Unconscious activation of negative emotional memories increases pain unpleasantness.

OBJECTIVE: The influence of unconscious emotional processes on pain remains poorly understood. The present study tested whether cues to forgotten unpleasant images might amplify pain (i.e., in the absence of conscious recall). METHODS: 72 healthy female adults (19 to 34 years) performed an adapted Think/No-think paradigm (T/NT) using 72 combinations of neutral face images (cues) paired with 36 neutral & 36 unpleasant images. After completion of the T/NT task, cues associated with forgotten neutral or unpleasant images were identified. Cues to either neutral or unpleasant images from the NT condition were then presented in randomized order while participants received intermediate-level thermal pain stimulation on the left hand. Ratings of both pain intensity and unpleasantness were acquired after each trial. RESULTS: Mean pain unpleasantness ratings were greater during presentation of cues to forgotten negative vs. neutral images (5.52 [SD = 2.06] vs. 5.23 [SD = 2.10]; p = 0.02). This pattern was also present when comparing cues to remembered negative vs. neutral images (5.62 [SD = 1.94] vs. 5.04 [SD = 1.90]; p < .001). Mean pain intensity ratings were higher for cues to negative vs. neutral images when remembered (5.48 [SD = 1.79] vs. 5.00 [SD = 1.69]; p < .001), but not when forgotten (5.27 [SD = 1.96] vs. 5.16 [SD = 1.93]; p = 0.30). CONCLUSIONS: Using an adapted T/NT-Pain paradigm, this study demonstrated that cues to non-recallable (but potentially unconsciously activated) negative emotional memories amplify pain unpleasantness, similar to known effects of conscious negative emotions.

Brains of endurance athletes differ in the association areas but not in the primary areas.

Regular participation in sports results in a series of physiological adaptations. However, little is known about the brain adaptations to physical activity. Here we aimed to investigate whether young endurance athletes and non-athletes differ in the gray and white matter of the brain and whether cardiorespiratory fitness (CRF) is associated with these differences. We assessed the CRF, volumes of the gray and white matter of the brain using structural magnetic resonance imaging (sMRI), and brain white matter connections using diffusion magnetic resonance imaging (dMRI) in 20 young male endurance athletes and 21 healthy non-athletes. While total brain volume was similar in both groups, the white matter volume was larger and the gray matter volume was smaller in the athletes compared to non-athletes. The reduction of gray matter was located in the association areas of the brain that are specialized in processing of sensory stimuli. In the microstructure analysis, significant group differences were found only in the association tracts, for example, the inferior occipito-frontal fascicle (IOFF) showing higher fractional anisotropy and lower radial diffusivity, indicating stronger myelination in this tract. Additionally, gray and white matter brain volumes, as well as association tracts correlated with CRF. No changes were observed in other brain areas or tracts. In summary, the brain signature of the endurance athlete is characterized by changes in the integration of sensory and motor information in the association areas.

Sex differences in the age-related decrease of spontaneous baroreflex function in healthy individuals.

The baroreflex is a powerful physiological mechanism for rapidly adjusting heart rate in response to changes in blood pressure. Spontaneous baroreflex sensitivity (BRS) has been shown to decrease with age. However, studies of sex differences in these age-related changes are rare. Here we investigated several markers of spontaneous baroreflex function in a large sample of healthy individuals. Cardiovascular signals were recorded in the supine position under carefully controlled resting conditions. After quality control, n = 980 subjects were divided into five age groups [age < 30 yr (n = 612), 30-39 yr (n = 140), 40-49 yr (n = 95), 50-59 yr (n = 61), and >60 yr (n = 72)]. Spontaneous baroreflex function was assessed in the time domain (bradycardic and tachycardic slope) and in the frequency domain in the low- and high-frequency band (LF-α, HF-α) applying the transfer function. General linear models showed a significant effect of factor age (P < 0.001) and an age × sex interaction effect (P < 0.05) on each indicator of the baroreflex function. Simple main effects showed a significantly higher BRS as indicated by tachycardic slope, LF-α and HF-α in middle-aged women compared with men (30-39 yr) and higher LF-α, bradycardic and tachycardic slope in men compared with women of the oldest age group (>60 yr). Changes in BRS over the lifespan suggest that baroreflex function declines more slowly but earlier in life in men than in women. Our findings could be linked to age-related changes in major sex hormone levels, suggesting significant implications for diverse cardiovascular outcomes and the implementation of targeted preventive strategies.NEW & NOTEWORTHY In this study, we demonstrate that the age-related decrease of spontaneous baroreflex sensitivity is different in men and women by analyzing resting state cardiovascular data of a large sample of healthy individuals.

