2026 ECNP Congress

PS01-1057

Altered resting-state network connectivity and its clinical correlates in anorexia nervosa: an independent component analysis study

Laura Raffaelli — M. Crespi, E. Mazza, M.C. Cavallini, E. Politi, F. Benedetti · IRCCS San Raffaele Scientific Institute, Psychiatry and Clinical Psychobiology, Milan, Italy

2026 ECNP Congress

Background

Anorexia nervosa (AN) is a severe psychiatric disorder characterized by marked clinical heterogeneity that extends beyond restrictive eating and weight-related concerns to include cognitive rigidity, obsessive–compulsive features, disturbances in body representation, and neuropsychological impairments (1). This multidimensional clinical phenotype suggests dysfunction across widespread neural systems rather than isolated regional abnormalities. Converging evidence from resting-state functional MRI (rs-fMRI) studies indicates alterations in large-scale brain networks in AN (2-3); however, the extent to which these network-level disruptions are associated with clinical symptomatology and cognitive deficits remains insufficiently understood.

Methods

We applied spatial group independent component analysis (ICA) to rs-fMRI data from 30 female inpatients with AN and 30 age-matched healthy controls (HC). This data-driven approach allowed us to identify intrinsic connectivity networks and characterize between-group differences in network-level functional connectivity. Subsequently, within the AN group, we examined associations between altered connectivity patterns and a broad range of clinical and neuropsychological measures, including eating disorder severity, obsessive–compulsive symptoms, body perception disturbances, and cognitive performance.

Results

Compared with HCs, patients with AN showed widespread functional connectivity alterations across large-scale networks, including the default mode network (DMN), frontopariental network (FPN), dorsal attention network (DAN), visual network (VN) and cerebellar systems. AN was characterized by reduced connectivity within posterior DMN regions, particularly involving the angular gyrus (t_peak = −5.10, p < 0.001, FWE-corrected; [−42, −46, 20]) and precuneus (t_peak =−6.59, p=0.042, FWE-corrected; [2, −64, 34]), as well as decreased connectivity between the DAN and prefrontal/parietal regions, including the MFG (t_peak=−4.51, p=0.036, FWE-corrected; [32, 12, 66]) and precuneus (t_peak =−5.53, p<0.001, FWE-corrected; [0, −66, 62]). Disrupted cerebellar–occipital integration was also observed. Conversely, increased connectivity emerged within posterior visual cortices and between the DAN and bilateral precentral gyri. Within the AN group, reduced DMN–precuneus connectivity was associated with greater eating disorder severity (R²=0.37, β=−0.52, t=−2.34, pFDR =0.027), higher obsessive–compulsive symptoms (R²=0.43, β =−0.051, t=−2.93, pFDR=0.045), and longer illness duration (R²=0.23, β=−0.08, t=−2.75, pFDR=0.048). Increased visual network connectivity predicted greater body preoccupation (R²=0.27, β=0.027, t=2.32, pFDR =0.041) and poorer psychomotor performance (R²=0.26, β =−0.026, t=−2.23, pFDR=0.034). Altered DAN–DMN connectivity was associated with higher eating disorder symptoms (R²=0.34, β =0.88, t=3.54, pFDR= 0.007), while altered occipital–cerebellar connectivity was associated with working memory deficits (R² = 0.19, β=−0.18, t=−2.32, pFDR=0.044).

Conclusions

These findings reveal a complex pattern of intrinsic dysorganization in AN, involving both hypo- and hyper-connectivity across multiple large-scale brain systems. Importantly, these alterations show clinically meaningful associations with symptom severity, illness chronicity, and cognitive dysfunction. Our results support a network-based model of AN, in which disrupted interactions between self-referential, attentional, and cognitive control systems contribute to the heterogeneous clinical presentation of the disorder. This integrative framework may help to better understand how large-scale brain dysfunction shapes the clinical and cognitive profile of AN.

References

  1. Van Eeden, A. E., Van Hoeken, D., & Hoek, H. W. (2021). Incidence, prevalence and mortality of anorexia nervosa and bulimia nervosa. Current opinion in psychiatry, 34(6), 515-524. 2)Gaudio, S., Wiemerslage, L., Brooks, S. J., & Schiöth, H. B. (2016). 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, 71, 578-589. 3)Esposito, R., Cieri, F., Chiacchiaretta, P., Cera, N., Lauriola, M., Di Giannantonio, M., … & Ferretti, A. (2018). Modifications in resting state functional anticorrelation between default mode network and dorsal attention network: comparison among young adults, healthy elders and mild cognitive impairment patients. Brain imaging and behavior, 12(1), 127-141.