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Learn more: PMC Disclaimer | PMC Copyright Notice J Headache Pain . 2026 Mar 5;27(1):99. doi: 10.1186/s10194-026-02318-x Search in PMC Search in PubMed View in NLM Catalog Add to search Altered dorsal anterior insula functional connectivity underlying abnormal interoceptive accuracy awareness in migraine without aura Ruihua Liu Ruihua Liu 1 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China Find articles by Ruihua Liu 1 , Yuanxiang Li Yuanxiang Li 2 Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China Find articles by Yuanxiang Li 2 , Ruidi Wang Ruidi Wang 3 State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China 4 Department of Psychology, University of Chinese Academy of Sciences, Beijing, China Find articles by Ruidi Wang 3, 4 , Aoxuan Liu Aoxuan Liu 1 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China Find articles by Aoxuan Liu 1 , Lingqi Zhao Lingqi Zhao 5 School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China Find articles by Lingqi Zhao 5 , Piaoyi Li Piaoyi Li 1 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China Find articles by Piaoyi Li 1 , Yonggang Wang Yonggang Wang 6 Headache Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China Find articles by Yonggang Wang 6 , Jin Cao Jin Cao 1 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China Find articles by Jin Cao 1, ✉ Author information Article notes Copyright and License information 1 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China 2 Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 3 State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China 4 Department of Psychology, University of Chinese Academy of Sciences, Beijing, China 5 School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China 6 Headache Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China ✉ Corresponding author. Received 2025 Dec 10; Accepted 2026 Feb 26; Collection date 2026. © The Author(s) 2026 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ . PMC Copyright notice PMCID: PMC13072554 PMID: 41787270 Abstract Background Abnormal interoception is increasingly recognized as a key feature of migraine. The dorsal anterior insula (dAI) is hypothesized to play a central role in interoceptive processing, yet the neural mechanisms underlying this abnormality remain unclear. We aimed to investigate interoceptive disturbances in migraine and to clarify the role of insula dysfunction, specifically dAI functional connectivity, in underlying these interoceptive alterations and potentially contributing to the pathophysiology of migraine. Methods We recruited 29 patients with migraine without aura and 32 matched healthy controls. All participants completed evaluations of interoceptive accuracy and resting-state functional magnetic resonance imaging scans. We applied a multivariate seed-based connectivity approach to examine the direct connectivity of the bilateral dAI and its link to interoceptive awareness in migraine patients. We conducted a simple mediation analysis to determine whether specific dAI connectivity mediated variations in interoceptive awareness across groups. Finally, serial multiple mediation analysis was applied to explore whether these effects were conveyed via subjective or objective accuracy metrics. Results Migraine patients showed significantly enhanced interoceptive accuracy awareness compared with controls. Across all participants, this awareness was positively associated with functional connectivity from the right dAI to the bilateral precentral gyrus (PreCG). Crucially, this specific right dAI-bilateral PreCG connectivity was markedly enhanced in migraine patients. Simple mediation results indicated that increased dAI connectivity substantially mediated the group difference in interoceptive accuracy awareness. Serial multiple mediation analysis revealed that this effect was predominantly driven by objective interoceptive processing. Conclusions The observed altered dAI connectivity and its relationship with interoceptive awareness suggest that dysfunctions in interoceptive processes, particularly within the dAI-PreCG network, may be integral to the neuropathology of migraine. Keywords: Migraine, Insula, Interoception, Effective connectivity Introduction Growing neurological, clinical, and neuroimaging evidence indicates that interoceptive dysfunction—impaired sensing and interpreting of internal bodily signals—plays a critical role in the development and progression of migraine [ 1 – 3 ]. Cardinal migraine symptoms, including headache, nausea, and vomiting, are widely regarded as interoceptive phenomena [ 4 , 5 ]. Interoceptive interventions, including body-directed therapies [ 6 ] and noninvasive auricular vagus nerve stimulation [ 2 ], have demonstrated benefits in reducing migraine frequency and symptom burden. Moreover, migraine patients exhibit structural [ 3 , 4 ] and functional [ 4 , 7 ] alterations in core interoceptive regions (e.g., the insula, anterior cingulate cortex, and amygdala). A systematic review further highlights that connectivity patterns involving these regions may serve as neuroimaging biomarkers to distinguish migraine from other headaches [ 8 ]. Collectively, these findings indicate that migraine involves a complex dysfunction of interoceptive processing [ 9 ]. Interoception refers to the brain’s perception, integration, and predictive representation of internal bodily signals, facilitating the continuous monitoring and modulation of physiological states [ 5 , 