Facial expressions of pain: the role of the serotonergic system.

RATIONALE: Although interest in the neurobiology of facial communication of pain has increased over the last decades, little is known about which neurotransmitter systems might be involved in regulating facial expressions of pain. OBJECTIVES: We aim to investigate whether the serotonergic system (5-HT), which has been implicated in various aspects of pain processing as well as in behavioral response inhibition, might play a role in facial expressions of pain. Using acute tryptophan depletion (ATD) to manipulate 5-HT function, we examined its effects on facial and subjective pain responses. METHODS: In a double-blind, placebo-controlled within-subject design, 27 participants received either an ATD or a control drink in two separate sessions. Approximately 5-h post-oral consumption, we assessed pain thresholds (heat, pressure) as well as facial and subjective responses to phasic heat pain. Moreover, situational pain catastrophizing and mood were assessed as affective state indicators. RESULTS: ATD neither influenced pain thresholds nor self-report ratings, nor catastrophizing or mood. Only facial responses were significantly affected by ATD. ATD led to a decrease in pain-indicative as well as in pain-non-indicative facial responses to painful heat, compared to the control condition. CONCLUSIONS: Decrease in brain 5-HT synthesis via ATD significantly reduced facial responses to phasic heat pain; possibly due to (i) diminished disposition to display social behavior or due to (ii) decreased facilitation of excitatory inputs to the facial motor neuron.

Testing visual self-misperception in anorexia nervosa using a symmetrical body size estimation paradigm.

OBJECTIVE: Individuals diagnosed with anorexia nervosa (AN) often report seeing themselves as overweight. While body size estimation tasks suggest that such individuals overestimate their body size, these tasks have failed to establish whether this misestimation stems from visual misperception. Misestimation might, instead, be due to response bias. We designed a paradigm to distinguish between visual and response bias contributions to body size misestimation: the symmetrical body size estimation (s-BSE) paradigm. METHOD: The s-BSE paradigm involves two tasks. In the conventional task, participants estimate the width of their photographed body by adjusting the size of a rectangle to match. In the transposed task, participants adjust the size of a photograph of their body to match the rectangle. If overestimation stems exclusively from visual misperception, then errors in each task would be equal and opposite. Using this paradigm, we compared the performance of women diagnosed with AN (n = 14) against women without any eating disorder (n = 40). RESULTS: In the conventional task, we replicated previous findings indicating that both women with AN and women without any eating disorder overestimate their body size. In the transposed task, neither group adjusted the bodies to be narrower than the rectangle. Participants with AN set their photographs to be significantly wider. DISCUSSION: While we replicated previous findings of body size overestimation amongst women with AN and those without any eating disorder, our results are inconsistent with the hypothesis that such overestimation stems exclusively from visual misperception and instead suggest a substantial response bias effect. PUBLIC SIGNIFICANCE: Women with anorexia nervosa overestimate their own body size. Research has not yet determined whether this overestimation stems from them seeing themselves as larger or other, non-visual factors. We employ a new method for distinguishing these possibilities and find that non-visual factors influence size estimates for women with and without anorexia nervosa. This method can help future research control for non-perceptual influences on participant responses.

Central Autonomic Network Alterations in Anorexia Nervosa Following Peripheral Adrenergic Stimulation.

