Novel B-cell subsets as potential biomarkers in idiopathic inflammatory myopathies: insights into disease pathogenesis and disease activity.

Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune disorders characterized by progressive muscle weakness and the histopathologic findings of inflammatory infiltrates in muscle tissue. Although their pathogenesis remains indefinite, the association of autoantibodies with clinical manifestations and the evidence of high effectiveness of depleting therapies suggest that B cells could be implicated. Therefore, we explored the landscape of peripheral B cells in this disease by multiparametric flow cytometry, finding significant numerical decreases in memory and double-negative subsets, as well as an expansion of the naive compartment relative to healthy controls, that contribute to defining disease-associated B-cell subset signatures and correlating with different clinical features of patients. Additionally, we determined the potential value of these subsets as diagnostic biomarkers, thus positioning B cells as neglected key elements possibly participating in idiopathic inflammatory myopathy onset or development.

Another in need enhances prosociality and modulates frontal theta oscillations in young adults.

Introduction: Decision-making is a process that can be strongly affected by social factors. Evidence has shown how people deviate from traditional rational-choice predictions under different levels of social interactions. The emergence of prosocial decision-making, defined as any action that is addressed to benefit another individual even at the expense of personal benefits, has been reported as an example of such social influence. Furthermore, brain evidence has shown the involvement of structures such as the prefrontal cortex, anterior insula, and midcingulate cortex during decision settings in which a decision maker interacts with others under physical pain or distress or while being observed by others. Methods: Using a slightly modified version of the dictator game and EEG recordings, we tested the hypothesis that the inclusion of another person into the decision setting increases prosocial decisions in young adults and that this increase is higher when the other person is associated with others in need. At the brain level, we hypothesized that the increase in prosocial decisions correlates with frontal theta activity. Results and Discussion: The results showed that including another person in the decision, setting increased prosocial behavior only when this presence was associated with someone in need. This effect was associated with an increase in frontocentral theta-oscillatory activity. These results suggest that the presence of someone in need enhances empathy concerns and norm compliance, raising the participants' prosocial decision-making.

Allostatic-interoceptive anticipation of social rejection.

Anticipating social stress evokes strong reactions in the organism, including interoceptive modulations. However, evidence for this claim comes from behavioral studies, often with inconsistent results, and relates almost solely to the reactive and recovery phase of social stress exposure. Here, we adopted an allostatic-interoceptive predictive coding framework to study interoceptive and exteroceptive anticipatory brain responses using a social rejection task. We analyzed the heart-evoked potential (HEP) and task-related oscillatory activity of 58 adolescents via scalp EEG, and 385 human intracranial recordings of three patients with intractable epilepsy. We found that anticipatory interoceptive signals increased in the face of unexpected social outcomes, reflected in larger negative HEP modulations. Such signals emerged from key brain allostatic-interoceptive network hubs, as shown by intracranial recordings. Exteroceptive signals were characterized by early activity between 1-15 Hz across conditions, and modulated by the probabilistic anticipation of reward-related outcomes, observed over distributed brain regions. Our findings suggest that the anticipation of a social outcome is characterized by allostatic-interoceptive modulations that prepare the organism for possible rejection. These results inform our understanding of interoceptive processing and constrain neurobiological models of social stress.

Autonomous sensory meridian response is associated with a larger heartbeat-evoked potential amplitude without differences in interoceptive awareness.

