Obsessive–compulsive disorder (OCD) is commonly associated with alterations in cortico-striato-thalamo-cortical brain networks. Yet, recent investigations of large-scale brain networks suggest that more diffuse alterations in brain connectivity may underlie its pathophysiology. Few studies have assessed functional connectivity within or between networks across the whole brain in pediatric OCD or how patterns of connectivity associate with treatment response. Resting-state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naive children and adolescents with OCD (12.8 ± 2.9 years) and 23 matched healthy control (HC) participants (11.0 ± 3.3 years) before participants with OCD completed a course of cognitive-behavioral therapy (CBT). Participants were re-scanned after 12–16 weeks. Whole-brain connectomic analyses were conducted to assess baseline group differences and group-by-time interactions, corrected for multiple comparisons. Relationships between functional connectivity and OCD symptoms pre- and post-CBT were examined using longitudinal cross-lagged panel modeling. Reduced connectivity in OCD relative to HC participants was detected between default mode and task-positive network regions. Greater (less altered) connectivity between left angular gyrus and left frontal pole predicted better response to CBT in the OCD group. Altered connectivity between task-positive and task-negative networks in pediatric OCD may contribute to the impaired control over intrusive thoughts early in the illness. This is the first study to show that altered connectivity between large-scale network regions may predict response to CBT in pediatric OCD, highlighting the clinical relevance of these networks as potential circuit-based targets for the development of novel treatments.
Subscribe to Journal
Get full journal access for 1 year
only $43.69 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Vaghi MM, Vertes PE, Kitzbichler MG, Apergis-Schoute AM, van der Flier FE, Fineberg NA, et al. Specific frontostriatal circuits for impaired cognitive flexibility and goal-directed planning in obsessive-compulsive disorder: evidence from resting-state functional connectivity. Biol Psychiatry 2017;81:708–17.
Sakai Y, Narumoto J, Nishida S, Nakamae T, Yamada K, Nishimura T, et al. Corticostriatal functional connectivity in non-medicated patients with obsessive-compulsive disorder. Eur Psychiatry 2011;26:463–9.
Posner J, Marsh R, Maia TV, Peterson BS, Gruber A, Simpson HB. Reduced functional connectivity within the limbic cortico-striato-thalamo-cortical loop in unmedicated adults with obsessive-compulsive disorder. Hum Brain Mapp. 2014;35:2852–60.
Ping L, Su-Fang L, Hai-Ying H, Zhang-Ye D, Jia L, Zhi-Hua G, et al. Abnormal spontaneous neural activity in obsessive-compulsive disorder: a resting-state functional magnetic resonance imaging study. PLoS ONE 2013;8:e67262.
Jung WH, Kang DH, Kim E, Shin KS, Jang JH, Kwon JS. Abnormal corticostriatal-limbic functional connectivity in obsessive-compulsive disorder during reward processing and resting-state. NeuroImage Clin. 2013;3:27–38.
Harrison BJ, Soriano-Mas C, Pujol J, Ortiz H, Lopez-Sola M, Hernandez-Ribas R, et al. Altered corticostriatal functional connectivity in obsessive-compulsive disorder. Arch Gen Psychiatry. 2009;66:1189–200.
Beucke JC, Sepulcre J, Talukdar T, Linnman C, Zschenderlein K, Endrass T, et al. Abnormally high degree connectivity of the orbitofrontal cortex in obsessive-compulsive disorder. JAMA Psychiatry 2013;70:619–29.
Bernstein GA, Mueller BA, Schreiner MW, Campbell SM, Regan EK, Nelson PM, et al. Abnormal striatal resting-state functional connectivity in adolescents with obsessive-compulsive disorder. Psychiatry Res Neuroimaging. 2016;247:49–56.
Abe Y, Sakai Y, Nishida S, Nakamae T, Yamada K, Fukui K, et al. Hyper-influence of the orbitofrontal cortex over the ventral striatum in obsessive-compulsive disorder. Eur Neuropsychopharmacol 2015;25:1898–905.
Takagi Y, Sakai Y, Lisi G, Yahata N, Abe Y, Nishida S, et al. A neural marker of obsessive-compulsive disorder from whole-brain functional connectivity. Sci Rep. 2017;7:7538.
Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev. 2008;32:525–49.
Anticevic A, Hu S, Zhang S, Savic A, Billingslea E, Wasylink S, et al. Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder. Biol Psychiatry 2014;75:595–605.