10 ]. It is commonly regarded as multifaceted, divided into objective and subjective dimensions of accuracy and attention based on the type and target of measurement [ 11 ]. While objective accuracy evaluates performance on behavioral tasks, such as the heartbeat tracking task (HTT) [ 12 ], subjective accuracy reflects self-reported beliefs about the precision with which one can perceive bodily states (e.g., the Interoceptive Accuracy Scale, IAS) [ 13 ]. While objective attention is assessed through methods like experience sampling that capture the extent to which interoceptive signals are the focus of attention [ 14 ], subjective attention measures self-reported attentiveness to physical sensations (e.g., the Interoceptive Attention Scale) [ 15 ]. The distinction between these elements is essential when assessing interoceptive awareness, which is defined as the metacognitive understanding of one’s interoceptive abilities [ 11 , 16 ]. It is quantified by the correspondence between subjective and objective measures within the same domain, typically accuracy. Previous case-control studies have reported that migraine patients exhibit heightened interoceptive awareness, often overestimating their interoceptive capacities [ 17 ]. However, this previous work defined “awareness” as the alignment between subjective sensitivity and objective accuracy. This methodology presents a dimensional mismatch because the subjective sensitivity was assessed using the Porges Body Perception Questionnaire, which reflects subjective attention rather than accuracy [ 11 , 18 ]. To achieve a consistent and accurate quantification of interoceptive awareness as a metacognitive construct [ 11 , 16 ], the present study assesses the correspondence between subjective accuracy (using a dedicated accuracy scale) and objective accuracy (using a heartbeat tracking task). Converging evidence indicates that the insula is fundamental to interoceptive processing [ 19 – 21 ]. The insula operates with a posterior-to-anterior functional gradient: the posterior insula (PI) generates primary interoceptive representations of visceral signals, which are then reprocessed in the anterior insula (AI) and incorporated into higher-level cognitive, affective, and conscious processes [ 19 , 20 ]. The AI, containing distinctive von Economo neurons, is a key substrate of awareness and a possible neural correlate of consciousness [ 20 ]. It can be further fractionated: the dorsal AI (dAI), which interfaces with the cognitive control network and is implicated in attention, cognitive regulation, and awareness, and the ventral AI (vAI), which is strongly connected to the limbic system and facilitates emotional processing [ 22 , 23 ]. These insights identify the dAI as an essential hub that integrates bodily states with higher-level awareness. This raises the possibility that aberrant dAI functional connectivity (FC) may be linked to altered interoceptive accuracy awareness in migraine. Migraine patients show altered insula connectivity, including significant disruptions in functional coupling [ 24 – 29 ]. For instance, increased insula connectivity with the default mode and central executive networks correlates positively with migraine duration [ 24 ]. Moreover, diminished connectivity from the dAI to the pallidum is negatively related to headache frequency, while heightened connectivity to the middle temporal gyrus is positively related to headache intensity [ 26 ]. Nevertheless, the insula’s contribution to altered interoceptive awareness in migraine remains incompletely understood. Clarifying this relationship is essential for advancing knowledge of migraine-related neural mechanisms. Interoceptive accuracy awareness can be quantified by the interoceptive trait prediction error (ITPE), computed as the difference between standardized subjective and objective accuracy scores [ 30 ]. According to this concept, aberrant dAI FC may affect higher-order interoceptive awareness by disrupting either subjective or objective interoceptive accuracy. Mechanistically, determining which pathway is predominantly impacted offers crucial insight into how migraine distorts interoceptive awareness and may inform targeted treatment strategies. Despite growing evidence for interoceptive dysfunction in migraine, several critical gaps remain. Existing research has frequently relied on dimensionally mismatched assessments of interoceptive awareness [ 17 ] and has seldom targeted the dAI—a key hub linking bodily signals to higher-order awareness. Moreover, few studies have directly related behavioral indices of interoceptive awareness to dAI-based functional connectivity. To address these gaps, the present study integrates dimensionally matched measures of interoceptive awareness with whole-brain connectivity analyses to examine the specific role of dAI connectivity in migraine-related interoceptive awareness disturbances. We primarily hypothesized that interoceptive awareness would differ in migraine patients and that shift would be related to abnormal dAI functional connectivity. As a secondary hypothesis, we proposed that dAI connectivity alterations would mediate group differences in awareness through either subjective or objective accuracy pathways. To investigate these hypotheses, resting-state functional magnetic resonance imaging (fMRI) data and interoceptive accuracy measures were acquired from migraine patients and healthy controls (HCs). Interoceptive accuracy awareness was quantified and compared between groups. Effective connectivity