Autonomous sensory meridian response (ASMR) describes the experience of a pleasant body sensation accompanied by a feeling of well-being and relaxation in response to specific audiovisual stimuli, such as whispers and personal attention. Previous work suggests a relationship between this experience with the processing of affective and body states; however, no research has explored differences in interoception between people experiencing ASMR and those who do not. We hypothesized that the ASMR experience is based on interoception processing. To test this, we assessed group differences across different dimensions of interoception: Interoceptive sensibility (IS), measured using the multidimensional assessment of interoceptive awareness (MAIA); Interoceptive accuracy score (IAS), measured by calculating performance in a heartbeat counting task (HCT), and the electrophysiological index of interoception, the heartbeat evoked potential (HEP), which was calculated during the HCT and an ASMR tingle reporting task (ASMR-TRT). Our results showed that IS and IAS, dimensions requiring conscious awareness, showed no differences between groups. However, HEP amplitude was larger in the ASMR group in both tasks. We concluded that the ASMR experience is based on an unconscious interoceptive mechanism, reflected by HEP, where exteroceptive social-affective stimuli are integrated to represent a body state of positive affective feelings and relaxation, as has been described for affective touch. The relevance of this finding relies on that interoceptive function, body regulation, and emotional/affective experiences are fundamental for well-being, and the relationship between ASMR and interoception opens the way to future research exploring the causal relationship between them and their potential clinical applications.

Arousal dysregulation and executive dysfunction in attention deficit hyperactivity disorder (ADHD).

Attention deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition, that continues to have an elusive etiological background. A number of extant models and theories have historically intended to explain the many factors contributing to ADHD behaviors. One of the most accepted hypotheses has been the executive dysfunction theory associating reduction in executive control to abnormalities in structure and operational dysfunction of dopaminergic signaling networks. Nevertheless, executive functions are not always impaired in ADHD, and the literature describes other symptoms commonly reported suggesting individuals with ADHD would appear to suffer from a more general deficit. Another existing line of research, that has gained much attention recently, establishes that ADHD would have dysregulated states of brain arousal that would account for its commonly observed cognitive deficits and behavioral symptoms, described as the state regulation theory, which has now included measures of autonomic function. This article describes some important aspects that compose and challenge these two most influential theoretical constructs, executive dysfunction and state-regulation, based on their empirical evidence, implying the need to reevaluate the norms used to classify individuals and establish ADHD diagnosis. Large number of controversial results continue to exist within the study of ADHD biological and/or performance markers, possibly due to such heterogeneity and variability within the same diagnosis. The need to resolve these issues and establish newly revised diagnostic criteria for ADHD is critical, as therapeutic success depends on having accurately identified underlying neurophysiological factors in order to appropriately address them in treatment.

Retroaortic Anomalous Coronary Artery Visualization on Transthoracic Echocardiogram.

Incidental findings are not uncommon in echocardiography. A transthoracic echocardiogram (TTE) of an adult woman with arterial hypertension showed a tubular structure with hyperechoic walls in the atrial side of the atrioventricular groove in apical views. Coronary computed tomography angiography correlated this finding with a retroaortic course of the anomalous circumflex artery (retroaortic anomalous coronary artery [RAC], benign coronary artery variant). Recently described as the RAC sign on TTE, practitioners should be aware of this finding to avoid mistaken it as artifacts, catheters/leads, or calcified mitral annulus.

The medial olivocochlear reflex strength is modulated during a visual working memory task.

Top-down modulation of sensory responses to distracting stimuli by selective attention has been proposed as an important mechanism by which our brain can maintain relevant information during working memory tasks. Previous works in visual working memory (VWM) have reported modulation of neural responses to distracting sounds at different levels of the central auditory pathways. Whether these modulations occur also at the level of the auditory receptor is unknown. Here, we hypothesize that cochlear responses to irrelevant auditory stimuli can be modulated by the medial olivocochlear system during VWM. Twenty-one subjects (13 males, mean age 25.3 yr) with normal hearing performed a visual change detection task with different VWM load conditions (high load = 4 visual objects; low load = 2 visual objects). Auditory stimuli were presented as distractors and allowed the measurement of distortion product otoacoustic emissions (DPOAEs) and scalp auditory evoked potentials. In addition, the medial olivocochlear reflex strength was evaluated by adding contralateral acoustic stimulation. We found larger contralateral acoustic suppression of DPOAEs during the visual working memory period (n = 21) compared with control experiments (n = 10), in which individuals were passively exposed to the same experimental conditions. These results show that during the visual working memory period there is a modulation of the medial olivocochlear reflex strength, suggesting a possible common mechanism for top-down filtering of auditory responses during cognitive processes.NEW & NOTEWORTHY The auditory efferent system has been proposed to function as a biological filter of cochlear responses during selective attention. Here, we recorded electroencephalographic activity and otoacoustic emissions in response to auditory distractors during a visual working memory task in humans. We found that the olivocochlear efferent activity is modulated during the visual working memory period suggesting a common mechanism for suppressing cochlear responses during selective attention and working memory.