BACKGROUND: Anorexia nervosa (AN) is characterized by low body weight, disturbed eating, body image disturbance, anxiety, and interoceptive dysfunction. However, the neural processes underlying these dysfunctions in AN are unclear. This investigation combined an interoceptive pharmacological probe, the peripheral ß-adrenergic agonist isoproterenol, with resting-state functional magnetic resonance imaging to examine whether individuals with AN relative to healthy comparison participants show dysregulated neural coupling in central autonomic network brain regions. METHODS: Resting-state functional magnetic resonance imaging was performed in 23 weight-restored female participants with AN and 23 age- and body mass index-matched healthy comparison participants before and after receiving isoproterenol infusions. Whole-brain functional connectivity (FC) changes were examined using central autonomic network seeds in the amygdala, anterior insular cortex, posterior cingulate cortex, and ventromedial prefrontal cortex after performing physiological noise correction procedures. RESULTS: Relative to healthy comparison participants, adrenergic stimulation caused widespread FC reductions in the AN group between central autonomic network regions and motor, premotor, frontal, parietal, and visual brain regions. Across both groups, these FC changes were inversely associated with trait anxiety (State-Trait Anxiety Inventory-Trait), trait depression (9-item Patient Health Questionnaire), and negative body image perception (Body Shape Questionnaire) measures, but not with changes in resting heart rate. These results were not accounted for by baseline group FC differences. CONCLUSIONS: Weight-restored females with AN show a widespread state-dependent disruption of signaling between central autonomic, frontoparietal, and sensorimotor brain networks that facilitate interoceptive representation and visceromotor regulation. Additionally, trait associations between central autonomic network regions and these other brain networks suggest that dysfunctional processing of interoceptive signaling may contribute to affective and body image disturbance in AN.

Dynamic changes in the central autonomic network of patients with anorexia nervosa.

Autonomic cardiac dysfunction is a common complication in patients with anorexia nervosa (AN). Despite its high prevalence, physicians often overlook this clinical condition, and little research has been dedicated so far. To probe the functional role of the neurocircuitry underpinning the poorly understood autonomic cardiac dysfunction, we examined dynamic functional differences in the central autonomic network (CAN) between 21 acute AN individuals and 24 age, sex and heart rate-matched healthy controls (HC). We assessed functional connectivity (FC) changes in CAN using seeds in the ventromedial prefrontal cortex, left and right anterior insular cortex, left and right amygdala and dorsal anterior cingulate cortex. The overall FC between the six investigated seeds is reduced in AN individuals compared to HC, although no changes were observed for single connections. Moreover, AN exhibited higher complexity in the FC time series of such CAN regions. Contrary to HC, we found that the degree of complexity between FC and heart rate (HR) series did not correlate in AN, suggesting a shift from central to peripheral control of the heart in AN individuals. Using dynamic FC analysis, we showed that the CAN transits across five functional states with no preference for any. Strikingly, at the state of weakest connectivity, the entropy significantly diverges between healthy and AN individuals, reaching its minimum and maximum values, respectively. Overall, our findings provide evidence that core regions of the CAN engaged in cardiac regulation are functionally affected in acute AN.

Associations of common genetic risk variants of the muscarinic acetylcholine receptor M2 with cardiac autonomic dysfunction in patients with schizophrenia.

OBJECTIVES: Decreased vagal modulation, which has consistently been observed in schizophrenic patients, might contribute to increased cardiac mortality in schizophrenia. Previously, associations between CHRM2 (Cholinergic Receptor Muscarinic 2) and cardiac autonomic features have been reported. Here, we tested for possible associations between these polymorphisms and heart rate variability in patients with schizophrenia. METHODS: A total of three single nucleotide polymorphisms (SNPs) in CHRM2 (rs73158705 A>G, rs8191992 T>A and rs2350782 T>C) that achieved significance (p < 5 * 10-8) in genome-wide association studies for cardiac autonomic features were genotyped in 88 drug-naïve patients, 61 patients receiving antipsychotic medication and 144 healthy controls. Genotypes were analysed for associations with parameters of heart rate variability and complexity, in each diagnostic group. RESULTS: We observed a significantly altered heart rate variability in unmedicated patients with identified genetic risk status in rs73158705 A>G, rs8191992 T>A and rs2350782 T>C as compared to genotype non-risk status. In patients receiving antipsychotic medication and healthy controls, these associations were not observed. DISCUSSION: We report novel candidate genetic associations with cardiac autonomic dysfunction in schizophrenia, but larger cohorts are required for replication.

Analysis of CACNA1C and KCNH2 Risk Variants on Cardiac Autonomic Function in Patients with Schizophrenia.

