the mechanisms by which stress triggers motor symptoms are not fully understood. Here, we report that CS functionally alters dorsomedial striatum (DMS) circuits in male mice, by affecting GABAergic interneuron populations and somatostatin positive (SOM) interneurons in particular. Specifically, we show that CS impairs communication between SOM interneurons and medium spiny neurons, promoting striatal overactivation/disinhibition and increased motor output. Using probabilistic machine learning to analyze animal behavior, we demonstrate that in vivo chemogenetic manipulation of SOM interneurons in DMS modulates motor phenotypes in stressed mice. Altogether, we propose a causal link between dysfunction of striatal SOM interneurons and motor symptoms in models of chronic stress.

Family still matters: Human social motivation across 42 countries during a global pandemic.

The COVID-19 pandemic caused drastic social changes for many people, including separation from friends and coworkers, enforced close contact with family, and reductions in mobility. Here we assess the extent to which people's evolutionarily-relevant basic motivations and goals-fundamental social motives such as Affiliation and Kin Care-might have been affected. To address this question, we gathered data on fundamental social motives in 42 countries (N = 15,915) across two waves, including 19 countries (N = 10,907) for which data were gathered both before and during the pandemic (pre-pandemic wave: 32 countries, N = 8998; 3302 male, 5585 female; M age  = 24.43, SD = 7.91; mid-pandemic wave: 29 countries, N = 6917; 2249 male, 4218 female; M age  = 28.59, SD = 11.31). Samples include data collected online (e.g., Prolific, MTurk), at universities, and via community sampling. We found that Disease Avoidance motivation was substantially higher during the pandemic, and that most of the other fundamental social motives showed small, yet significant, differences across waves. Most sensibly, concern with caring for one's children was higher during the pandemic, and concerns with Mate Seeking and Status were lower. Earlier findings showing the prioritization of family motives over mating motives (and even over Disease Avoidance motives) were replicated during the pandemic. Finally, well-being remained positively associated with family-related motives and negatively associated with mating motives during the pandemic, as in the pre-pandemic samples. Our results provide further evidence for the robust primacy of family-related motivations even during this unique disruption of social life.

Shaping social behavior in an enriched environment.

Access to vital needs shapes social orders. In rats, social systems tend to maintain a certain stability, but alterations in the physical environment can change inter-individual relations, which consequently can alter social orders. Principles governing social systems are, however, difficult to study and most analyses have been restricted to dyads of animals over short periods of time, hardly capturing the complexity and temporal dynamics of social interactions. Herein, we studied social interactions in a colony of six rats living in a customized enriched environment (PhenoWorld, PhW), under variable conditions of access/availability to limited resources. Reductions in food accessibility and availability resulted in a marked heterogeneity in sniffing, chasing and fighting/struggling behaviors, and, in the latter condition, an overall increase of these displays. The introduction of the possibility of interaction with a female rat also increased the amount of sniffing and fighting/struggling in a homogeneous manner. Results also showed that individual food retrieval success had no association with fighting/struggling when food pellets are delivered to the animals. However, there was a statistically significant correlation between fighting/struggling and impulsivity as measured by the amount of premature responses in the Variable-to-Signal-Test outside of the PhW providing external validation to our measures. To sum up, through continuous monitoring of a group of rats in the PhW, we demonstrated how variations in access to reinforcers modulate social behavior.

Fundamental social motives measured across forty-two cultures in two waves.

How does psychology vary across human societies? The fundamental social motives framework adopts an evolutionary approach to capture the broad range of human social goals within a taxonomy of ancestrally recurring threats and opportunities. These motives-self-protection, disease avoidance, affiliation, status, mate acquisition, mate retention, and kin care-are high in fitness relevance and everyday salience, yet understudied cross-culturally. Here, we gathered data on these motives in 42 countries (N = 15,915) in two cross-sectional waves, including 19 countries (N = 10,907) for which data were gathered in both waves. Wave 1 was collected from mid-2016 through late 2019 (32 countries, N = 8,998; 3,302 male, 5,585 female; Mage = 24.43, SD = 7.91). Wave 2 was collected from April through November 2020, during the COVID-19 pandemic (29 countries, N = 6,917; 2,249 male, 4,218 female; Mage = 28.59, SD = 11.31). These data can be used to assess differences and similarities in people's fundamental social motives both across and within cultures, at different time points, and in relation to other commonly studied cultural indicators and outcomes.

