Attenuation of self-produced touch in the posterior insula reflects body image disturbances in anorexia nervosa | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Attenuation of self-produced touch in the posterior insula reflects body image disturbances in anorexia nervosa Morgan Frost-Karlsson, Maria Zetterqvist, Håkan Olausson, Rebecca Boehme This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7479995/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 10 You are reading this latest preprint version Abstract Body image disturbance (BID) is a core feature of anorexia nervosa (AN), encompassing multimodal distortions in bodily self-perception. Affective touch, a gentle, emotionally salient tactile stimulus, is implicated in body ownership but has not been extensively studied in AN. Affective touch is processed in the insula, an area involved in interoception and bodily self-awareness which has been shown to be altered both structurally and functionally in AN. This study explored the neural mechanisms underlying BID by examining how individuals with AN process self-produced affective touch. Women with AN (n=44) and age-matched healthy controls (HC, n=40), participated in a self-other-object touch task during functional brain imaging and filled out questionnaires related to body image and eating disorder symptomatology. During self-touch, individuals with AN exhibited increased activation in the right posterior insula compared to object-touch, whereas HC did not. This insular activation correlated positively with BID measures in AN but negatively in HC, suggesting divergent processing of self-related tactile input. Here we identify the posterior insula as a potential neural marker of disturbed embodiment and demonstrate that the sensory processes which typically stabilize body ownership may exacerbate distorted body perception in AN. Broadening BID research beyond the visual modality opens new avenues for translational research and treatment. Biological sciences/Neuroscience Biological sciences/Psychology Social science/Psychology prediction errors bodily self fMRI anorexia nervosa body image disturbance insula Figures Figure 1 Figure 2 Introduction Body image disturbance (BID) is one of the hallmark features of anorexia nervosa (AN), a severe eating disorder characterized by distorted body perception, weight loss, and intense fear of gaining weight. Individuals with AN consistently perceive their bodies as larger than they are and engage in extreme behaviors to control their weight. The maladaptive perceptions of the body are not merely cognitive distortions but are intricately connected to neural mechanisms involved in bodily self-awareness, interoception, and affect regulation [ 1 ]. Individuals with AN perceive their bodies as larger than reality but this isn’t just a visual misestimation, they feel their bodies as larger across modalities (individuals with AN overestimate tactile distances on their bodies [ 2 ], and can even turn their shoulders to fit through a doorway, [ 3 ]). As this is specific to their own bodies and not bodies in general, and it is multimodal, understanding embodiment and neural processing of self-produced percepts is important for understanding the disorder. However, most research focuses on the visual modality and thus fails to encapsulate the multimodal nature of BID[ 4 ]. Affective touch, characterized by gentle, caress-like tactile stimulation, plays a crucial role in the development and maintenance of our sense of self and body ownership. Affective touch is primarily mediated by C-tactile (CT) afferents, which are specialized nerve fibers that respond optimally to slow, gentle stroking [ 5 ]. Research on affective touch in AN is limited but suggests that women with AN experience a tactile hypersensitivity which correlates with body image disturbance [ 6 ]. CT-mediated touch has also been found to be less pleasant in AN compared to healthy women, which persists even after recovery [ 7 , 8 ]. Notably, a recent study found differential modulation of multisensory body processing in AN and highlights the need for research and treatment incorporating components of bodily self-awareness[ 4 ]. Tactile stimulation that is effective in activating CT fibers activates the contralateral posterior insular cortex [ 5 , 9 ]. The insula is involved in integrating sensory information from the body and emotional processing, helping form a cohesive sense of self [ 10 ]. Functional imaging studies have consistently shown altered insular structure and activity in individuals with AN (see, e.g. [ 11 – 17 ]), with some structural alterations persisting after recovery [ 11 ]. The posterior insula is associated with sensorimotor integration, interoception [ 18 ], changes in interoceptive states and somatosensory processes [ 19 ]. Given the posterior insula’s role in interoception and body ownership, altered posterior insular structure and/or function could potentially be an important marker for pathophysiology in AN both before onset and after recovery [ 13 ]. Our previous research in healthy populations has found attenuation of self-produced touch in the insula (among other areas) [ 20 ], while AN had greater activation across multiple brain regions during self-touch compared to both controls and adults on the Autism Spectrum [ 21 ]. We suggest that this could be due to an inaccurate estimate of the bodily self which causes a prediction error during self-produced percepts. The Predictive Coding Framework suggests that the brain continuously makes predictions about sensory inputs and compares them to incoming sensory data. When there is a discrepancy between the predicted and actual sensory input, the brain generates a "prediction error" and updates its internal model to better predict future inputs. This process is crucial for perception, learning, and decision-making [ 22 ]. This process might be altered in AN. According to the Allocentric Lock Hypothesis [ 23 ], individuals with AN have difficulties integrating multisensory information and struggle to perceive their bodies accurately from their own perspective, which leads to them being “locked” in a distorted body schema which does not update according to accurate sensory input. From a predictive coding lens, this could look like constant prediction errors due to a failure to update the body schema; incoming sensory input about the own body is mismatched with the flawed self-model. Neuroimaging studies have shown increased prediction errors in AN in regard to taste reward [ 24 ], as well as increased sensitivity to salient stimuli and greater intolerance of uncertainty [ 25 ]. BID precedes onset of AN [ 26 ] and may contribute to AN outcome and relapse [ 27 ]. As BID is such a dominant and predictive feature of AN, studying its mechanisms is necessary for deeper understanding of AN. Legrand [ 28 ] states, “it is important to keep in mind that, in anorexia, not only the represented body (fat) differs from the biological body (skinny), but also the representation of one's body (oversized) differs from the representation of other's body (not oversized). To understand how/why subjects over-estimate their body only, and not those of others, self-representation and self-attribution of one's body must be considered carefully. These dimensions, however, are usually neglected by empirical research.”(page 732). Due to the dearth of research on affective touch in AN, and the role that affective self-touch plays in bodily self-perception [ 29 ], employing an affective touch paradigm to study potential mechanisms of BID could be informative. Relapse is prevalent in AN [ 30 ] and studying the mechanisms of BID can inform new treatment options. In this study we measured insular activation using functional magnetic resonance imaging (fMRI) during self-produced affective touch, a highly predictable process, and assessed this activation in relation to measures of BID. We expected to see greater insular activation in AN than controls during self-produced touch, and that this activation would relate to symptom severity and body image disturbances. By focusing on this key but understudied modality, we aimed to extend body image research beyond vision and identify potential neural markers of disturbed embodiment in AN. Results Participant Demographics & Questionnaires In total, 44 women with AN and 39 HC were analyzed. Groups were matched in age (AN: M = 21.4 years, SD = 3.4; HC: M = 21.9 years, SD = 2.8) but differed significantly in BMI (AN: M = 19.0, SD = 1.3; HC: M = 21.8, SD = 2.4, p < 0.001). As expected, the AN group reported markedly higher body image disturbance and eating disorder symptomatology than HC. On BAT, AN scored well above the clinical cut-off of 36 [31], (M = 63.6, SD = 16.2) compared to HC (M = 19.1, SD = 9.6, p < 0.001). A similar pattern emerged on EDE-Q, in which cut-off is 2.8 [32] (AN: M = 13.7, SD = 19.9; HC: M = 0.9, SD = 1.5, p < 0.001), and on FRS (AN: M = 2.07, SD = 1.96; HC: M = 0.46, SD = 0.8, p < 0.001) For demographic and questionnaire values, see Table 1 . Table 1 : Participant demographics and questionnaire results. (means and standard deviations) AN, anorexia nervosa; HC, healthy control; BMI, body mass index; BAT, body attitude test; FRS, figure rating scale; EDE-Q, eating disorders examination questionnaire. AN (N=44) HC (N=39) t/W-value; p-value Age 21.425 (3.4) 21.9 (2.8) t= 0.689; p=0.493 BMI 19 (1.3) 21.8 (2.4) t= 6.711; p< 0.001 BAT 63.58 (16.24) 19.11(9.6) W= 19.5; p<0.001 FRS 2.07 (1.96) 0.46(0.8) W= 338.5; p<0.001 EDE-Q 13.65 (19.9) 0.88(1.5) W= 29; p<0.001 Main Effects of Touch Condition HC: In line with previous findings, healthy participants showed the expected attenuation of self-produced touch. During (self-object) touch, HC displayed significant activation in the right primary somatosensory cortex (S1), and widespread deactivations in the superior temporal sulcus (STS), superior temporal gyrus (STG), bilateral insula, hippocampus, and amygdala ( p (FWE) < 0.05). ( Figure 1a ). For values, see Table 2 . AN: In contrast, women with AN showed increased activation in the right posterior insula and right S1 during (self-object) touch. Deactivations were observed in the amygdala, hippocampus, and STG bilaterally, as well as in the fusiform gyrus. In our region-of-interest (ROI), the right posterior insula, AN showed significant activation ([36 −16 18], T = 6.56, p = 0.001). ( Figure 1b ). For values, see Table 2 . Table 2: Whole Brain Level Analysis for (self-object) touch. S1, primary somatosensory cortex; STG, superior temporal gyrus; STS, superior temporal sulcus; M1, primary motor cortex. P-values of FWE-correction for the whole brain at voxel-level. Group Type Region Hemisphere Coordinates (MNI) t-Value, p-value AN Activation S1 Right 32 -30 64 7.08, 0.000 Insula Right 38 -16 18 6.56, 0.001 Deactivation Amygdala Left -24 -10 -18 6.89, 0.000 Hippocampus Right 34 -12 -18 6.89, 0.000 Hippocampus Left -36 -26 -18 6.76, 0.000 Fusiform Gyrus Right 44 18 -32 6.86, 0.001 Amygdala Right 