Cardiac sympathetic-vagal activity initiates a functional brain–body response to emotional arousal

A century-long debate on bodily states and emotions persists. While the involvement of bodily activity in emotion physiology is widely recognized, the specificity and causal role of such activity related to brain dynamics has not yet been demonstrated. We hypothesize that the peripheral neural control on cardiovascular activity prompts and sustains brain dynamics during an emotional experience, so these afferent inputs are processed by the brain by triggering a concurrent efferent information transfer to the body. To this end, we investigated the functional brain–heart interplay under emotion elicitation in publicly available data from 62 healthy subjects using a computational model based on synthetic data generation of electroencephalography and electrocardiography signals. Our findings show that sympathovagal activity plays a leading and causal role in initiating the emotional response, in which ascending modulations from vagal activity precede neural dynamics and correlate to the reported level of arousal. The subsequent dynamic interplay observed between the central and autonomic nervous systems sustains the processing of emotional arousal. These findings should be particularly revealing for the psychophysiology and neuroscience of emotions.

“What Is an Emotion?” by William James (1), published more than a century ago, started the scientific debate on the nature of emotions. However, a shared and definitive theory of emotions is not in place yet, and the very definition of emotions and their nature is still a matter of debate. While more “classical” theories point to emotions as “the functional states of the brain that provide causal explanations of certain complex behaviors—like evading a predator or attacking prey” (2), other theories suggest how they are constructions of the world, not reactions to it (3). Namely, emotions are internal states constructed on the basis of previous experiences as predictive schemes to react to external stimuli.The role of bodily activity in emotions is often questioned. Despite the vast literature showing bodily correlates with emotions, a long-lasting debate about the relationship between bodily states and emotions persists (4). For instance, a feeling is defined as the subjective metarepresentation and labeling of physiological changes (such as an increase in heart rate, the increase of blood pressure, or changes in peristalsis) (5) that are strictly related to the body state on the one hand and to emotions on the other. To this extent, emotions are complex psychological phenomena in which feelings are interpreted and labeled. In a particular psychopathological condition known as alexithymia, individuals experience difficulties in experiencing and understanding emotions to various degrees (6). Indeed, some of these patients can perceive the physical changes connected to a feeling but are unable to label it as emotion, so that emotional experience is described only as its physical counterpart [e.g., described an experience as “I have my heart beating too fast” instead of “I’m fearful” (7)]. From a biological point of view the way in which physical changes become feelings and emotions is based on the interplay between the central and the autonomic nervous systems.The central nervous system (CNS) communicates with the autonomic nervous system (ANS) through interoceptive neural circuits that contribute to physiological functions beyond homeostatic control, from the emotional experience and the genesis of feelings (8) to decision making (9, 10). The debate about the role of the ANS in emotions can be condensed into two views: specificity or causation (4). The specificity view is related to the James–Lange theory, which states that bodily responses precede emotions’ central processing, meaning that bodily states would be a response to the environment, followed by an interpretation carried out by the CNS that would result in the feeling felt. However, causation theories represent an updated view of the James–Lange theory, suggesting that peripheral changes influence the conscious emotional experience; from a biological point of view this may reflect the fact that autonomic nervous signals from the body do influence perceptual activity in the brain (11, 12). In this regard, subjective perception may be influenced or shaped by ascending communication from visceral inputs to the brain (13–15).Functional models of CNS and ANS interplay have described bidirectional dynamics in emotions (16–18). In particular, the functional brain–heart interplay (BHI) involves brain structures that comprise the central autonomic network (CAN), which has been described as being in charge of autonomic control (19, 20). Moreover, the default mode network (DMN) has been found to be involved in autonomic control (21) and tasks of self-related cognition and interoception (22, 23), suggesting that the DMN participates in both ascending and descending communications with the heart. Finally, the constructed emotion theory suggests how DMN together with other intrinsic networks is crucial in the genesis of emotion and emotional experience (3).Psychophysiological studies have uncovered several correlates of different autonomic signals in the brain during emotional experiences (24–27). To understand these correlations and the functional interactions between the heart and brain, various signal processing methods have been proposed to investigate functional BHI through noninvasive recordings (28). The study of emotions using these methods comprises the analysis of heartbeat-evoked potentials (29), nonlinear couplings (30), and information transfer modeling (31). However, the causative role of bodily inputs remains unknown (4) and, more specifically, the temporal and causal links between cortical and peripheral neural dynamics in both ascending and descending directions, i.e., from the brain to the body and from the body to the brain, are still to be clarified.In this study, we take a step forward in answering these scientific questions and investigate whether peripheral neural dynamics play a causal role in the genesis of emotions. We applied a mathematical model of functional BHI based on synthetic data generation (SDG) (32), estimating the directionality of the functional interplay using simultaneous electroencephalography (EEG) and electrocardiography (ECG) recordings gathered from healthy subjects undergoing emotion elicitations with video clips, the publicly available DEAP and MAHNOB datasets (33, 34). ECG series were analyzed to derive heart-rate variability (HRV) series, which result from the concurrent activity of the sympathetic and parasympathetic (vagal) branches of the ANS acting to regulate the heartbeat. We hypothesize that, from a neurobiological point of view, feelings and subsequent emotional experiences arise from the mutual interplay between brain and body, particularly in which the CNS integrates the afferent ANS information outflow, namely from-heart-to-brain interplay, which actually triggers a cascade of cortical neural activations that, in turn, modulate directed neural control onto the heart, namely from brain-to-heart interplay.     