BACKGROUND: Cardiac autonomic dysfunction (CADF) is a major contributor to increased cardiac mortality in schizophrenia patients. The aberrant function of voltage-gated ion channels, which are widely distributed in the brain and heart, may link schizophrenia and CADF. In search of channel-encoding genes that are associated with both CADF and schizophrenia, CACNA1C and KCNH2 are promising candidates. In this study, we tested for associations between genetic findings in both genes and CADF parameters in schizophrenia patients whose heart functions were not influenced by psychopharmaceuticals. METHODS: First, we searched the literature for single-nucleotide polymorphisms (SNPs) in CACNA1C and KCNH2 that showed genome-wide significant association with schizophrenia. Subsequently, we looked for such robust associations with CADF traits at these loci. A total of 5 CACNA1C SNPs and 9 KCNH2 SNPs were found and genotyped in 77 unmedicated schizophrenia patients and 144 healthy controls. Genotype-related impacts on heart rate (HR) dynamics and QT variability indices (QTvi) were analyzed separately in patients and healthy controls. RESULTS: We observed significantly increased QTvi in unmedicated patients with CADF-associated risk in CACNA1C rs2283274 C and schizophrenia-associated risk in rs2239061 G compared to the non-risk allele in these patients. Moreover, unmedicated patients with previously identified schizophrenia risk alleles in KCNH2 rs11763131 A, rs3807373 A, rs3800779 C, rs748693 G, and 1036145 T showed increased mean HR and QTvi as compared to non-risk alleles. CONCLUSIONS: We propose a potential pleiotropic role for common variation in CACNA1C and KCNH2 associated with CADF in schizophrenia patients, independent of antipsychotic medication, that predisposes them to cardiac arrhythmias and premature death.

Central autonomic network alterations in male endurance athletes.

Physical exercise causes marked adjustments in brain function and the cardiovascular system. Brain regions of the so-called central autonomic network (CAN) are likely to show exercise-related alterations due to their involvement in cardiac control, yet exercise-induced CAN changes remain unclear. Here we investigate the effects of intensive exercise on brain regions involved in cardiac autonomic regulation using resting-state functional connectivity (rsFC). We explored rsFC of six core regions within CAN, namely ventromedial prefrontal cortex, dorsolateral anterior cingulate cortex, left/right amygdala, and left/right anterior insula, in 20 endurance athletes and 21 non-athletes. We showed that athletes had enhanced rsFC within CAN and sensorimotor areas compared to non-athletes. Likewise, we identified two networks with increased rsFC encompassing autonomic and motor-related areas using network-based statistics analysis. In addition, rsFC displayed an inverse relationship with heart rate, where the stronger rsFC in athletes correlates with their slower heart rate. Despite this significant relationship, mediation analysis revealed that heart rate is a weak mediator of the effect of intensive physical training on rsFC. Our findings prove that physical exercise enhances brain connectivity in central autonomic and sensorimotor networks and highlight the close link between brain and heart.

Depressive rumination and heart rate variability: A pilot study on the effect of biofeedback on rumination and its physiological concomitants.

Objective: Recent studies suggest that lower resting heart rate variability (HRV) is associated with elevated vulnerability to depressive rumination. In this study, we tested whether increases in HRV after HRV-biofeedback training are accompanied by reductions in rumination levels. Materials and methods: Sixteen patients suffering from depression completed a 6-week HRV-biofeedback training and fourteen patients completed a control condition in which there was no intervention (waitlist). The training included five sessions per week at home using a smartphone application and an ECG belt. Depressive symptoms and autonomic function at rest and during induced rumination were assessed before and after each of the two conditions. We used a well-established rumination induction task to provoke a state of pervasive rumination while recording various physiological signals simultaneously. Changes in HRV, respiration rate, skin conductance, and pupil diameter were compared between conditions and time points. Results: A significant correlation was found between resting HRV and rumination levels, both assessed at the first laboratory session (r = -0.43, p < 0.05). Induction of rumination led to an acceleration of heart rate and skin conductance increases. After biofeedback training, resting vagal HRV was increased (p < 0.01) and self-ratings of state anxiety (p < 0.05), rumination (p < 0.05), perceived stress (p < 0.05), and depressive symptoms (QIDS, BDI; both p < 0.05) were decreased. In the control condition, there were no changes in autonomic indices or depressive symptomatology. A significant interaction effect group x time on HRV was observed. Conclusion: Our results indicate that a smartphone-based HRV-biofeedback intervention can be applied to improve cardiovagal function and to reduce depressive symptoms including self-rated rumination tendencies.

Autonomic aging - A dataset to quantify changes of cardiovascular autonomic function during healthy aging.