24 -8 -18 6.80, 0.001 STG Left -50 -2 -16 4.93, 0.003 STG Right 50 8 -29 6.04, 0.012 HC Activation S1 Right 26 -24 56 6.18, 0.003 Deactivation Hippocampus Right 36 -26 8 7.67, 0.001 Amygdala Right 24 -6 -18 7.17, 0.003 STG Right 52 2 -10 6.53, 0.013 M1 Right 60 14 34 6.45, 0.015 STS Left -58 -16 -20 5.08, 0.015 Insula Right 32 10 -12 6.33, 0.020 STG Left -46 -16 -8 6.17, 0.029 Insula Left -36 10 -8 5.98, 0.045 Other-touch condition : For completeness, we also assessed other-touch relative to baseline. In HC, other-touch elicited robust activations across sensory and interoceptive regions (insula, thalamus, S1, fusiform gyrus, pACC), whereas AN showed more limited activations, mainly in medial frontal and hippocampal areas. Both groups also displayed widespread deactivations during other-touch, in frontal, insular, and parietal regions. (for values, see supplementary table 1 ). Differences Between AN and HC At the whole-brain level, no significant group differences emerged for (self-object) touch. However, in an exploratory analysis of extracted mean posterior insula ROI beta-values, AN showed greater mean activation than HC (AN: M = 0.01, SD = 0.34; HC: M = –0.145, SD = 0.32; T = –2.156, p = 0.034). Relationships Between Brain Activation and Body Image Disturbance Posterior insula activation during self-touch was significantly associated with measures of body image disturbance. A correlation was found between insular activation during self-touch (i.e. [self-object]) and BAT scores for both groups, but in different directions ( figure 2a): there was a positive relationship in AN, (r=0.369, p=0.013), and a negative relationship in HC (r=-0.389, p=0.019). A similar pattern was found for the FRS ( figure 2b ): AN (r=0.34, p=0.022), and HC (r=-.506, p=0.002). The correlation coefficients differed significantly between groups for both FRS (Z=4.016, p<.001) and BAT (Z=3.211, p=.001). No correlations were found between insular activation and EDE-Q scores (AN: r=0.229, p=0.131, HC: r=0.098, p=0.599). For the other-touch condition, no correlations were found between insular activation and BAT (HC r= 0.02, p=0.91; AN r=-0.081, p=0.596), FRS (HC r=0.223, p= 0.197; AN r=-0.120, p=0.434), or EDE-Q (HC r=0.166, p= 0.364; AN r=-0.156, p=0.31). Discussion Altered processing of self-touch in the posterior insula, a hub for bodily self-perception, related distinctly to body image experiences in anorexia patients and control participants. Self-touch is a crucial contributing factor to the development and maintenance of the bodily self-model in healthy individuals; in AN, an altered relationship between self-touch and disturbed body image suggests a potentially different underlying mechanism for this maintenance. An alternative explanation could be that AN patients have developed compensatory mechanisms to integrate contradictory multisensory evidence concerning their body shape. In the AN group, we found right posterior insular activation during self-touch compared to object-touch. The control group did not show this insula activation during self-touch. However, there was no group difference when comparing AN to controls at the whole brain level. Comparing the extracted ROI values, we found greater activation in the right posterior insula in AN compared to controls. This shows a weak difference between groups which at both the whole brain level and insula ROI did not survive FWE correction, suggesting a certain overlap in activity levels between groups. Insular activity during self-touch in AN could reflect a prediction error during a self-produced tactile event, a percept which in healthy populations is usually highly predictable and attenuated (typically resulting in bilateral insular deactivation) [20, 33]. Prediction errors during heat and taste perception tasks have been shown to be heightened in the right insula in AN [34, 35]. Heightened insular activity during self-touch could reflect an emotional response (of anxiety or disgust, for example) to touching one’s own body, as has been suggested in AN [36, 37] and bulimia [38]. The posterior insula has been implicated in emotion regulation in addition to the functions listed above; however, in this case we would also expect to see increased activation in other emotion processing areas. Instead, we find bilateral amygdala deactivations in both groups at the whole brain level during (self-object) touch, rendering the implication of insular activation as a result solely from an emotional response unlikely. Amygdala deactivation during self-produced touch has been found previously in healthy populations [20], and indicates a decrease in emotional salience and valence during self-produced touch. In AN, the activation in the right posterior insula correlated positively with body image disturbances – i.e., more activation corresponds to increased body image disturbances (greater body dissatisfaction and greater difference between estimated and actual body size). This is in line with a previous study on the visual modality which found increased insular activation in AN when comparing images of self and other, and correlated with body satisfaction [12]. Structural alterations in the posterior insula are also associated with body image disturbances, and increased gray matter in the posterior insula in AN is associated with longer duration of the disorder and body shape dissatisfaction [17]. Other studies find decreased resting state connectivity in the posterior insula in AN, potentially reflecting a pathophysiological calibration [39] and/or integration [14] of internal (interoceptive, homeostatic) and external (somatic, visuospatial) bodily signals. Controls displayed the opposite relationship: increased activation was associated with decreased body image disturbances; i.e., more activation corresponded to increased body satisfaction. This could be a consequence of greater suppression of body-related input, perhaps as a sort of coping mechanism. We found that insular activation did not correlate with EDE-Q scores in either group, which does not align with previous findings of increased right posterior insular gray matter correlating with EDE-Q scores in AN [16]. The EDE-Q measures eating disorder symptomatology rather than body dissatisfaction, suggesting that the activation in response to our self-touch task is not related to the physical symptoms of AN but rather body dysmorphia and the mental representation of the body. We found more activations in the right posterior insula during the (other-object) touch condition in HC than in AN. We did not find correlations between this activation and BAT or FRS scores for either group, implicating this region in processing of self-generated touch, specifically, and not in the processing of affective skin-to-skin touch in general. A limitation with these findings, and with AN research in general, is that it is difficult to disentangle the effects of malnourishment from underlying differences in neural mechanisms. Importantly, the average BMI of our participants was within the lower healthy range, however one cannot discount the symptomatology of AN and the effects that a starvation state may have on brain function and behavior. Overall, our findings indicate that individuals with AN show increased activation in the right posterior insula during self-produced affective touch. While we did not find this activation for HC, we did not find a significant difference between groups, except for an exploratory comparison of extracted parameters. This indicates an overlap of activation during self-touch between groups, probably driven by individual variance. This individual variance related differently to body image disturbance: correlations between insular activation and scores from self-report questionnaires on body image disturbances were found for both HC and AN, but in opposite directions. This points to a processing difference between those who are dissatisfied with their body but do not have an eating disorder and those who are dissatisfied with their body and have AN. This difference could be due to increased prediction errors in the right posterior insula during self-touch in AN. Further studies evaluating AN through the lens of self-produced sensory input is valuable and could further elaborate on the role of prediction errors in onset and/or duration of AN. Therapeutic interventions that incorporate adapting to self-touch or other types of self-produced input could hold promise for improving outcomes in individuals with AN. Methods Participants The study was approved by the Regional Ethical Board of Linköping (2017/443-31, 2018/444-32) and the Swedish Ethical Review Authority (2019-02821), and conducted in accordance with the Declaration of Helsinki. Participants provided written informed consent and completed the Body Attitude Test (BAT; [31]), Eating Disorder Examination Questionnaire (EDE-Q [32]), and Figure Rating Scale (FRS; [40]), to assess body image disturbances and the severity of eating disorder symptomatology. Adults (aged 18-35) with AN were recruited through the Child and Adolescent Psychiatric Clinic (18–24 years) and the Psychiatric clinic (25–35 years) in Linköping, Region Östergötland. Clinical staff first informed potential participants of the study. Interested participants were then contacted by a research nurse (not involved in patients’ treatment) who gave further verbal and written information about the study and screened the participants for the inclusion and exclusion criteria. Participants were included on the conditions: DSM-5 diagnosis of anorexia nervosa, including atypical anorexia nervosa and unspecified (all restrictive type), BMI ≤ 20 kg/m2, and MRI-compatibility. Participants were either free of psychotropic medications or on stable (at least three months on the same dose) medication with antidepressants. On-demand use of mild anxiolytics and hypnotics, treatment with central stimulants (if avoided on MRI day) were also accepted. Exclusion criteria were: psychotic disorder, bipolar disorder, substance use disorder, ongoing treatment with antipsychotics or tricyclic antidepressants, previous severe head injury, birth before 33 weeks' gestation, hearing impairment, previous epilepsy or seizure, claustrophobia, pregnancy, and cognitive disabilities. In total 44 participants were included in the current study. Healthy controls (HC) were recruited online through social media advertisements and on the university website as well as through our local participant database. Participants were included based on Swedish fluency, acceptance of skin-to-skin touch on the arm, and willingness to undergo an MRI scan. Exclusion criteria were assessed via a standardized phone interview screening [41] and included any psychiatric diagnoses or medication, history of disordered eating, excessive substance use, chronic pain, and any health issues related to touch perception or MRI safety. In total 40 participants were recruited and, with one participant not completing all of the questionnaires, 39 participants