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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., (© 2023 Wiley Periodicals LLC.)

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 β-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., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

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., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Structural brain abnormalities are a consistent finding in anorexia nervosa (AN) and proposed as a state biomarker of the disorder. Yet little is known about how regional structural changes affect intrinsic resting-state functional brain connectivity (rsFC). Using a cross-sectional, multimodal imaging approach, we investigated the association between regional cortical thickness abnormalities and rsFC in AN. Twenty-two acute AN patients and twenty-six age- and gender-matched healthy controls underwent a resting-state functional magnetic resonance imaging scan and cognitive tests. We performed group comparisons of whole-brain cortical thickness, seed-based rsFC, and network-based statistical (NBS) analyses. AN patients showed cortical thinning in the precuneus and inferior parietal lobules, regions involved in visuospatial memory and imagery. Cortical thickness in the precuneus correlated with nutritional state and cognitive functions in AN, strengthening the evidence for a critical role of this region in the disorder. Cortical thinning was accompanied by functional connectivity reductions in major brain networks, namely default mode, sensorimotor and visual networks. Similar to the seed-based approach, the NBS analysis revealed a single network of reduced functional connectivity in patients, comprising mainly sensorimotor- occipital regions. Our findings provide evidence that structural and functional brain abnormalities in AN are confined to specific regions and networks involved in visuospatial and somatosensory processing. We show that structural changes of the precuneus are linked to nutritional and functional states in AN, and future longitudinal research should assess how precuneus changes might be related to the evolution of the disorder.

Anorexia nervosa (AN) is highly heritable, and the perspective on the etiology of AN has changed from a behavioral to a neurobiological and neurodevelopmental view. However, cortical folding as an important marker for deviations in brain development has yet rarely been explored in AN. Hence, in order to determine potential cortical folding alterations, we investigated fine-grained cortical folding in a cohort of 26 patients with AN, of whom 6 patients were recovered regarding their weight at the time point of MRI measurement. MRI-derived cortical folding was computed and compared between patients and healthy controls at about 150,000 points per hemisphere using a surface-based technique (FreeSurfer). Patients with AN exhibited highly significant increased cortical folding in a right dorsolateral prefrontal cortex region (DLPFC). Furthermore, a statistical trend in the same direction was found in the right visual cortex. We did not find a correlation of local cortical folding and current symptoms of the disease. In conclusion, our analyses provide first evidence that altered DLPFC cortical folding plays a role in the etiology of AN. The absence of correlations with clinical parameters implicates a relatively independence of cortical folding alterations from the current symptomatology and might thus be regarded as a trait characteristic of the disease potentially related to other neurobiological features of AN.

Background: The dysfunction of specific brain areas might account for the distortion of body image in patients with anorexia nervosa. The present study was designed to reveal brain regions that are abnormal in structure and function in patients with this disorder. We hypothesized, based on brain areas of altered activity in patients with anorexia nervosa and regions involved in pain processing, an interrelation of structural aberrations in the frontoparietal-cingulate network and aberrant functional activation during thermal pain processing in patients with the disorder., Methods: We determined pain thresholds outside the MRI scanner in patients with anorexia nervosa and matched healthy controls. Thereafter, thermal pain stimuli were applied during fMRI imaging. Structural analyses with high-resolution structural T1-weighted volumes were performed using voxel-based morphometry and a surface-based approach., Results: Twenty-six patients and 26 controls participated in our study, and owing to technical difficulties, 15 participants in each group were included in our fMRI analysis. Structural analyses revealed significantly decreased grey matter volume and cortical thickness in the frontoparietal-cingulate network in patients with anorexia nervosa. We detected an increased blood oxygen level-dependent signal in patients during the painful 45 °C condition in the midcingulate and posterior cingulate cortex, which positively correlated with increased pain thresholds. Decreased grey matter and cortical thickness correlated negatively with pain thresholds, symptom severity and illness duration, but not with body mass index., Limitations: The lack of a specific quantification of body image distortion is a limitation of our study., Conclusion: This study provides further evidence for confined structural and functional brain abnormalities in patients with anorexia nervosa in brain regions that are involved in perception and integration of bodily stimuli. The association of structural and functional deviations with thermal thresholds as well as with clinical characteristics might indicate a common neuronal origin.

