Altered cerebellar-insular-parietal-cingular subnetwork in adolescents in the earliest stages of anorexia nervosa: a network-based statistic analysis

Santino Gaudio, Gaia Olivo, Bruno Beomonte Zobel, Helgi B Schiöth, Santino Gaudio, Gaia Olivo, Bruno Beomonte Zobel, Helgi B Schiöth

Abstract

To date, few functional magnetic resonance imaging (fMRI) studies have explored resting-state functional connectivity (RSFC) in long-lasting anorexia nervosa (AN) patients via graph analysis. The aim of the present study is to investigate, via a graph approach (i.e., the network-based statistic), RSFC in a sample of adolescents at the earliest stages of AN (i.e., AN duration less than 6 months). Resting-state fMRI data was obtained from 15 treatment-naive female adolescents with AN restrictive type (AN-r) in its earliest stages and 15 age-matched healthy female controls. A network-based statistic analysis was used to isolate networks of interconnected nodes that differ between the two groups. Group comparison showed a decreased connectivity in a sub-network of connections encompassing the left and right rostral ACC, left paracentral lobule, left cerebellum (10th sub-division), left posterior insula, left medial fronto-orbital gyrus, and right superior occipital gyrus in AN patients. Results were not associated to alterations in intranodal or global connectivity. No sub-networks with an increased connectivity were identified in AN patients. Our findings suggest that RSFC may be specifically affected at the earliest stages of AN. Considering that the altered sub-network comprises areas mainly involved in somatosensory and interoceptive information and processing and in emotional processes, it could sustain abnormal integration of somatosensory and homeostatic signals, which may explain body image disturbances in AN. Further studies with larger samples and longitudinal designs are needed to confirm our findings and better understand the role and consequences of such functional alterations in AN.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1. Network-based statistics results.
Fig. 1. Network-based statistics results.
The figure shows the sub-network with decreased connectivity in AN patients compared to controls, identified by the NBS. The nodes and the links are overlayed to a surface rendering of the brain in two different projections (a, axial; b, oblique). The brain surface with nodes representation was generated with the BRAPH toolbox

References

    1. American Psychiatric Association, American Psychiatric Association. DSM-5 Task Force. Diagnostic and Statistical Manual of Mental Disorders: DSM-5, 5th edn., xliv, 947pp. (American Psychiatric Association, Washington, DC, 2013).
    1. Arcelus J, Mitchell AJ, Wales J, Nielsen S. Mortality rates in patients with anorexia nervosa and other eating disorders. A meta-analysis of 36 studies. Arch. Gen. Psychiatry. 2011;68:724–731. doi: 10.1001/archgenpsychiatry.2011.74.
    1. Kaye WH, Wierenga CE, Bailer UF, Simmons AN, Bischoff-Grethe A. Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa. Trends Neurosci. 2013;36:110–120. doi: 10.1016/j.tins.2013.01.003.
    1. Zipfel S, Giel KE, Bulik CM, Hay P, Schmidt U. Anorexia nervosa: aetiology, assessment, and treatment. Lancet Psychiatry. 2015;2:1099–1111. doi: 10.1016/S2215-0366(15)00356-9.
    1. Titova OE, Hjorth OC, Schioth HB, Brooks SJ. Anorexia nervosa is linked to reduced brain structure in reward and somatosensory regions: a meta-analysis of VBM studies. BMC Psychiatry. 2013;13:110. doi: 10.1186/1471-244X-13-110.
    1. Lazaro L, et al. Normal gray and white matter volume after weight restoration in adolescents with anorexia nervosa. Int. J. Eat. Disord. 2013;46:841–848. doi: 10.1002/eat.22161.
    1. Gaudio S, Quattrocchi CC. Neural basis of a multidimensional model of body image distortion in anorexia nervosa. Neurosci. Biobehav. Rev. 2012;36:1839–1847. doi: 10.1016/j.neubiorev.2012.05.003.
    1. Gaudio S, Wiemerslage L, Brooks SJ, Schioth HB. 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. Neurosci. Biobehav. Rev. 2016;71:578–589. doi: 10.1016/j.neubiorev.2016.09.032.