were included in the analyses for HC. Touch task Participants performed the self-other-touch task as standardized in previous literature [20, 42]: they lay in an fMRI with their left arm across their abdomen and a pillow on the abdomen beside the arm. The right arm was propped up as close to the left arm and pillow as possible using pillows. The touch task consisted of three conditions: self-touch, other-touch, and object-touch. During self-touch, participants gently stroked their left forearm with their right hand. During other-touch, participants were gently stroked on the left forearm by a female researcher. During object-touch, participants stroked a pillow with their right hand. The object-touch condition was used as a control for the movement in the self-touch condition. Goggles displayed instructions for the task. Instructions read (in Swedish), ‘Active, please stroke your arm’, ‘Passive, the researcher will stroke your arm’, ‘Active, please stroke the object’. Instructions were provided on a white background for three seconds before turning green to indicate when the condition should begin. Each condition lasted for 12 seconds, with 12 seconds of rest in between. Conditions were repeated ten times each, for a total of 30 trials in random order. fMRI A 3.0 Tesla scanner (Prisma; Siemens) with a 64-channel head coil was used to acquire T1-weighted anatomical images (repetition time = 2300 ms; echo time = 2.36 ms; flip angle = 8°; field of view = 288 × 288 mm2; voxel resolution = 0.87 × 0.87 × 0.90 mm3) and T2-weighted echo-planar images (EPIs) containing 48 multiband slices (repetition time: 1030 ms; echo time: 30 ms; slice thickness: 3 mm; matrix size: 64 × 64; field of view: 192 × 192 mm2; in-plane voxel resolution: 3 mm2; flip angle: 63°). Statistical parametric mapping (SPM12; Wellcome Department of Imaging Neuroscience) in Matlab R2018b (MathWorks) was used to analyze fMRI data. Preprocessing steps included: Correction for motion using SPM’s realign-module registering to the mean EPI after a first realignment (quality = 0.9, separation = 4, smoothing = 5 full width at half-maximum kernel, interpolation with 4th degree B-Spline), coregistration of the anatomical image and mean EPI using normalized mutual information, segmentation of the T1 image using the unified segmentation approach [43], and spatial normalization of T1 and EPIs to the Montreal Neurological Institute T1 template (using forward deformations from the segmentation step, voxel size 2*2*2 for resampling, and 4th Degree B-Spline for interpolation). All functional images were spatially smoothed with an isotropic Gaussian kernel of 6-mm full width at half-maximum. Analysis At the single-subject level, regressors of interest consisted of self-touch, other-touch, and object-touch blocks. Regressors of no-interest were added for the cue phase (separately for each block), and arm movements after each active block (1 sec) when subjects moved the arm back into the resting position. To account for movement-associated variance, realignment parameters and their first temporal derivates were included as regressors of no interest, as well as a regressor censoring scans with more than 1 mm scan-to-scan movement. For the analysis here, our hypothesis concerned the self-touch condition. Therefore, contrast maps were generated for the self-touch vs. object-touch condition at the single subject level. At the group-level, one sample t-test for the self-object contrast was calculated for evaluation of the AN group and extraction of beta-parameters. For completeness, a one-sample t-test per group was evaluated for the other-touch condition as well. Two sample t-tests were used for between-group comparisons. For whole-brain analyses, results were corrected for multiple comparisons using the family-wise error (FWE) correction at the voxel-level [44]. Additionally, as an exploratory analysis, a region of interest (ROI) mask [45, 46] was used for the posterior insula, which is known to process affective touch, to obtain a small volume correction given our hypothesis. Mean beta-parameters from this ROI were extracted and correlated with values from BAT and FRS questionnaires. Due to inequality of variance, Mann-Whitney tests were performed for between-group measures for the questionnaires. Declarations Acknowledgements We thank Lisa Engberg and Anna Elander for help with patient recruitment, and Adam Enmalm for help with data collection. Funding Declaration This research was funded by grants from the Swedish Medical Research Council (2015-02684) to HO, from ALF, Region Östergötland (RÖ-702221; RÖ-837632; RÖ-893981; RÖ-940701) to MZ, from the Swedish Society of Medicine (SLS-784151; SLS-960468; SLS-878101) to MZ and RB, and from Lions Forskningsfond (liu-2019-01191) to RB. CRediT authorship contribution statement Morgan Frost-Karlsson: Conceptualization, Data curation, Formal analysis, Investigation, Project administration, Visualization, Writing – original draft, Writing – review & editing. Maria Zetterqvist: Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing – review & editing. Håkan Olausson: Conceptualization, Funding acquisition, Methodology, Resources, Supervision, Writing – review & editing. Rebecca Boehme: Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Software, Supervision, Writing – review & editing. Data Availability Statement The datasets analyzed during the current study are not publicly available due to ethical considerations, but are available from the corresponding author on reasonable request. Competing Interest Statement The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper. References Fairburn, C.G., Cognitive behavior therapy and eating disorders . 2008: Guilford Press. Keizer, A., et al., Tactile body image disturbance in anorexia nervosa. Psychiatry research, 2011. 190 (1): p. 115–120. Keizer, A., et al., Too fat to fit through the door: first evidence for disturbed body-scaled action in anorexia nervosa during locomotion. PLOS one, 2013. 8 (5): p. e64602. Salvato, G., et al., Dissociations between bodily self-awareness components in women with Anorexia Nervosa. Translational Psychiatry, 2025. 15 (1): p. 109. McGlone, F., J. Wessberg, and H. Olausson, Discriminative and affective touch: sensing and feeling. Neuron, 2014. 82 (4): p. 737–755. Zucker, N.L., et al., Subjective experience of sensation in anorexia nervosa. Behaviour research and therapy, 2013. 51 (6): p. 256–265. Crucianelli, L., et al., The perception of affective touch in anorexia nervosa. Psychiatry research, 2016. 239 : p. 72–78. Crucianelli, L., et al., The anticipation and perception of affective touch in women with and recovered from Anorexia Nervosa. neuroscience, 2021. 464 : p. 143–155. Olausson, H., et al., Unmyelinated tactile afferents signal touch and project to insular cortex. Nature neuroscience, 2002. 5 (9): p. 900–904. Craig, A.D., How do you feel—now? The anterior insula and human awareness. Nature reviews neuroscience, 2009. 10 (1): p. 59–70. Frank, G.K., et al., Alterations in brain structures related to taste reward circuitry in ill and recovered anorexia nervosa and in bulimia nervosa. American Journal of Psychiatry, 2013. 170 (10): p. 1152–1160. Friederich, H.-C., et al., Neural correlates of body dissatisfaction in anorexia nervosa. Neuropsychologia, 2010. 48 (10): p. 2878–2885. Gaudio, S., et al., A systematic review of resting-state functional-MRI studies in anorexia nervosa: evidence for functional connectivity impairment in cognitive control and visuospatial and body-signal integration. Neuroscience & Biobehavioral Reviews, 2016. 71 : p. 578–589. Geisler, D., et al., Abnormal functional global and local brain connectivity in female patients with anorexia nervosa. Journal of Psychiatry and Neuroscience, 2016. 41 (1): p. 6–15. Lucherini Angeletti, L., et al., Anorexia nervosa as a disorder of the subcortical–cortical interoceptive-self. Eating and Weight Disorders-Studies on Anorexia, Bulimia and Obesity, 2022. 27 (8): p. 3063–3081. Tose, K., et al., Systematic reduction of gray matter volume in anorexia nervosa, but relative enlargement with clinical symptoms in the prefrontal and posterior insular cortices: a multicenter neuroimaging study. Molecular Psychiatry, 2024. 29 (4): p. 891–901. Zucker, N.L., et al., The clinical significance of posterior insular volume in adolescent anorexia nervosa. Psychosomatic medicine, 2017. 79 (9): p. 1025–1035. Kurth, F., et al., A link between the systems: functional differentiation and integration within the human insula revealed by meta-analysis. Brain Structure and Function, 2010. 214 : p. 519–534. Klein, T.A., M. Ullsperger, and C. Danielmeier, Error awareness and the insula: links to neurological and psychiatric diseases. Frontiers in human neuroscience, 2013. 7 : p. 14. Boehme, R., et al., Distinction of self-produced touch and social touch at cortical and spinal cord levels. Proceedings of the National Academy of Sciences, 2019. 116 (6): p. 2290–2299. Frost-Karlsson, M., et al., Neural processing of self-touch and other-touch in anorexia nervosa and autism spectrum condition. NeuroImage: Clinical, 2022. 36 : p. 103264. Friston, K., The free-energy principle: a unified brain theory? Nature reviews neuroscience, 2010. 11 (2): p. 127–138. Riva, G., Neuroscience and eating disorders: The allocentric lock hypothesis. Medical Hypotheses, 2012. 78 (2): p. 254–257. Frank, G.K., et al., Prediction error and somatosensory insula activation in women recovered from anorexia nervosa. Journal of Psychiatry and Neuroscience, 2016. 41 (5): p. 304–311. Jappe, L.M., et al., Heightened sensitivity to reward and punishment in anorexia nervosa. International Journal of Eating Disorders, 2011. 44 (4): p. 317–324. Cash, T.F. and E.A. Deagle III, The nature and extent of body ‐image disturbances in anorexia nervosa and bulimia nervosa: A meta ‐analysis. International journal of eating disorders, 1997. 22 (2): p. 107–126. Keel, P.K., et al., Postremission predictors of relapse in women with eating disorders. American Journal of Psychiatry, 2005. 162 (12): p. 2263–2268. Legrand, D., Subjective and physical dimensions of bodily self-consciousness, and their dis-integration in anorexia nervosa. Neuropsychologia, 2010. 48 (3): p. 726–737. Böhme, R., The Touched Body and the Experience of Self . 2025, Springer. Berends, T., et al., Rate, timing and predictors of relapse in patients with anorexia nervosa following a relapse prevention program: a cohort study. BMC psychiatry, 2016. 16 (1): p. 1–7. Probst, M., et al., The Body Attitude Test for patients with an eating disorder: Psychometric characteristics of a new questionnaire. Eating disorders, 1995. 3 (2): p. 133–144. Hilbert, A., et al., Eating disorder examination-questionnaire. Diagnostica, 2007. 53 (3): p. 144–154. Blakemore, S.J., S.J. Goodbody, and D.M. Wolpert, Predicting the consequences of our own actions: the role of sensorimotor context estimation. Journal of Neuroscience, 1998. 