of the dAI was analyzed using a multivariate seed-based connectivity (mSBC) approach, while discounting effects from other insular subregions. The analyses proceeded as follows: (1) identify relevant dAI connections associated with interoceptive awareness across all participants, followed by group comparisons; (2) simple mediation analysis to test whether dAI connectivity accounted for group differences in awareness; and (3) serial multiple mediation analysis to determine whether these effects were mediated through subjective or objective accuracy. Methods The research was authorized by the Medical Ethics Committee of Beijing University of Chinese Medicine (2024BZYLL0910). In accordance with the Declaration of Helsinki, each participant provided written informed consent prior to being included in the study. Participants Thirty-two patients with episodic migraine (EM) without aura were enrolled in the Headache Center, Beijing Tiantan Hospital, Capital Medical University. Each patient’s diagnosis was confirmed by at least two senior neurologists. Inclusion criteria: (1) diagnosis of EM without aura, according to the International Classification of Headache Disorders, 3rd Edition (ICHD-Ⅲ); (2) age between 18 and 65 years; (3) self-reported right-handedness; (4) eligibility for magnetic resonance imaging (MRI) scans; (5) interictal period, defined as more than 72 h after the last migraine attack and at least 48 h before the next; (6) no use of migraine preventive medications in the past 3 months and no intake of acute medication within 72 h prior to scanning. Exclusion criteria: (1) significant brain lesions; (2) other types of headaches; (3) other chronic pain conditions; and (4) pregnancy or lactation. Thirty-two healthy participants, matched in age and gender, were enlisted as controls. They had no history of neurological or mental problems. Applicable inclusion/exclusion criteria from the migraine group (e.g., medication usage, chronic pain disorders, pregnancy or lactation) were uniformly applied to the healthy participants to ensure group homogeneity. Clinical assessments Migraine duration, monthly migraine days, headache intensity measured by the visual analogue scale (VAS), as well as Headache Impact Test-6 (HIT-6) and Migraine-Specific Quality of Life Questionnaire (MSQ) scores, were collected for all patients. Behavioral assessments Subjective interoceptive accuracy The 20-item IAS was used to evaluate self-reported beliefs regarding interoceptive accuracy, covering bodily sensations such as heart rate and pain [ 11 , 13 ]. Scores range from 20 to 100 (5-point scale, 1–5 per item), with higher scores reflecting greater perceived accuracy. Objective interoceptive accuracy The HTT assessed objective interoceptive accuracy [ 11 , 12 , 31 ]. Participants were instructed to silently count their perceived heartbeats between “start” and “stop” without checking their pulse or estimating heart rate. The task comprised four randomized trials lasting 25, 35, 45, and 60 s. Electrocardiogram signals were continuously recorded using a Biopac multi-channel system to obtain actual heartbeats. Participants were not provided with any information about trial durations or their performance during the task. Objective accuracy was calculated as: 1 − (|nbeatsreal − nbeatsreported|)/((nbeatsreal + nbeatsreported)/2) [ 31 ]. The overall objective accuracy score (range 0–1) was averaged across trials, with higher scores reflecting greater objective accuracy. Interoceptive accuracy awareness Interoceptive awareness was quantified using the ITPE, which captures the correspondence between subjective and objective measures within the same interoceptive domain [ 11 , 16 , 30 ]. ITPE was defined as the difference between Z-scores of subjective and objective measures, with Z-scores standardized across the complete sample to uphold group-level distinctions [ 30 ]. For interoceptive accuracy, ITPE was calculated as IAS Z-scores minus HTT Z-scores. Positive values reflect overestimation of accuracy, whereas negative values reflect underestimation. MRI data acquisition All imaging was performed at the Center for Biomedical Imaging Research, Tsinghua University, using a 3T Siemens MAGNETOM Prisma scanner. During the 9-min blood oxygen level dependent (BOLD) signal scan, participants were required to remain still and awake, maintain their eyes open and fixated on a cross, and refrain from deliberate thinking. High-resolution 3D T1-weighted anatomical images were acquired using a MPRAGE sequence (repetition time (TR) = 1500 ms; echo time (TE) = 1.87 ms; field of view (FOV) = 256 × 256 mm²; slice thickness = 0.8 mm; 208 slices; flip angle = 10°). Resting-state BOLD functional images were collected using a gradient echo-planar imaging sequence (TR/TE = 750/30 ms; FOV = 216 × 216 mm²; slice thickness = 2.4 mm; slice gap = 1 mm; flip angle = 60°), yielding 697 volumes. fMRI data preprocessing Preprocessing was performed in the CONN toolbox version 22 ( https://www.nitrc.org/projects/conn ) [ 32 ]. The pipeline comprised: (1) removal of the first five volumes; (2) slice-timing correction (multiband acceleration factor = 6; interleaved acquisition order, e.g., 1, 8, 5, 2, 9, 6, 3, 10, 7, 4, …; reference slice = middle slice); (3) realignment; (4) outlier detection (scans with framewise displacement (FD) > 0.5 mm or global BOLD signal changes > 3 s.d. flagged as outliers); (5) co-registration; (6) segmentation in native space; (7) normalization to the Montreal Neurological Institute (MNI) space; (8) spatial