Beucke JC, Sepulcre J, Eldaief MC, Sebold M, Kathmann N, Kaufmann C. Default mode network subsystem alterations in obsessive-compulsive disorder. Br J Psychiatry. 2014;205:376–82.
Goncalves OF, Soares JM, Carvalho S, Leite J, Ganho-Avila A, Fernandes-Goncalves A, et al. Patterns of default mode network deactivation in obsessive compulsive disorder. Sci Rep. 2017;7:44468.
Hou JM, Zhao M, Zhang W, Song LH, Wu WJ, Wang J, et al. Resting-state functional connectivity abnormalities in patients with obsessive-compulsive disorder and their healthy first-degree relatives. J Psychiatry Neurosci. 2014;39:304–11.
Posner J, Song I, Lee S, Rodriguez CI, Moore H, Marsh R, et al. Increased functional connectivity between the default mode and salience networks in unmedicated adults with obsessive-compulsive disorder. Hum Brain Mapp. 2017;38:678–87.
Stern ER, Fitzgerald KD, Welsh RC, Abelson JL, Taylor SF. Resting-state functional connectivity between fronto-parietal and default mode networks in obsessive-compulsive disorder. PLoS ONE 2012;7:e36356.
Tian L, Meng C, Jiang Y, Tang Q, Wang S, Xie X, et al. Abnormal functional connectivity of brain network hubs associated with symptom severity in treatment-naive patients with obsessive-compulsive disorder: a resting-state functional MRI study. Prog Neuropsychopharmacol Biol Psychiatry. 2016;66:104–11.
Zhu Y, Fan Q, Zhang H, Qiu J, Tan L, Xiao Z, et al. Altered intrinsic insular activity predicts symptom severity in unmedicated obsessive-compulsive disorder patients: a resting state functional magnetic resonance imaging study. BMC Psychiatry 2016;16:104.
Armstrong CC, Moody TD, Feusner JD, McCracken JT, Chang S, Levitt JG, et al. Graph-theoretical analysis of resting-state fMRI in pediatric obsessive-compulsive disorder. J Affect Disord. 2016;193:175–84.
Chen Y, Meng X, Hu Q, Cui H, Ding Y, Kang L, et al. Altered resting-state functional organization within the central executive network in obsessive-compulsive disorder. Psychiatry Clin Neurosci. 2016;70:448–56.
Ost LG, Havnen A, Hansen B, Kvale G. Cognitive behavioral treatments of obsessive-compulsive disorder. A systematic review and meta-analysis of studies published 1993-2014. Clin Psychol Rev. 2015;40:156–69.
Rosa-Alcazar AI, Sanchez-Meca J, Gomez-Conesa A, Marin-Martinez F. Psychological treatment of obsessive-compulsive disorder: a meta-analysis. Clin Psychol Rev. 2008;28:1310–25.
Rosa-Alcazar AI, Sanchez-Meca J, Rosa-Alcazar A, Iniesta-Sepulveda M, Olivares-Rodriguez J, Parada-Navas JL. Psychological treatment of obsessive-compulsive disorder in children and adolescents: a meta-analysis. Span J Psychol. 2015;18:E20.
Simpson HB, Liebowitz MR, Foa EB, Kozak MJ, Schmidt AB, Rowan V, et al. Post-treatment effects of exposure therapy and clomipramine in obsessive-compulsive disorder. Depress Anxiety 2004;19:225–33.
Abramowitz JS, Whiteside SP, Deacon BJ. The effectiveness of treatment for pediatric obsessive-compulsive disorder: a meta-analysis. Behav Ther 2005;36:55–63.
Ost LG, Riise EN, Wergeland GJ, Hansen B, Kvale G. Cognitive behavioral and pharmacological treatments of OCD in children: a systematic review and meta-analysis. J Anxiety Disord. 2016;43:58–69.
Watson HJ, Rees CS. Meta-analysis of randomized, controlled treatment trials for pediatric obsessive-compulsive disorder. J Child Psychol Psychiatry Allied Discip. 2008;49:489–98.
Abramowitz JS. The psychological treatment of obsessive-compulsive disorder. Can J Psychiatry. 2006;51:407–16.
Franklin ME, Sapyta J, Freeman JB, Khanna M, Compton S, Almirall D, et al. Cognitive behavior therapy augmentation of pharmacotherapy in pediatric obsessive-compulsive disorder: the Pediatric OCD Treatment Study II (POTS II) randomized controlled trial. JAMA 2011;306:1224–32.
Olatunji BO, Ferreira-Garcia R, Caseras X, Fullana MA, Wooderson S, Speckens A, et al. Predicting response to cognitive behavioral therapy in contamination-based obsessive-compulsive disorder from functional magnetic resonance imaging. Psychological Med 2014;44:2125–37.
Pediatric OCDTST. Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial. JAMA 2004;292:1969–76.
Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci. 2012;16:43–51.
Pauls DL, Abramovitch A, Rauch SL, Geller DA. Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective. Nat Rev Neurosci. 2014;15:410–24.
Saxena S, Rauch SL. Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder. Psychiatr Clin North Am. 2000;23:563–86.
Admon R, Bleich-Cohen M, Weizmant R, Poyurovsky M, Faragian S, Hendler T. Functional and structural neural indices of risk aversion in obsessive-compulsive disorder (OCD). Psychiatry Res 2012;203:207–13.
Boedhoe PS, Schmaal L, Abe Y, Ameis SH, Arnold PD, Batistuzzo MC, et al. Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and mega-analysis. Am J Psychiatry. 2017;174:60–69.
Boedhoe PSW, Schmaal L, Abe Y, Alonso P, Ameis SH, Anticevic A, et al. Cortical abnormalities associated with pediatric and adult obsessive-compulsive disorder: findings from the ENIGMA Obsessive-Compulsive Disorder Working Group. Am J Psychiatry. 2018;175:453–62.
de Wit SJ, Alonso P, Schweren L, Mataix-Cols D, Lochner C, Menchon JM, et al. Multicenter voxel-based morphometry mega-analysis of structural brain scans in obsessive-compulsive disorder. Am J Psychiatry. 2014;171:340–9.
He X, Steinberg E, Stefan M, Fontaine M, Simpson HB, Marsh R. Altered frontal interhemispheric and fronto-limbic structural connectivity in unmedicated adults with obsessive-compulsive disorder. Hum Brain Mapp. 2018;39:803–10.
Hu X, Liu Q, Li B, Tang W, Sun H, Li F, et al. Multivariate pattern analysis of obsessive-compulsive disorder using structural neuroanatomy. Eur Neuropsychopharmacol 2016;26:246–54.
Li F, Huang X, Tang W, Yang Y, Li B, Kemp GJ, et al. Multivariate pattern analysis of DTI reveals differential white matter in individuals with obsessive-compulsive disorder. Hum Brain Mapp. 2014;35:2643–51.
Marsh R, Horga G, Parashar N, Wang Z, Peterson BS, Simpson HB. Altered activation in fronto-striatal circuits during sequential processing of conflict in unmedicated adults with obsessive-compulsive disorder. Biol Psychiatry 2014;75:615–22.
Nakamae T, Sakai Y, Abe Y, Nishida S, Fukui K, Yamada K, et al. Altered fronto-striatal fiber topography and connectivity in obsessive-compulsive disorder. PLoS ONE 2014;9:e112075.
Rotge JY, Guehl D, Dilharreguy B, Cuny E, Tignol J, Bioulac B, et al. Provocation of obsessive-compulsive symptoms: a quantitative voxel-based meta-analysis of functional neuroimaging studies. J Psychiatry Neurosci. 2008;33:405–12.
Soriano-Mas C, Pujol J, Alonso P, Cardoner N, Menchon JM, Harrison BJ, et al. Identifying patients with obsessive-compulsive disorder using whole-brain anatomy. Neuroimage 2007;35:1028–37.
Gursel DA, Avram M, Sorg C, Brandl F, Koch K. Frontoparietal areas link impairments of large-scale intrinsic brain networks with aberrant fronto-striatal interactions in OCD: a meta-analysis of resting-state functional connectivity. Neurosci Biobehav Rev. 2018;87:151–60.
Feusner JD, Moody T, Lai TM, Sheen C, Khalsa S, Brown J, et al. Brain connectivity and prediction of relapse after cognitive-behavioral therapy in obsessive-compulsive disorder. Front Psychiatry 2015;6:74.
Gottlich M, Kramer UM, Kordon A, Hohagen F, Zurowski B. Resting-state connectivity of the amygdala predicts response to cognitive behavioral therapy in obsessive compulsive disorder. Biol Psychol 2015;111:100–9.
Gruner P, Vo A, Argyelan M, Ikuta T, Degnan AJ, John M, et al. Independent component analysis of resting state activity in pediatric obsessive-compulsive disorder. Hum Brain Mapp. 2014;35:5306–15.
Meunier D, Ersche KD, Craig KJ, Fornito A, Merlo-Pich E, Fineberg NA, et al. Brain functional connectivity in stimulant drug dependence and obsessive-compulsive disorder. Neuroimage 2012;59:1461–8.
Moody TD, Morfini F, Cheng G, Sheen C, Tadayonnejad R, Reggente N, et al. Mechanisms of cognitive-behavioral therapy for obsessive-compulsive disorder involve robust and extensive increases in brain network connectivity. Transl Psychiatry 2017;7:e1230.
Reggente N, Moody TD, Morfini F, Sheen C, Rissman J, O’Neill J, et al. Multivariate resting-state functional connectivity predicts response to cognitive behavioral therapy in obsessive-compulsive disorder. Proc Natl Acad Sci USA. 2018;115:2222–27.
Shin DJ, Jung WH, He Y, Wang J, Shim G, Byun MS, et al. The effects of pharmacological treatment on functional brain connectome in obsessive-compulsive disorder. Biol Psychiatry 2014;75:606–14.
Zhang T, Wang J, Yang Y, Wu Q, Li B, Chen L, et al. Abnormal small-world architecture of top-down control networks in obsessive-compulsive disorder. J Psychiatry Neurosci. 2011;36:23–31.
Morgieve M, N’Diaye K, Haynes WI, Granger B, Clair AH, Pelissolo A, et al. Dynamics of psychotherapy-related cerebral haemodynamic changes in obsessive compulsive disorder using a personalized exposure task in functional magnetic resonance imaging. Psychological Med 2014;44:1461–73.
Nabeyama M, Nakagawa A, Yoshiura T, Nakao T, Nakatani E, Togao O, et al. Functional MRI study of brain activation alterations in patients with obsessive-compulsive disorder after symptom improvement. Psychiatry Res 2008;163:236–47.
Nakao T, Nakagawa A, Yoshiura T, Nakatani E, Nabeyama M, Yoshizato C, et al. Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement: a functional magnetic resonance imaging study. Biol Psychiatry 2005;57:901–10.
Yang XY, Sun J, Luo J, Zhong ZX, Li P, Yao SM, et al. Regional homogeneity of spontaneous brain activity in adult patients with obsessive-compulsive disorder before and after cognitive behavioural therapy. J Affect Disord. 2015;188:243–51.
Cole DA, Maxwell SE. Testing mediational models with longitudinal data: questions and tips in the use of structural equation modeling. J Abnorm Psychol. 2003;112:558–77.
Jöreskog KG. A general method for estimating a linear structural equation system. In: Goldberger AS, Duncan OD, (eds.) Structural equation models in the social sciences. New York: Seminar Press; 1973. p 255–84.
Jöreskog KG, Sörbom D, Magidson J. Advances in factor analysis and structural equation models. New York: University Press of America; 1979.
Cyr M, Fontaine M, Stefan M, Terranova K, Kopala-Sibley DC, Attia E, et al. A longitudinal functional magnetic resonance imaging study of task control circuits and bulimic symptoms over adolescence. J Child Psychol Psychiatry Allied Discip. 2018;59:752–62.
Allen M. Cross-Lagged Panel Analysis. The SAGE Encyclopedia of Communication Research Methods. 2017.
Finkel SE. Causal analysis with panel data. Thousand Oaks, CA: Sage Publications, Inc; 1995.
Gordon EM, Laumann TO, Adeyemo B, Huckins JF, Kelley WM, Petersen SE. Generation and evaluation of a cortical area parcellation from resting-state correlations. Cereb Cortex 2016;26:288–303.
Power JD, Schlaggar BL, Petersen SE. Studying brain organization via spontaneous fMRI signal. Neuron 2014;84:681–96.
Albano AM, Siverman WK. The anxiety disorders interview schedule for DSM-5-child and parent versions. New York: Oxford University Press; in Press.
Wechsler D. Wechsler abbreviated scale of intelligence. San Antonio, TX: The Psychological Corporation; 1999.
Riddle MA, Scahill L, King RA, Hardin MT, Anderson GM, Ort SI, et al. Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 1992;31:1062–9.
Scahill L, Riddle MA, McSwiggin-Hardin M, Ort SI, King RA, Goodman WK, et al. Children’s Yale-Brown Obsessive Compulsive Scale: reliability and validity. J Am Acad Child Adolesc Psychiatry. 1997;36:844–52.
Guy W Clinical Global Impressions. ECDEU Assessment Manual for Psychopharmacology-Revised. Rcokville, MD: U.S. Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology Branch, Division of Extramural Research Programs, Washington, DC; 1976.
March JS, Mulle K. OCD in children and adolescents: a cognitive-behavioral treatment manual. 1st ed. New York: The Guilford Press; 1998.
Van Essen DC, Ugurbil K, Auerbach E, Barch D, Behrens TE, Bucholz R, et al. The Human Connectome Project: a data acquisition perspective. Neuroimage 2012;62:2222–31.
Glasser MF, Sotiropoulos SN, Wilson JA, Coalson TS, Fischl B, Andersson JL, et al. The minimal preprocessing pipelines for the Human Connectome Project. Neuroimage 2013;80:105–24.
Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, et al. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 2002;33:341–55.
Zalesky A, Fornito A, Bullmore ET. Network-based statistic: identifying differences in brain networks. Neuroimage 2010;53:1197–207.
Finkel SE. Causal analysis with panel data. Beverly Hills: Sage Publications; 1995.
Curtis CE, D’Esposito M. Persistent activity in the prefrontal cortex during working memory. Trends Cogn Sci. 2003;7:415–23.
Kerns JG, Cohen JD, MacDonald AW 3rd, Cho RY, Stenger VA, Carter CS. Anterior cingulate conflict monitoring and adjustments in control. Science. 2004;303:1023–6.
Menon V, Adleman NE, White CD, Glover GH, Reiss AL. Error-related brain activation during a Go/NoGo response inhibition task. Hum Brain Mapp. 2001;12:131–43.
Ridderinkhof KR, Ullsperger M, Crone EA, Nieuwenhuis S. The role of the medial frontal cortex in cognitive control. Science. 2004;306:443–7.
Beckmann CF, DeLuca M, Devlin JT, Smith SM. Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond B Biol Sci. 2005;360:1001–13.
Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995;34:537–41.
Biswal BB, Van Kylen J, Hyde JS. Simultaneous assessment of flow and BOLD signals in resting-state functional connectivity maps. NMR Biomed 1997;10:165–70.
Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci USA. 2005;102:9673–8.
Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci USA. 2003;100:253–8.
Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc Natl Acad Sci USA. 2001;98:676–82.
Shulman GL, Fiez JA, Corbetta M, Buckner RL, Miezin FM, Raichle ME, et al. Common blood flow changes across visual tasks: ii. decreases in cerebral cortex. J Cogn Neurosci. 1997;9:648–63.
Harrison BJ, Pujol J, Lopez-Sola M, Hernandez-Ribas R, Deus J, Ortiz H, et al. Consistency and functional specialization in the default mode brain network. Proc Natl Acad Sci USA. 2008;105:9781–6.
Mason MF, Norton MI, Van Horn JD, Wegner DM, Grafton ST, Macrae CN. Wandering minds: the default network and stimulus-independent thought. Science 2007;315:393–5.
McKiernan KA, D’Angelo BR, Kaufman JN, Binder JR. Interrupting the “stream of consciousness”: an fMRI investigation. Neuroimage 2006;29:1185–91.
Menon V. Large-scale brain networks and psychopathology: a unifying triple network model. Trends Cogn Sci. 2011;15:483–506.
Bernstein GA, Cullen KR, Harris EC, Conelea CA, Zagoloff AD, Carstedt PA, et al. Sertraline effects on striatal resting-state functional connectivity in youth with OCD: a pilot study. J Am Acad Child Adolesc Psychiatry. 2019;58:486–495.
Abramowitz JS, Deacon BJ, Olatunji BO, Wheaton MG, Berman NC, Losardo D, et al. Assessment of obsessive-compulsive symptom dimensions: development and evaluation of the dimensional obsessive-compulsive scale. Psychol Assess 2010;22:180–98.
Mataix-Cols D, Rosario-Campos MC, Leckman JF. A multidimensional model of obsessive-compulsive disorder. Am J Psychiatry. 2005;162:228–38.
McKay D, Abramowitz JS, Calamari JE, Kyrios M, Radomsky A, Sookman D, et al. A critical evaluation of obsessive-compulsive disorder subtypes: symptoms versus mechanisms. Clin Psychol Rev. 2004;24:283–313.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Cyr, M., Pagliaccio, D., Yanes-Lukin, P. et al. Altered network connectivity predicts response to cognitive-behavioral therapy in pediatric obsessive–compulsive disorder. Neuropsychopharmacol. (2020). https://doi.org/10.1038/s41386-020-0613-3