18 (18): p. 7511–7518. Bär, K.J., et al., Insular dysfunction and descending pain inhibition in anorexia nervosa. Acta Psychiatrica Scandinavica, 2013. 127 (4): p. 269–278. Monteleone, A.M., et al., Altered processing of rewarding and aversive basic taste stimuli in symptomatic women with anorexia nervosa and bulimia nervosa: An fMRI study. Journal of psychiatric research, 2017. 90 : p. 94–101. Uher, R., et al., Functional neuroanatomy of body shape perception in healthy and eating-disordered women. Biological psychiatry, 2005. 58 (12): p. 990–997. Bischoff-Grethe, A., et al., Neural hypersensitivity to pleasant touch in women remitted from anorexia nervosa. Translational psychiatry, 2018. 8 (1): p. 161. Wierenga, C.E., et al., Increased anticipatory brain response to pleasant touch in women remitted from bulimia nervosa. Translational psychiatry, 2020. 10 (1): p. 236. Ehrlich, S., et al., Reduced functional connectivity in the thalamo ‐insular subnetwork in patients with acute anorexia nervosa. Human Brain Mapping, 2015. 36 (5): p. 1772–1781. Thompson, J.K. and M.N. Altabe, Psychometric qualities of the figure rating scale. International Journal of Eating Disorders, 1991. 10 (5): p. 615–619. Alexander, M.J., et al., Mental health screening in addiction, corrections and social service settings: Validating the MMS. International Journal of Mental Health and Addiction, 2008. 6 : p. 105–119. Frost-Karlsson, M., et al., Altered somatosensory processing in adult attention deficit hyperactivity disorder. BMC psychiatry, 2024. 24 (1): p. 558. Ashburner, J. and K.J. Friston, Unified segmentation. neuroimage, 2005. 26 (3): p. 839–851. Eklund, A., T.E. Nichols, and H. Knutsson, Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. Proceedings of the national academy of sciences, 2016. 113 (28): p. 7900–7905. Larsson, M.B., et al., Brain responses to visceral stimuli reflect visceral sensitivity thresholds in patients with irritable bowel syndrome. Gastroenterology, 2012. 142 (3): p. 463–472. e3. Boehme, R., et al., Anhedonia to gentle touch in fibromyalgia: normal sensory processing but abnormal evaluation. Brain Sciences, 2020. 10 (5): p. 306. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7479995","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":509253805,"identity":"cf0013cd-78e5-4748-8739-7a28d2702914","order_by":0,"name":"Morgan Frost-Karlsson","email":"data:image/png;base64,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","orcid":"","institution":"Linköping University","correspondingAuthor":true,"prefix":"","firstName":"Morgan","middleName":"","lastName":"Frost-Karlsson","suffix":""},{"id":509253806,"identity":"49925bc3-dc1d-48a7-af7e-8b8839086eec","order_by":1,"name":"Maria Zetterqvist","email":"","orcid":"","institution":"Linköping University","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Zetterqvist","suffix":""},{"id":509253807,"identity":"aa7de549-8dc7-4570-a208-92bb4917858c","order_by":2,"name":"Håkan Olausson","email":"","orcid":"","institution":"Linköping University","correspondingAuthor":false,"prefix":"","firstName":"Håkan","middleName":"","lastName":"Olausson","suffix":""},{"id":509253808,"identity":"9da11077-6965-4573-b2a6-1fc7b85b59f6","order_by":3,"name":"Rebecca Boehme","email":"","orcid":"","institution":"Linköping University","correspondingAuthor":false,"prefix":"","firstName":"Rebecca","middleName":"","lastName":"Boehme","suffix":""}],"badges":[],"createdAt":"2025-08-28 11:53:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7479995/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7479995/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90884285,"identity":"ccdb7ef8-6389-471f-8c01-9371ed942b77","added_by":"auto","created_at":"2025-09-09 10:00:05","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":432667,"visible":true,"origin":"","legend":"\u003cp\u003ea. Activation (orange) and deactivation (blue) during (self-object) touch in HC (T-test, p(FWE-corrected at the whole brain level)\u0026lt;.05) [28 -24 -12]. b. Activation (orange) and deactivation (blue) during (self-object) touch in AN (T-test, p(FWE-corrected at the whole brain level )\u0026lt;.05). [37 -14 -19]. Color bars display t-values.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7479995/v1/12d658fefc4ae44899d7b4f6.png"},{"id":90884283,"identity":"d5033a41-b37a-400d-a557-291cf46900b0","added_by":"auto","created_at":"2025-09-09 10:00:05","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":49628,"visible":true,"origin":"","legend":"\u003cp\u003eScores from BAT (a) and FRS (b) correlated with the extracted mean beta values from posterior insula ROI during (self-object) touch, in opposite directions for the two groups. Insular activation (Y-axis) refers to the extracted ROI values.\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7479995/v1/c7b83e34eb6bba5013bf4e75.png"},{"id":90888398,"identity":"abf03085-779c-4538-8314-f60055ca7390","added_by":"auto","created_at":"2025-09-09 10:32:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1253253,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7479995/v1/25f8c74a-395f-42dd-bd02-9620c07baeb5.pdf"},{"id":90884284,"identity":"c4565345-aba6-4bcb-98aa-ed44153a10d0","added_by":"auto","created_at":"2025-09-09 10:00:05","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":18899,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-7479995/v1/291a620705b7968e5341593b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Attenuation of self-produced touch in the posterior insula reflects body image disturbances in anorexia nervosa","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBody image disturbance (BID) is one of the hallmark features of anorexia nervosa (AN), a severe eating disorder characterized by distorted body perception, weight loss, and intense fear of gaining weight. Individuals with AN consistently perceive their bodies as larger than they are and engage in extreme behaviors to control their weight. The maladaptive perceptions of the body are not merely cognitive distortions but are intricately connected to neural mechanisms involved in bodily self-awareness, interoception, and affect regulation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Individuals with AN perceive their bodies as larger than reality but this isn\u0026rsquo;t just a visual misestimation, they \u003cem\u003efeel\u003c/em\u003e their bodies as larger across modalities (individuals with AN overestimate tactile distances on their bodies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], and can even turn their shoulders to fit through a doorway, [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]). As this is specific to their own bodies and not bodies in general, and it is multimodal, understanding embodiment and neural processing of self-produced percepts is important for understanding the disorder. However, most research focuses on the visual modality and thus fails to encapsulate the multimodal nature of BID[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAffective touch, characterized by gentle, caress-like tactile stimulation, plays a crucial role in the development and maintenance of our sense of self and body ownership. Affective touch is primarily mediated by C-tactile (CT) afferents, which are specialized nerve fibers that respond optimally to slow, gentle stroking [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Research on affective touch in AN is limited but suggests that women with AN experience a tactile hypersensitivity which correlates with body image disturbance [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. CT-mediated touch has also been found to be less pleasant in AN compared to healthy women, which persists even after recovery [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Notably, a recent study found differential modulation of multisensory body processing in AN and highlights the need for research and treatment incorporating components of bodily self-awareness[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTactile stimulation that is effective in activating CT fibers activates the contralateral posterior insular cortex [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The insula is involved in integrating sensory information from the body and emotional processing, helping form a cohesive sense of self [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Functional imaging studies have consistently shown altered insular structure and activity in individuals with AN (see, e.g. [\u003cspan additionalcitationids=\"CR12 CR13 CR14 CR15 CR16\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]), with some structural alterations persisting after recovery [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The posterior insula is associated with sensorimotor integration, interoception [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], changes in interoceptive states and somatosensory processes [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Given the posterior insula\u0026rsquo;s role in interoception and body ownership, altered posterior insular structure and/or function could potentially be an important marker for pathophysiology in AN both before onset and after recovery [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur previous research in healthy populations has found attenuation of self-produced touch in the insula (among other areas) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], while AN had greater activation across multiple brain regions during self-touch compared to both controls and adults on the Autism Spectrum [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. We suggest that this could be due to an inaccurate estimate of the bodily self which causes a prediction error during self-produced percepts.\u003c/p\u003e\u003cp\u003eThe Predictive Coding Framework suggests that the brain continuously makes predictions about sensory inputs and compares them to incoming sensory data. When there is a discrepancy between the predicted and actual sensory input, the brain generates a \"prediction error\" and updates its internal model to better predict future inputs. This process is crucial for perception, learning, and decision-making [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. This process might be altered in AN. According to the Allocentric Lock Hypothesis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], individuals with AN have difficulties integrating multisensory information and struggle to perceive their bodies accurately from their own perspective, which leads to them being \u0026ldquo;locked\u0026rdquo; in a distorted body schema which does not update according to accurate sensory input. From a predictive coding lens, this could look like constant prediction errors due to a failure to update the body schema; incoming sensory input about the own body is mismatched with the flawed self-model. Neuroimaging studies have shown increased prediction errors in AN in regard to taste reward [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], as well as increased sensitivity to salient stimuli and greater intolerance of uncertainty [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eBID precedes onset of AN [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] and may contribute to AN outcome and relapse [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. As BID is such a dominant and predictive feature of AN, studying its mechanisms is necessary for deeper understanding of AN. Legrand [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] states, \u0026ldquo;it is important to keep in mind that, in anorexia, not only the represented body (fat) differs from the biological body (skinny), but also the representation of one's body (oversized) differs from the representation of other's body (not oversized). To understand how/why subjects over-estimate their body only, and not those of others, self-representation and self-attribution of one's body must be considered carefully. These dimensions, however, are usually neglected by empirical research.