Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression

IMPORTANCE: Clinical research has shown that persistent negative beliefs maintain depression and that subanesthetic ketamine infusions induce rapid antidepressant responses. OBJECTIVE: To evaluate whether ketamine alters belief updating and how such cognitive effects are associated with the clinical effects of ketamine. DESIGN, SETTING, AND PARTICIPANTS: To evaluate whether ketamine alters belief updating and how such cognitive effects are associated with the clinical effects of ketamine. EXPOSURES: Patients with TRD were observed 24 hours before single ketamine infusion, 4 hours after the infusion, and 4 hours after the third infusion, which was 1 week after the first infusion. Healthy control participants were observed twice 1 week apart without ketamine exposure. MAIN OUTCOMES AND MEASURES: Montgomery-Åsberg Depression Rating Scale score and belief updating after belief updating when patients received good news and bad news measured by a cognitive belief-updating task and mathematically formalized by a computational reinforcement learning model. RESULTS: Of 56 included participants, 29 (52%) were male, and the mean (SEM) age was 52.3 (1.2) years. A total of 26 patients with TRD and 30 control participants were included. A significant group × testing time point × news valence interaction showed that patients with TRD updated their beliefs more after good than bad news following a single ketamine infusion (controlled for age and education: β = −0.91; 95% CI, −1.58 to −0.24; t216 = −2.67; P = .008) than controls. Computational modeling showed that this effect was associated with asymmetrical learning rates (LRs) after ketamine treatment (good news LRs after ketamine, 0.51 [SEM, 0.04]; bad news LRs after ketamine 0.36 [SEM, 0.03], t25 = 3.8; P < .001) and partially mediated early antidepressant responses (path a*b: β = −1.00 [SEM, 0.66]; t26 = −1.53; z = −1.98; P = .04). CONCLUSIONS AND RELEVANCE: These findings provide novel insights into the cognitive mechanisms of the action of ketamine in patients with TRD, with promising perspectives for augmented psychotherapy for individuals with mood disorders

Taste matters: mapping expectancy-based appetitive placebo effects onto the brain

Expectancies, which are higher order prognostic beliefs, can have powerful effects on experiences, behavior and brain. However, it is unknown where, how, and when, in the brain, prognostic beliefs influence appetitive interoceptive experiences and related economic behavior. This study combined a placebo intervention on hunger with computational modelling and functional magnetic resonance imaging of value-based decision-making. The results show that prognostic beliefs about hunger shape hunger experiences, how much participants value food and food-value encoding in the prefrontal cortex. Computational modelling further revealed that these placebo effects were underpinned by how much and when during the decision process taste and health information are integrated into the accumulation of evidence toward a food choice. The drift weights of both sources of information further moderated ventromedial and dorsolateral prefrontal cortex interactions during choice formation. These findings provide novel insights into the neurocognitive mechanisms that translate higher order prognostic beliefs into non-aversive interoceptive sensitivity and shape decision-making

Conselho de saúde: uma reflexão sobre os processos de participação dos conselheiros

Este estudo tem como objetivo identificar os motivos que levam os conselheiros a se inserir, continuar e/ ou desligar-se do conselho municipal de saúde. Está sustentado teoricamente no conceito de participação de Bordenave e Demo. A metodologia utilizada baseia-se na abordagem qualitativa do tipo estudo de caso instrumental. Para a coleta de dados, utilizou-se análise documental, entrevistas individuais e observação. Os resultados apontam que os motivos referidos para iniciar, permanecer e se desligar incluem: convite ou indicação; o gostar e conceder oportunidade a outras pessoas. A participação, para além da presença física, demanda inúmeros recursos, como: conhecimento, tempo, acesso e compreensão das informações, articulação, comprometimento, descentralização do poder, entre outros. Neste sentido, a participação nos conselhos é um processo em construção que deve ser fortalecido para efetivar o exercício do controle social na área da saúde, conforme tem sido preconizado pela legislação brasileira

Quantifying Cerebral Contributions to Pain beyond Nociception

Cerebral processes contribute to pain beyond the level of nociceptive input and mediate psychological and behavioural influences. However, cerebral contributions beyond nociception are not yet well characterized, leading to a predominant focus on nociception when studying pain and developing interventions. Here we use functional magnetic resonance imaging combined with machine learning to develop a multivariate pattern signature—termed the stimulus intensity independent pain signature-1 (SIIPS1)—that predicts pain above and beyond nociceptive input in four training data sets (Studies 1–4, N¼137). The SIIPS1 includes patterns of activity in nucleus accumbens, lateral prefrontal and parahippocampal cortices, and other regions. In cross-validated analyses of Studies 1–4 and in two independent test data sets (Studies 5–6, N¼46), SIIPS1 responses explain variation in trial-by-trial pain ratings not captured by a previous fMRI-based marker for nociceptive pain. In addition, SIIPS1 responses mediate the pain-modulating effects of three psychological manipulations of expectations and perceived control. The SIIPS1 provides an extensible characterization of cerebral contributions to pain and specific brain targets for interventions

Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly

Background: The HIV-1 p6 Gag protein regulates the final abscission step of nascent virions from the cell membrane by the action of two late assembly (L-) domains. Although p6 is located within one of the most polymorphic regions of the HIV-1 gag gene, the 52 amino acid peptide binds at least to two cellular budding factors (Tsg101 and ALIX), is a substrate for phosphorylation, ubiquitination, and sumoylation, and mediates the incorporation of the HIV-1 accessory protein Vpr into viral particles. As expected, known functional domains mostly overlap with several conserved residues in p6. In this study, we investigated the importance of the highly conserved serine residue at position 40, which until now has not been assigned to any known function of p6. Results: Consistently with previous data, we found that mutation of Ser-40 has no effect on ALIX mediated rescue of HIV-1 L-domain mutants. However, the only feasible S40F mutation that preserves the overlapping pol open reading frame (ORF) reduces virus replication in T-cell lines and in human lymphocyte tissue cultivated ex vivo. Most intriguingly, L-domain mediated virus release is not dependent on the integrity of Ser-40. However, the S40F mutation significantly reduces the specific infectivity of released virions. Further, it was observed that mutation of Ser-40 selectively interferes with the cleavage between capsid (CA) and the spacer peptide SP1 in Gag, without affecting cleavage of other Gag products. This deficiency in processing of CA, in consequence, led to an irregular morphology of the virus core and the formation of an electron dense extra core structure. Moreover, the defects induced by the S40F mutation in p6 can be rescued by the A1V mutation in SP1 that generally enhances processing of the CA-SP1 cleavage site. Conclusions: Overall, these data support a so far unrecognized function of p6 mediated by Ser-40 that occurs independently of the L-domain function, but selectively affects CA maturation and virus core formation, and consequently the infectivity of released virions

Group-regularized individual prediction: theory and application to pain

Multivariate pattern analysis (MVPA) has become an important tool for identifying brain representations of psychological processes and clinical outcomes using fMRI and related methods. Such methods can be used to predict or ‘decode’ psychological states in individual subjects. Single-subject MVPA approaches, however, are limited by the amount and quality of individual-subject data. In spite of higher spatial resolution, predictive accuracy from single-subject data often does not exceed what can be accomplished using coarser, group-level maps, because single-subject patterns are trained on limited amounts of often-noisy data. Here, we present a method that combines population-level priors, in the form of biomarker patterns developed on prior samples, with single-subject MVPA maps to improve single-subject prediction. Theoretical results and simulations motivate a weighting based on the relative variances of biomarker-based prediction—based on population-level predictive maps from prior groups—and individual-subject, cross-validated prediction. Empirical results predicting pain using brain activity on a trial-by-trial basis (single-trial prediction) across 6 studies (N = 180 participants) confirm the theoretical predictions. Regularization based on a population-level biomarker—in this case, the Neurologic Pain Signature (NPS)—improved single-subject prediction accuracy compared with idiographic maps based on the individuals' data alone. The regularization scheme that we propose, which we term group-regularized individual prediction (GRIP), can be applied broadly to within-person MVPA-based prediction. We also show how GRIP can be used to evaluate data quality and provide benchmarks for the appropriateness of population-level maps like the NPS for a given individual or study

Mitochondrial DNA control region data from indigenous Angolan Khoe-San lineages

Here we provide 129 complete mitochondrial control region sequences of indigenous Khoe-San individuals from Angola to contribute to the still underrepresented pool of data from Africa. The dataset consists of exclusively African lineages with a majority of Sub-Saharan haplogroups. The probability of a random match was calculated as 0.09. The data set comprises 21 haplotypes occurring more than once and 17 unique haplotypes. Upon publication, haplotypes were incorporated in the EMPOP database (www.empop.org; EMP00069) [1].http://www.elsevier.com/locate/fsi

Uma visão dos alunos e do professor sobre o uso de simulações como complemento à aprendizagem de Física

Foi implementado um ambiente virtual de aprendizagem para auxiliar as aulas presenciais de Física, cuja ênfase foi a utilização de simulações de experimentos. Os recursos que o ambiente apresenta possibilitaram organizar as informações de forma eficiente, estimulam a interatividade e manipulação dos conteúdos através do desenvolvimento de atividades adequadas (leituras, testes online, simulações de fenômenos físicos de difícil visualização), assim como fornecem subsídios para uma aprendizagem significativa. A avaliação do ambiente por alunos durante o ano 2003 indica que a sua utilização contribuiu para estabelecer as condições necessárias para alcançar uma aprendizagem significativa por parte dos alunos.A virtual learning environment was implemented to aid physics classrooms lessons, whose emphasis was the use of experiments simulation. For its construction, the appropriated tools and techniques were explored. The resources within the environment allowed an efficient organization of the information, helps to stimulate the interactivity and the manipulation of the contents through the development of adequate activities (readings, online tests, physical phenomena of difficult visualization simulations), as well supply subsidies to a meaningful learning. The evaluation of the environment made by the students during the year 2003 indicates that it contributes to establish the necessary conditions to reach a significant learning in a classroom.Eje: III - Workshop de tecnología informática aplicada en educaciónRed de Universidades con Carreras en Informática (RedUNCI