Neural Connectivity Evidence for a Categorical-Dimensional Hybrid Model of Autism Spectrum Disorder

Autism spectrum disorder (ASD) encompasses a complex presentation of symptoms that include deficits in social interaction and repetitive or stereotyped interests/behaviors. In keeping with the increasing recognition of both the dimensional characteristics of ASD symptoms and the categorical nature of a diagnosis, we sought to delineate their neural mechanisms based on the functional connectivity of four known neural networks (i.e., the default-mode network, the dorsal attention network, the salience network, and the executive control network)

Neural Systems Underlying Individual Differences in Intertemporal Decision-making

Excessively choosing immediate over larger future rewards, or delay discounting (DD), associates with multiple clinical conditions. Individual differences in DD likely depend on variations in the activation of and functional interactions between networks, representing possible endophenotypes for associated disorders, including alcohol use disorders (AUDs). Numerous fMRI studies have probed the neural bases of DD, but investigations of large-scale networks remains scant. We addressed this gap by testing whether activation within large-scale networks during “Now/Later” decision-making predicts individual differences in DD. To do so, we scanned 95 social drinkers (18–40 years; 50 females) using fMRI during hypothetical choices between small monetary amounts available “today” or larger amounts available later. We identified neural networks engaged during Now/Later choice using independent component analysis (ICA) and tested the relationship between component activation and degree of DD. The activity of two components during Now/Later choice correlated with individual DD rates: a temporal lobe network positively correlated with DD, while a frontoparietal-striatal network negatively correlated with DD. Activation differences between these networks predicted individual differences in DD and their negative correlation during Now/Later choice suggests functional competition. A generalized psychophysiological interactions (gPPI) analysis confirmed a decrease in their functional connectivity during decision-making. The functional connectivity of these two networks negatively correlates with alcohol-related harm, potentially implicating these networks in AUDs. These findings provide novel insight into the neural underpinnings of individual differences in impulsive decision making with potential implications for addiction and related disorders in which impulsivity is a defining feature

COMT Val158Met Polymorphism Exerts Sex-Dependent Effects on fMRI Measures of Brain Function

Evidence suggests that dopamine levels in the prefrontal cortex (PFC) modulate executive functions. A key regulator of PFC dopamine is catechol-O-methyltransferase (COMT). The activity level of the COMT enzyme are influenced by sex and the Val158Met polymorphism (rs4680) of the COMT gene, with male sex and Val alleles both being associated with higher bulk enzyme activity, and presumably lower PFC dopamine. COMT genotype has not only been associated with individual differences in frontal dopamine-mediated behaviors, but also with variations in neuroimaging measures of brain activity and functional connectivity. In this study, we investigated whether COMT genotype predicts individual differences in neural activity and connectivity, and whether such effects are sex-dependent. We tested 93 healthy adults (48 females), genotyped for the Val158Met polymorphism, in a delay discounting task and at rest during fMRI. Delay discounting behavior was predicted by an interaction of COMT genotype and sex, consistent with a U-shaped relationship with enzyme activity. COMT genotype and sex similarly exhibited U-shaped relationships with individual differences in neural activation, particularly among networks that were most engaged by the task, including the default-mode network. Effects of COMT genotype and sex on functional connectivity during rest were also U-shaped. In contrast, flexible reorganization of network connections across task conditions varied linearly with COMT among both sexes. These data provide insight into the potential influences of COMT-regulated variations in catecholamine levels on brain function, which may represent endophenotypes for disorders of impulsivity

Network connectivity abnormality profile supports a categorical-dimensional hybrid model of ADHD: Categorical-Dimensional Hybrid Model of ADHD

Attention-deficit/hyperactivity disorder (ADHD) is characterized by inattention, hyperactivity and impulsivity, but there is no consensus regarding whether ADHD exists on the extreme end of a continuum of normal behavior or represents a discrete disorder. In this study, we sought to characterize both the categorical and dimensional variations in network functional connectivity in order to identify neural connectivity mechanisms of ADHD. Functional connectivity analyses of resting-state fMRI data from 155 children with ADHD and 145 typically-developing children (TDC) defined the dorsal attention network (DA), default mode network (DM), salience processing network (SAL) and executive control network (CON). Regional alterations in connectivity associated with categorical diagnoses and dimensional symptom measures (inattention and hyperactivity/impulsivity) as well as their interaction were systematically characterized. Dimensional relationships between symptom severity measures and functional connectivity that did not differ between TDC and children with ADHD were observed for each network, supporting a dimensional characterization of ADHD. However, categorical differences in functional connectivity magnitude between TDC and children with ADHD were detected after accounting for dimensional relationships, indicating the existence of categorical mechanisms independent of dimensional effects. Additionally, differential dimensional relationships for TDC versus ADHD children demonstrated categorical differences in brain-behavior relationships. The patterns of network functional organization associated with categorical versus dimensional measures of ADHD accentuate the complexity of this disorder and support a dual characterization of ADHD etiology featuring both dimensional and categorical mechanisms

Effects of childhood maltreatment on the neural correlates of stress- and drug cue-induced cocaine craving: Trauma and cocaine craving