\u0026rdquo;(page 732). Due to the dearth of research on affective touch in AN, and the role that affective self-touch plays in bodily self-perception [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], employing an affective touch paradigm to study potential mechanisms of BID could be informative. Relapse is prevalent in AN [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] and studying the mechanisms of BID can inform new treatment options.\u003c/p\u003e\u003cp\u003eIn this study we measured insular activation using functional magnetic resonance imaging (fMRI) during self-produced affective touch, a highly predictable process, and assessed this activation in relation to measures of BID. We expected to see greater insular activation in AN than controls during self-produced touch, and that this activation would relate to symptom severity and body image disturbances. By focusing on this key but understudied modality, we aimed to extend body image research beyond vision and identify potential neural markers of disturbed embodiment in AN.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eParticipant Demographics \u0026amp; Questionnaires\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn total, 44 women with AN and 39 HC were analyzed. Groups were matched in age (AN: M = 21.4 years, SD = 3.4; HC: M = 21.9 years, SD = 2.8) but differed significantly in BMI (AN: M = 19.0, SD = 1.3; HC: M = 21.8, SD = 2.4, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001). As expected, the AN group reported markedly higher body image disturbance and eating disorder symptomatology than HC. On BAT, AN scored well above the clinical cut-off of 36 [31], (M = 63.6, SD = 16.2) compared to HC (M = 19.1, SD = 9.6, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001). A similar pattern emerged on EDE-Q, in which cut-off is 2.8 [32] (AN: M = 13.7, SD = 19.9; HC: M = 0.9, SD = 1.5, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), and on FRS (AN: M = 2.07, SD = 1.96; HC: M = 0.46, SD = 0.8, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001)\u003c/p\u003e\n\u003cp\u003eFor demographic and questionnaire values, see \u003cem\u003eTable 1\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTable 1\u003c/em\u003e: Participant demographics and questionnaire results. (means and standard deviations) AN, anorexia nervosa; HC, healthy control; BMI, body mass index; BAT, body attitude test; FRS, figure rating scale; EDE-Q, eating disorders examination questionnaire.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"380\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAN\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(N=44)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHC\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(N=39)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u003cstrong\u003et/W-value;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Age\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e21.425 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e21.9 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003et= 0.689; p=0.493\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cem\u003eBMI\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e19 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e21.8 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003et= 6.711;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cem\u003eBAT\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e63.58 (16.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e19.11(9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eW= 19.5; p\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cem\u003eFRS\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e2.07 (1.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.46(0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eW= 338.5; p\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 71px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; EDE-Q\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003e13.65 (19.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 98px;\"\u003e\n \u003cp\u003e0.88(1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eW= 29;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eMain Effects of Touch Condition\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eHC:\u003c/em\u003e In line with previous findings, healthy participants showed the expected attenuation of self-produced touch. During (self-object) touch, HC displayed significant activation in the right primary somatosensory cortex (S1), and widespread deactivations in the superior temporal sulcus (STS), superior temporal gyrus (STG), bilateral insula, hippocampus, and amygdala (\u003cem\u003ep\u003c/em\u003e(FWE) \u0026lt; 0.05). (\u003cem\u003eFigure 1a\u003c/em\u003e). For values, see \u003cem\u003eTable 2\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAN:\u003c/em\u003e In contrast, women with AN showed increased activation in the right posterior insula and right S1 during (self-object) touch. Deactivations were observed in the amygdala, hippocampus, and STG bilaterally, as well as in the fusiform gyrus. In our region-of-interest (ROI), the right posterior insula, AN showed significant activation ([36 \u0026minus;16 18], \u003cem\u003eT\u003c/em\u003e = 6.56, \u003cem\u003ep\u003c/em\u003e = 0.001). (\u003cem\u003eFigure 1b\u003c/em\u003e). For values, see \u003cem\u003eTable 2\u003c/em\u003e.\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTable 2:\u0026nbsp;\u003c/em\u003eWhole Brain Level Analysis for (self-object) touch. S1, primary somatosensory cortex; STG, superior temporal gyrus; STS, superior temporal sulcus; M1, primary motor cortex. P-values of FWE-correction for the whole brain at voxel-level.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eGroup\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHemisphere\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCoordinates (MNI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003et-Value,\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003eAN\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eActivation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eS1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e32 -30 64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e7.08, 0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eInsula\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e38 -16 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.56, 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eDeactivation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eAmygdala\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e-24 -10 -18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.89, 0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eHippocampus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e34 -12 -18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.89, 0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eHippocampus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e-36 -26 -18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.76, 0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eFusiform Gyrus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e44 18 -32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.86, 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eAmygdala\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e24 -8 -18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.80, 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eSTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e-50 -2 -16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e4.93, 0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eSTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e50 8 -29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.04, 0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003eHC\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eActivation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eS1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e26 -24 56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.18, 0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eDeactivation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eHippocampus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e36 -26 8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e7.67, 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eAmygdala\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e24 -6 -18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e7.17, 0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eSTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e52 2 -10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.53, 0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eM1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e60 14 34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.45, 0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eSTS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e-58 -16 -20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e5.08, 0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eInsula\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e32 10 -12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.33, 0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eSTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e-46 -16 -8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6.17, 0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eInsula\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e-36 10 -8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e5.98, 0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eOther-touch condition\u003c/em\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eFor completeness, we also assessed other-touch relative to baseline. In HC, other-touch elicited robust activations across sensory and interoceptive regions (insula, thalamus, S1, fusiform gyrus, pACC), whereas AN showed more limited activations, mainly in medial frontal and hippocampal areas. Both groups also displayed widespread deactivations during other-touch, in frontal, insular, and parietal regions. (for values, see \u003cem\u003esupplementary table 1\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDifferences Between AN and HC\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAt the whole-brain level, no significant group differences emerged for (self-object) touch. However, in an exploratory analysis of extracted mean posterior insula ROI beta-values, AN showed greater mean activation than HC (AN: M = 0.01, SD = 0.34; HC: M = \u0026ndash;0.145, SD = 0.32; T = \u0026ndash;2.156, p = 0.034).