    1. Fox MD, Greicius M. Clinical applications of resting state functional connectivity. Front. Syst. Neurosci. 2010;4:19.
    1. Biswal BB, et al. Toward discovery science of human brain function. Proc. Natl Acad. Sci. USA. 2010;107:4734–4739. doi: 10.1073/pnas.0911855107.
    1. van den Heuvel MP, Hulshoff Pol HE. Exploring the brain network: a review on resting-state fMRI functional connectivity. Eur. Neuropsychopharmacol. 2010;20:519–534. doi: 10.1016/j.euroneuro.2010.03.008.
    1. Barkhof F, Haller S, Rombouts SA. Resting-state functional MR imaging: a new window to the brain. Radiology. 2014;272:29–49. doi: 10.1148/radiol.14132388.
    1. Damoiseaux JS, et al. Consistent resting-state networks across healthy subjects. Proc. Natl Acad. Sci. USA. 2006;103:13848–13853. doi: 10.1073/pnas.0601417103.
    1. Smith SM, et al. Correspondence of the brain’s functional architecture during activation and rest. Proc. Natl Acad. Sci. USA. 2009;106:13040–13045. doi: 10.1073/pnas.0905267106.
    1. Rubinov M, Sporns O. Complex network measures of brain connectivity: uses and interpretations. Neuroimage. 2010;52:1059–1069. doi: 10.1016/j.neuroimage.2009.10.003.
    1. Zalesky A, Fornito A, Bullmore ET. Network-based statistic: identifying differences in brain networks. Neuroimage. 2010;53:1197–1207. doi: 10.1016/j.neuroimage.2010.06.041.
    1. Boehm I, et al. Increased resting state functional connectivity in the fronto-parietal and default mode network in anorexia nervosa. Front. Behav. Neurosci. 2014;8:346. doi: 10.3389/fnbeh.2014.00346.
    1. Cowdrey FA, Filippini N, Park RJ, Smith SM, McCabe C. Increased resting state functional connectivity in the default mode network in recovered anorexia nervosa. Hum. Brain Mapp. 2014;35:483–491. doi: 10.1002/hbm.22202.
    1. Favaro A, et al. Disruption of visuospatial and somatosensory functional connectivity in anorexia nervosa. Biol. Psychiatry. 2012;72:864–870. doi: 10.1016/j.biopsych.2012.04.025.
    1. Gaudio S, et al. Altered resting state functional connectivity of anterior cingulate cortex in drug naive adolescents at the earliest stages of anorexia nervosa. Sci. Rep. 2015;5:10818. doi: 10.1038/srep10818.
    1. Phillipou A, et al. Resting state functional connectivity in anorexia nervosa. Psychiatry Res. 2016;251:45–52. doi: 10.1016/j.pscychresns.2016.04.008.
    1. Scaife JC, Godier LR, Filippini N, Harmer CJ, Park RJ. Reduced resting-state functional connectivity in current and recovered restrictive anorexia nervosa. Front. Psychiatry. 2017;8:30. doi: 10.3389/fpsyt.2017.00030.
    1. Lee S, et al. Resting-state synchrony between anterior cingulate cortex and precuneus relates to body shape concern in anorexia nervosa and bulimia nervosa. Psychiatry Res. 2014;221:43–48. doi: 10.1016/j.pscychresns.2013.11.004.
    1. Biezonski D, Cha J, Steinglass J, Posner J. Evidence for thalamocortical circuit abnormalities and associated cognitive dysfunctions in underweight individuals with anorexia nervosa. Neuropsychopharmacology. 2016;41:1560–1568. doi: 10.1038/npp.2015.314.
    1. Collantoni E, et al. Functional connectivity correlates of response inhibition impairment in anorexia nervosa. Psychiatry Res. 2016;247:9–16. doi: 10.1016/j.pscychresns.2015.11.008.
    1. Ehrlich S, et al. Reduced functional connectivity in the thalamo-insular subnetwork in patients with acute anorexia nervosa. Hum. Brain Mapp. 2015;36:1772–1781. doi: 10.1002/hbm.22736.