Electrophysiological Dynamics of Visual Speech Processing and the Role of Orofacial Effectors for Cross-Modal Predictions.

The human brain generates predictions about future events. During face-to-face conversations, visemic information is used to predict upcoming auditory input. Recent studies suggest that the speech motor system plays a role in these cross-modal predictions, however, usually only audio-visual paradigms are employed. Here we tested whether speech sounds can be predicted on the basis of visemic information only, and to what extent interfering with orofacial articulatory effectors can affect these predictions. We registered EEG and employed N400 as an index of such predictions. Our results show that N400's amplitude was strongly modulated by visemic salience, coherent with cross-modal speech predictions. Additionally, N400 ceased to be evoked when syllables' visemes were presented backwards, suggesting that predictions occur only when the observed viseme matched an existing articuleme in the observer's speech motor system (i.e., the articulatory neural sequence required to produce a particular phoneme/viseme). Importantly, we found that interfering with the motor articulatory system strongly disrupted cross-modal predictions. We also observed a late P1000 that was evoked only for syllable-related visual stimuli, but whose amplitude was not modulated by interfering with the motor system. The present study provides further evidence of the importance of the speech production system for speech sounds predictions based on visemic information at the pre-lexical level. The implications of these results are discussed in the context of a hypothesized trimodal repertoire for speech, in which speech perception is conceived as a highly interactive process that involves not only your ears but also your eyes, lips and tongue.

Recomendaciones para el uso de la hormona de crecimiento humana recombinante en pacientes pediátricos de talla baja en Colombia / Recommendations for treatment with recombinant human growth hormone in pediatric patients in Colombia

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Abstract In Colombia there are no guidelines for diagnosis and management of patients with short stature and for the use of recombinant human growth hormone, mainly caused by the diversity of training centers in pediatric endocrinology. In response to this situation, the Asociación Colegio Colombiana de Endocrinología Pediátrica leds the first colombian short stature expert committee in order to standardize the use of human recombinant growth hormone. This work had the participation and endorsement of a consortium of clinical experts representing the Sociedad Colombiana de Pediatría, Secretaría Distrital de Salud de Bogotá- Subred Integrada de Servicios de Salud Suroccidente, Fundación Universitaria Sanitas, Universidad de los Andes and some public and private health institutions in the country, in addition to the participation of methodological experts from the Instituto Global de Excelencia Clínica Keralty. By reviewing the literature and with the best available evidence, we proposed to unify definitions, a diagnostic algorithm, biochemical and dynamic tests with their reference parameters, a description of the considerations about growth hormone use among the indications approved by regulatory agency for medications and food in Colombia and finally a proposal for an informed consent and a medication fact sheet available for parents and patients.

Influence of violent contexts on facial reactions elicited by angry and neutral faces.

This study focuses on determining whether violent contexts influence the perception of aggressiveness in faces analysing spontaneous corrugator supercilii activity. Participants viewed pictures of neutral and angry faces preceded by a contextual sentence describing either violent or neutral actions. They were instructed to judge each face according to whether it was aggressive or non-aggressive. Results show a higher level of perceived aggressiveness for neutral faces preceded by violent contexts, accompanied by longer reaction times, and a significant increase of corrugator activity. Angry faces preceded by neutral contexts were judged as less aggressive and elicited less corrugator activity. In conclusion, our results provide evidence that facial reactions and aggressiveness judgment for faces are context-dependent. With this work, we contribute to the view that contextual cues guide the face's emotional meaning, under top-down processing.