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eRelationships Between Brain Activation and Body Image Disturbance\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePosterior insula activation during self-touch was significantly associated with measures of body image disturbance.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA correlation was found between insular activation during self-touch (i.e. [self-object]) and BAT scores for both groups, but in different directions (\u003cem\u003efigure 2a):\u003c/em\u003e there was a positive relationship in AN, (r=0.369, p=0.013), and a negative relationship in HC (r=-0.389, p=0.019). A similar pattern was found for the FRS (\u003cem\u003efigure 2b\u003c/em\u003e): AN (r=0.34, p=0.022), and HC (r=-.506, p=0.002).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe correlation coefficients differed significantly between groups for both FRS (Z=4.016, p\u0026lt;.001) and BAT (Z=3.211, p=.001).\u003c/p\u003e\n\u003cp\u003eNo correlations were found between insular activation and EDE-Q scores (AN: r=0.229, p=0.131, HC: r=0.098, p=0.599).\u003c/p\u003e\n\u003cp\u003eFor the other-touch condition, no correlations were found between insular activation and BAT (HC r= 0.02, p=0.91; AN r=-0.081, p=0.596), FRS (HC r=0.223, p= 0.197; AN r=-0.120, p=0.434), or EDE-Q (HC r=0.166, p= 0.364; AN r=-0.156, p=0.31).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAltered processing of self-touch in the posterior insula, a hub for bodily self-perception, related distinctly to body image experiences in anorexia patients and control participants. Self-touch is a crucial contributing factor to the development and maintenance of the bodily self-model in healthy individuals; in AN, an altered relationship between self-touch and disturbed body image suggests a potentially different underlying mechanism for this maintenance. An alternative explanation could be that AN patients have developed compensatory mechanisms to integrate contradictory multisensory evidence concerning their body shape.\u003c/p\u003e\n\u003cp\u003eIn the AN group, we found right posterior insular activation during self-touch compared to object-touch. The control group did not show this insula activation during self-touch. However, there was no group difference when comparing AN to controls at the whole brain level. Comparing the extracted ROI values, we found greater activation in the right posterior insula in AN compared to controls. This shows a weak difference between groups which at both the whole brain level and insula ROI did not survive FWE correction, suggesting a certain overlap in activity levels between groups.\u003c/p\u003e\n\u003cp\u003eInsular activity during self-touch in AN could reflect a prediction error during a self-produced tactile event, a percept which in healthy populations is usually highly predictable and attenuated (typically resulting in bilateral insular deactivation) [20, 33]. Prediction errors during heat and taste perception tasks have been shown to be heightened in the right insula in AN [34, 35].\u003c/p\u003e\n\u003cp\u003eHeightened insular activity during self-touch could reflect an emotional response (of anxiety or disgust, for example) to touching one\u0026rsquo;s own body, as has been suggested in AN [36, 37]\u0026nbsp; and bulimia [38]. The posterior insula has been implicated in emotion regulation in addition to the functions listed above; however, in this case we would also expect to see increased activation in other emotion processing areas. Instead, we find bilateral amygdala deactivations in both groups at the whole brain level during (self-object) touch, rendering the implication of insular activation as a result solely from an emotional response unlikely. Amygdala deactivation during self-produced touch has been found previously in healthy populations [20], and indicates a decrease in emotional salience and valence during self-produced touch.\u003c/p\u003e\n\u003cp\u003eIn AN, the activation in the right posterior insula correlated positively with body image disturbances \u0026ndash; i.e., more activation corresponds to increased body image disturbances (greater body dissatisfaction and greater difference between estimated and actual body size). This is in line with a previous study on the visual modality which found increased insular activation in AN when comparing images of self and other, and correlated with body satisfaction [12]. Structural alterations in the posterior insula are also associated with body image disturbances, and increased gray matter in the posterior insula in AN is associated with longer duration of the disorder and body shape dissatisfaction [17]. Other studies find decreased resting state connectivity in the posterior insula in AN, potentially reflecting a pathophysiological calibration [39] and/or integration [14] of internal (interoceptive, homeostatic) and external (somatic, visuospatial) bodily signals.\u003c/p\u003e\n\u003cp\u003eControls displayed the opposite relationship: increased activation was associated with decreased body image disturbances; i.e., more activation corresponded to increased body satisfaction. This could be a consequence of greater suppression of body-related input, perhaps as a sort of coping mechanism.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe found that insular activation did not correlate with EDE-Q scores in either group, which does not align with previous findings of increased right posterior insular gray matter correlating with EDE-Q scores in AN [16]. The EDE-Q measures eating disorder symptomatology rather than body dissatisfaction, suggesting that the activation in response to our self-touch task is not related to the physical symptoms of AN but rather body dysmorphia and the mental representation of the body.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe found more activations in the right posterior insula during the (other-object) touch condition in HC than in AN. We did not find correlations between this activation and BAT or FRS scores for either group, implicating this region in processing of self-generated touch, specifically, and not in the processing of affective skin-to-skin touch in general. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA limitation with these findings, and with AN research in general, is that it is difficult to disentangle the effects of malnourishment from underlying differences in neural mechanisms. Importantly, the average BMI of our participants was within the lower healthy range, however one cannot discount the symptomatology of AN and the effects that a starvation state may have on brain function and behavior.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOverall, our findings indicate that individuals with AN show increased activation in the right posterior insula during self-produced affective touch. While we did not find this activation for HC, we did not find a significant difference between groups, except for an exploratory comparison of extracted parameters. This indicates an overlap of activation during self-touch between groups, probably driven by individual variance. This individual variance related differently to body image disturbance: correlations between insular activation and scores from self-report questionnaires on body image disturbances were found for both HC and AN, but in opposite directions. This points to a processing difference between those who are dissatisfied with their body but do not have an eating disorder and those who are dissatisfied with their body and have AN. This difference could be due to increased prediction errors in the right posterior insula during self-touch in AN. Further studies evaluating AN through the lens of self-produced sensory input is valuable and could further elaborate on the role of prediction errors in onset and/or duration of AN. Therapeutic interventions that incorporate adapting to self-touch or other types of self-produced input could hold promise for improving outcomes in individuals with AN.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003eParticipants\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Regional Ethical Board of Link\u0026ouml;ping (2017/443-31, 2018/444-32) and the Swedish Ethical Review Authority (2019-02821), and conducted in accordance with the Declaration of Helsinki. Participants provided written informed consent and completed the Body Attitude Test (BAT; [31]), Eating Disorder Examination Questionnaire (EDE-Q [32]), \u0026nbsp;and Figure Rating Scale (FRS; [40]), to assess body image disturbances and the severity of eating disorder symptomatology.\u003c/p\u003e\n\u003cp\u003eAdults (aged 18-35) with AN were recruited through the Child and Adolescent Psychiatric Clinic (18\u0026ndash;24\u0026nbsp;years) and the Psychiatric clinic (25\u0026ndash;35\u0026nbsp;years) in Link\u0026ouml;ping, Region \u0026Ouml;sterg\u0026ouml;tland. Clinical staff first informed potential participants of the study. Interested participants were then contacted by a research nurse (not involved in patients\u0026rsquo; treatment) who gave further verbal and written information about the study and screened the participants for the inclusion and exclusion criteria. Participants were included on the conditions: DSM-5 diagnosis of anorexia nervosa, including atypical anorexia nervosa and unspecified (all restrictive type), BMI\u0026nbsp;\u0026le;\u0026nbsp;20\u0026nbsp;kg/m2, and MRI-compatibility. Participants were either free of psychotropic medications or on stable (at least three months on the same dose) medication with antidepressants. On-demand use of mild anxiolytics and hypnotics, treatment with central stimulants (if avoided on MRI day) were also accepted. Exclusion criteria were: psychotic disorder, bipolar disorder, substance use disorder, ongoing treatment with antipsychotics or tricyclic antidepressants, previous severe head injury, birth before 33 weeks\u0026apos; gestation, hearing impairment, previous epilepsy or seizure, claustrophobia, pregnancy, and cognitive disabilities. In total 44 participants were included in the current study.