Too Many Males or Too Many Females? Classroom Sex Ratio, Life History Strategies and Risk-Taking Behaviors.

Prior research finds that sex ratio, defined as the proportion of males and females in a given context, is related to engagement in risk-taking behaviors. However, most research operationalizes sex ratio at a local context (e.g., regional or county), which fails to reflect with precision the sex ratios contexts of individuals at a closer level. Furthermore, the relationship between sex ratio and risk-taking behaviors may be affected by individuals' life history strategy, with previous studies showing fast life history strategies linked to risk-taking behaviors, compared to slow life history strategies. The present study analyzes the relationship between classroom sex ratio and risk-taking behaviors and the interaction between classroom sex ratio and life history strategy in adolescents. The sample comprised 1214 participants nested in 57 classrooms, 49.75% females, 91.5% Spanish and a mean age of 16.15 years (SD = 1.23, range 14-21). Results from multilevel modeling showed a negative relation between classroom sex ratio and risk-taking behaviors in female adolescents with faster life history strategy. By contrast, classroom sex ratio in male adolescents related positively to risk-taking behaviors but did not interact with life history strategy. These findings underscore the importance of studying proximate sex ratio on risk-taking behaviors in adolescents and underline its potential influence in the development and expression of life history strategies.

Psychosocial and Sociodemographic Determinants Related to Chronic Diseases in Immigrants Residing in Spain.

The aim of the study is to analyze the effect of the psychosocial determinants of satisfaction with social support, resilience and satisfaction with life, and the sociodemographic determinants of age, gender and length of residence on chronic diseases in immigrants living in Spain. The sample was composed of 1131 immigrants from Africa, Eastern Europe, Latin America and Asia. 47.1% were men and 52.9% were women. Most relevant results point to age as the sociodemographic variable with the highest predictive effect in the six chronic diseases analyzed. Gender, in this case female, predicts arthrosis, chronic back pain and migraine, whereas length of residence was only significant in the case of chronic allergies. Regarding psychosocial variables, resilience is a good predictor of hypertension, chronic allergies and arthrosis. However, satisfaction with social support appears to be the best predictor for chronic back pain in the regression equation, satisfaction with life being a significant variable in migraine, arthrosis, allergies and high cholesterol. Results are notably relevant for the design of preventive health programs in immigrants, as well as in ensuring their appropriate access to the health system so that their chronic diseases can be diagnosed. Given the relevance and incidence of the chronic diseases analyzed in immigrants, preventive strategies should be improved to tackle chronic diseases that can have a serious impact on immigrants' health.

Systematic Review of Integration and Radicalization Prevention Programs for Migrants in the US, Canada, and Europe.

Background: International migration processes are some of the most important events of our time. Migrating implies a broad range of factors that affect integration, and which may be linked to radicalization. Host countries use different methods for the integration of migrants. The aim of this systematic review is to analyze intervention programs that aim at promoting social integration and preventing the radicalization of migrants, with the objective of studying actions carried out in the US, Canada, and Europe to this effect. Method: Worldwide known bibliographic databases (PsyCINFO, Sociological Abstracts, Psycarticles, Psychology Database, Medline, SCOPUS, and Google Scholar) were used to search studies published before January 2019 and which analyzed integration or radicalization prevention programs with migrants. Results: A total of 601 studies were screened, from which 18 met the inclusion criteria. The analysis of programs addressed to migrant women points to a decrease in loneliness and depression and an increase of migrants' perception of social support and self-esteem. Programs carried out in schools and families improve children's knowledge of their culture and that of others, increase their feelings of inclusion, and reduce their aggressiveness, stress, and anxiety. Language programs promote communication and employment search, as well as improve migrants' quality of life. One of the most effective activities included in these programs is to connect recently arrived migrants with local population and/or long-term residents. The latter act as mentors and teachers, helping recently arrived migrants understand resources and to be more integrated in the new country, as well as reducing discrimination from the local population. Conclusions: The review concluded the importance of intervention programs for integration, migrants' quality of life, prevention of extreme behaviors, and intercultural cohabitation. Future programs must be more detailed regarding participants' information and carry out more comprehensive assessments.