Neurocognitive mechanisms underlying working memory encoding and retrieval in Attention-Deficit/Hyperactivity Disorder.

Working memory (WM) impairments in ADHD have been consistently reported along with deficits in attentional control. Yet, it is not clear which specific WM processes are affected in this condition. A deficient coupling between attention and WM has been reported. Nevertheless, most studies focus on the capacity to retain information rather than on the attention-dependent stages of encoding and retrieval. The current study uses a visual short-term memory binding task, measuring both behavioral and electrophysiological responses to characterize WM encoding, binding and retrieval comparing ADHD and non-ADHD matched adolescents. ADHD exhibited poorer accuracy and larger reaction times than non-ADHD on all conditions but especially when a change across encoding and test displays occurred. Binding manipulation affected equally both groups. Encoding P3 was larger in the non-ADHD group. Retrieval P3 discriminated change only in the non-ADHD group. Binding-dependent ERP modulations did not reveal group differences. Encoding and retrieval P3 were significantly correlated only in non-ADHD. These results suggest that while binding processes seem to be intact in ADHD, attention-related encoding and retrieval processes are compromised, resulting in a failure in the prioritization of relevant information. This new evidence can also inform recent theories of binding in visual WM.

Data from brain activity during visual working memory replicates the correlation between contralateral delay activity and memory capacity.

This article provides data from statistical analysis of event-related brain potentials (ERPs) and behavioural performance from 23 participants during a working memory task. Specifically, we used the change detection task from Vogel 2004, using the same timing but a modified size and distance between stimuli. Contralateral delay activity (CDA) was calculated from posterior parieto-occipital electrodes and then it was compared between conditions with different memory load (one, two and four items). Working memory capacity (WMC) was calculated from behavioural data using the formula developed by Pashler (1988). Correlation was performed between WMC and the CDA amplitude difference (from two to four items). The correlation replicates the results from the original paper of Vogel 2004 [1], even though some parameters are different from the original design.

Humor Improves Women's but Impairs Men's Iowa Gambling Task Performance.

The Iowa Gambling Task (IGT) is a popular method for examining real-life decision-making. Research has shown gender related differences in performance, in that men consistently outperform women. It has been suggested that these performance differences are related to decreased emotional control in women compared to men. Given the likely role of emotion in these gender differences, in the present study, we examine the effect of a humor induction on IGT performance and whether the effect of humor is moderated by gender. IGT performance and parameters from the Expectancy Valence Model (EVM) were measured in 68 university students (34 men; mean age 22.02, SD = 4.3 and 34 women; mean age 22.3, SD = 4.1) during a 100 trial-IGT task. Participants were exposed to a brief video before each of the IGT decisions available; one half of the samples (17 men and 17 women) was exposed to 100 humor videos, while the other half was exposed to 100 non-humor videos during the task. We observed a significant interaction between gender and humor, such that under humor, women's performance during the last block (trials 80-100) improved (compared to women under non-humor), whereas men's performance during the last block was worse (compared to men under non-humor). Consistent with previous work, under non-humor, men outperformed women in the last block. Lastly, our EVM results show that humor impacts the learning mechanisms of decision-making differently in men and women. Humor impaired men's ability to acquire knowledge about the payoff structure of the decks, and as a consequence, they were stuck in suboptimal performance. On the other hand, humor facilitated women's ability to explore and to learn from experience, improving performance. These findings deepen our understanding of the mechanisms underlying IGT decision-making and differential effects of humor in men and women.

Origin and evolution of human speech: Emergence from a trimodal auditory, visual and vocal network.