\u003c/p\u003e\n\u003cp\u003eHealthy controls (HC) were recruited online through social media advertisements and on the university website as well as through our local participant database. Participants were included based on Swedish fluency, acceptance of skin-to-skin touch on the arm, and willingness to undergo an MRI scan. Exclusion criteria were assessed via a standardized phone interview screening [41] and included any psychiatric diagnoses or medication, history of disordered eating, excessive substance use, chronic pain, and any health issues related to touch perception or MRI safety. In total 40 participants were recruited and, with one participant not completing all of the questionnaires, 39 participants were included in the analyses for HC.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTouch task\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eParticipants performed the self-other-touch task as standardized in previous literature [20, 42]: they lay in an fMRI with their left arm across their abdomen and a pillow on the abdomen beside the arm. The right arm was propped up as close to the left arm and pillow as possible using pillows. The touch task consisted of three conditions: self-touch, other-touch, and object-touch. During self-touch, participants gently stroked their left forearm with their right hand. During other-touch, participants were gently stroked on the left forearm by a female researcher. During object-touch, participants stroked a pillow with their right hand. The object-touch condition was used as a control for the movement in the self-touch condition. Goggles displayed instructions for the task. Instructions read (in Swedish), \u0026lsquo;Active, please stroke your arm\u0026rsquo;, \u0026lsquo;Passive, the researcher will stroke your arm\u0026rsquo;, \u0026lsquo;Active, please stroke the object\u0026rsquo;. Instructions were provided on a white background for three seconds before turning green to indicate when the condition should begin. Each condition lasted for 12 seconds, with 12 seconds of rest in between. Conditions were repeated ten times each, for a total of 30 trials in random order.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003efMRI\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA 3.0 Tesla scanner (Prisma; Siemens) with a 64-channel head coil was used to acquire T1-weighted anatomical images (repetition time = 2300 ms; echo time = 2.36 ms; flip angle = 8\u0026deg;; field of view = 288 \u0026times; 288 mm2; voxel resolution = 0.87 \u0026times; 0.87 \u0026times; 0.90 mm3) and T2-weighted echo-planar images (EPIs) containing 48 multiband slices (repetition time: 1030 ms; echo time: 30 ms; slice thickness: 3 mm; matrix size: 64 \u0026times; 64; field of view: 192 \u0026times; 192 mm2; in-plane voxel resolution: 3 mm2; flip angle: 63\u0026deg;). Statistical parametric mapping (SPM12; Wellcome Department of Imaging Neuroscience) in Matlab R2018b (MathWorks) was used to analyze fMRI data. Preprocessing steps included: Correction for motion using SPM\u0026rsquo;s realign-module registering to the mean EPI after a first realignment (quality = 0.9, separation = 4, smoothing = 5 full width at half-maximum kernel, interpolation with 4th degree B-Spline), coregistration of the anatomical image and mean EPI using normalized mutual information, segmentation of the T1 image using the unified segmentation approach [43], and spatial normalization of T1 and EPIs to the Montreal Neurological Institute T1 template (using forward deformations from the segmentation step, voxel size 2*2*2 for resampling, and 4th Degree B-Spline for interpolation). All functional images were spatially smoothed with an isotropic Gaussian kernel of 6-mm full width at half-maximum.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAnalysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAt the single-subject level, regressors of interest consisted of self-touch, other-touch, and object-touch blocks. Regressors of no-interest were added for the cue phase (separately for each block), and arm movements after each active block (1\u0026thinsp;sec) when subjects moved the arm back into the resting position. To account for movement-associated variance, realignment parameters and their first temporal derivates were included as regressors of no interest, as well as a regressor censoring scans with more than 1\u0026thinsp;mm scan-to-scan movement. For the analysis here, our hypothesis concerned the self-touch condition. Therefore, contrast maps were generated for the self-touch vs. object-touch condition at the single subject level.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt the group-level, one sample t-test for the self-object contrast was calculated for evaluation of the AN group and extraction of beta-parameters. For completeness, a one-sample t-test per group was evaluated for the other-touch condition as well. Two sample t-tests were used for between-group comparisons. For whole-brain analyses, results were corrected for multiple comparisons using the family-wise error (FWE) correction at the voxel-level [44]. Additionally, as an exploratory analysis, a region of interest (ROI) mask [45, 46] was used for the posterior insula, which is known to process affective touch, \u0026nbsp;to obtain a small volume correction given our hypothesis. Mean beta-parameters from this ROI were extracted and correlated with values from BAT and FRS questionnaires.\u003c/p\u003e\n\u003cp\u003eDue to inequality of variance, Mann-Whitney tests were performed for between-group measures for the questionnaires.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Lisa Engberg and Anna Elander for help with patient recruitment, and Adam Enmalm for help with data collection.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by grants from the Swedish Medical Research Council (2015-02684) to HO, from ALF, Region \u0026Ouml;sterg\u0026ouml;tland (R\u0026Ouml;-702221; R\u0026Ouml;-837632; R\u0026Ouml;-893981; R\u0026Ouml;-940701) to MZ, from the Swedish Society of Medicine (SLS-784151; SLS-960468; SLS-878101) to MZ and RB, and from Lions Forskningsfond (liu-2019-01191) to RB.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRediT authorship contribution statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMorgan Frost-Karlsson:\u003c/em\u003e Conceptualization, Data curation, Formal analysis, Investigation, Project administration, Visualization, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing. \u003cem\u003eMaria Zetterqvist:\u003c/em\u003e Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing \u0026ndash; review \u0026amp; editing. \u003cem\u003eH\u0026aring;kan Olausson:\u0026nbsp;\u003c/em\u003eConceptualization, Funding acquisition, Methodology, Resources, Supervision, Writing \u0026ndash; review \u0026amp; editing. \u003cem\u003eRebecca Boehme:\u003c/em\u003e Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Software, Supervision, Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during the current study are not publicly available due to ethical considerations, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFairburn, C.G., \u003cem\u003eCognitive behavior therapy and eating disorders\u003c/em\u003e. 2008: Guilford Press.\u003c/li\u003e\n\u003cli\u003eKeizer, A., et al., \u003cem\u003eTactile body image disturbance in anorexia nervosa.\u003c/em\u003e Psychiatry research, 2011. \u003cstrong\u003e190\u003c/strong\u003e(1): p. 115\u0026ndash;120.\u003c/li\u003e\n\u003cli\u003eKeizer, A., et al., \u003cem\u003eToo fat to fit through the door: first evidence for disturbed body-scaled action in anorexia nervosa during locomotion.\u003c/em\u003e PLOS one, 2013. \u003cstrong\u003e8\u003c/strong\u003e(5): p. e64602.\u003c/li\u003e\n\u003cli\u003eSalvato, G., et al., \u003cem\u003eDissociations between bodily self-awareness components in women with Anorexia Nervosa.\u003c/em\u003e Translational Psychiatry, 2025. \u003cstrong\u003e15\u003c/strong\u003e(1): p. 109.\u003c/li\u003e\n\u003cli\u003eMcGlone, F., J. Wessberg, and H. Olausson, \u003cem\u003eDiscriminative and affective touch: sensing and feeling.\u003c/em\u003e Neuron, 2014. \u003cstrong\u003e82\u003c/strong\u003e(4): p. 737\u0026ndash;755.\u003c/li\u003e\n\u003cli\u003eZucker, N.L., et al., \u003cem\u003eSubjective experience of sensation in anorexia nervosa.\u003c/em\u003e Behaviour research and therapy, 2013. \u003cstrong\u003e51\u003c/strong\u003e(6): p. 256\u0026ndash;265.\u003c/li\u003e\n\u003cli\u003eCrucianelli, L., et al., \u003cem\u003eThe perception of affective touch in anorexia nervosa.\u003c/em\u003e Psychiatry research, 2016. \u003cstrong\u003e239\u003c/strong\u003e: p. 72\u0026ndash;78.\u003c/li\u003e\n\u003cli\u003eCrucianelli, L., et al., \u003cem\u003eThe anticipation and perception of affective touch in women with and recovered from Anorexia Nervosa.\u003c/em\u003e neuroscience, 2021. \u003cstrong\u003e464\u003c/strong\u003e: p. 143\u0026ndash;155.\u003c/li\u003e\n\u003cli\u003eOlausson, H., et al., \u003cem\u003eUnmyelinated tactile afferents signal touch and project to insular cortex.\u003c/em\u003e Nature neuroscience, 2002. \u003cstrong\u003e5\u003c/strong\u003e(9): p. 900\u0026ndash;904.\u003c/li\u003e\n\u003cli\u003eCraig, A.D., \u003cem\u003eHow do you feel\u0026mdash;now? The anterior insula and human awareness.\u003c/em\u003e Nature reviews neuroscience, 2009. \u003cstrong\u003e10\u003c/strong\u003e(1): p. 59\u0026ndash;70.\u003c/li\u003e\n\u003cli\u003eFrank, G.K., et al., \u003cem\u003eAlterations in brain structures related to taste reward circuitry in ill and recovered anorexia nervosa and in bulimia nervosa.\u003c/em\u003e American Journal of Psychiatry, 2013. \u003cstrong\u003e170\u003c/strong\u003e(10): p. 1152\u0026ndash;1160.\u003c/li\u003e\n\u003cli\u003eFriederich, H.-C., et al., \u003cem\u003eNeural correlates of body dissatisfaction in anorexia nervosa.\u003c/em\u003e Neuropsychologia, 2010. \u003cstrong\u003e48\u003c/strong\u003e(10): p. 2878\u0026ndash;2885.\u003c/li\u003e\n\u003cli\u003eGaudio, S., et al., \u003cem\u003eA systematic review of resting-state functional-MRI studies in anorexia nervosa: evidence for functional connectivity impairment in cognitive control and visuospatial and body-signal integration.\u003c/em\u003e Neuroscience \u0026amp; Biobehavioral Reviews, 2016. \u003cstrong\u003e71\u003c/strong\u003e: p. 578\u0026ndash;589.\u003c/li\u003e\n\u003cli\u003eGeisler, D., et al., \u003cem\u003eAbnormal functional global and local brain connectivity in female patients with anorexia nervosa.\u003c/em\u003e Journal of Psychiatry and Neuroscience, 2016. \u003cstrong\u003e41\u003c/strong\u003e(1): p. 6\u0026ndash;15.\u003c/li\u003e\n\u003cli\u003eLucherini Angeletti, L., et al., \u003cem\u003eAnorexia nervosa as a disorder of the subcortical\u0026ndash;cortical interoceptive-self.\u003c/em\u003e Eating and Weight Disorders-Studies on Anorexia, Bulimia and Obesity, 2022. \u003cstrong\u003e27\u003c/strong\u003e(8): p. 3063\u0026ndash;3081.\u003c/li\u003e\n\u003cli\u003eTose, K., et al., \u003cem\u003eSystematic reduction of gray matter volume in anorexia nervosa, but relative enlargement with clinical symptoms in the prefrontal and posterior insular cortices: a multicenter neuroimaging study.