Autonomic regulation of blood pressure and cardiac rhythm progressively declines with increasing age. Impaired cardiovascular control promotes a variety of age-related cardio-vascular conditions. This study aims to provide a database of high-resolution biological signals to describe the effect of healthy aging on cardiovascular regulation. Electrocardiogram and continuous non-invasive blood pressure signals were recorded simultaneously at rest in 1,121 healthy volunteers. With this database, we provide raw signals as well as basic demographic information such as gender and body mass index. To demonstrate validity of the acquired data, we present the well-known decline of heart rate variability with increasing age in this database.

Using machine learning to estimate the calendar age based on autonomic cardiovascular function.

Introduction: Aging is accompanied by physiological changes in cardiovascular regulation that can be evaluated using a variety of metrics. In this study, we employ machine learning on autonomic cardiovascular indices in order to estimate participants' age. Methods: We analyzed a database including resting state electrocardiogram and continuous blood pressure recordings of healthy volunteers. A total of 884 data sets met the inclusion criteria. Data of 72 other participants with an BMI indicating obesity (>30 kg/m²) were withheld as an evaluation sample. For all participants, 29 different cardiovascular indices were calculated including heart rate variability, blood pressure variability, baroreflex function, pulse wave dynamics, and QT interval characteristics. Based on cardiovascular indices, sex and device, four different approaches were applied in order to estimate the calendar age of healthy subjects, i.e., relevance vector regression (RVR), Gaussian process regression (GPR), support vector regression (SVR), and linear regression (LR). To estimate age in the obese group, we drew normal-weight controls from the large sample to build a training set and a validation set that had an age distribution similar to the obesity test sample. Results: In a five-fold cross validation scheme, we found the GPR model to be suited best to estimate calendar age, with a correlation of r=0.81 and a mean absolute error of MAE=5.6 years. In men, the error (MAE=5.4 years) seemed to be lower than that in women (MAE=6.0 years). In comparison to normal-weight subjects, GPR and SVR significantly overestimated the age of obese participants compared with controls. The highest age gap indicated advanced cardiovascular aging by 5.7 years in obese participants. Discussion: In conclusion, machine learning can be used to estimate age on cardiovascular function in a healthy population when considering previous models of biological aging. The estimated age might serve as a comprehensive and readily interpretable marker of cardiovascular function. Whether it is a useful risk predictor should be investigated in future studies.

Estimating Resting HRV during fMRI: A Comparison between Laboratory and Scanner Environment.

Heart rate variability (HRV) is regularly assessed in neuroimaging studies as an indicator of autonomic, emotional or cognitive processes. In this study, we investigated the influence of a loud and cramped environment during magnetic resonance imaging (MRI) on resting HRV measures. We compared recordings during functional MRI sessions with recordings in our autonomic laboratory (LAB) in 101 healthy subjects. In the LAB, we recorded an electrocardiogram (ECG) and a photoplethysmogram (PPG) over 15 min. During resting state functional MRI, we acquired a PPG for 15 min. We assessed anxiety levels before the scanning in each subject. In 27 participants, we performed follow-up sessions to investigate a possible effect of habituation. We found a high intra-class correlation ranging between 0.775 and 0.996, indicating high consistency across conditions. We observed no systematic influence of the MRI environment on any HRV index when PPG signals were analyzed. However, SDNN and RMSSD were significantly higher when extracted from the PPG compared to the ECG. Although we found a significant correlation of anxiety and the decrease in HRV from LAB to MRI, a familiarization session did not change the HRV outcome. Our results suggest that psychological factors are less influential on the HRV outcome during MRI than the methodological choice of the cardiac signal to analyze.

Identifying Distinguishable Clinical Profiles Between Single Suicide Attempters and Re-Attempters.