Double-Layer Flexible Neural Probe With Closely Spaced Electrodes for High-Density in vivo Brain Recordings.

Flexible polymer neural probes are an attractive emerging approach for invasive brain recordings, given that they can minimize the risks of brain damage or glial scaring. However, densely packed electrode sites, which can facilitate neuronal data analysis, are not widely available in flexible probes. Here, we present a new flexible polyimide neural probe, based on standard and low-cost lithography processes, which has 32 closely spaced 10 µm diameter gold electrode sites at two different depths from the probe surface arranged in a matrix, with inter-site distances of only 5 µm. The double-layer design and fabrication approach implemented also provides additional stiffening just sufficient to prevent probe buckling during brain insertion. This approach avoids typical laborious augmentation strategies used to increase flexible probes' mechanical rigidity while allowing a small brain insertion footprint. Chemical composition analysis and metrology of structural, mechanical, and electrical properties demonstrated the viability of this fabrication approach. Finally, in vivo functional assessment tests in the mouse cortex were performed as well as histological assessment of the insertion footprint, validating the biological applicability of this flexible neural probe for acquiring high quality neuronal recordings with high signal to noise ratio (SNR) and reduced acute trauma.

Hybrid Multisite Silicon Neural Probe with Integrated Flexible Connector for Interchangeable Packaging.

Multisite neural probes are a fundamental tool to study brain function. Hybrid silicon/polymer neural probes combine rigid silicon and flexible polymer parts into one single device and allow, for example, the precise integration of complex probe geometries, such as multishank designs, with flexible biocompatible cabling. Despite these advantages and benefiting from highly reproducible fabrication methods on both silicon and polymer substrates, they have not been widely available. This paper presents the development, fabrication, characterization, and in vivo electrophysiological assessment of a hybrid multisite multishank silicon probe with a monolithically integrated polyimide flexible interconnect cable. The fabrication process was optimized at wafer level, and several neural probes with 64 gold electrode sites equally distributed along 8 shanks with an integrated 8 µm thick highly flexible polyimide interconnect cable were produced. The monolithic integration of the polyimide cable in the same fabrication process removed the necessity of the postfabrication bonding of the cable to the probe. This is the highest electrode site density and thinnest flexible cable ever reported for a hybrid silicon/polymer probe. Additionally, to avoid the time-consuming bonding of the probe to definitive packaging, the flexible cable was designed to terminate in a connector pad that can mate with commercial zero-insertion force (ZIF) connectors for electronics interfacing. This allows great experimental flexibility because interchangeable packaging can be used according to experimental demands. High-density distributed in vivo electrophysiological recordings were obtained from the hybrid neural probes with low intrinsic noise and high signal-to-noise ratio (SNR).

Applying an Evolutionary Approach of Risk-Taking Behaviors in Adolescents.

Risk-taking behaviors in adolescents have traditionally been analyzed from a psychopathological approach, with an excessive emphasis on their potential costs. From evolutionary theory we propose that risk-taking behaviors can be means through which adolescents obtain potential benefits for survival and reproduction. The present study analyses sex differences in three contexts of risk (i.e., risk propensity, expected benefits and risk perception) in the evolutionary specific domains and the predictive value of these domains over risk-taking behaviors, separately in female and male adolescents. 749 adolescents (females = 370) valued their risk perception, expected benefits and risk propensity through the Evolutionary Domain-Specific Risk Scale, as well as their engagement in risk-taking behaviors through the Risky Behavior Questionnaire. Male adolescents showed lower risk perception in two evolutionary domains, expected higher benefits in two other domains and showed higher risk propensity in six domains. Female adolescents showed lower risk perception in two domains. Additionally, risk perception, expected benefits and risk propensity in the evolutionary domains predicted the engagement in risk-taking behaviors in male adolescents, whereas in female adolescents only expected benefits and risk propensity showed a predictive effect over risk-taking behaviors. These results suggest the potential role of evolutionary mechanisms on risk-taking behaviors in adolescents. Results have practical implications for interventions programs aimed at reducing risk-taking behaviors. In addition to considering sex differences, intervention programs should consider alternative behaviors through which adolescents can reach their evolutionary goals, and handle the risks related to those behaviors that cannot be replaced but have potential benefits for adolescents.

