Psicobiologia dell'ansia sociale: studio di risonanza magnetica funzionale dello stato di riposo cerebrale

Negli ultimi anni ha acquisito sempre più interesse lo studio dello stato di riposo cerebrale, ovverosia del segnale neuronale proprio dell’individuo sveglio e all’erta, ma non impegnato in alcuno sforzo cognitivo mirato. Si ritiene infatti che l'attività rilevabile in questa condizione sia il risultato dell’interazione fra numerose reti cerebrali altamente organizzate e che sia in grado di influenzare in modo significativo le attivazioni specifiche rilevate durante i compiti finalizzati. È stato ipotizzato, inoltre, che tramite il suo studio si possano ottenere correlati funzionali misurabili di variabili psicometriche, monitorando la loro eventuale evoluzione fino alla patologia. Nell'ottica di una visione dimensionale della malattia mentale, l'ansia sociale può essere facilmente intesa e misurata come una variabile continua in ogni individuo, estesa dalla semplice "timidezza" ai fenomeni di evitamento e panico in situazioni sociali propri della fobia sociale conclamata. Per questo motivo tale dimensione è stata oggetto di studio nella presente tesi, nella quale sono stati confrontati i punteggi sulla scala Liebowitz (LSAS) dell'ansia sociale di 36 soggetti e due misure funzionali calcolate a partire dai loro dati acquisiti in stato di riposo tramite risonanza magnetica funzionale cerebrale: la connettività del Default Mode Network e l'indice di Hurst. Il Default Mode Network è un insieme di aree cerebrali attive e funzionalmente connesse in stato di riposo che riducono fortemente la loro scarica spontanea durante l'attività finalizzata (Raichle et al 2001). Queste sono: corteccia cingolata posteriore/precuneo (PCC), corteccia prefrontale mediale (MPFC) e corteccia parietale mediale (MPC), laterale (LPC) e inferiore (IPC). Nel presente lavoro, lo studio del DMN ha reso possibile la valutazione dell'integrità dei collegamenti funzionali fra aree diverse in individui con vari gradi di ansia sociale. L'indice di Hurst (H) è un indice frattale impiegato per descrivere l'andamento del segnale emodinamico all'interno delle singole aree cerebrali. Si tratta di un numero compreso fra 0 e 1 che descrive la tendenza relativa della serie temporale di regredire verso la sua media o di spostarsi in una direzione. In condizioni fisiologiche, gli indici di Hurst del segnale emodinamico cerebrale presentano solitamente un intervallo ristretto di valori \citep{Herman2009}. ${H}$ troppo discostati dalla norma potrebbero dunque rappresentare la presenza di una patologia o la progressione verso di essa. La connettività del DMN con il resto del cervello e gli (H) di ogni voxel sono stati confrontati con i valori LSAS dei 36 soggetti tramite due procedure distinte. La prima è stata una regressione lineare fra gli indici funzionali di ogni partecipante e il loro punteggio di LSAS, la seconda è stata un confronto tramite t-test fra i 12 individui con LSAS > 30 e 12 altri. I risultati hanno indicato che un aumento di LSAS è correlato a una connettività funzionale ridotta fra insula e DMN a riposo. Questo potrebbe essere indice di uno stato di allarme in grado di sfuggire ai normali meccanismi di controllo dell'attività cerebrale, generando una predisposizione a sviluppare ansia e preoccupazione con più facilità in risposta a stimoli sociali, come volti e sguardi, ed enterocettivi. Fra i soggetti con LSAS > 30 sono state inoltre ritrovate differenze significative della connettività del DMN con precuneo, PCC, IPL e insula. La sincronia minore fra le oscillazioni di queste aree e quelle del resto del DMN potrebbe portare questi individui ad assegnare una maggior quota di attenzione sia alle percezioni enterocettive che alle proprie elaborazioni cognitive egodistoniche (bias attenzionale). Per quanto riguarda l'indice di Hurst, è stata rilevata una correlazione positiva fra H e i punteggi sulla scala LSAS dei soggetti a livello di SPL e precuneo, aree coinvolte nei fenomeni attentivi e nell'integrazione degli stimoli tattili e visivi (Shomstein et al 2012). L'aumento di H in queste sedi potrebbe riflettere una loro maggiore "rigidità" nell'adattarsi agli impulsi provenienti da altre aree corticali che potrebbe esitare in difficoltà per il paziente nel variare l'allocazione della propria attenzione verso stimoli esterni in grado di smentire il suo giudizio riguardo alle proprie abilità sociali. I risultati del presente studio forniscono una nuova base biologica a un'osservazione che era stata già formulata in ambito psicologico, clinico e psicometrico: l'ansia sociale si comporta come una dimensione estesa su un continuum che va dalla normale timidezza alla patologia. Il fatto che questi risultati siano stati ottenuti a riposo, infine, potrebbe indicare che l'ansia sociale è una dimensione di tratto in grado di modificare la predisposizione a valutare le percezioni in un modo piuttosto che in un altro e di influenzare le successive elaborazioni cognitive