More than 800,000 individuals die from suicide each year in the world, which has a devastating impact on families and society. Ten to twenty times more attempt suicide. Previous studies showed that suicide attempters represent a heterogeneous group regarding demographic characteristics, individual characteristics of a suicidal attempt, and the assumed clinical factors, e.g., hopelessness or impulsivity, thus differently contributing to the likelihood of suicidal behavior. Therefore, in the present study, we aim to give a comprehensive clinical description of patients with repeated suicide attempts compared to single attempters. We explored putative differences between groups in clinical variables and personality traits, sociodemographic information, and specific suicide attempt-related information. A sample of patients with a recent suicide attempt (n = 252), defined according to DSM-5 criteria for a suicidal behavior disorder (SBD), was recruited in four psychiatric hospitals in Thuringia, Germany. We used a structured clinical interview to assess the psychiatric diagnosis, sociodemographic data, and to collect information regarding the characteristics of the suicide attempt. Several clinical questionnaires were used to measure the suicide intent and suicidal ideations, depression severity, hopelessness, impulsivity, aggression, anger expression, and the presence of childhood trauma. Univariate and multivariate statistical methods were applied to evaluate the postulated risk factors and, to distinguish groups based on these measures. The performed statistical analyses indicated that suicide attempters represent a relatively heterogeneous group, nevertheless associated with specific clinical profiles. We demonstrated that the re-attempters had more severe psychopathology with significantly higher levels of self-reported depression, suicidal ideation as well as hopelessness. Furthermore, re-attempters had more often first-degree relatives with suicidal behavior and emotional abuse during childhood. They also exhibited a higher degree of specific personality traits, i.e., more "urgency" as a reaction to negative emotions, higher excitability, higher self-aggressiveness, and trait anger. The multivariate discriminant analysis significantly discriminated the re-attempters from single attempters by higher levels of self-aggressiveness and suicidal ideation. The findings might contribute to a better understanding of the complex mechanisms leading to suicidal behavior, which might improve the early identification and specific treatment of subjects at risk for repeated suicidal behavior.

Neural mechanisms of pain processing differ between endurance athletes and nonathletes: A functional connectivity magnetic resonance imaging study.

Pain perception and the ability to modulate arising pain vary tremendously between individuals. It has been shown that endurance athletes possess higher pain tolerance thresholds and a greater effect of conditioned pain modulation than nonathletes, both indicating a more efficient system of endogenous pain inhibition. The aim of the present study was to focus on the neural mechanisms of pain processing in endurance athletes that have not been investigated yet. Therefore, we analyzed the pain processing of 18 male athletes and 19 healthy male nonathletes using functional magnetic resonance imaging. We found lower pain ratings in endurance athletes compared to nonathletes to physically identical painful stimulation. Furthermore, brain activations of athletes versus nonathletes during painful heat stimulation revealed reduced activation in several brain regions that are typically activated by nociceptive stimulation. This included the thalamus, primary and secondary somatosensory cortex, insula, anterior cingulate cortex, midcingulate cortex, dorsolateral prefrontal cortex, and brain stem (BS). Functional connectivity analyses revealed stronger network during painful heat stimulation in athletes between the analyzed brain regions except for connections with the BS that showed reduced functional connectivity in athletes. Post hoc correlation analyses revealed associations of the subject's fitness level and the brain activation strengths, subject's fitness level and functional connectivity, and brain activation strengths and functional connectivity. Together, our results demonstrate for the first time that endurance athletes do not only differ in behavioral variables compared to nonathletes, but also in the neural processing of pain elicited by noxious heat.

The Influence of Heart Rate Variability Biofeedback on Cardiac Regulation and Functional Brain Connectivity.

BACKGROUND: Heart rate variability (HRV) biofeedback has a beneficial impact on perceived stress and emotion regulation. However, its impact on brain function is still unclear. In this study, we aimed to investigate the effect of an 8-week HRV-biofeedback intervention on functional brain connectivity in healthy subjects. METHODS: HRV biofeedback was carried out in five sessions per week, including four at home and one in our lab. A control group played jump'n'run games instead of the training. Functional magnetic resonance imaging was conducted before and after the intervention in both groups. To compute resting state functional connectivity (RSFC), we defined regions of interest in the ventral medial prefrontal cortex (VMPFC) and a total of 260 independent anatomical regions for network-based analysis. Changes of RSFC of the VMPFC to other brain regions were compared between groups. Temporal changes of HRV during the resting state recording were correlated to dynamic functional connectivity of the VMPFC. RESULTS: First, we corroborated the role of the VMPFC in cardiac autonomic regulation. We found that temporal changes of HRV were correlated to dynamic changes of prefrontal connectivity, especially to the middle cingulate cortex, the left insula, supplementary motor area, dorsal and ventral lateral prefrontal regions. The biofeedback group showed a drop in heart rate by 5.2 beats/min and an increased SDNN as a measure of HRV by 8.6 ms (18%) after the intervention. Functional connectivity of the VMPFC increased mainly to the insula, the amygdala, the middle cingulate cortex, and lateral prefrontal regions after biofeedback intervention when compared to changes in the control group. Network-based statistic showed that biofeedback had an influence on a broad functional network of brain regions. CONCLUSION: Our results show that increased heart rate variability induced by HRV-biofeedback is accompanied by changes in functional brain connectivity during resting state.