Discrimination and Psychosocial Well-Being of Migrants in Spain: The Moderating Role of Sense of Community.

The discrimination migrants perceive during their adaptation process is one of the main sources of stress and it affects their well-being, health and integration severely. The present study analyses how the sense of community (SOC) can have a protective effect against the perception of discrimination and its negative consequences by verifying the following theoretical model: discrimination predicts three indicators of psychosocial well-being (psychological distress, satisfaction with life and feelings of social exclusion). Furthermore, the theoretical model proposed also considers the hypothesis that SOC has a moderating role on the effect of perceived discrimination regarding the three variables mentioned above. 1714 migrants from Eastern Europe, Africa and Latin America who live in Málaga, Spain, participated in the study. Data were collected using random-route sampling and survey methodology. After carrying out multiple regression analyses, using the PROCESS tool in SPSS 20, the theoretical model was verified: SOC reduces the negative effects of perceived discrimination for the variables psychological distress, satisfaction with life and social exclusion feelings. Therefore, migrants who have a greater SOC experience fewer negative consequences, as compared to those with a lower SOC, for whom the consequences of such variables are more negative. These results highlight the importance for migrants to rebuild social networks in the host country and develop a good SOC. Results also allow the development of intervention patterns to favor positive interactions between native population and migrants.

Botulinum Neurotoxin-A Injection in Adult Cervical Dystonia and Spastic Paresis: Results From the INPUT (INjection Practice, Usage and Training) Survey.

Botulinum toxin-A (BoNT-A) is an effective treatment for cervical dystonia (CD) and spastic paresis (SP), but it requires in-depth knowledge of anatomy and injection techniques. The Ixcellence Network® is an educational programme to provide neurology, neuropaediatrics, and physical medicine and rehabilitation (PMR) specialists with access to best clinical practices and innovations regarding SP and CD management with BoNT-A. To assess the benefits of such educational programmes and identify unmet needs, a multidisciplinary scientific committee designed INPUT (INjection Practice, Usage & Training), an international multicentric survey describing training and practices among this trained and experienced population. A self-completed questionnaire was sent online to 553 trainees and 14 trainers from the Ixcellence Network®. Among the 131 respondents, 92% specialized in PMR (48%) or neurology (44%), with a mean experience of 15.5 years in their clinical fields and 10.9 years of BoNT-A injection. Most of them (98%) reported having received training before performing their first BoNT-A injection and attending specific courses on how to perform it without any instrumental guidance (76%), and with ultrasound (73%), electrical stimulation (44%) or electromyography (41%). In terms of practices, 92% of respondents reported using at least one guidance technique while injecting, with ultrasound being the most used technique (48%). Attending specific courses was significantly associated with greater self-confidence and use, e.g. for injection with ultrasound, mean self-confidence, on a scale from 1 (not confident) to 10 (fully confident), was 7.9 for trained respondents (vs 4.0 for untrained respondents, p < 0.001) of whom 70% stated that they used this technique regularly or systematically (vs. 11% of untrained healthcare professionals (HCPs), p < 0.0001). Moreover, 84% of respondents reported having trained colleagues, residents or fellows through theoretical (70%) or practical teaching in individuals (80%) or in small groups (65%). Overall, 86% of respondents reported a notable increase over the past 5 years of the number of patients treated with BoNT-A. INPUT is the first international survey describing training and practices in SP and CD management of physicians who attended a dedicated educational programme. The results highlighted the importance of training for self-confidence, and the use of specific techniques and new approaches.

Perceived Discrimination, Psychological Distress and Cardiovascular Risk in Migrants in Spain.