smoothing with a 6-mm full-width at half maximum (FWHM) Gaussian kernel; (9) denoising including regression of white matter (WM), cerebrospinal fluid (CSF), motion parameters, identified outlier scans, and linear trends, without global signal regression; followed by (10) band-pass filtering (0.008–0.1 Hz). Participants with a mean Jenkinson FD ≥ 0.2 were excluded from all analyses; three patients met this criterion and were removed. Demographic and behavioral data analysis Gender differences were assessed using the chi-square test. Continuous variables, including age and behavioral measures, were evaluated for normality with the Shapiro-Wilk test. Group comparisons were conducted using independent-samples t tests for normally distributed data and Mann–Whitney U tests for non-normal data. A two-tailed p < 0.05 was considered statistically significant. Functional connectivity analysis Seed-based connectivity analyses were conducted in the CONN toolbox. Six spherical regions of interest (ROIs; radius = 6 mm), representing the tripartite functional subdivision of the insula [ 23 ], were defined at the following MNI coordinates: left PI (− 38, − 6, 5) and right PI (35, − 11, 6); left vAI (− 33, 13, − 7) and right vAI (32, 10, − 6); as well as left dAI (L_dAI: −38, 6, 2) and right dAI (R_dAI: 35, 7, 3). The bilateral dAI, given its established role in higher-level interoceptive awareness, was designated as the seed for whole-brain connectivity analyses, while the remaining insular ROIs were included to control for shared variance. Effective connectivity was assessed using mSBC, generating semipartial correlation maps by correlating the dAI BOLD signal with that of each voxel while discounting the effects of the other insular ROIs. Regression analyses across all participants were performed to identify dAI connectivity associated with interoceptive accuracy awareness ( p < 0.001 uncorrected at the voxel level and p < 0.05 FDR-corrected at the cluster level). Connectivity measures were then compared between groups, with multiple comparisons corrected using FDR. All statistical tests were two-tailed, with significance defined as p < 0.05 FDR-corrected. We adopted cluster-level FDR correction because it provides an effective balance between sensitivity and error control [ 33 ]. This approach helps to reduce excessive false negatives in high-dimensional voxel-wise analyses and maintains statistical power even with a relatively small sample size [ 34 ], making it particularly suitable for the current seed-based connectivity study. Simple mediation model analysis Mediation analyses were performed with the SPSS PROCESS macro (Model 4) to examine whether dAI connectivity mediates the effect of group (migraine vs. control) on interoceptive accuracy awareness. The group served as the independent variable, interoceptive accuracy awareness as the dependent variable, and dAI connectivity as the mediator. Anxiety and depression scores were included as covariates to account for the common comorbidity of migraine with affective symptoms. Mediation was significant if the bootstrapped 95% confidence interval (5,000 samples) for the indirect effect excluded zero; the direct effect was significant at p < 0.05. Serial multiple mediation analysis We adopted a two-step analytic strategy to determine whether dAI FC influences interoceptive accuracy awareness via subjective or objective interoceptive accuracy. First, Pearson correlation analyses were conducted to assess whether dAI FC was significantly associated with subjective or objective accuracy. Measures that demonstrated significant associations were then entered into serial multiple mediation analyses using PROCESS Model 6. The independent variable was group (migraine vs. control), the dependent variable was interoceptive accuracy awareness, and the mediators, in series, were dAI FC and either subjective or objective interoceptive accuracy. Anxiety and depression scores were included as covariates. Mediation was deemed significant if the bootstrapped 95% confidence interval (5,000 samples) for the indirect effect did not include zero, and direct effects were evaluated at p < 0.05. Results Demographic and clinical characteristics The final analysis included 29 patients with migraine and 32 HCs. Demographic and clinical characteristics are detailed in Table 1 . There were no significant group differences in sex ( P = 0.41) or age ( P = 0.26). Table 1. Demographic and clinical features of participants Demographics Sample size MO HC P -value 29 32 Age 31.97 ± 7.60 29.69 ± 7.91 0.26 Gender 22 females (76%) 21 females (66%) 0.41 Clinical symptoms Duration (Years) 13.34 ± 5.42 -- -- Pain intensity (VAS) 7.66 ± 1.42 -- -- Monthly migraine days 4.31 ± 2.29 -- -- HIT-6 66.52 ± 5.90 -- -- MSQ 54.26 ± 23.40 -- -- Open in a new tab Abbreviations: MO, Migraine without aura; HC, Healthy control; VAS, Visual analogue scale; HIT-6, Headache Impact Test-6; MSQ, Migraine Specific Quality of Life Questionnaire Values are mean ± standard deviation Subjective and objective interoceptive accuracy Subjective interoceptive accuracy did not differ significantly between groups ( P = 0.515). However, objective interoceptive accuracy differed significantly between groups, with migraine patients exhibiting lower performance than HCs ( P = 0.004). Interoceptive accuracy awareness In HCs, interoceptive accuracy awareness deviated marginally from zero ( t = 2.049, P = 0.049, 95% CI [-1.010, -0.002]), reflecting a modest propensity for underestimation. Conversely, migraine