Attenuated neuronal and autonomic responses during error processing in anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a severe psychiatric illness with alarming mortality rates. Nevertheless, despite former and recent research results, the etiology of AN is still poorly understood. Of particular interest is that, despite exaggerated response control and increased perfectionism scores, patients with AN seem not to perform better that those unaffected in tasks that require inhibitory control. One reason might be aberrant processing of errors. The objective of our study was thus to obtain further insight into the pathopsychology of AN. We were particularly interested in neuronal and autonomic responses during error processing and their association with behavior. METHODS: We analyzed 16 acute patients suffering from restrictive type AN and 21 healthy controls using functional magnetic resonance imaging (fMRI) with simultaneous physiological recordings during a Go/Nogo response inhibition task. Data were corrected for noise due to cardiac and respiratory influence. RESULTS: Patients and controls had similarly successful response inhibition in Nogo trials. However, in failed Nogo trials, controls had significantly greater skin conductance responses (SCR) than in correct Nogo trials. Patients did not exhibit elevated SCR to errors. Furthermore, we found significantly increased neuronal responses, especially in the amygdala and hippocampus, in controls compared to patients during error trials. We also found significant positive correlations in controls but not in patients between Nogo performance and activation in the salience network core regions after errors. CONCLUSION: Acute restrictive type AN patients seem to lack neuronal and autonomic responses to errors that might impede a flexible behavior adaption.

Cognitive effects of rapid-acting treatments for resistant depression: Just adverse, or contributing to clinical efficacy?

Major Depressive Disorder is a major public health problem and has a high rate of treatment resistance. Fear conditioning has been proposed as a potential mechanism sustaining negative affect in mood disorders. With the aim of exploring cognitive effects of rapid-acting antidepressant treatments as a potential mechanism of action that can be targeted by neuromodulation, we performed a narrative review of the extant literature on effects of electroconvulsive therapy, ketamine or esketamine, and sleep deprivation on emotional/fear memory retrieval-reconsolidation. We explore interference with reconsolidation as a potential common pathway that explains in part the efficacy of rapid-acting antidepressant treatments with disparate mechanisms of action. We propose the testable hypothesis that fear learning circuits can be specifically targeted by neuromodulation to attempt rapid amelioration of depressive symptoms (especially repetitive negative thinking) while limiting unspecific, untoward cognitive side effects.

Conditioned Pain Modulation (CPM) Effects Captured in Facial Expressions.

PURPOSE: Conditioned pain modulation (CPM) is most often assessed using self-report of pain. However, self-report of pain is not always available (eg in individuals with cognitive impairment) and is susceptible to report bias. In comparison, the facial expression of pain is more reflex-like and represents one of the most sensitive and specific non-verbal signals of pain. The aim of the present study was to investigate whether the facial expression of pain is sensitive enough to capture endogenous pain inhibition as elicited during CPM paradigms. PATIENTS AND METHODS: In total, 26 female participants took part in this study. Facial and verbal responses to phasic heat pain were assessed once while participants immersed their hand in a hot water bath and once without additional stimulation. Facial responses were analyzed using the Facial Action Coding System (FACS). Verbal responses were assessed using a Numerical Rating Scale (NRS). RESULTS: Pain-relevant facial responses as well as pain ratings to phasic heat pain were significantly reduced when participants simultaneously immersed their hand in a hot water bath compared to baseline. Thus, CPM effects could be demonstrated both on subjective as well as on facial responses. Moreover, CPM-induced changes in pain-relevant facial responses and in NRS ratings were significantly correlated. CONCLUSION: The present study shows that facial expressions of pain are sensitive enough to capture CPM effects. Given the proven clinical usefulness of assessing CPM, the parallel assessment of verbal and facial CPM effects might be a promising approach with wider scope of applications. Further research in other demographic healthy participant and clinical cohorts is warranted.