Objective: Reduced perception of pain is a well-established phenomenon in patients with anorexia nervosa (AN). We tested the hypothesis that altered processing of pain within the insula might account for reduced perception of pain., Method: Heat pain thresholds were obtained in nineteen patients with AN and matched controls. Thereafter, a thermode was used to deliver thermal painful stimuli to the right arm during functional magnetic resonance imaging (fMRI) measurements. Stimuli were initiated for 10 s from a baseline resting temperature (32°C) to three different levels (37, 42, 45°C)., Results: Significantly increased heat pain thresholds were observed in patients. A stronger activation during heat pain perception was found in the left posterior insula in controls. In contrast, higher levels of activity were shown in the ipsilateral pons in patients when compared to controls. In patients, we found a significant interrelation between the depression score (Beck depression inventory) and heat pain activations., Conclusion: We suggest that reduced activity in the left posterior insula might contribute to increased pain thresholds in patients, while increased activations in the right anterior insula and pons mirror augmented sympathetic modulation putatively related to amplification of adrenergic descending pain inhibition. In addition, pain thresholds and brain activations were influenced by disease-inherent depressed mood., (© 2012 John Wiley & Sons A/S.)

The perception and processing of pain is disturbed in many psychiatric diseases. Some diseases are known to show decreased perception of pain (e.g. borderline personality disorder), while others are associated with augmented pain perception (e.g. alcohol and drug dependence). The close relationship between psychiatric diseases and pain is most probably caused by aberrant processing of pain in brain structures, known to be involved in psychiatric disorders as well. Aberrant perception and processing of pain in patients with anorexia nervosa (AN) will be used to demonstrate this close relationship. Dysfunction within the insula has been suggested to account for many features of AN and might contribute to reduced pain perception. Moreover, it might lead to increased adrenergic descending inhibition associated with increased sympathetic modulation. Thus, pain research might be able to alter our view on autonomic regulation, which is putatively associated with increased cardiac mortality of the disease.

Objective: Increased mortality in anorexia nervosa is associated with autonomic dysfunction and prolongation of the QT interval. In this study, we examined the relative importance of repolarization abnormalities and vagal modulation of heart rate. In particular, we hypothesized that patients with anorexia nervosa show increased QT interval variability, particularly since this measure has been shown to correlate with serious cardiac arrhythmias., Method: We assessed linear and nonlinear heart rate variability (HRV) parameters as well as measures of QT variability in 20 female patients with anorexia nervosa and 20 controls. In patients, parameters were correlated with serum electrolytes., Results: QT variability was significantly increased in the patient group and correlated negatively with serum potassium concentrations. HRV measures showed a shift of autonomic balance towards vagal predominance., Discussion: The increase in QT variability might at least in part account for the higher risk of cardiac arrhythmias in patients with anorexia nervosa. Once validated in a prospective study design, parameters of QT variability might serve as surrogate markers for arrhythmia risk stratification in anorexia nervosa. Supplementation with potassium might normalize QT variability abnormalities., (© 2009 by Wiley Periodicals, Inc.)

Objectives: The underlying mechanisms of reduced pain perception in anorexia nervosa (AN) are unknown. To gain more insight into the pathology, the authors investigated pain perception, autonomic function, and endocrine parameters before and during successful treatment of adolescent AN patients., Method: Heat pain perception was assessed in 15 female adolescent AN patients and matched controls. Results were correlated with autonomic and endocrine parameters (free triiodothyronine, free cortisol). Autonomic function was studied using heart rate variability and pupillary light reflex assessment. To investigate the influence of therapy on these parameters, data were obtained at three different time points., Results: Heat pain thresholds were significantly increased in the acute state and decreased after weight had been regained for 6 months. Similarly, an increased parasympathetic tone was present in the acute state only. The relative amplitude of the pupillary light reflex showed a positive correlation to pain thresholds over time and predicted disease progression. In addition, the authors found a negative correlation between increased pain thresholds and low free cortisol., Conclusion: Increased pain thresholds are associated with increased parasympathetic tone and a hypothyroid state in AN. This may either indicate common central mechanisms or suggest a causative interaction.