patients showed values significantly greater than zero ( t = 2.358, P = 0.026, 95% CI [0.081, 1.148]), indicating a bias toward inflated self-evaluation of interoceptive performance. Overall, migraine patients exhibited considerably elevated interoceptive accuracy awareness compared to HCs, characterized by heightened subjective confidence alongside reduced objective accuracy ( t = 3.122, P = 0.003; M MO = 0.61, SD MO = 1.40, M HC = -0.51, SD HC = 1.40; Cohen’s d = 0.80; Fig. 1 A). Fig. 1. Open in a new tab Altered interoceptive accuracy awareness and dAI functional connectivity in MO. A The interoceptive accuracy awareness was increased in MO compared with HC. B Warm color represents the R_dAI FC correlated with interoceptive accuracy awareness. Cool color represents the L_dAI FC correlated with interoceptive accuracy awareness. C Correlation between interoceptive accuracy awareness and R_dAI-PreCG, L_dAI-PCu, and L_dAI-PCC FC in all subjects, HC, and MO. D MO showed significantly increased effective FC between the R_dAI and PreCG compared with HC. n.s. not significant; *: P < 0.05; **: P < 0.01; ***: P < 0.001 Whole-group regression: dAI connectivity related to interoceptive accuracy awareness Regression analysis across all participants revealed that interoceptive accuracy awareness was favorably correlated with R_dAI connectivity and inversely related with L_dAI connectivity. Specifically, interoceptive accuracy awareness showed a positive relationship with FC between R_dAI and the bilateral precentral gyrus (PreCG, k = 95, t = 4.51, P -FDR = 0.022; Table 2 ; Fig. 1 B, C), but a negative association with L_dAI connectivity to the bilateral precuneus (Pcu, k = 143, t = -4.77, P -FDR = 0.006; Table 2 ; Fig. 1 B, C) and to the bilateral posterior cingulate cortex (PCC, k = 96, t = -4.01, P -FDR = 0.027; Table 2 ; Fig. 1 B, C). Table 2. Left and right dAI direct connectivity associated with interoceptive accuracy awareness Seed Brain regions MNI coordinates x y z ——————— x y z Peak T value Cluster size Cluster level P -FDR corr. R_dAI Bilateral PreCG -2 -32 66 4.51 95 0.022 L_dAI Bilateral PCu 0 -70 26 -4.77 143 0.006 Bilateral PCC -8 -54 26 -4.01 96 0.027 Open in a new tab Abbreviations: R_dAI, right dorsal anterior insula; PreCG, precentral gyrus; L_dAI, left dorsal anterior insula; PCu, precuneus; PCC, posterior cingulate cortex Group differences in dAI connectivity related to interoceptive accuracy awareness The R_dAI-bilateral PreCG connectivity, positively linked with interoceptive accuracy awareness, was significantly greater in migraine patients than HCs ( P -FDR = 0.022; Cohen’s d = 0.60; Fig. 1 D). However, there were no appreciable differences in the connectivity between the L_dAI and the PCu or the PCC between the groups. Simple mediation model results The causal direction is deduced from theoretical presumptions rather than temporal precedence because these analyses are based on cross-sectional resting-state data. Simple mediation analysis showed that the R_dAI-bilateral PreCG FC significantly mediated the relationship between group and interoceptive accuracy awareness (total effect = 0.903, P = 0.0007; indirect effect = 0.302, 95% CI [0.073, 0.618]; Fig. 2 A). Fig. 2. Open in a new tab Path analyses of dAI functional connectivity effects on group differences in interoceptive accuracy awareness. A R_dAI-PreCG direct FC mediates group variations in interoceptive accuracy awareness. B Correlation of objective and subjective interoceptive accuracy with R_dAI-PreCG FC across all subjects, HC, and MO. C R_dAI-PreCG FC mediates group differences in interoceptive awareness via objective interoceptive accuracy. n.s., not significant; *: P < 0.05; **: P < 0.01; ***: P < 0.001. All mediation analyses were adjusted for anxiety and depression scores Serial multiple mediation analysis As noted above, the inferred causal direction is based on theory. Correlation analysis revealed that, across all subjects and within HCs, R_dAI-PreCG FC was significantly negatively correlated with objective interoceptive accuracy, whereas in patients, this coupling was disrupted (Fig. 2 B). There was no significant association found between R_dAI-PreCG FC and subjective interoceptive accuracy (Fig. 2 B). Based on these findings, we applied serial multiple mediation analysis to determine whether R_dAI-PreCG FC contributed to group differences in interoceptive accuracy awareness via objective accuracy. The analysis demonstrated a substantial serial indirect effect (group → R_dAI-PreCG FC strength → objective interoceptive accuracy → interoceptive accuracy awareness; indirect effect = 0.179, 95% CI [0.050, 0.360]; Fig. 2 C). In contrast, the pathway eliminating objective accuracy (group → R_dAI-PreCG FC strength → interoceptive accuracy awareness) was not significant (indirect effect = 0.123, 95% CI [-0.052, 0.356]; Fig. 2 C). These findings demonstrate that the effect of R_dAI-PreCG FC on awareness is particularly mediated through objective accuracy. Discussion Interoception’s role in migraine continues to be a major focus of research [ 1 , 17 , 35 ]. Given its central role in interoceptive awareness, the dorsal anterior insula warrants further investigation in migraine patients. In this study, we employed multivariate seed-based connectivity to investigate how changes in dAI connectivity, a region crucial to the neural mechanisms of migraine, relate to interoceptive accuracy awareness. Our principal findings demonstrate that interoceptive accuracy awareness is markedly altered in migraine patients and correlates with dAI connectivity. Importantly, this awareness bias is partly mediated by enhanced right dAI connectivity, which impacts awareness by altering objective accuracy. Notably, migraine patients exhibited significantly heightened interoceptive accuracy awareness, indicating a tendency to overestimate the accuracy of sensing internal bodily states [ 11 , 30 ], which is consistent with prior reports of heightened interoceptive awareness in migraine [ 17 ]. Notably, earlier studies defined interoceptive awareness as the alignment between subjective attention and objective accuracy, creating a dimensional mismatch, whereas our approach quantifies it along the same accuracy dimension, directly addressing this issue. Despite these methodological differences, the overall evidence indicates that patients may overestimate their capacity to accurately perceive subtle physiological signals, including vomiting or pain [ 5 , 13 ]. Importantly, this pattern may help distinguish migraine from other chronic pain conditions. A recent meta-analysis noted that only a small number of studies have examined interoceptive awareness in chronic pain populations (e.g., fibromyalgia, primary pain, secondary musculoskeletal pain, and neuropathic pain) and reported no significant differences compared with pain-free controls [ 36 ]. While the evidence remains limited, these findings imply that interoceptive overestimation may be more characteristic of migraine than of chronic pain conditions more broadly. A central observation is a positive correlation between interoceptive accuracy awareness and FC between the right dAI and the bilateral PreCG across all participants. The insula, a central hub of interoceptive system, exhibits greater connectivity in individuals with more precise bodily signal perception [ 10 ]. The anterior insula is central to the posterior-to-anterior functional hierarchy, integrating ascending physiological input with higher-order cognitive and awareness processes [ 19 , 20 ]. This region is notable for the presence of specialized von Economo neurons, which are commonly regarded as the primary cellular substrate of awareness and a possible neurological correlate of consciousness [ 20 ]. The dAI, strongly connected to the cognitive control network, supports the integration of bodily states with higher-level awareness and is essential for the accurate monitoring and evaluation of interoceptive signals [ 22 , 23 ]. The PreCG has been increasingly implicated in interoceptive processing. It shows robust activation during interoceptive tasks, suggesting its engagement in processing internal bodily signals [ 37 ]. Moreover, it contributes to the integration of multiple body-related signals, supporting bodily self-awareness [ 38 ]. Recent interoceptive predictive coding models highlight the involvement of the sensorimotor cortex, including the PreCG, in interoceptive prediction and its interaction with interoceptive states [ 39 ]. The PreCG also plays a crucial part in embodied processing by transforming sensory input from the body into more concretized body-state representations that support bodily perception at the awareness level [ 40 , 41 ]. For instance, interoceptive signals originating from the anterior insula, such as heartbeat or respiration, can be shaped within the PreCG into more specific representational formats, forming part of the basis for the conscious perception of these internal states. The interaction between R_dAI and PreCG may represent an “over-embodied” pattern of interoceptive processing, in which bodily information becomes overly concretized or granted excessive representational weight, making it appear more important and reliable for conscious judgments, reinforcing confidence in one’s interoceptive abilities. This interpretation is consistent with the embodied predictive interoceptive coding model, which contends that overweighed physiological signals might bias subjective awareness toward amplified internal experiences [ 42 ]. Therefore, enhanced R_dAI-PreCG connection may lead to overconfidence in body sensations at the awareness level, with subjective evaluations frequently surpassing objective performance. Migraine patients without aura showed substantially greater right dAI-bilateral PreCG connectivity than healthy controls, accompanied by enhanced interoceptive accuracy awareness. Previous migraine research has reported altered insular connectivity with regions involved in emotion (e.g., amygdala) [ 7 ], sensorimotor processing (e.g., postcentral gyrus, sensorimotor network) [ 28 , 43 ], and cognition (e.g., precuneus) [ 44 ], among others. However, the role of insular connectivity in migraine-related interoceptive disturbances remains largely unexplored. Our findings suggest that altered R_dAI-PreCG connectivity likely generates overspecification of body signals, reinforcing confidence in one’s interoceptive capacity. Simple mediation analysis indicated that the R_dAI-PreCG connectivity significantly mediated group disparities in interoceptive accuracy awareness. Together, these results indicate that enhanced dAI-PreCG connectivity may contribute to inflated self-evaluations of bodily perception in migraine, offering novel insights into the insula’s role in migraine-related interoceptive dysfunction. Specifically, enhanced dAI–PreCG FC may interfere with precise interoceptive monitoring and interpretation, thereby undermining predictive and adaptive regulation of bodily processes, resulting in a failure to