The aim of the present study is to determine the effect of discrimination and psychological distress on the cardiovascular health of immigrants, as well as to analyse potential differences based on age, gender, length of residence in host country and geographic origin. The sample was formed by 1714 immigrants from Africa, Eastern Europe and Latin America. Of the sample, 48.7% were men and 51.3% were women. Most relevant results show that discrimination (t = 4.27; p = 0.000) and psychological distress (t = 4.35; p = 0.000) experienced by immigrants predict their cardiovascular risk. Furthermore, psychological distress mediates the relation between discrimination and risk (t = 4.03; p = 0.000). Significant differences between men and women were found, as well as differences based on ethnicity, although to a lesser extent. Age affects the relation between discrimination, psychological distress and arterial hypertension and hypercholesterolemia. Results are notably relevant for the design of preventive health programmes for immigrants and intervention strategies in order to prevent diseases that may imply cardiovascular risks and seriously affect immigrants' health.

The moderating effect of gender as a protective factor against discrimination in migrants from Latin America and China.

This study analysed the association between discrimination and satisfaction with life (SWL) in migrant groups by investigating whether different types of social support (SS; emotional, instrumental, and informational) and networks (family, immigrant and native friends, neighbours, and the community) buffer the negative effects of discrimination on SWL among migrant men and women from different backgrounds. Participants were 631 migrants from Latin America and China residing in Malaga (Spain). We identified behaviour patterns that suggest that SS has different effects on men and women from the same place of origin and similar effects on women and men from different places of origin. In conclusion, the main differences in the effects of SS as a buffer mechanism are not determined by cultural factors. It is more likely that they are determined by differential gender-role socialization, which would lead women to positively value social support.

COVID-19 pandemic. What should Physical and Rehabilitation Medicine specialists do? A clinician's perspective.

COVID-19 pandemic is rapidly spreading all over the world, creating the risk for a healthcare collapse. While acute care and intensive care units are the main pillars of the early response to the disease, rehabilitative medicine should play an important part in allowing COVID-19 survivors to reduce disability and optimize the function of acute hospital setting. The aim of this study was to share the experience and the international perspective of different rehabilitation centers, treating COVID-19 survivors. A group of Physical Medicine and Rehabilitation specialists from eleven different countries in Europe and North America have shared their clinical experience in dealing with COVID-19 survivors and how they have managed the re-organization of rehabilitation services. In our experience the most important sequelae of severe and critical forms of COVID-19 are: 1) respiratory; 2) cognitive, central and peripheral nervous system; 3) deconditioning; 4) critical illness related myopathy and neuropathy; 5) dysphagia; 6) joint stiffness and pain; 7) psychiatric. We analyze all these consequences and propose some practical treatment options, based on current evidence and clinical experience, as well as several suggestions for management of rehabilitation services and patients with suspected or confirmed infection by SARS-CoV-2. COVID-19 survivors have some specific rehabilitation needs. Experience from other centers may help colleagues in organizing their services and providing better care to their patients.

A versatile and modular tetrode-based device for single-unit recordings in rodent ex vivo and in vivo acute preparations.

BACKGROUND: The demand for affordable tools for recording extracellular activity and successfully isolating single units from different brain preparations has pushed researchers and companies to invest in developing and fabricating new recording devices. However, depending on the brain region of interest, experimental question or type of preparation, different devices are required thus adding substantial financial burden to laboratories. NEW METHOD: We have developed a simple and affordable tetrode-based device that allows interchangeable extracellular recordings of neuronal activity between in vivo and ex vivo preparations and can be easily implemented in all wet-bench laboratories. RESULTS: Spontaneous activity from several putative single neurons could be easily recorded and isolated by lowering the device into ex vivo cerebellum brain slices. The same device was also used in vivo, lowered into primary auditory cortex of adult anesthetized transgenic mice expressing channelrhodopsin in cortical neurons. Acoustic stimulation of the contralateral ear or direct laser optogenetic stimulation successfully evoked cortical activity at the recording site. Several isolated putative single neurons presented time-locked activity response to the different stimuli. COMPARISON WITH EXISTING METHODS: Besides low fabrication cost, our device uses an omnetics connector compatible with the majority of headstages already available at most electrophysiology laboratories. The device allows custom tetrode configuration arrays and extensions for optogenetics and pharmacology, providing experimental flexibility not available in commercial off-the-shelf microelectrode arrays and silicon probes. CONCLUSIONS: We developed an affordable, versatile and modular device to facilitate tetrode extracellular recordings interchangeably between in vivo anaesthetized animals and ex vivo brain slice recordings.