Interoceptive cardiac signals selectively enhance fear memories

Fear is coupled to states of physiological arousal. We tested how learning and memory of threat, i.e. conditioned fear, is influenced by interoceptive signals. Forty healthy individuals were exposed to two threat (CS+, paired with electrocutaneous shocks) and two safety (CS-) stimuli, specifically time-locked to either cardiac ventricular systole (when arterial baroreceptors signal cardiovascular arousal to brainstem), or diastole (when these afferent signals are quiescent). Threat learning was indexed objectively using skin conductance responses (SCRs). During acquisition of threat contingencies, cardiac effects dominated: Stimuli (both CS+ and CS-) presented at systole evoked greater SCR responses, relative to stimuli (both CS+ and CS-) presented at diastole. This difference was amplified in more anxious individuals. Learning of conditioned fear was established by the end of the acquisition phase, which was followed by an extinction phase when unpaired CSs were presented at either the same or switched cardiac contingencies. One day later, electrocutaneous shocks triggered the reinstatement of fear responses. Subsequent presentation of stimuli previously encoded at systole evoked higher SCRs. Moreover, only those participants for whom stimuli had the same cardiac-contingency over both acquisition and extinction phases retained conditioned fear memory (i.e. CS + > CS-). Our findings reveal two important cardiac afferent effects on threat learning and memory: 1) Cardiac signals bias processing towards threat. 2) Cardiac signals are a context for fear memory; altering this context can disrupt the memory. These observations suggest how threat reactivity may be reinforced and maintained by both acute and enduring states of cardiac arousal

Facilitating stress prevention in micro and small-sized enterprises:Protocol for a mixed method study to evaluate the effectiveness and implementation process of targeted web-based interventions

BACKGROUND: Workplace-related stress is a major risk factor for mental and physical health problems and related sickness absence and productivity loss. Despite evidence regarding the effectiveness of different workplace-based interventions, the implementation of stress prevention interventions is rare, especially in micro and small-sized enterprises (MSE) with fewer than 50 employees. The joint research project “PragmatiKK”(+) aims to identify and address the specific barriers to the implementation of stress prevention interventions in MSE. This study protocol describes a mixed method study design to evaluate the effectiveness of adapted stress prevention interventions and the implementation process via an integrated web-based platform (“System P”) specifically targeted at MSE. METHODS: First, we develop a web-based intervention, which accounts for the specific working conditions in MSE and addresses stress prevention at a structural and behavioral level. Second, we use common methods of implementation research to perform an effect and process evaluation. We analyze the effectiveness of the web-based stress prevention interventions by comparing depressive symptoms at baseline and follow-up (after 6 months and 12 months). Indicators for a successful implementation process include acceptability, adoption, feasibility, reach, dose, and fidelity, which we will measure with quantitative web-based questionnaires and qualitative interviews. We will also analyze the accumulated usage data from the web-based platform. DISCUSSION: Collecting data on the implementation process and the effectiveness of a web-based intervention will help to identify and overcome common barriers to stress prevention in MSE. This can improve the mental health of employees in MSE, which constitute more than 90% of all enterprises in Germany. (+) Full Project Name: „PragmatiKK - Pragmatische Lösungen für die Implementation von Maßnahmen zur Stressprävention in Kleinst- und Kleinbetrieben “(= Pragmatic solutions for the implementation of stress prevention interventions in micro and small-sized enterprises). TRIAL REGISTRATION: German Register of Clinical Studies (DRKS): DRKS00026154, date of registration: 2021-09-16. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-12921-7

Anger in brain and body: the neural and physiological perturbation of decision-making by emotion

Emotion and cognition are dynamically coupled to bodily arousal: The induction of anger, even unconsciously, can reprioritise neural and physiological resources toward action states that bias cognitive processes. Here we examine behavioural, neural and bodily effects of covert anger processing and its influence on cognition, indexed by lexical decision-making. While recording beat-to-beat blood pressure, the words ANGER or RELAX were presented subliminally just prior to rapid word/non-word reaction-time judgements of letter-strings. Subliminal ANGER primes delayed the time taken to reach rapid lexical decisions, relative to RELAX primes. However, individuals with high trait anger were speeded up by subliminal anger primes. ANGER primes increased systolic blood pressure and the magnitude of this increase predicted reaction time prolongation. Within the brain, ANGER trials evoked an enhancement of activity within dorsal pons and an attenuation of activity within visual occipitotemporal and attentional parietal cortices. Activity within periaqueductal grey matter, occipital and parietal regions increased linearly with evoked blood pressure changes, indicating neural substrates through which covert anger impairs semantic decisions, putatively through its expression as visceral arousal. The behavioural and physiological impact of anger states compromises the efficiency of cognitive processing through action-ready changes in autonomic response that skew regional neural activity

Monogenic variants in dystonia: an exome-wide sequencing study

Background Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia. Methods For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow. Findings We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222;excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism. Interpretation In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations

The Lonely Brain:Associations Between Social Isolation and (Cerebro-) Vascular Disease From the Perspective of Social Neuroscience

The current COVID-19 pandemic led to a considerable reduction in in-person social contacts all over the world. In most individuals, reduced social contacts lead to the perception of social isolation causing feelings of loneliness, which are experienced as stressful. Experiencing social distress due to actual or perceived social isolation has been associated with negative health outcomes such as depression, (cerebro-) vascular disease and mortality. Concrete mechanisms behind this association are still a matter of debate. A group of researchers around Hugo Critchley with special contributions of Sarah Garfinkel and Lisa Quadt proposes a framework for the underlying brain-body interactions including elements from models of social homeostasis and interoceptive predictive processing that provides important insights and testable pathways. While in a previous publication, we reviewed literature on the observed association between social isolation and stroke and coronary heart disease, we now extent this review by presenting a comprehensive model to explain underlying pathomechanisms from the perspective of social neuroscience. Further, we discuss how neurodivergent people, e.g. autistic individuals or persons with attention deficit disorders, might differ in these pathomechanisms and why they are especially vulnerable to social isolation. Finally, we discuss clinical implications for the prevention and therapy of (cerebro-) vascular diseases