In recent years, there have been important additions to the classical model of speech processing as originally depicted by the Broca-Wernicke model consisting of an anterior, productive region and a posterior, perceptive region, both connected via the arcuate fasciculus. The modern view implies a separation into a dorsal and a ventral pathway conveying different kinds of linguistic information, which parallels the organization of the visual system. Furthermore, this organization is highly conserved in evolution and can be seen as the neural scaffolding from which the speech networks originated. In this chapter we emphasize that the speech networks are embedded in a multimodal system encompassing audio-vocal and visuo-vocal connections, which can be referred to an ancestral audio-visuo-motor pathway present in nonhuman primates. Likewise, we propose a trimodal repertoire for speech processing and acquisition involving auditory, visual and motor representations of the basic elements of speech: phoneme, observation of mouth movements, and articulatory processes. Finally, we discuss this proposal in the context of a scenario for early speech acquisition in infants and in human evolution.

Enhanced response inhibition and reduced midfrontal theta activity in experienced Vipassana meditators.

Response inhibition - the ability to suppress inappropriate thoughts and actions - is a fundamental aspect of cognitive control. Recent research suggests that mental training by meditation may improve cognitive control. Yet, it is still unclear if and how, at the neural level, long-term meditation practice may affect (emotional) response inhibition. The present study aimed to address this outstanding question, and used an emotional Go/Nogo task and electroencephalography (EEG) to examine possible differences in behavioral and electrophysiological indices of response inhibition between Vipassana meditators and an experience-matched active control group (athletes). Behaviorally, meditators made significantly less errors than controls on the emotional Go/Nogo task, independent of the emotional context, while being equally fast. This improvement in response inhibition at the behavioral level was accompanied by a decrease in midfrontal theta activity in Nogo vs. Go trials in the meditators compared to controls. Yet, no changes in ERP indices of response inhibition, as indexed by the amplitude of the N2 and P3 components, were observed. Finally, the meditators subjectively evaluated the emotional pictures lower in valence and arousal. Collectively, these results suggest that meditation may improve response inhibition and control over emotional reactivity.

Emotional Influences on Cognitive Flexibility Depend on Individual Differences: A Combined Micro-Phenomenological and Psychophysiological Study.

Imagine a scenario where you are cooking and suddenly, the contents of the pot start to come out, and the oven bell rings. You would have to stop what you are doing and start responding to the changing demands, switching between different objects, operations and mental sets. This ability is known as cognitive flexibility. Now, add to this scenario a strong emotional atmosphere that invades you as you spontaneously recall a difficult situation you had that morning. How would you behave? Recent studies suggest that emotional states do modulate cognitive flexibility, but these findings are still controversial. Moreover, there is a lack of evidence regarding the underlying brain processes. The purpose of the present study was, therefore, to examine such interaction while monitoring changes in ongoing cortical activity using EEG. In order to answer this question, we used two musical stimuli to induce emotional states (positive/high arousal/open stance and negative/high arousal/closed stance). Twenty-nine participants performed two blocks of the Madrid Card Sorting Task in a neutral silence condition and then four blocks while listening to the counterbalanced musical stimuli. To explore this interaction, we used a combination of first-person (micro-phenomenological interview) and third-person (behavior and EEG) approaches. Our results show that compared to the positive stimuli and silence condition, negative stimuli decrease reaction times (RTs) for the shift signal. Our data show that the valance of the first emotional block is determinant in the RTs of the subsequent blocks. Additionally, the analysis of the micro-phenomenological interview and the integration of first- and third-person data show that the emotional disposition generated by the music could facilitate task performance for some participants or hamper it for others, independently of its emotional valence. When the emotional disposition hampered task execution, RTs were slower, and the P300 potential showed a reduced amplitude compared to the facilitated condition. These findings show that the interaction between emotion and cognitive flexibility is more complex than previously thought and points to a new way of understanding the underlying mechanisms by incorporating an in-depth analysis of individual subjective experience.

Beta Oscillations Distinguish Between Two Forms of Mental Imagery While Gamma and Theta Activity Reflects Auditory Attention.

Visual sensory processing of external events decreases when attention is internally oriented toward self-generated thoughts and also differences in attenuation have been shown depending on the thought's modality (visual or auditory thought). The present study aims to assess whether such modulations occurs also in auditory modality. In order to investigate auditory sensory modulations, we compared a passive listening condition with two conditions in which attention was internally oriented as a part of a task; a visual imagery condition and an inner speech condition. EEG signal was recorded from 20 participants while they were exposed to auditory probes during these three conditions. ERP results showed no differences in N1 auditory response comparing the three conditions reflecting maintenance of evoked electrophysiological reactivity for auditory modality. Nonetheless, time-frequency analyses showed that gamma and theta power in frontal regions was higher for passive listening than for internal attentional conditions. Specifically, the reduced amplitude in early gamma and theta band during both inward attention conditions may reflect reduced conscious attention of the current auditory stimulation. Finally, different pattern of beta band activity was observed only during visual imagery which can reflect cross-modal integration between visual and auditory modalities and it can distinguish this form of mental imagery from the inner speech. Taken together, these results showed that attentional suppression mechanisms in auditory modality are different from visual modality during mental imagery processes. Our results about oscillatory activity also confirm the important role of gamma oscillations in auditory processing and the differential neural dynamics underlying the visual and auditory/verbal imagery.

Mood Detection in Ambiguous Messages: The Interaction Between Text and Emoticons.

Face-to-face communication has several sources of contextual information that enables language comprehension. This information is used, for instance, to perceive mood of interlocutors, clarifying ambiguous messages. However, these contextual cues are absent in text-based communication. Emoticons have been proposed as cues used to stress the emotional intentions on this channel of communication. Most studies have suggested that their role is to contribute to a more accurate perception of emotions. Nevertheless, it is not clear if their influence on disambiguation is independent of their emotional valence and its interaction with text message valence. In the present study, we designed an emotional congruence paradigm, where participants read a set of messages composed by a positive or negative emotional situation sentence followed by a positive or negative emoticon. Participants were instructed to indicate if the sender was in a good or bad mood. With the aim of analyzing the disambiguation process and observing if the role of the emoticons in disambiguation is different according their valence, we measure the rate of responses of perceived mood and the reaction times (RTs) for each condition. Our results showed that the perceived mood in ambiguous messages tends to be more negative regardless of emotion valence. Nonetheless, we observed that this tendency was not the same for positive and negative emoticons. Specifically, negative mood perception was higher for incongruent positive emoticons. On the other hand, RTs for positive emoticons were faster than for the negative ones. Responses for incongruent messages were slower than for the congruent ones. However, the incongruent condition showed different RTs depending on the emoticons' valence. In the incongruent condition, responses for negative emoticons was the slowest. Results are discussed taking into account previous observations about the potential role of emoticons in mood perception and cognitive processing. We concluded that the role of emoticons in disambiguation and mood perception is due to the interaction of emoticon valence with the entire message.

Modeling Search Behaviors during the Acquisition of Expertise in a Sequential Decision-Making Task.

Our daily interaction with the world is plagued of situations in which we develop expertise through self-motivated repetition of the same task. In many of these interactions, and especially when dealing with computer and machine interfaces, we must deal with sequences of decisions and actions. For instance, when drawing cash from an ATM machine, choices are presented in a step-by-step fashion and a specific sequence of choices must be performed in order to produce the expected outcome. But, as we become experts in the use of such interfaces, is it possible to identify specific search and learning strategies? And if so, can we use this information to predict future actions? In addition to better understanding the cognitive processes underlying sequential decision making, this could allow building adaptive interfaces that can facilitate interaction at different moments of the learning curve. Here we tackle the question of modeling sequential decision-making behavior in a simple human-computer interface that instantiates a 4-level binary decision tree (BDT) task. We record behavioral data from voluntary participants while they attempt to solve the task. Using a Hidden Markov Model-based approach that capitalizes on the hierarchical structure of behavior, we then model their performance during the interaction. Our results show that partitioning the problem space into a small set of hierarchically related stereotyped strategies can potentially capture a host of individual decision making policies. This allows us to follow how participants learn and develop expertise in the use of the interface. Moreover, using a Mixture of Experts based on these stereotyped strategies, the model is able to predict the behavior of participants that master the task.