    1. Lord A, et al. Brain parcellation choice affects disease-related topology differences increasingly from global to local network levels. Psychiatry Res. 2016;249:12–19. doi: 10.1016/j.pscychresns.2016.02.001.
    1. Geisler D, et al. Abnormal functional global and local brain connectivity in female patients with anorexia nervosa. J. Psychiatry Neurosci. 2016;41:6–15. doi: 10.1503/jpn.140310.
    1. Gaudio S, et al. White matter abnormalities in treatment-naive adolescents at the earliest stages of anorexia nervosa: a diffusion tensor imaging study. Psychiatry Res. 2017;266:138–145. doi: 10.1016/j.pscychresns.2017.06.011.
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR, 4th edn., xxxv, 943pp. (American Psychiatric Association, Washington, DC, 2000).
    1. First, M. B., Spitzer, R. L., Gibbon, M., Williams, J. B. W. Structured Clinical Interview for DSM-IV Axis I Disorders (American Psychiatric Press, Washington, DC, 1995).
    1. Gaudio S, Di Ciommo V. Prevalence of personality disorders and their clinical correlates in outpatient adolescents with anorexia nervosa. Psychosom. Med. 2011;73:769–774. doi: 10.1097/PSY.0b013e318235b9b5.
    1. First MB, Gibbon M, Spitzer RL, Williams JBW, Smith Benjamin L. Structured Clinical Interview for DSM-IV Axis II Disorders. Washington, DC: American Psychiatric Press; 1997.
    1. Garner, D. M. Eating Disorder Inventory-2: Professional Manual (Psychological Assessment Resources, Odessa, FL, 1991).
    1. Beck, A. T., Steer, R. A., Brown, G. K. Beck Depression Inventory–Second Edition: Manual (The Psychological Corporation, San Antonio, TX, 1996).
    1. Spielberger CD. Manual for the State-Trait Anxiety Inventory (Form Y) Menlo Park, CA: Mind Garden; 1983.
    1. De Vico Fallani, F., Richiardi, J., Chavez, M., Achard, S. Graph analysis of functional brain networks: practical issues in translational neuroscience. Philos. Trans. R. Soc. Lond. B Biol. Sci.369, 20130521 (2014).
    1. Tzourio-Mazoyer N, et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage. 2002;15:273–289. doi: 10.1006/nimg.2001.0978.
    1. Palomero-Gallagher N, Vogt BA, Schleicher A, Mayberg HS, Zilles K. Receptor architecture of human cingulate cortex: evaluation of the four-region neurobiological model. Hum. Brain Mapp. 2009;30:2336–2355. doi: 10.1002/hbm.20667.
    1. Dou W, et al. Systematic regional variations of GABA, glutamine, and glutamate concentrations follow receptor fingerprints of human cingulate cortex. J. Neurosci. 2013;33:12698–12704. doi: 10.1523/JNEUROSCI.1758-13.2013.
    1. Mesulam MM, Mufson EJ. Insula of the old world monkey. I. Architectonics in the insulo-orbito-temporal component of the paralimbic brain. J. Comp. Neurol. 1982;212:1–22. doi: 10.1002/cne.902120102.
    1. Deen B, Pitskel NB, Pelphrey KA. Three systems of insular functional connectivity identified with cluster analysis. Cereb. Cortex. 2011;21:1498–1506. doi: 10.1093/cercor/bhq186.
    1. Zhou Y, Shi L, Cui X, Wang S, Luo X. Functional connectivity of the caudal anterior cingulate cortex is decreased in autism. PLoS ONE. 2016;11:e0151879. doi: 10.1371/journal.pone.0151879.
    1. Kelly AM, et al. Development of anterior cingulate functional connectivity from late childhood to early adulthood. Cereb. Cortex. 2009;19:640–657. doi: 10.1093/cercor/bhn117.
    1. Yun JY, et al. Executive dysfunction in obsessive-compulsive disorder and anterior cingulate-based resting state functional connectivity. Psychiatry Investig. 2017;14:333–343. doi: 10.4306/pi.2017.14.3.333.