Childhood adversity negatively influences all stages of the addiction process and is associated with persistent alterations in neuroendocrine, autonomic and brain responses to stress. We sought to characterize the impact of childhood abuse and neglect on the neural correlates of stress- and drug cue-induced drug craving associated with cocaine addiction. Cocaine-dependent men with (n=20) and without (n=18) moderate to severe childhood maltreatment histories underwent fMRI during script-guided mental imagery of personalized stress, drug use, and neutral experiences. Compared to the neutral script, the stress and drug use scripts activated striatal, prefrontal, posterior cingulate, temporal and cerebellar regions consistent with prior studies of induced states of stress and drug craving. For the stress script, maltreated men exhibited reduced activation of the anterior precuneus and supplementary motor area (SMA); the interaction of maltreatment severity and stress-induced craving responses predicted lesser rostral anterior cingulate cortex activation. For the drug use script, maltreated men exhibited greater left dorsolateral prefrontal cortex activation. The interaction of maltreatment severity and craving responses was associated with greater activation of the visual cortex and SMA, whereas a maltreatment-by-anxiety interaction effect included lesser ventromedial prefrontal cortex activation. The outcomes indicate an association of childhood maltreatment with a heightened appetitive anticipatory response to drug cues and a diminished engagement of regulatory and controlled action selection processes in response to stress- or drug cue-induced drug craving and anxiety responses for cocaine-dependent men. These findings provide novel insights into possible brain mechanisms by which childhood maltreatment heightens risk for relapse in drug-dependent individuals

Metodologias em EaD e suas Implicações no Ensino em Odontologia Durante a Pandemia da COVID-19: Revisão de Literatura

Dental education, in the face of the COVID-19 pandemic, needed to be rethought and directed to the new reality that was abruptly imposed by social isolation. In view of this new reality, remote classes have become the safest and most viable alternative to reduce the losses resulting from the absence of face-to-face meetings and, more than that, to allow the students' learning to not be totally interrupted. Therefore, the objective of this review was to discuss the implications of distance learning methodologies for teaching in Dentistry, whether in the theoretical or practical components of undergraduate courses, in addition to addressing the valuable use of technological resources and innovative methodologies in this new educational scenario. Keywords: Dental education. Methodology. Innovation. dentistry. COVID-19.  O ensino odontológico, frente à pandemia da COVID-19, precisou ser repensado e direcionado para a nova realidade que lhe foi abruptamente imposta pelo isolamento social. Diante dessa nova realidade, aulas remotas tornaram-se a alternativa mais segura e viável para reduzir os prejuízos decorrentes da ausência de encontros presenciais e, mais do que isso, para permitir que o aprendizado dos alunos não fosse totalmente interrompido. Portanto, o objetivo desta revisão foi discutir as implicações das metologias em educação a distância (EaD) no ensino em Odontologia, nos componentes teórico e prático da graduação, além de abordar a valiosa utilização de recursos tecnológicos e metodologias inovadoras neste novo cenário educacional. Palavras-chave: Educação em odontologia. Metodologia. Inovação. Odontologia. COVID-19

Standard Bismuth Quadruple Therapy versus Concomitant Therapy for the First-Line Treatment of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

(1) Background: Whether standard bismuth quadruple therapy (BQT) is superior to concomitant therapy for the first-line treatment of Helicobacter (H.) pylori infection is unclear. The aim of this systematic review and meta-analysis was to compare the efficacy of standard BQT versus concomitant therapy for H. pylori eradication in subjects naive to treatment. (2) Methods: Online databases were searched for randomized controlled trials. We pooled risk ratio (RR) of individual studies for dichotomous outcomes using a random-effect model. (3) Results: Six studies with 1810 adults were included. Overall intention-to-treat (ITT) eradication rate was 87.4% with BQT and 85.2% with concomitant therapy (RR 1.01, 95%CI:0.94-1.07). Subgroup analysis of five Asian studies showed a small but significant superiority of BQT over concomitant therapy (87.5% vs. 84.5%; RR 1.04, 95%CI:1.01-1.08). Pooling four studies at low risk of bias yielded a similar result (88.2% vs. 84.5%; RR 1.05, 95%CI:1.01-1.09). There was no difference between the regimens in the frequency of adverse events (RR = 0.97, 95%CI:0.79-1.2). (4) Conclusions: The efficacy of BQT seems to be similar to concomitant therapy, with similar side effect profile. However, BQT showed a small but significant benefit over concomitant therapy in Asian populations and in studies at low risk of bias

Sarcopenia Predicts Major Complications after Resection for Primary Hepatocellular Carcinoma in Compensated Cirrhosis

The burden of post-operative complications of patients undergoing liver resection for hepatocellular carcinoma (HCC) is a cause of morbidity and mortality. Recently, sarcopenia has been reported to influence the outcome of patients with cirrhosis. We aimed to assess factors associated with sarcopenia and its prognostic role in liver surgery candidates. We included all patients with compensated advanced chronic liver disease (cACLD) undergoing liver resection for primary HCC consecutively referred to the University of Bologna from 2014 to 2019 with an available preoperative abdominal CT-scan performed within the previous three months. A total of 159 patients were included. The median age was 68 years, and 80.5% of the patients were male. Sarcopenia was present in 82 patients (51.6%). Age and body mass index (BMI) were associated with the presence of sarcopenia at multivariate analysis. Thirteen (8.2%) patients developed major complications and 14 (8.9%) presented PHLF grade B-C. The model for end-stage liver disease score was associated with the development of major complications, whereas cACLD presence, thrombocytopenia, portal hypertension (PH), Child-Pugh score and Albumin-Bilirubin score were found to be predictors of clinically significative PHLF. The rate of major complications was 11.8% in sarcopenic patients with cACLD compared with no complications (0%) in patients without sarcopenia and cACLD (p = 0.032). The rate of major complications was significantly higher in patients with (16.3%) vs. patients without (0%) sarcopenia (p = 0.012) in patients with PH. In conclusion, sarcopenia, which is associated with age and BMI, may improve the risk stratification of post-hepatectomy major complications in patients with cACLD and PH