maintain internal stability and function [ 10 , 42 , 45 ]. This interoceptive dysfunction may also dysregulate external sensory processing, contributing to heightened sensitivity to visual and auditory stimuli, including photophobia and phonophobia [ 1 , 10 , 46 ]. For example, studies of photophobia in migraine have shown that abnormal light processing is not restricted to visual pathways but involves cross-talk with trigeminal nociceptive circuits and autonomic regulatory systems, suggesting that disrupted interoceptive regulation can amplify sensory hypersensitivities [ 47 , 48 ]. Furthermore, variations in bodily states are intrinsically linked to the core affective dimensions—valence (pleasant-unpleasant) and arousal (activation-deactivation)—which collectively provide consciousness with its fundamental affective tone [ 10 , 49 , 50 ]. Accordingly, negative affective symptoms, such as anxiety, may be indicative of a sustained negative shift in affective tone associated with disrupted processing of bodily signals. This interpretation may also account for migraineurs’ heightened sensitivity to negative emotional stimuli [ 51 ]. For instance, Klamer et al. reported that migraineurs exhibited greater neural synchrony in multisensory integration regions and higher subjective ratings during exposure to negative valence emotional stimuli [ 51 ]. A persistent negative affective tone, arising from aberrant allostatic interoceptive processing, may bias patients toward stronger reactivity when encountering negative input, amplifying both behavioral sensitivity and the neural synchrony observed. Overall, increased dAI-PreCG connectivity may underlie migraine patients’ overestimation of interoceptive ability, potentially facilitating disease progression by interfering with the encoding and regulation of internal physiological signals. In other chronic pain conditions, insular connectivity alterations have also been reported, but these changes mainly involve networks supporting pain modulation [ 52 , 53 ], emotional processing [ 54 ], and cognitive control [ 55 ]. By contrast, the dAI-PreCG connectivity observed in migraine appears to diverge from patterns commonly described in other chronic pain populations and may be more closely related to migraine-associated interoceptive disturbances, rather than a general feature of chronic pain. The serial multiple mediation analysis provided a critical distinction, suggesting that the influence of the R_dAI-PreCG pathway on interoceptive awareness is primarily achieved by objective interoceptive processing. This indicates as this pathway strengthens, physiological signals may become overspecified or assigned excessive representational weight prior to awareness, thereby appearing disproportionately salient and dependable during conscious evaluation. This indirectly promotes overconfidence by reducing the accuracy of objective signal itself. These findings shed light on how this pathway distorts interoceptive accuracy awareness: its effects arise primarily from alterations in objective interoceptive accuracy, rather than biases in subjective evaluations of bodily sensations. This distinction implies that restoring accurate interoceptive awareness necessitates normalizing objective interoceptive signal processing, not merely altering subjective beliefs about bodily sensations. Interventions that directly enhance objective interoceptive ability are therefore more likely to recalibrate awareness. Cardiac biofeedback training is one prominent example. Multiple studies indicate that it considerably increases objective interoceptive accuracy without shifting subjective confidence in the short term [ 56 , 57 ]. This distinction shows that such interventions can particularly influence body signal processing that underlies objective interoception. Other approaches have also been found to improve objective interoceptive accuracy, such as heartbeat perceptual training [ 56 ], sensorimotor training [ 58 ], and real-time fMRI neurofeedback that modulates insular activity [ 59 ]. These therapies may be especially beneficial in correcting the overconfidence that arises from abnormal objective processing in migraine. In conclusion, the R_dAI-PreCG connectivity appears to influence exaggerated interoceptive confidence by altering objective interoceptive accuracy, suggesting that normalizing objective processing—such as cardiac biofeedback, sensorimotor training, and insula-based neurofeedback—represents promising avenues for restoring accurate interoceptive awareness in migraine patients. Notably, the key effects were restricted to the right dAI. This hemispheric specificity is consistent with prior interoception research suggesting functional differentiation within the insula. Specifically, interoceptive attention has been linked to the bilateral dorsal mid-anterior insula, whereas interoceptive accuracy appears to rely more strongly on the right dAI [ 60 , 61 ]. Importantly, converging neurobiological and neuroimaging evidence further indicates that the right AI plays a critical role in interoceptive awareness, supporting the monitoring and evaluation of internal bodily states [ 62 , 63 ]. Accordingly, the right-lateralized involvement of the dAI observed here may reflect its specific role in interoceptive accuracy awareness and provide a neural basis for the overestimation of interoceptive accuracy in migraine. Our research is subject to several potential limitations. First, the relatively modest sample size of migraine patients limited the