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Disruption of effective connectivity from the dorsolateral prefrontal cortex to the orbitofrontal cortex by negative emotional distraction in obsessive–compulsive disorder

  • H. J. Han (a1), W. H. Jung (a2) (a3), J.-Y. Yun (a2) (a4), J. W. Park (a4), K. K. Cho (a1), J.-W. Hur (a1) (a2), N. Y. Shin (a2), T. Y. Lee (a2) and J. S. Kwon (a1) (a2) (a4)...



Obsessive–compulsive disorder (OCD) has been associated with abnormal cognitive and emotional functions and these dysfunctions may be dependent on the disruption of dynamic interactions within neuronal circuits associated with emotion regulation. Although several studies have shown the aberrant cognitive–affective processing in OCD patients, little is known about how to characterize effective connectivity of the disrupted neural interactions. In the present study, we applied effective connectivity analysis using dynamic causal modeling to explore the disturbed neural interactions in OCD patients.


A total of 20 patients and 21 matched healthy controls performed a delayed-response working memory task under emotional or non-emotional distraction while undergoing functional magnetic resonance imaging.


During the delay interval under negative emotional distraction, both groups showed similar patterns of activations in the amygdala. However, under negative emotional distraction, the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) exhibited significant differences between groups. Bayesian model averaging indicated that the connection from the DLPFC to the OFC was negatively modulated by negative emotional distraction in patients, when compared with healthy controls (p < 0.05, Bonferroni-corrected).


Exaggerated recruitment of the DLPFC may induce the reduction of top-down prefrontal control input over the OFC, leading to abnormal cortico-cortical interaction. This disrupted cortico-cortical interaction under negative emotional distraction may be responsible for dysfunctions of cognitive and emotional processing in OCD patients and may be a component of the pathophysiology associated with OCD.


Corresponding author

* Address for correspondence: J. S. Kwon, M. D., Ph.D., Department of Psychiatry, Seoul National University College of Medicine, 28 Yeongon-dong, Chongno-gu, Seoul 110-744, South Korea. (Email:


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Anderson, AK, Christoff, K, Panitz, D, De Rosa, E, Gabrieli, JD (2003). Neural correlates of the automatic processing of threat facial signals. Journal of Neuroscience 23, 56275633.
Beck, AT, Epstein, N, Brown, G, Steer, RA (1988). An inventory for measuring clinical anxiety: psychometric properties. Journal of Consulting and Clinical Psychology 56, 893897.
Beck, AT, Ward, CH, Mendelson, M, Mock, J, Erbaugh, J (1961). An inventory for measuring depression. Archives of General Psychiatry 4, 561571.
Cannistraro, PA, Wright, CI, Wedig, MM, Martis, B, Shin, LM, Wilhelm, S, Rauch, SL (2004). Amygdala responses to human faces in obsessive–compulsive disorder. Biological Psychiatry 56, 916920.
Cardoner, N, Harrison, BJ, Pujol, J, Soriano-Mas, C, Hernandez-Ribas, R, Lopez-Sola, M, Real, E, Deus, J, Ortiz, H, Alonso, P, Menchon, JM (2011). Enhanced brain responsiveness during active emotional face processing in obsessive compulsive disorder. World Journal of Biological Psychiatry 12, 349363.
Ciesielski, KT, Hamalainen, MS, Lesnik, PG, Geller, DA, Ahlfors, SP (2005). Increased MEG activation in OCD reflects a compensatory mechanism specific to the phase of a visual working memory task. NeuroImage 24, 11801191.
Choi, JS, Kang, DH, Kim, JJ, Ha, TH, Lee, JM, Youn, T, Kim, IY, Kim, SI, Kwon, JS (2004). Left anterior subregion of orbitofrontal cortex volume reduction and impaired organizational strategies in obsessive–compulsive disorder. Journal of Psychiatry Research 38, 193199.
Davis, M (1992). The role of the amygdala in fear and anxiety. Annual Review of Neuroscience 15, 353375.
Davis, M, Whalen, PJ (2001). The amygdala: vigilance and emotion. Molecular Psychiatry 6, 1334.
de Vries, FE, de Wit, SJ, Cath, DC, van der Werf, YD, van der Borden, V, van Rossum, TB, van Balkom, AJ, van der Wee, NJ, Veltman, DJ, van den Heuvel, OA (2014). Compensatory frontoparietal activity during working memory: an endophenotype of obsessive–compulsive disorder. Biological Psychiatry 76, 878887.
de Wit, SJ, de Vries, FE, van der Werf, YD, Cath, DC, Heslenfeld, DJ, Veltman, EM, van Balkom, AJ, Veltman, DJ, van den Heuvel, OA (2012). Presupplementary motor area hyperactivity during response inhibition: a candidate endophenotype of obsessive–compulsive disorder. American Journal of Psychiatry 169, 11001118.
de Wit, SJ, van der Werf, YD, Mataix-Cols, D, Trujillo, JP, van Oppen, P, Veltman, DJ, van den Heuvel, OA (2015). Emotion regulation before and after transcranial magnetic stimulation in obsessive compulsive disorder. Psychological Medicine 45, 30593073.
Denkova, E, Wong, G, Dolcos, S, Sung, K, Wang, L, Coupland, N, Dolcos, F (2010). The impact of anxiety-inducing distraction on cognitive performance: a combined brain imaging and personality investigation. PLoS ONE 5, e14150.
Diwadkar, VA, Wadehra, S, Pruitt, P, Keshavan, MS, Rajan, U, Zajac-Benitez, C, Eickhoff, SB (2012). Disordered corticolimbic interactions during affective processing in children and adolescents at risk for schizophrenia revealed by functional magnetic resonance imaging and dynamic causal modeling. Archive of General Psychiatry 69, 231242.
Dolcos, F, Diaz-Granados, P, Wang, L, McCarthy, G (2008). Opposing influences of emotional and non-emotional distracters upon sustained prefrontal cortex activity during a delayed-response working memory task. Neuropsychologia 46, 326335.
Dolcos, F, Iordan, AD, Dolcos, S (2011). Neural correlates of emotion–cognition interactions: a review of evidence from brain imaging investigations. Journal of Cognitive Psychology (Hove) 23, 669694.
Dolcos, F, McCarthy, G (2006). Brain systems mediating cognitive interference by emotional distraction. Journal of Neuroscience 26, 20722079.
Etkin, A, Egner, T, Peraza, DM, Kandel, ER, Hirsch, J (2006). Resolving emotional conflict: a role for the rostral anterior cingulate cortex in modulating activity in the amygdala. Neuron 51, 871882.
Evans, DW, Lewis, MD, Lobst, E (2004). The role of the orbitofrontal cortex in normally developing compulsive-like behavior and obsessive–compulsive disorder. Brain and Cognition 55, 220234.
First, MB, Spitzer, RL, Gibbon, M, Williams, JBM (1996). Structured Clinical Interview for DSM-IV Axis I Disorders, Non-Patient Edition. Biometrics Research, New York State Psychiatric Institute: New York.
Golkar, A, Lonsdorf, TB, Olsson, A, Lindstrom, KM, Berrebi, J, Fransson, P, Schalling, M, Ingvar, M, Ohman, A (2012). Distinct contributions of the dorsolateral prefrontal and orbitofrontal cortex during emotion regulation. PLOS ONE 11, e48107.
Goodman, WK, Price, LH, Rasmussen, SA, Mazure, C, Delgado, P, Heninger, GR, Charney, DS (1989 a). The Yale–Brown Obsessive Compulsive Scale. II. Validity. Archives of General Psychiatry 46, 10121016.
Goodman, WK, Price, LH, Rasmussen, SA, Mazure, C, Fleischmann, RL, Hill, CL, Heninger, GR, Charney, DS (1989 b). The Yale–Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Archives of General Psychiatry 46, 10061011.
Han, HJ, Lee, K, Kim, HT, Kim, H (2013). Distinctive amygdala subregions involved in emotion-modulated Stroop interference. Social Cognitive and Affective Neuroscience 9, 689698.
Henseler, I, Gruber, O, Kraft, S, Krick, C, Reith, W, Falkai, P (2008). Compensatory hyperactivations as markers of latent working memory dysfunctions in patients with obsessive–compulsive disorder: an fMRI study. Journal of Psychiatry and Neuroscience 33, 209215.
Hoeting, J, Madigan, D, Raftery, A, Volinsky, C (1999). Bayesian model averaging: a tutorial. Statistical Science 14, 382417.
Kringelbach, ML, Rolls, ET (2004). The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Progress in Neurobiology 72, 341372.
Kwon, JS, Jang, JH, Choi, JS, Kang, DH (2009). Neuroimaging in obsessive–compulsive disorder. Expert Review of Neurotherapeutics 9, 255269.
Lang, P, Bradley, M, Cuthberg, B (1997). International Affective Picture System. NIMH Center for the Study of Emotion and Attention: Gainesville, FL.
Lawrence, NS, An, SK, Mataix-Cols, D, Ruths, F, Speckens, A, Phillips, ML (2007). Neural responses to facial expressions of disgust but not fear are modulated by washing symptoms in OCD. Biological Psychiatry 61, 10721080.
Lochner, C, Kinnear, CJ, Hemmings, SM, Seller, C, Niehaus, DJ, Knowles, JA, Daniels, W, Moolman-Smook, JC, Seedat, S, Stein, DJ (2005). Hoarding in obsessive–compulsive disorder: clinical and genetic correlates. Journal of Clinical Psychiatry 66, 11551160.
Mataix-Cols, D, Rauch, SL, Manzo, PA, Jenike, MA, Baer, L (1999). Use of factor-analyzed symptom dimensions to predict outcome with serotonin reuptake inhibitors and placebo in the treatment of obsessive–compulsive disorder. American Journal of Psychiatry 156, 14091416.
Menzies, L, Chamberlain, SR, Laird, AR, Thelen, SM, Sahakian, BJ, Bullmore, ET (2008). Integrating evidence from neuroimaging and neuropsychological studies of obsessive–compulsive disorder: the orbitofronto-striatal model revisited. Neuroscience and Biobehavioral Reviews 32, 525549.
Milad, MR, Rauch, SL (2012). Obsessive–compulsive disorder: beyond segregated cortico-striatal pathways. Trends in Cognitive Sciences 16, 4351.
Moghaddam, B, Homayoun, H (2008). Divergent plasticity of prefrontal cortex networks. Neuropsychopharmacology 33, 4255.
Ochsner, KN, Gross, JJ (2005). The cognitive control of emotion. Trends in Cognitive Sciences 9, 242249.
Ochsner, KN, Ray, RD, Cooper, JC, Robertson, ER, Chopra, S, Gabrieli, JD, Gross, JJ (2004). For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion. NeuroImage 23, 483499.
Ongur, D, Price, JL (2000). The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cerebral Cortex 10, 206219.
Penny, WD, Stephan, KE, Daunizeau, J, Rosa, MJ, Friston, KJ, Schofield, TM, Leff, AP (2010). Comparing families of dynamic causal models. PLoS Computational Biology 6, e1000709.
Petrides, M (2000). The role of the mid-dorsolateral prefrontal cortex in working memory. Experimental Brain Research 133, 4454.
Phillips, ML, Ladouceur, CD, Drevets, WC (2008). A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Molecular Psychiatry 13, 829, 833857.
Pujol, J, Torres, L, Deus, J, Cardoner, N, Pifarre, J, Capdevila, A, Vallejo, J (1999). Functional magnetic resonance imaging study of frontal lobe activation during word generation in obsessive–compulsive disorder. Biological Psychiatry 45, 891897.
Rule, RR, Shimamura, AP, Knight, RT (2002). Orbitofrontal cortex and dynamic filtering of emotional stimuli. Cognitive, Affective and Behavioral Neuroscience 2, 264270.
Savage, CR, Baer, L, Keuthen, NJ, Brown, HD, Rauch, SL, Jenike, MA (1999). Organizational strategies mediate nonverbal memory impairment in obsessive–compulsive disorder. Biological Psychiatry 45, 905916.
Saxena, S, Brody, AL, Maidment, KM, Smith, EC, Zohrabi, N, Katz, E, Baker, SK, Baxter, LR Jr. (2004). Cerebral glucose metabolism in obsessive–compulsive hoarding. American Journal of Psychiatry 161, 10381048.
Saxena, S, Brody, AL, Schwartz, JM, Baxter, LR (1998). Neuroimaging and frontal–subcortical circuitry in obsessive–compulsive disorder. British Journal of Psychiatry Supplement, issue 35, 2637.
Saxena, S, Rauch, SL (2000). Functional neuroimaging and the neuroanatomy of obsessive–compulsive disorder. Psychiatric Clinics of North America 23, 563586.
Simon, D, Adler, N, Kaufmann, C, Kaufmann, N (2014). Amygdala hyperactivation during symptom provocation in obsessive–compulsive disorder and its modulation by distraction. NeuroImage: Clinical 4, 549557.
Simon, D, Kaufmann, C, Kniesche, R, Kischkel, E, Kathmann, N (2013). Autonomic responses and neural–cardiac coupling during individually tailored symptom provocation in obsessive–compulsive disorder. Journal of Anxiety Disorder 27, 635644.
Simon, D, Kaufmann, C, Musch, K, Kischkel, E, Kathmann, N (2010). Fronto-striato-limbic hyperactivation in obsessive–compulsive disorder during individually tailored symptom provocation. Psychophysiology 47, 728738.
Sladky, R, Hoflich, A, Kublbock, M, Kraus, C, Baldinger, P, Moser, E, Lanzenberger, R, Windischberger, C (2013). Disrupted effective connectivity between the amygdala and orbitofrontal cortex in social anxiety disorder during emotion discrimination revealed by dynamic causal modeling for fMRI. Cerebral Cortex 25, 895903.
Stephan, KE, Penny, WD, Moran, RJ, den Ouden, HE, Daunizeau, J, Friston, KJ (2010). Ten simple rules for dynamic causal modeling. NeuroImage 49, 30993109.
Stern, MR, Nota, JA, Heimberg, RG, Holaway, RM, Coles, ME (2014). An initial examination of emotion regulation and obsessive compulsive symptoms. Journal of Obsessive–Compulsive and Related Disorders 3, 109114.
Taylor, SF, Liberzon, I (2007). Neural correlates of emotion regulation in psychopathology. Trends in Cognitive Sciences 11, 413418.
van der Wee, NJ, Ramsey, NF, Jansma, JM, Denys, DA, van Megen, HJ, Westenberg, HM, Kahn, RS (2003). Spatial working memory deficits in obsessive compulsive disorder are associated with excessive engagement of the medial frontal cortex. NeuroImage 20, 22712280.
van Velzen, LS, de Wit, SJ, Ćurĉić-Blake, B, Cath, DC, de Vries, FE, Veltman, DJ, van der Werf, YD, van den Heuvel, OA (2015). Altered inhibition-related frontolimbic connectivity in obsessive–compulsive disorder. Human Brain Mapping 36, 40644075.
Worsley, KJ, Marrett, S, Neelin, P, Vandal, AC, Friston, KJ, Evans, AC (1996). A unified statistical approach for determining significant signals in images of cerebral activation. Human Brain Mapping 4, 5873.
Zald, DH, Kim, SW (1996). Anatomy and function of the orbital frontal cortex, II: function and relevance to obsessive–compulsive disorder. Journal of Neuropsychiatry and Clinical Neuroscience 8, 249261.
Zetsche, U, Rief, W, Westermann, S, Exner, C (2015). Cognitive deficits are a matter of emotional context: inflexible strategy use mediates context-specific learning impairments in OCD. Cognition and Emotion 29, 360371.


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Disruption of effective connectivity from the dorsolateral prefrontal cortex to the orbitofrontal cortex by negative emotional distraction in obsessive–compulsive disorder

  • H. J. Han (a1), W. H. Jung (a2) (a3), J.-Y. Yun (a2) (a4), J. W. Park (a4), K. K. Cho (a1), J.-W. Hur (a1) (a2), N. Y. Shin (a2), T. Y. Lee (a2) and J. S. Kwon (a1) (a2) (a4)...


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