Impaired reward processing in the human prefrontal cortex distinguishes between persistent and remittent attention deficit hyperactivity disorder

Symptoms of attention deficit hyperactivity disorder (ADHD) in children often persist into adulthood and can lead to severe antisocial behavior. However, to-date it remains unclear whether neuro-functional abnormalities cause ADHD, which in turn can then provide a marker of persistent ADHD. Using event-related functional magnetic resonance imaging (fMRI), we measured blood oxygenation level dependent (BOLD) signal changes in subjects during a reversal learning task in which choice of the correct stimulus led to a probabilistically determined ‘monetary’ reward or punishment. Participants were diagnosed with ADHD during their childhood (N = 32) and were paired with age, gender, and education matched healthy controls (N = 32). Reassessment of the ADHD group as adults resulted in a split between either persistent (persisters, N = 17) or remitted ADHDs (remitters, N = 15). All three groups showed significantly decreased activation in the medial prefrontal cortex (PFC) and the left striatum during punished correct responses, however only remitters and controls presented significant psycho-physiological interaction between these fronto-striatal reward and outcome valence networks. Comparing persisters to remitters and controls showed significantly inverted responses to punishment (P < 0.05, family-wise error corrected) in left PFC region. Interestingly, the decreased activation shown after punishment was located in different areas of the PFC for remitters compared with controls, suggesting that remitters might have learned compensation strategies to overcome their ADHD symptoms. Thus, fMRI helps understanding the neuro-functional basis of ADHD related behavior differences and differentiates between persistent and remittent ADHD

A Comprehensive Atlas of Perineuronal Net Distribution and Colocalization with Parvalbumin in the Adult Mouse Brain

Perineuronal nets (PNNs) surround specific neurons in the brain and are involved in various forms of plasticity and clinical conditions. However, our understanding of the PNN role in these phenomena is limited by the lack of highly quantitative maps of PNN distribution and association with specific cell types. Here, we present a comprehensive atlas of Wisteria Floribunda Agglutinin (WFA) positive PNNs and colocalization with parvalbumin (PV) cells for over 600 regions of the adult mouse brain. Data analysis shows that PV expression is a good predictor of PNN aggregation. In the cortex, PNNs are dramatically enriched in layer 4 of all primary sensory areas in correlation with thalamocortical input density, and their distribution mirrors intracortical connectivity patterns. Gene expression analysis identifies many PNN correlated genes. Strikingly, PNN anticorrelated transcripts are enriched in synaptic plasticity genes, generalizing PNN role as circuit stability factors

Tradução para o português do Brasil da peça teatral The Playboy of the Western World, de J. M. Synge

O dramaturgo John Millington Synge nasceu em 16 de abril de 1871, em Rathfarnham ”“ aproximadamente 20 minutos de Dublin ”“ na Irlanda. Fez parte da geração de autores que atuaram no renascimento literário irlandês, como William Butler Yeats e Lady Augusta Gregory. Entre suas peças publicadas estão: In the Shadow of the Glen (primeira encenação em 1903), Riders to the Sea (1904) e The Well of the Saints (1905) ”“ sua primeira peça em três atos. &nbsp

The human connectome project for disordered emotional states: Protocol and rationale for a research domain criteria study of brain connectivity in young adult anxiety and depression