\u003c/em\u003e Molecular Psychiatry, 2024. \u003cstrong\u003e29\u003c/strong\u003e(4): p. 891\u0026ndash;901.\u003c/li\u003e\n\u003cli\u003eZucker, N.L., et al., \u003cem\u003eThe clinical significance of posterior insular volume in adolescent anorexia nervosa.\u003c/em\u003e Psychosomatic medicine, 2017. \u003cstrong\u003e79\u003c/strong\u003e(9): p. 1025\u0026ndash;1035.\u003c/li\u003e\n\u003cli\u003eKurth, F., et al., \u003cem\u003eA link between the systems: functional differentiation and integration within the human insula revealed by meta-analysis.\u003c/em\u003e Brain Structure and Function, 2010. \u003cstrong\u003e214\u003c/strong\u003e: p. 519\u0026ndash;534.\u003c/li\u003e\n\u003cli\u003eKlein, T.A., M. Ullsperger, and C. Danielmeier, \u003cem\u003eError awareness and the insula: links to neurological and psychiatric diseases.\u003c/em\u003e Frontiers in human neuroscience, 2013. \u003cstrong\u003e7\u003c/strong\u003e: p. 14.\u003c/li\u003e\n\u003cli\u003eBoehme, R., et al., \u003cem\u003eDistinction of self-produced touch and social touch at cortical and spinal cord levels.\u003c/em\u003e Proceedings of the National Academy of Sciences, 2019. \u003cstrong\u003e116\u003c/strong\u003e(6): p. 2290\u0026ndash;2299.\u003c/li\u003e\n\u003cli\u003eFrost-Karlsson, M., et al., \u003cem\u003eNeural processing of self-touch and other-touch in anorexia nervosa and autism spectrum condition.\u003c/em\u003e NeuroImage: Clinical, 2022. \u003cstrong\u003e36\u003c/strong\u003e: p. 103264.\u003c/li\u003e\n\u003cli\u003eFriston, K., \u003cem\u003eThe free-energy principle: a unified brain theory?\u003c/em\u003e Nature reviews neuroscience, 2010. \u003cstrong\u003e11\u003c/strong\u003e(2): p. 127\u0026ndash;138.\u003c/li\u003e\n\u003cli\u003eRiva, G., \u003cem\u003eNeuroscience and eating disorders: The allocentric lock hypothesis.\u003c/em\u003e Medical Hypotheses, 2012. \u003cstrong\u003e78\u003c/strong\u003e(2): p. 254\u0026ndash;257.\u003c/li\u003e\n\u003cli\u003eFrank, G.K., et al., \u003cem\u003ePrediction error and somatosensory insula activation in women recovered from anorexia nervosa.\u003c/em\u003e Journal of Psychiatry and Neuroscience, 2016. \u003cstrong\u003e41\u003c/strong\u003e(5): p. 304\u0026ndash;311.\u003c/li\u003e\n\u003cli\u003eJappe, L.M., et al., \u003cem\u003eHeightened sensitivity to reward and punishment in anorexia nervosa.\u003c/em\u003e International Journal of Eating Disorders, 2011. \u003cstrong\u003e44\u003c/strong\u003e(4): p. 317\u0026ndash;324.\u003c/li\u003e\n\u003cli\u003eCash, T.F. and E.A. Deagle III, \u003cem\u003eThe nature and extent of body\u003c/em\u003e\u003cem\u003e‐image disturbances in anorexia nervosa and bulimia nervosa: A meta\u003c/em\u003e\u003cem\u003e‐analysis.\u003c/em\u003e International journal of eating disorders, 1997. \u003cstrong\u003e22\u003c/strong\u003e(2): p. 107\u0026ndash;126.\u003c/li\u003e\n\u003cli\u003eKeel, P.K., et al., \u003cem\u003ePostremission predictors of relapse in women with eating disorders.\u003c/em\u003e American Journal of Psychiatry, 2005. \u003cstrong\u003e162\u003c/strong\u003e(12): p. 2263\u0026ndash;2268.\u003c/li\u003e\n\u003cli\u003eLegrand, D., \u003cem\u003eSubjective and physical dimensions of bodily self-consciousness, and their dis-integration in anorexia nervosa.\u003c/em\u003e Neuropsychologia, 2010. \u003cstrong\u003e48\u003c/strong\u003e(3): p. 726\u0026ndash;737.\u003c/li\u003e\n\u003cli\u003eB\u0026ouml;hme, R., \u003cem\u003eThe Touched Body and the Experience of Self\u003c/em\u003e. 2025, Springer.\u003c/li\u003e\n\u003cli\u003eBerends, T., et al., \u003cem\u003eRate, timing and predictors of relapse in patients with anorexia nervosa following a relapse prevention program: a cohort study.\u003c/em\u003e BMC psychiatry, 2016. \u003cstrong\u003e16\u003c/strong\u003e(1): p. 1\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eProbst, M., et al., \u003cem\u003eThe Body Attitude Test for patients with an eating disorder: Psychometric characteristics of a new questionnaire.\u003c/em\u003e Eating disorders, 1995. \u003cstrong\u003e3\u003c/strong\u003e(2): p. 133\u0026ndash;144.\u003c/li\u003e\n\u003cli\u003eHilbert, A., et al., \u003cem\u003eEating disorder examination-questionnaire.\u003c/em\u003e Diagnostica, 2007. \u003cstrong\u003e53\u003c/strong\u003e(3): p. 144\u0026ndash;154.\u003c/li\u003e\n\u003cli\u003eBlakemore, S.J., S.J. Goodbody, and D.M. Wolpert, \u003cem\u003ePredicting the consequences of our own actions: the role of sensorimotor context estimation.\u003c/em\u003e Journal of Neuroscience, 1998. \u003cstrong\u003e18\u003c/strong\u003e(18): p. 7511\u0026ndash;7518.\u003c/li\u003e\n\u003cli\u003eB\u0026auml;r, K.J., et al., \u003cem\u003eInsular dysfunction and descending pain inhibition in anorexia nervosa.\u003c/em\u003e Acta Psychiatrica Scandinavica, 2013. \u003cstrong\u003e127\u003c/strong\u003e(4): p. 269\u0026ndash;278.\u003c/li\u003e\n\u003cli\u003eMonteleone, A.M., et al., \u003cem\u003eAltered processing of rewarding and aversive basic taste stimuli in symptomatic women with anorexia nervosa and bulimia nervosa: An fMRI study.\u003c/em\u003e Journal of psychiatric research, 2017. \u003cstrong\u003e90\u003c/strong\u003e: p. 94\u0026ndash;101.\u003c/li\u003e\n\u003cli\u003eUher, R., et al., \u003cem\u003eFunctional neuroanatomy of body shape perception in healthy and eating-disordered women.\u003c/em\u003e Biological psychiatry, 2005. \u003cstrong\u003e58\u003c/strong\u003e(12): p. 990\u0026ndash;997.\u003c/li\u003e\n\u003cli\u003eBischoff-Grethe, A., et al., \u003cem\u003eNeural hypersensitivity to pleasant touch in women remitted from anorexia nervosa.\u003c/em\u003e Translational psychiatry, 2018. \u003cstrong\u003e8\u003c/strong\u003e(1): p. 161.\u003c/li\u003e\n\u003cli\u003eWierenga, C.E., et al., \u003cem\u003eIncreased anticipatory brain response to pleasant touch in women remitted from bulimia nervosa.\u003c/em\u003e Translational psychiatry, 2020. \u003cstrong\u003e10\u003c/strong\u003e(1): p. 236.\u003c/li\u003e\n\u003cli\u003eEhrlich, S., et al., \u003cem\u003eReduced functional connectivity in the thalamo\u003c/em\u003e\u003cem\u003e‐insular subnetwork in patients with acute anorexia nervosa.\u003c/em\u003e Human Brain Mapping, 2015. \u003cstrong\u003e36\u003c/strong\u003e(5): p. 1772\u0026ndash;1781.\u003c/li\u003e\n\u003cli\u003eThompson, J.K. and M.N. Altabe, \u003cem\u003ePsychometric qualities of the figure rating scale.\u003c/em\u003e International Journal of Eating Disorders, 1991. \u003cstrong\u003e10\u003c/strong\u003e(5): p. 615\u0026ndash;619.\u003c/li\u003e\n\u003cli\u003eAlexander, M.J., et al., \u003cem\u003eMental health screening in addiction, corrections and social service settings: Validating the MMS.\u003c/em\u003e International Journal of Mental Health and Addiction, 2008. \u003cstrong\u003e6\u003c/strong\u003e: p. 105\u0026ndash;119.\u003c/li\u003e\n\u003cli\u003eFrost-Karlsson, M., et al., \u003cem\u003eAltered somatosensory processing in adult attention deficit hyperactivity disorder.\u003c/em\u003e BMC psychiatry, 2024. \u003cstrong\u003e24\u003c/strong\u003e(1): p. 558.\u003c/li\u003e\n\u003cli\u003eAshburner, J. and K.J. Friston, \u003cem\u003eUnified segmentation.\u003c/em\u003e neuroimage, 2005. \u003cstrong\u003e26\u003c/strong\u003e(3): p. 839\u0026ndash;851.\u003c/li\u003e\n\u003cli\u003eEklund, A., T.E. Nichols, and H. Knutsson, \u003cem\u003eCluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates.\u003c/em\u003e Proceedings of the national academy of sciences, 2016. \u003cstrong\u003e113\u003c/strong\u003e(28): p. 7900\u0026ndash;7905.\u003c/li\u003e\n\u003cli\u003eLarsson, M.B., et al., \u003cem\u003eBrain responses to visceral stimuli reflect visceral sensitivity thresholds in patients with irritable bowel syndrome.\u003c/em\u003e Gastroenterology, 2012. \u003cstrong\u003e142\u003c/strong\u003e(3): p. 463\u0026ndash;472. e3.\u003c/li\u003e\n\u003cli\u003eBoehme, R., et al., \u003cem\u003eAnhedonia to gentle touch in fibromyalgia: normal sensory processing but abnormal evaluation.\u003c/em\u003e Brain Sciences, 2020. \u003cstrong\u003e10\u003c/strong\u003e(5): p. 306.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"prediction errors, bodily self, fMRI, anorexia nervosa, body image disturbance, insula","lastPublishedDoi":"10.21203/rs.3.rs-7479995/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7479995/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBody image disturbance (BID) is a core feature of anorexia nervosa (AN), encompassing multimodal distortions in bodily self-perception. Affective touch, a gentle, emotionally salient tactile stimulus, is implicated in body ownership but has not been extensively studied in AN. Affective touch is processed in the insula, an area involved in interoception and bodily self-awareness which has been shown to be altered both structurally and functionally in AN. This study explored the neural mechanisms underlying BID by examining how individuals with AN process self-produced affective touch. Women with AN (n=44) and age-matched healthy controls (HC, n=40), participated in a self-other-object touch task during functional brain imaging and filled out questionnaires related to body image and eating disorder symptomatology. During self-touch, individuals with AN exhibited increased activation in the right posterior insula compared to object-touch, whereas HC did not. This insular activation correlated positively with BID measures in AN but negatively in HC, suggesting divergent processing of self-related tactile input. Here we identify the posterior insula as a potential neural marker of disturbed embodiment and demonstrate that the sensory processes which typically stabilize body ownership may exacerbate distorted body perception in AN. Broadening BID research beyond the visual modality opens new avenues for translational research and treatment.\u003c/p\u003e","manuscriptTitle":"Attenuation of self-produced touch in the posterior insula reflects body image disturbances in anorexia nervosa","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 10:00:01","doi":"10.21203/rs.3.rs-7479995/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-16T08:46:01+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-15T15:30:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-15T10:20:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"190836794009670684798495851007873428389","date":"2025-12-05T07:50:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"9055762306680023597837007766383690559","date":"2025-12-03T21:05:18+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-03T20:12:18+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-03T19:59:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-02T06:40:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-29T14:54:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-08-28T11:43:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
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