Hostname: page-component-745bb68f8f-f46jp Total loading time: 0 Render date: 2025-02-12T01:45:41.924Z Has data issue: false hasContentIssue false
  • English
  • Français

Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder

Published online by Cambridge University Press:  06 August 2018

S. Saxena ,
A. L. Brody ,
J. M. Schwartz  and
L. R. Baxter
S. Saxena
Affiliation:
UCLA Department of Psychiatry and Biobehavioral Sciences, UCLA Neuropsychiatric Institute, Los Angeles
A. L. Brody
Affiliation:
UCLA Department of Psychiatry and Biobehavioral Sciences, UCLA Neuropsychiatric Institute, Los Angeles
J. M. Schwartz
Affiliation:
UCLA Department of Psychiatry and Biobehavioral Sciences, UCLA Neuropsychiatric Institute, Los Angeles
L. R. Baxter
Affiliation:
UCLA Department of Psychiatry and Biobehavioral Sciences, UCLA Neuropsychiatric Institute, and Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham AL, USA
Get access Rights & Permissions [Opens in a new window]

Abstract

Background Neuroimaging studies provide strong evidence that the pathophysiology of obsessive-compulsive disorder (OCD) involves abnormal functioning along specific frontal-subcortical brain circuits.

Method A literature search was carried out for all brain imaging studies of patients with OCD. We also reviewed the basic science literature on the functional neuroanatomy of cortico-basal ganglia circuits, and integrated this information with neuroimaging data in OCD to formulate a theoretical model of brain mediation of OCD symptoms and response to treatment.

Results At least a subgroup of patients with OCD may have abnormal basal ganglia development. Functional neuroimaging studies indicate that OCD symptoms are associated with increased activity in orbitofrontal cortex, caudate nucleus, thalamus and anterior cingulate gyrus.