statistical power of the analyses and prevented subgroup analyses based on key migraine-related clinical symptoms (e.g., nausea, vomiting, photophobia, and phonophobia). Accordingly, these findings should be considered preliminary until replicated in larger and more clinically diverse cohorts. Future studies are warranted to systematically assess and stratify patients according to major clinical features, which will help clarify the relationship between interoceptive dysfunction and specific migraine symptoms. Second, as a cross-sectional study, the present work cannot establish causal relationships between altered dAI-PreCG connectivity and interoceptive awareness. Future longitudinal or interventional investigations are needed to determine the directionality of these associations and further clarify their clinical relevance in migraine. In addition, no significant association was observed between core migraine features and interoceptive accuracy awareness or dAI–PreCG connectivity. This lack of correlation indicates that altered dAI-PreCG connectivity may represent a stable neural predisposition (trait) rather than a direct driver of acute attack fluctuations (state) [ 64 ]. Put differently, these connectivity changes may represent a relatively stable neural trait associated with migraine that differentiates patients from HCs, while the occurrence and severity of acute symptoms are shaped by transient internal and external factors and do not necessarily track with these stable network features. This may also reflect methodological variation in how awareness was quantified. Although the present study adopted a well-established prediction error approach, future work may benefit from evaluating awareness with receiver operating characteristic curves and corresponding area under the curve values [ 11 , 16 ]. Last but not least, we utilized the HTT to quantify objective interoceptive accuracy, a conventional and widely accepted methodology. Nonetheless, it is essential to acknowledge that this method primarily evaluated cardiac interoception, neglecting other interoceptive modalities such as respiratory, gastric, or broader visceral sensations. Given the diverse dimensions of interoception, forthcoming research endeavors could amalgamate assessments across various modalities. For instance, incorporating tasks like the respiratory resistance sensitivity task for respiratory interoception [ 65 ], the two-step water load test for gastric interoception [ 66 ], and other visceral paradigms [ 67 ] can lead to a more comprehensive evaluation of interoceptive processes. Despite these limitations, our findings illuminate how insula-related interoceptive alterations may contribute to migraine-related neural mechanisms. Conclusion We identified that migraine patients showed markedly heightened interoceptive accuracy awareness. Moreover, group differences in this awareness were significantly mediated by the effective connectivity between the R_dAI and bilateral PreCG via objective accuracy, revealing the neural basis of overestimated interoceptive ability in migraine. Taken together, our findings indicate that insula-centered interoceptive dysfunction, particularly within the dAI–PreCG network, may play a pivotal role in the neuropathological mechanisms of migraine. Acknowledgements We sincerely thank Professor Yiheng Tu and his research team at the Institute of Psychology, Chinese Academy of Sciences, for their guidance and invaluable contributions throughout the study. Abbreviations HTT Heartbeat tracking task IAS Interoceptive accuracy scale PI Posterior insula AI Anterior insula dAI Dorsal anterior insula vAI Ventral anterior insula FC Functional connectivity ITPE Interoceptive trait prediction error fMRI Functional magnetic resonance imaging HC Healthy control mSBC Multivariate seed-based connectivity EM Episodic migraine ICHD-Ⅲ International Classification of Headache Disorders, 3rd Edition MRI Magnetic resonance imaging VAS Visual analogue scale HIT-6 Headache Impact Test-6 MSQ Migraine-Specific Quality of Life Questionnaire BOLD Blood oxygenation level dependent TR Repetition time TE Echo time FOV Field of view FD Framewise displacement MNI Montreal Neurological Institute FWHM Full-width at half maximum WM White matter CSF Cerebrospinal fluid ROIs Regions of interest L_dAI Left dorsal anterior insula R_dAI Right dorsal anterior insula MO Migraine without aura PreCG Precentral gyrus PCu Precuneus PCC Posterior cingulate cortex Author contributions JC conceived the study and edited the manuscript. Data collection was conducted by the entire author team. RL conducted the data analysis and was the major contributor to writing the manuscript. The final text was reviewed and approved by all authors. Funding This study was funded by the China Association for Science and Technology Young Talent Support Project (CACM-2023-QNRC1-04), Beijing Natural Science Foundation General Project (7242224), and National Natural Science Foundation of China (82474651). Data availability The datasets used in this study are available from the corresponding author upon reasonable request by competent investigators. Declarations Ethics approval and consent to participate This study was approved by the Medical Ethics Committee of Beijing University of Chinese Medicine (Reference No. 2024BZYLL0910). All participants provided written informed consent prior to participation. Consent for publication All authors have provided their consent for publication. 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