Nutritional Status after Roux-En-Y (Rygb) and One Anastomosis Gastric Bypass (Oagb) at 6-Month Follow-Up: A Comparative Study

Introduction: Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) are two effective bariatric surgical procedures with positive outcomes in terms of weight loss, comorbidities remission, and adverse events profiles. OAGB seems to carry a higher risk of malnutrition, but existing data are controversial. The aim of this study is to objectively evaluate and compare malnutrition in patients undergoing RYGB and OAGB. Methods: Retrospective monocentric study of obese patients undergoing RYGB or OAGB between the 15 September 2020 and the 31 May 2021. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score and compared between groups. The primary outcome was the mean CONUT score at 6 months. The secondary outcomes included the incidence of malnutrition, comorbidities, including hypertension, insulin resistance and type II diabetes mellitus, and weight loss. Results: 78 patients were included: 30 underwent RYGB and 48 underwent OAGB. At 6-Month Follow-Up there was no difference between groups in the mean CONUT score nor in incidence of malnutrition. In both groups, the nutritional status significantly worsened 6 months after surgery (preoperative and postoperative score of 0.48 ± 0.9 and 1.38 ± 1.5; p = 0.0066 for RYGB and of 0.86 ± 1.5 and 1.45 ± 1.3; p = 0.0422 for OAGB). Type II Diabetes mellitus (DMII) and hypertension remission were significant in the OAGB group with a 100% relative remission in the DMII-OAGB group (p = 0.0265), and a 67% relative remission in the hypertension-OAGB group (p = 0.0031). Conclusions: No difference in nutritional status has been detected between patients undergoing RYGB or OAGB at the 6-Month Follow-Up. Both procedures may have significant mal-absorptive effects leading to decline in nutritional status. OAGB may be more efficacious in inducing DMII and hypertension remission. Larger prospective studies dedicated specifically to nutritional status after gastric bypass are needed to confirm the impact of different bypass procedures on nutritional status.     

Effects of Turmeric Powder on Aflatoxin M1 and Aflatoxicol Excretion in Milk from Dairy Cows Exposed to Aflatoxin B1 at the EU Maximum Tolerable Levels

Due to the climatic change, an increase in aflatoxin B1 (AFB1) maize contamination has been reported in Europe. As an alternative to mineral binders, natural phytogenic compounds are increasingly used to counteract the negative effects of AFB1 in farm animals. In cows, even low dietary AFB1 concentrations may result in the milk excretion of the genotoxic carcinogen metabolite aflatoxin M1 (AFM1). In this study, we tested the ability of dietary turmeric powder (TP), an extract from Curcuma longa (CL) rich in curcumin and curcuminoids, in reducing AFM1 mammary excretion in Holstein–Friesian cows. Both active principles are reported to inhibit AFM1 hepatic synthesis and interact with drug transporters involved in AFB1 absorption and excretion. A crossover design was applied to two groups of cows (n = 4 each) with a 4-day washout. Animals received a diet contaminated with low AFB1 levels (5 ± 1 µg/kg) for 10 days ± TP supplementation (20 g/head/day). TP treatment had no impact on milk yield, milk composition or somatic cell count. Despite a tendency toward a lower average AFM1 milk content in the last four days of the treatment (below EU limits), no statistically significant differences with the AFB1 group occurred. Since the bioavailability of TP active principles may be a major issue, further investigations with different CL preparations are warranted.     

Imaging Therapeutic PARP Inhibition In Vivo through Bioorthogonally Developed Companion Imaging Agents

A number of small-molecule poly (ADP-ribose) polymerase (PARP) inhibitors are currently undergoing advanced clinical trials. Determining the distribution and target inhibitory activity of these drugs in individual subjects, however, has proven problematic. Here, we used a PARP agent for positron emission tomography-computed tomography (PET-CT) imaging (¹⁸F-BO), which we developed based on the Olaparib scaffold using rapid bioorthogonal conjugation chemistries. We show that the bioorthogonal ¹⁸F modification of the parent molecule is simple, highly efficient, and well tolerated, resulting in a half maximal inhibitory concentration (IC₅₀) of 17.9 ± 1.1 nM. Intravital imaging showed ubiquitous distribution of the drug and uptake into cancer cells, with ultimate localization within the nucleus, all of which were inhibitable. Whole-body PET-CT imaging showed tumoral uptake of the drug, which decreased significantly, after a daily dose of Olaparib. Standard ¹⁸F-fludeoxyglucose imaging, however, failed to detect such therapy-induced changes. This research represents a step toward developing a more generic approach for the rapid codevelopment of companion imaging agents based on small-molecule therapeutic inhibitors.     

Age-dependent alteration in muscle regeneration: the critical role of tissue niche

Although adult skeletal muscle is composed of fully differentiated fibers, it retains the capacity to regenerate in response to injury and to modify its contractile and metabolic properties in response to changing demands. The major role in the growth, remodeling and regeneration is played by satellite cells, a quiescent population of myogenic precursor cells that reside between the basal lamina and plasmalemma and that are rapidly activated in response to appropriate stimuli. However, in pathologic conditions or during aging, the complete regenerative program can be precluded by fibrotic tissue formation and resulting in functional impairment of the skeletal muscle. Our study, along with other studies, demonstrated that although the regenerative program can also be impaired by the limited proliferative capacity of satellite cells, this limit is not reached during normal aging, and it is more likely that the restricted muscle repair program in aging is presumably due to missing signals that usually render the damaged muscle a permissive environment for regenerative activity.     

Hepatitis E Virus Genotype 4 Outbreak,Italy, 2011

During 2011, 5 persons in the area of Lazio, Italy were infected with a monophyletic strain of hepatitis E virus that showed high sequence homology with isolates from swine in China. Detection of this genotype in Italy parallels findings in other countries in Europe, signaling the possible spread of strains new to Western countries.