Conclusions OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, perhaps due to an imbalance of tone between direct and indirect striatopallidal pathways. We present a model which describes how frontal-subcortical brain circuitry may mediate OCD symptomatology, and suggest a hypothesis for how successful treatments may ameliorate symptoms, via their effects on circuit activity.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 173 , Issue S35: New perspectives in research and treatment of obsessive-compulsive disorder , August 1998 , pp. 26 - 37
Copyright
Copyright © 1998 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adams, B. L., Warneke, L. B., McEwan, A. J. B., et al (1993) Single photon emission computerized tomography in obsessive-compulsive disorder: a preliminary study. Journal of Psychiatry and Neuroscience, 18, 109–112.Google ScholarPubMed
Alexander, G. E., DeLong, M. R. & Strick, R L. (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9, 357–381.CrossRefGoogle ScholarPubMed
Alexander, G. E. & Crutcher, M. D. (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends in Neurosciences, 13, 266–271.CrossRefGoogle ScholarPubMed
American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM-111-R). Washington, DC: APA.Google Scholar
Andreasen, N. (1989) Brain Imaging: Applications in Psychiatry. Washington, DC: American Psychiatric Press.Google Scholar
Aylward, E. H., Harris, G. H., Hoehn-Saric, R., et al (1996) Normal caudate nucleus in obsessive-compulsive disorder assessed by quantitative neuroimaging. Archives of General Psychiatry, 53, 577–584.CrossRefGoogle ScholarPubMed
Baxter, L. R. (1992) Neuroimaging studies of obsessive-compulsive disorder. Psychiatric Clinics of North America, 15, 871–884 CrossRefGoogle ScholarPubMed
Baxter, L. R., Phelps, M. E., Mazziotta, J. C., et al (1987a) Local cerebral glucose metabolic rates in obsessive-compulsive disorder – a comparison with rates in unipolar depression and in normal controls. Archives of General Psychiatry, 44, 211–218.CrossRefGoogle ScholarPubMed
Baxter, L. R., Schwartz, J. M., Mazziotta, J. C., et al (1987b) Cerebral glucose metabolic rates in non-depressed obsessive-compulsives. American Journal of Psychiatry, 145, 1560–1563.Google Scholar
Baxter, L. R., Schwartz, J. M., Guze, B. H., et al (1990) Neuroimaging in obsessive-compulsive disorder: Seeking the mediating neuroanatomy. In Obsessive-Compulsive Disorders: Theory and Management, edn 2 (eds Jenicke, M. A., Baer, L. & Minichiello, W E.), pp. 167–188. Chicago: Year Book Medical Publishers.Google Scholar
Baxter, L. R., Schwartz, J. M., Bergman, K. S., et al (1992) Caudate glucose metabolic rate changes with both drug and behaviour therapy for obsessive-compulsive disorder. Archives of General Psychiatry, 49, 681–689.CrossRefGoogle ScholarPubMed
Baxter, L. R., Saxena, S., Brody, A. L., et al (1996) Brain mediation of obsessive-compulsive disorder symptoms: evidence from functional brain imaging studies in the human and nonhuman primate. Seminars in Clinical Neuropsychiatry, 1, 32–47.Google ScholarPubMed
Baxter, L. R., Ackermann, R. F., Swerdlow, N. R., et al (1998) Sepcific brain system mediation of OCD responsive to either medication or behavior therapy. In NIMH-OC Foundation Monograph (eds W Goodman & J. Maser), in press.Google Scholar
Behar, D., Rapoport, J. L., Berg, C. J., et al (1984) Computerized tomography and neuropsychological test measures in adolescents with obsessive-compulsive disorder. American Journal of Psychiatry, 141, 363–369.Google ScholarPubMed
Benkelfat, C., E., Nordahl, T., Semple, W. E., et al (1990) Local cerebral glucose metabolic rates in obsessive-compulsive disorder: Patients treated with clomipramine. Archives of General Psychiatry, 47, 840–848.CrossRefGoogle ScholarPubMed
Besson, M. J., Graybiel, A. M. & Nastuk, M. A. (1988) {3H} SCH 23390 binding to D1 receptors in the basal ganglia of the cat and primate: delineation of striosomal compartments and pallidal and nigral subdivisions. Neuroscience, 26, 101–119.CrossRefGoogle Scholar
Birken, D. & Oldendorf, W. H. (1989) NAA: a literature review of a compound prominent in ‘H NMR spectroscopic studies of brain. Neuroscience and Biobehavioural Reviews, 13, 23–31.CrossRefGoogle Scholar
Breiter, H. C., Rauch, S. L., Kwong, K. K., et al (1996) Functioning magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder. Archives of General Psychiatry, 49, 595–606.CrossRefGoogle Scholar
Brody, A. L. & Saxena, S. (1996) Brain imaging in obsessive-compulsive disorder: evidence for the involvement of frontal-subcortical circuitry in the mediation of symptomatology. CNS Spectrums, 1, 27–41.Google Scholar
Burke, R. E. & Baimbridge, K. G. (1993) Relative loss of the striatal striosome compartment, defined by calbindin-D28k immunostaining, following developmental hypoxic-ischemic injury. Neuroscience, 56, 305–315.Google Scholar
Cummings, J. L. (1993) Frontal-subcortical circuits and human behavior. Archives of Neurology, 50, 873–880.CrossRefGoogle ScholarPubMed
De Long, M. R. (1990) Primate models of movement disorders of basal ganglia origin. Trends in Neurosciences, 13, 281–285.CrossRefGoogle ScholarPubMed
Ebert, D., Speck, O., Konig, A., et al (1997) H-magnetic resonance spectroscopy in obsessive-compulsive disorder: evidence for neuronal loss in the cingulate gyrus and the right striatum. Psychiatry Research: Neuroimaging, 74, 173–176.CrossRefGoogle Scholar
Eblen, F. & Graybiel, A. M. (1995) Highly restricted origin of prefrontal cortical inputs to striosomes in the macaque monkey. Journal of Neuroscience, 15, 5999–6013.CrossRefGoogle ScholarPubMed
Garber, H. J., Ananth, J. V., Chiu, L. C., et al (1989) Nuclear magnetic resonance study of obsessive-compulsive disorder. American Journal of Psychiatry 146, 1001–1005.Google ScholarPubMed