Available online 5 March 2020.Through the Human Connectome Project (HCP) our understanding of the functional connectome of the healthy brain has been dramatically accelerated. Given the pressing public health need, we must increase our understanding of how connectome dysfunctions give rise to disordered mental states. Mental disorders arising from high levels of negative emotion or from the loss of positive emotional experience affect over 400 million people globally. Such states of disordered emotion cut across multiple diagnostic categories of mood and anxiety disorders and are compounded by accompanying disruptions in cognitive function. Not surprisingly, these forms of psychopathology are the leading cause of disability worldwide. The Research Domain Criteria (RDoC) initiative spearheaded by NIMH offers a framework for characterizing the relations among connectome dysfunctions, anchored in neural circuits and phenotypic profiles of behavior and self-reported symptoms. Here, we report on our Connectomes Related to Human Disease protocol for integrating an RDoC framework with HCP protocols to characterize connectome dysfunctions in disordered emotional states, and present quality control data from a representative sample of participants. We focus on three RDoC domains and constructs most relevant to depression and anxiety: 1) loss and acute threat within the Negative Valence System (NVS) domain; 2) reward valuation and responsiveness within the Positive Valence System (PVS) domain; and 3) working memory and cognitive control within the Cognitive System (CS) domain. For 29 healthy controls, we present preliminary imaging data: functional magnetic resonance imaging collected in the resting state and in tasks matching our constructs of interest (“Emotion”, “Gambling” and “Continuous Performance” tasks), as well as diffusion-weighted imaging. All functional scans demonstrated good signal-to-noise ratio. Established neural networks were robustly identified in the resting state condition by independent component analysis. Processing of negative emotional faces significantly activated the bilateral dorsolateral prefrontal and occipital cortices, fusiform gyrus and amygdalae. Reward elicited a response in the bilateral dorsolateral prefrontal, parietal and occipital cortices, and in the striatum. Working memory was associated with activation in the dorsolateral prefrontal, parietal, motor, temporal and insular cortices, in the striatum and cerebellum. Diffusion tractography showed consistent profiles of fractional anisotropy along known white matter tracts. We also show that results are comparable to those in a matched sample from the HCP Healthy Young Adult data release. These preliminary data provide the foundation for acquisition of 250 subjects who are experiencing disordered emotional states. When complete, these data will be used to develop a neurobiological model that maps connectome dysfunctions to specific behaviors and symptoms.This work was supported by the National Institutes of Health [grant number U01MH109985 under PAR-14-281]

DNA methylation differences at the glucocorticoid receptor gene in depression are related to functional alterations in hypothalamic-pituitary-adrenal axis activity and to early life emotional abuse

Depression is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis activity. A proposed mechanism to explain these alterations are changes in DNA methylation levels, secondary to early life adversity (ELA), at stress-related genes. Two gene regions that have been implicated in the literature, the glucocorticoid receptor gene (NR3C1) exon 1F and the FKBP5 gene intron 7 were examined in 67 individuals (33 depressed patients and 34 controls). We investigated whether cortisol concentrations, evaluated in 25 depressed patients and 20 controls, and measures of ELA were associated with the degree of methylation at these candidate gene regions. Mean NR3C1 exon 1F DNA methylation levels were significantly increased in the depressed cohort and the degree of methylation was found to be positively associated with morning cortisol concentrations. DNA methylation levels at specific CG sites within the NR3C1 exon 1F were related to childhood emotional abuse severity. DNA methylation at CG38 was related to both HPA axis and childhood emotional abuse measures in the depressed group. No FKBP5 differences were revealed. Our findings suggest that hypermethylation at the NR3C1 exon 1F may occur in depression. This locus-specific epigenetic change is associated with higher basal HPA axis activity, possibly reflecting acquired glucocorticoid receptor resistance

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Shedding light on typical species : implications for habitat monitoring

Habitat monitoring in Europe is regulated by Article 17 of the Habitats Directive, which suggests the use of typical species to assess habitat conservation status. Yet, the Directive uses the term “typical” species but does not provide a definition, either for its use in reporting or for its use in impact assessments. To address the issue, an online workshop was organized by the Italian Society for Vegetation Science (SISV) to shed light on the diversity of perspectives regarding the different concepts of typical species, and to discuss the possible implications for habitat monitoring. To this aim, we inquired 73 people with a very different degree of expertise in the field of vegetation science by means of a tailored survey composed of six questions. We analysed the data using Pearson's Chi-squared test to verify that the answers diverged from a random distribution and checked the effect of the degree of experience of the surveyees on the results. We found that most of the surveyees agreed on the use of the phytosociological method for habitat monitoring and of the diagnostic and characteristic species to evaluate the structural and functional conservation status of habitats. With this contribution, we shed light on the meaning of “typical” species in the context of habitat monitoring