    1. Mijalkov M, et al. BRAPH: a graph theory software for the analysis of brain connectivity. PLoS ONE. 2017;12:e0178798. doi: 10.1371/journal.pone.0178798.
    1. Kullmann S, et al. Aberrant network integrity of the inferior frontal cortex in women with anorexia nervosa. Neuroimage Clin. 2014;4:615–622. doi: 10.1016/j.nicl.2014.04.002.
    1. Amianto F, et al. Intrinsic connectivity networks within cerebellum and beyond in eating disorders. Cerebellum. 2013;12:623–631. doi: 10.1007/s12311-013-0471-1.
    1. Stoodley CJ, Limperopoulos C. Structure-function relationships in the developing cerebellum: evidence from early-life cerebellar injury and neurodevelopmental disorders. Semin. Fetal Neonatal Med. 2016;21:356–364. doi: 10.1016/j.siny.2016.04.010.
    1. Ceylan ME, Donmez A, Ulsalver BO. The contribution of the cerebellum in the hierarchial development of the self. Cerebellum. 2015;14:711–721. doi: 10.1007/s12311-015-0675-7.
    1. Cauda F, et al. Functional connectivity of the insula in the resting brain. Neuroimage. 2011;55:8–23. doi: 10.1016/j.neuroimage.2010.11.049.
    1. Craig AD. How do you feel? Interoception: the sense of the physiological condition of the body. Nat. Rev. Neurosci. 2002;3:655–666. doi: 10.1038/nrn894.
    1. Taylor KS, Seminowicz DA, Davis KD. Two systems of resting state connectivity between the insula and cingulate cortex. Hum. Brain Mapp. 2009;30:2731–2745. doi: 10.1002/hbm.20705.
    1. Roy M, Piche M, Chen JI, Peretz I, Rainville P. Cerebral and spinal modulation of pain by emotions. Proc. Natl Acad. Sci. USA. 2009;106:20900–20905. doi: 10.1073/pnas.0904706106.
    1. Etkin A, Egner T, Peraza DM, Kandel ER, Hirsch J. Resolving emotional conflict: a role for the rostral anterior cingulate cortex in modulating activity in the amygdala. Neuron. 2006;51:871–882. doi: 10.1016/j.neuron.2006.07.029.
    1. Szekely A, Silton RL, Heller W, Miller GA, Mohanty A. Differential functional connectivity of rostral anterior cingulate cortex during emotional interference. Soc. Cogn. Affect. Neurosci. 2017;12:476–486.
    1. Hagmann P, et al. Mapping the structural core of human cerebral cortex. PLoS Biol. 2008;6:e159. doi: 10.1371/journal.pbio.0060159.
    1. Matthys K, et al. Mirror-induced visual illusion of hand movements: a functional magnetic resonance imaging study. Arch. Phys. Med. Rehabil. 2009;90:675–681. doi: 10.1016/j.apmr.2008.09.571.
    1. Oakes TR, et al. Integrating VBM into the General Linear Model with voxelwise anatomical covariates. Neuroimage. 2007;34:500–508. doi: 10.1016/j.neuroimage.2006.10.007.
    1. Dakanalis, A. et al. Body-image distortion in anorexia nervosa. Nat. Rev. Dis. Primers2, 16026 (2016).
    1. Gaudio S, Brooks SJ, Riva G. Nonvisual multisensory impairment of body perception in anorexia nervosa: a systematic review of neuropsychological studies. PLoS ONE. 2014;9:e110087. doi: 10.1371/journal.pone.0110087.
    1. McCabe C, Mishor Z. Antidepressant medications reduce subcortical-cortical resting-state functional connectivity in healthy volunteers. Neuroimage. 2011;57:1317–1323. doi: 10.1016/j.neuroimage.2011.05.051.
    1. Cullen KR, et al. Abnormal amygdala resting-state functional connectivity in adolescent depression. JAMA Psychiatry. 2014;71:1138–1147. doi: 10.1001/jamapsychiatry.2014.1087.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner