Reduced threat avoidance but increased stress induced approach bias in women taking oral contraceptives.

Recent research has increasingly acknowledged the impact of oral contraceptives on affective behavior and stress responses; however, the underlying mechanisms are still not well understood. Studies have previously shown that steroid hormones modulate automatic approach and avoidance behavior. Here, we thus investigated the effects of oral contraceptives on approach and avoidance behavior and whether these effects are modulated by stress. The study comprised 130 female participants, half of whom were using oral contraceptives, while the other half were not using any hormonal contraception (NC). The participants completed the Approach Avoidance Task (AAT), which measures automatic approach and avoidance behavior to socio-affective signals. The AAT was run once before and once after a stress manipulation using the Socially Evaluated Cold Pressor Test. OC users showed absent avoidance behavior to social threat signals and a stress-induced increase in approach behavior to positive social signals. The latter was found in particular in women taking androgenic acting OC, demonstrating that different OC preparations need to be taken into account in research on OC effects. However, OC and NC group did not differ in their cortisol stress response. Overall, the results suggest that OC usage impacts on approach and avoidance behavior to social signals, which might also contribute to the development of affective side effects.

Slips of the tongue in patients with Gilles de la Tourette syndrome.

BACKGROUND: Motor and vocal tics are the main symptom of Gilles de la Tourette-syndrome (GTS). A particular complex vocal tic comprises the utterance of swear words, termed coprolalia. Since taboo words are socially inappropriate, they are normally suppressed by people, which implies cognitive control processes. METHOD: To investigate the control of the unintentional pronunciation of taboo words and the associated processes of conflict monitoring, we used the "Spoonerisms of Laboratory Induced Predisposition" (SLIP) paradigm. Participants read multiple inductor word pairs with the same phonemes, followed by pronouncing a target pair with inverse phonemes. This led to a conflict between two competing speech plans: the correct word pair and the word pair with inverted phonemes. Latter speech error, a spoonerism, could result in a neutral or taboo word. We investigated 19 patients with GTS and 23 typically developed controls (TDC) and measured participants' electroencephalography (EEG) during the SLIP task. RESULTS: At the behavioral level less taboo than neutral word spoonerisms occurred in both groups without significant differences. Event-related brain potentials (ERP) revealed a difference between taboo and neutral word conditions in the GTS group at the midline electrodes in a time range of 250-400 ms after the speech prompt, which was not found in the TDC group. The extent of this effect depended on the number of inductor word pairs, suggesting an increasing level of cognitive control in the GTS group. CONCLUSION: The differences between taboo and neutral word conditions in patients with GTS compared to TDC suggest an altered recruitment of cognitive control processes in GTS, likely enlisted to suppress taboo words.

Trajectories and contributing factors of neural compensation in healthy and pathological aging.

Neural degeneration is a hallmark of healthy aging and can be associated with specific cognitive impairments. However, neural degeneration per se is not matched by unremitting declines in cognitive abilities. Instead, middle-aged and older adults typically maintain surprisingly high levels of cognitive functioning, suggesting that the human brain can adapt to structural degeneration by neural compensation. Here, we summarize prevailing theories and recent empirical studies on neural compensation with a focus on often neglected contributing factors, such as lifestyle, metabolism and neural plasticity. We suggest that these factors moderate the relationship between structural integrity and neural compensation, maintaining psychological well-being and behavioral functioning. Finally, we discuss that a breakdown in neural compensation may pose a tipping point that distinguishes the trajectories of healthy vs pathological aging, but conjoint support from psychology and cognitive neuroscience for this alluring view is still scarce. Therefore, future experiments that target the concomitant processes of neural compensation and associated behavior will foster a comprehensive understanding of both healthy and pathological aging.

Neural, physiological and behavioural correlates of empathy for pain in Tourette syndrome.

Persons with Tourette syndrome show altered social behaviours, such as echophenomena and increased personal distress in emotional situations. These symptoms may reflect an overactive mirror neuron system, causing both increased automatic imitation and a stronger tendency to share others' emotions. To test this, we measured the individual level of echophenomena with a video protocol and experimentally induced empathy for pain in 21 participants with Tourette syndrome and 25 matched controls. In the empathy for pain paradigm, pictures of hands and feet in painful or neutral situations were presented, while we measured participants' EEG and skin conductance response. Changes in somatosensory mu suppression during the observation of the pictures and pain ratings were compared between groups, and correlations were calculated with the occurrence of echophenomena, self-reported empathy and clinical measures. Our Tourette syndrome sample showed significantly more echophenomena than controls, but the groups showed no behavioural differences in empathic abilities. However, controls, but not patients with Tourette syndrome, showed the predicted increased mu suppression when watching painful compared to neutral actions. While echophenomena were present in all persons with Tourette syndrome, the hypothesis of an overactive mirror neuron system in Tourette syndrome could not be substantiated. On the contrary, the Tourette syndrome group showed a noticeable lack of mu attenuation in response to pain stimuli. In conclusion, we found a first hint of altered processing of others' emotional states in a brain region associated with the mirror neuron system.

Effects of social presence on behavioral, neural, and physiological aspects of empathy for pain.

In mediated interactions (e.g. video calls), less information is available about the other. To investigate how this affects our empathy for one another, we conducted an electroencephalogram study, in which 30 human participants observed 1 of 5 targets undergoing painful electric stimulation, once in a direct interaction and once in a live, video-mediated interaction. We found that observers were as accurate in judging others' pain and showed as much affective empathy via video as in a direct encounter. While mu suppression, a common neural marker of empathy, was not sensitive to others' pain, theta responses to others' pain as well as skin conductance coupling between participants were reduced in the video-mediated condition. We conclude that physical proximity with its rich social cues is important for nuanced physiological resonance with the other's experience. More studies are warranted to confirm these results and to understand their behavioral significance for remote social interactions.

Aggressive and psychopathic traits are linked to the acquisition of stable but imprecise hostile expectations.

Individuals with hostile expectations (HEX) anticipate harm from seemingly neutral or ambiguous stimuli. However, it is unclear how HEX are acquired, and whether specific components of HEX learning can predict antisocial thought, conduct, and personality. In an online sample of healthy young individuals (n = 256, 69% women), we administered a virtual shooting task and applied computational modelling of behaviour to investigate HEX learning and its constellation of correlates. HEX acquisition was best explained by a hierarchical reinforcement learning mechanism. Crucially, we found that individuals with relatively higher self-reported aggressiveness and psychopathy developed stronger and less accurate hostile beliefs as well as larger prediction errors. Moreover, aggressive and psychopathic traits were associated with more temporally stable hostility representations. Our study thus shows that aggressiveness and psychopathy are linked with the acquisition of robust yet imprecise hostile beliefs through reinforcement learning.

Studying trait-characteristics and neural correlates of the emotional ego- and altercentric bias using an audiovisual paradigm.

In social interactions, emotional biases can arise when the emotional state of oneself and another person are incongruent. A person's ability to judge the other's emotional state can then be biased by their own emotional state, leading to an emotional egocentric bias (EEB). Alternatively, a person's perception of their own emotional state can be biased by the other's emotional state leading to an emotional altercentric bias (EAB). Using a modified audiovisual paradigm, we examined in three studies (n = 171; two online & one lab-based study) whether emotional biases can be considered traits by measuring two timepoints within participant and relating empathy trait scores to emotional biases, as well as the electrophysiological correlates of emotional biases. In all studies, we found a congruency effect, reflecting an EEB and EAB of small size. Both biases failed to correlate significantly within participants across timepoints and did not display significant relationships with empathy trait scores. On the electrophysiological level, we did not find any neural emotional bias effects in the time-frequency domain. Our results suggest that EEB and EAB effects are strongly task sensitive. Caution is warranted when studying interindividual differences in emotional biases using this paradigm, as they did not show significant test-retest reliabilities.

Is sex still binary?

In this perspective article we discuss the limitations of sex as a binary concept and how it is challenged by medical developments and a better understanding of gender diversity. Recent data indicate that sex is not a simple binary classification based solely on genitalia at birth or reproductive capacity but encompasses various biological characteristics such as chromosomes, hormones, and secondary sexual characteristics. The existence of individuals with differences in sex development (DSD) who do not fit typical male or female categories further demonstrates the complexity of sex. We argue that the belief that sex is strictly binary based on gametes is insufficient, as there are multiple levels of sex beyond reproductivity. We also explore the role of sex in sex determination, gene expression, brain development, and behavioural patterns and emphasize the importance of recognizing sex diversity in personalized medicine, as sex can influence disease presentation, drug response, and treatment effectiveness. Finally, we call for an inter- and transdisciplinary approach to study sex diversity and develop new categories and methodologies that go beyond a binary model.

Association of stress-related neural activity and baseline interleukin-6 plasma levels in healthy adults.

Several studies suggest a link between acute changes in inflammatory parameters due to an endotoxin or (psychological) stressor and the brain's stress response. The extent to which basal circulating levels of inflammatory markers are associated with the brain's stress response has been hardly investigated so far. In the present study, baseline plasma levels of the cytokine interleukin (IL)-6 were obtained and linked to neural markers of psychosocial stress using a modified version of the Montreal Imaging Stress Task in a sample of N = 65 healthy subjects (N = 39 female). Of three a-priori defined regions of interest - the amygdala, anterior insula, and anterior cingulate cortex - baseline IL-6 was significantly and negatively associated with stress-related neural activation in the right amygdala and left anterior insula. Our results suggest that baseline cytokines might be related to differences in the neural stress response and that this relationship could be inverse to that previously reported for induced acute changes in inflammation markers.

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): third Paediatric (Paedi-EUROMACS) report.

OBJECTIVES: A third paediatric report has been generated from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). The purpose of EUROMACS, which is operated by the European Association for Cardio-Thoracic Surgery, is to gather data related to durable mechanical circulatory support for scientific purposes and to publish reports with respect to the course of mechanical circulatory support therapy. Since the first report issued, efforts to increase compliance and participation have been extended. Additionally, the data provided the opportunity to analyse patients of younger age and lower weight. METHODS: Participating hospitals contributed pre-, peri- and long-term postoperative data on mechanical circulatory support implants to the registry. Data for all implants in paediatric patients (<19 years of age) performed from 1 January 2000 to 31 December 2020 were analysed. This report includes updates of patient characteristics, implant frequency, outcome (including mortality rates, transplants and recovery rates) as well as adverse events including neurological dysfunction, device malfunction, major infection and bleeding. RESULTS: Twenty-five hospitals contributed 537 registered implants in 480 patients. The most frequent aetiology of heart failure was any form of cardiomyopathy (59%), followed by congenital heart disease and myocarditis (15% and 14%, respectively). Competing outcomes analysis revealed that a total of 86% survived to transplant or recovery or are ongoing; at the 2-year follow-up examination, 21.9% died while on support. At 12 months, 45.1% received transplants, 7.5% were weaned from their device and 20.8% died. The 3-month adverse events rate was 1.59 per patient-year for device malfunction including pump exchange, 0.7 for major bleeding, 0.78 for major infection and 0.71 for neurological events. CONCLUSIONS: The overall survival rate was 79.2% at 12 months following ventricular assist device implant. The comparison of survival rates of the early and later eras shows no significant difference. A focus on specific subgroups showed that survival was less in patients of younger age (<1 year of age; P = 0.01) and lower weight (<20 kg; P = 0.015). Transplant rates at 6 months continue to be low (33.2%).

Abnormal processing of interpersonal cues during an aggressive encounter in women with borderline personality disorder: Neural and behavioral findings.

Inappropriate aggression is a prominent and clinically relevant interpersonal dysfunction of individuals with borderline personality disorder (BPD). Previous studies have shown that individuals with BPD interpret interpersonal signals in a hostile manner, but it is uncertain how this negativity bias impacts decision-making during aggressive encounters. In the present neuroimaging study, 48 medication-free women with BPD and 28 age- and intelligence-matched women played the Social Threat Aggression Paradigm (STAP), a competitive reaction time task in which the winner delivers an aversive sound blast to the loser. Crucially, in the STAP the alleged opponent displays either an angry or neutral facial expression at the beginning of each trial and selects increasingly loud blasts in order to provoke participants. Relative to healthy controls, women with BPD differentiated less between angry and neutral facial expressions, both in terms of aggressive behavior and of activity in medial prefrontal cortex, amygdala, and temporal pole. On the one hand, and contrary to our hypotheses, neural and behavioral responses to angry faces were reduced in women with BPD compared to healthy women. On the other hand, provocation heightened subsequent amygdala responses to neutral faces in BPD, and this was in turn associated with aggressive behavior, supporting a default negativity bias in BPD. The neurocognitive processes by which these alterations might guide aggressive behavior irrespective of interpersonal cues are presented and discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Social Context and Rejection Expectations Modulate Neural and Behavioral Responses to Social Feedback.

When meeting other people, some are optimistic and expect to be accepted by others, whereas others are pessimistic and expect mostly rejections. How social feedback is evaluated in situations that meet or do not meet these biases and how people differ in their response to rejection and acceptance depending on the social situation are unknown. In this study, participants experienced rejection and acceptance by peers in two different social contexts, one with high (negative context) and the other with low probability of rejection (positive context). We examined how the neural and behavioral responses to rejection are altered by this context and whether it depends on the individual's sensitivity to rejection. Behavioral results show that, on average, people maintain an optimistic bias even when mostly experiencing rejection. Importantly, personality differences in rejection sensitivity affected both prior expectations to be rejected in the paradigm and the extent to which expectations changed during the paradigm. The context also strongly modulated ERPs and theta responses to rejection and acceptance feedback. Specifically, valence effects on neural responses were enhanced in the negative context, suggesting a greater relevance to monitor social feedback in such a situation. Moreover, midfrontal theta predicted how expectations were changed in response to prediction errors, stressing a role for theta in learning from social feedback. Surprisingly, interindividual differences in rejection sensitivity did not affect neural responses to feedback. Our results stress the importance of considering the interaction between subjective expectations and the social context for behavioral and neural responses to social rejection.

Structural covariance of amygdala subregions is associated with trait aggression and endogenous testosterone in healthy individuals.

Many studies point toward volume reductions in the amygdala as a potential neurostructural marker for trait aggression. However, most of these findings stem from clinical samples, rendering unclear whether the findings generalize to non-clinical populations. Furthermore, the notion of neural networks suggests that interregional correlations in gray matter volume (i.e., structural covariance) can explain individual differences in aggressive behavior beyond local univariate associations. Here, we tested whether structural covariance between amygdala subregions and the rest of the brain is associated with self-reported aggression in a large sample of healthy young students (n = 263; 49% women). Salivary testosterone concentrations were measured for a subset of n = 40 male and n = 36 female subjects, allowing us to investigate the influence of endogenous testosterone on structural covariance. Aggressive individuals showed enhanced covariance between left superficial amygdala (SFA) and left dorsal anterior insula (dAI), but lower covariance between right laterobasal amygdala (LBA) and right dorsolateral prefrontal cortex (dlPFC). These structural patterns overlap with functional networks involved in the genesis and regulation of aggressive behavior, respectively. With increasing endogenous testosterone, we observed stronger structural covariance between right centromedial amygdala (CMA) and right medial prefrontal cortex in men and between left CMA and bilateral orbitofrontal cortex in women. These results speak for structural covariance of amygdala subregions as a robust correlate of trait aggression in healthy individuals. Moreover, regions that showed structural covariance with the amygdala modulated by either testosterone or aggression did not overlap, suggesting a complex role of testosterone in human social behavior beyond facilitating aggressiveness.

Validity and Prognostic Value of a Polygenic Risk Score for Parkinson's Disease.

Idiopathic Parkinson's disease (PD) is a complex multifactorial disorder caused by the interplay of both genetic and non-genetic risk factors. Polygenic risk scores (PRSs) are one way to aggregate the effects of a large number of genetic variants upon the risk for a disease like PD in a single quantity. However, reassessment of the performance of a given PRS in independent data sets is a precondition for establishing the PRS as a valid tool to this end. We studied a previously proposed PRS for PD in a separate genetic data set, comprising 1914 PD cases and 4464 controls, and were able to replicate its ability to differentiate between cases and controls. We also assessed theoretically the prognostic value of the PD-PRS, i.e., its ability to predict the development of PD in later life for healthy individuals. As it turned out, the PD-PRS alone can be expected to perform poorly in this regard. Therefore, we conclude that the PD-PRS could serve as an important research tool, but that meaningful PRS-based prognosis of PD at an individual level is not feasible.

Intact Proactive Motor Inhibition after Unilateral Prefrontal Cortex or Basal Ganglia Lesions.

Previous research provided evidence for the critical importance of the PFC and BG for reactive motor inhibition, that is, when actions are cancelled in response to external signals. Less is known about the role of the PFC and BG in proactive motor inhibition, referring to preparation for an upcoming stop signal. In this study, patients with unilateral lesions to the BG or lateral PFC performed in a cued go/no-go task, whereas their EEG was recorded. The paradigm called for cue-based preparation for upcoming, lateralized no-go signals. Based on previous findings, we focused on EEG indices of cognitive control (prefrontal beta), motor preparation (sensorimotor mu/beta, contingent negative variation [CNV]), and preparatory attention (occipital alpha, CNV). On a behavioral level, no differences between patients and controls were found, suggesting an intact ability to proactively prepare for motor inhibition. Patients showed an altered preparatory CNV effect, but no other differences in electrophysiological activity related to proactive and reactive motor inhibition. Our results suggest a context-dependent role of BG and PFC structures in motor inhibition, being critical in reactive, unpredictable contexts, but less so in situations where one can prepare for stopping on a short timescale.

Patients with Ventromedial Prefrontal Lesions Show an Implicit Approach Bias to Angry Faces.

Damage to the ventromedial PFC (VMPFC) can cause maladaptive social behavior, but the cognitive processes underlying these behavioral changes are still uncertain. Here, we tested whether patients with acquired VMPFC lesions show altered approach-avoidance tendencies to emotional facial expressions. Thirteen patients with focal VMPFC lesions and 31 age- and gender-matched healthy controls performed an implicit approach-avoidance task in which they either pushed or pulled a joystick depending on stimulus color. Whereas controls avoided angry faces, VMPFC patients displayed an incongruent response pattern characterized by both increased approach and reduced avoidance of angry facial expressions. The approach bias was stronger in patients with higher self-reported impulsivity and disinhibition and in those with larger lesions. We further used linear ballistic accumulator modeling to investigate latent parameters underlying approach-avoidance decisions. Controls displayed negative drift rates when approaching angry faces, whereas VMPFC lesions abolished this pattern. In addition, VMPFC patients had weaker response drifts than controls during avoidance. Finally, patients showed reduced drift rate variability and shorter nondecision times, indicating impulsive and rigid decision-making. Our findings thus suggest that VMPFC damage alters the pace of evidence accumulation in response to social signals, eliminating a default, protective avoidant bias and facilitating a dysfunctional approach behavior.

Motor Sequence Learning Deficits in Idiopathic Parkinson's Disease Are Associated With Increased Substantia Nigra Activity.

Previous studies have shown that persons with Parkinson's disease (pwPD) share specific deficits in learning new sequential movements, but the neural substrates of this impairment remain unclear. In addition, the degree to which striatal dopaminergic denervation in PD affects the cortico-striato-thalamo-cerebellar motor learning network remains unknown. We aimed to answer these questions using fMRI in 16 pwPD and 16 healthy age-matched control subjects while they performed an implicit motor sequence learning task. While learning was absent in both pwPD and controls assessed with reaction time differences between sequential and random trials, larger error-rates during the latter suggest that at least some of the complex sequence was encoded. Moreover, we found that while healthy controls could improve general task performance indexed by decreased reaction times across both sequence and random blocks, pwPD could not, suggesting disease-specific deficits in learning of stimulus-response associations. Using fMRI, we found that this effect in pwPD was correlated with decreased activity in the hippocampus over time. Importantly, activity in the substantia nigra (SN) and adjacent bilateral midbrain was specifically increased during sequence learning in pwPD compared to healthy controls, and significantly correlated with sequence-specific learning deficits. As increased SN activity was also associated (on trend) with higher doses of dopaminergic medication as well as disease duration, the results suggest that learning deficits in PD are associated with disease progression, indexing an increased drive to recruit dopaminergic neurons in the SN, however, unsuccessfully. Finally, there were no differences between pwPD and controls in task modulation of the cortico-striato-thalamo-cerebellar network. However, a restricted nigral-striatal model showed that negative modulation of SN to putamen connection was larger in pwPD compared to controls during random trials, while no differences between the groups were found during sequence learning. We speculate that learning-specific SN recruitment leads to a relative increase in SN- > putamen connectivity, which returns to a pathological reduced state when no learning takes place.

A Multi-center Genome-wide Association Study of Cervical Dystonia.

BACKGROUND: Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibility. OBJECTIVE: To identify robust genetic variants and loci in a large multicenter cervical dystonia cohort using a genome-wide approach. METHODS: We performed a genome-wide association study using cervical dystonia samples from the Dystonia Coalition. Logistic and linear regressions, including age, sex, and population structure as covariates, were employed to assess variant- and gene-based genetic associations with disease status and age at onset. We also performed a replication study for an identified genome-wide significant signal. RESULTS: After quality control, 919 cervical dystonia patients compared with 1491 controls of European ancestry were included in the analyses. We identified one genome-wide significant variant (rs2219975, chromosome 3, upstream of COL8A1, P-value 3.04 × 10-8 ). The association was not replicated in a newly genotyped sample of 473 cervical dystonia cases and 481 controls. Gene-based analysis identified DENND1A to be significantly associated with cervical dystonia (P-value 1.23 × 10-6 ). One low-frequency variant was associated with lower age-at-onset (16.4 ± 2.9 years, P-value = 3.07 × 10-8 , minor allele frequency = 0.01), located within the GABBR2 gene on chromosome 9 (rs147331823). CONCLUSION: The genetic underpinnings of cervical dystonia are complex and likely consist of multiple distinct variants of small effect sizes. Larger sample sizes may be needed to provide sufficient statistical power to address the presumably multi-genic etiology of cervical dystonia. © 2021 International Parkinson and Movement Disorder Society.

Alpha oscillations modulate premotor-cerebellar connectivity in motor learning: Insights from transcranial alternating current stimulation.

Alpha oscillations (8-13 Hz) have been suggested to play an important role in dynamic neural processes underlying learning and memory. The goal of this study was to scrutinize the role of alpha oscillations in communication within a cortico-cerebellar network implicated in motor sequence learning. To this end, we conducted two EEG experiments using a serial reaction time task. In the first experiment, we explored changes in alpha power and cross-channel alpha coherence as subjects learned a motor sequence. We found a gradual decrease in spectral alpha power over left premotor cortex (PMC) and sensorimotor cortex (SM1) during learning blocks. In addition, alpha coherence between left PMC/SM1 and left cerebellar crus I was specifically decreased during sequence learning, possibly reflecting a functional decoupling in the broader motor learning network. In the second experiment in a different cohort, we applied 10Hz transcranial alternating current stimulation (tACS), a method shown to entrain local oscillatory activity, to left M1 (lM1) and right cerebellum (rCB) during sequence learning. We observed a tendency for diminished learning following rCB tACS compared to sham, but not following lM1 tACS. Learning-related alpha power following rCB tACS was increased in left PMC, possibly reflecting increase in local inhibitory neural activity. Importantly, learning-specific alpha coherence between left PMC and right cerebellar lobule VIIb was enhanced following rCB tACS. These findings provide strong evidence for a causal role of alpha oscillations in controlling information transfer in a premotor-cerebellar loop during motor sequence learning. Our findings are consistent with a model in which sequence learning may be impaired by enhancing premotor cortical alpha oscillation via external modulation of cerebellar oscillations.