Gerfen, C. R. (1992) The neostriatal mosaic: multiple levels of compartmental organization in the basal ganglia. Annual Review of Neuroscience, 115, 285–320.CrossRefGoogle Scholar
Gerfen, C. R., Engber, T. M., Mahan, L. C., et al (1990) D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science, 250, 1429–1432.Google Scholar
Gold, J. M., Berman, K. F., Randolph, C., et al (1996) PET validation of a novel prefrontal task: delayed response alternation. Neuropsychology, 10, 3–10.CrossRefGoogle Scholar
Goodman, W. K., Price, L. H., Rasmussen, S. A., et al (1989) The Yale-Brown Obsessive-Compulsive scale. I: Development, use and reliability. Archives of General Psychiatry, 46, 1006–1011.CrossRefGoogle ScholarPubMed
Graybiel, A. M. (1990) Neurotransmitters and neuromodulators in the basal ganglia. Trends in Neurosciences, 13, 244–254.CrossRefGoogle ScholarPubMed
Hall, H., Sedvall, G., Magnusson, O., et al (1994) Distribution of D1 and D2-dopamine receptors, and dopamine and its metabolites in the human brain. Neuropsychopharmacology, 11, 245–256.CrossRefGoogle ScholarPubMed
Hedreen, J. C. & Folstein, S. E. (1995) Early loss of neostriatal striosome neurons in Huntington's disease. Journal of Neuropathology and Experimental Neurology, 54, 105–120.CrossRefGoogle ScholarPubMed
Hoehn-Saric, R., Pearlson, G. D., Harris, G. J., et al (1991) Effects of fluoxetine on regional cerebral blood flow in obsessive-compulsive patients. American Journal of Psychiatry, 148, 1243–1245.Google ScholarPubMed
Hoehn-Saric, R. & Benkelfat, C. (1995) Structural and functional brain imaging in obsessive-compulsive disorder. In Current Insights in Obsessive Compulsive Disorder (eds. Hollander, E., Zohar, J., Marazzati, D., et al), pp. 183–211. New York: John Wiley & Sons Ltd.Google Scholar
Hollander, E., Prohovnik, I. & Stein, D. J. (1995) Increased cerebral blood flow during m-CPP exacerbation of obsessive-compulsive disorder. Journal of Neuropsychiatry and Clinical Neurosciences, 7, 485–490.Google ScholarPubMed
Hyde, T. M., Stacey, M. E., Coppola, R., et al (1995) Cerebral morphometric abnormalities inTourettes syndrome: a quantitative MRI study of monozygotic twins. Neurology, 45, 1176–1182.CrossRefGoogle ScholarPubMed
Insel, T. R. (1988) Obsessive-compulsive disorder: A neuroethological perspective. Psychopharmacological Bulletin, 24, 365–369.Google ScholarPubMed
Insel, T. R. (1992) Toward a neuroanatomy of obsessive-compulsive disorder. Archives of General Psychiatry, 49, 739–744.CrossRefGoogle Scholar
Insel, T. R., Donnelly, E. F., Lalakea, M. L., et al, (1983) Neurobiological and neuropsychological studies of patients with obsessive-compulsive disorder. Biological Psychiatry, 18, 741–751.Google Scholar
Jenike, M. A., Breiter, H. C., Baer, L., et al (1996) Cerebral structural abnormalities in obsessive-compulsive disorder: A quantitative morphometric magnetic resonance imaging study. Archives of General Psychiatry, 53, 625–632.CrossRefGoogle ScholarPubMed
Joel, D. & Weinger, J. (1994) The organization of the basal ganglia thalamocortical circuits: Open interconnected rather than closed segregated. Neuroscience, 63, 363–379.CrossRefGoogle ScholarPubMed
Kellner, C. H., Jolley, R. R., Holgate, R. C., et al (1991) Brain MRI in obsessive-compulsive disorder. Psychiatry Research 36, 45–49.Google Scholar
Lavoie, B. & Parent, A. (1990) Immunohistochemical study of the serotoninergic innervation of the basal ganglia in the squirrel monkey. Journal of Comparative Neurology, 299, 1–16.Google Scholar
Lucey, J. V., Costa, D. C., Adshead, G., et al (1997) Brain blood flow in anxiety disorders. OCD, panic disorder with agoraphobia, and post-traumatic stress disorder on 99mTcHMPAO single photon emission tomography (SPECT). British Journal of Psychiatry, 171, 346–350.CrossRefGoogle Scholar
Luxenberg, J. S., Swedo, S. E., Flamant, M. F., et al (1988) Neuroanatomical abnormalities in obsessive-compulsive disorder determined with quantitative x-ray computed tomography. American Journal of Psychiatry, 145, 1089–1093.Google Scholar
Machlin, S. R., Harris, G. J., Pearlson, G. D., et al (1991) Elevated medial-frontal cerebral blood flow in obsessive-compulsive patients: A SPECT study. American Journal of Psychiatry, 148, 1240–1242.Google ScholarPubMed
Maier, M. (1995) In vivo magnetic resonance spectroscopy. British Journal of Psychiatry, 167, 299–306.CrossRefGoogle ScholarPubMed
Mansari, M. E., Bouchard, C. & Blier, P. (1995) Alteration of serotonin release in the guinea pig orbitofrontal cortex by selective serotonin reuptake inhibitors. Neuropsychopharmacology, 13, 117–127.CrossRefGoogle ScholarPubMed
Martinot, J. L., Allilaire, J. F., Mazoyer, B. M., et al (1990a) Obsessive-compulsive disorder: A clinical, neuropsychological and positron emission tomography study. Acta Psychiatrica Scandinavica, 82, 233–242.CrossRefGoogle ScholarPubMed
Martinot, J. L., Allilaire, J. F., Mazoyer, B. M., et al (1990b) Left prefrontal glucose hypometabolism in the depressed state: A confirmation. American Journal of Psychiatry, 147, 1313–1317.Google ScholarPubMed
McDougle, C. J., Goodman, W. K., Price, L. H., et al (1990) Neuroleptic addition in fluvoxamine-refractory obsessive-compulsive disorder. American Journal of Psychiatry, 145, 1173–1174.Google Scholar
McDougle, C. J., Goodman, W. K., Price, L. H., et al (1995) Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder: a double-blind, placebo-controlled study in patients with and without tics. Archives of General Psychiatry, 51, 302–308.CrossRefGoogle Scholar
McGuire, P. K., Bench, C. J., Frith, C. D., et al (1994) Functional anatomy of obsessive-compulsive phenomena. British Journal of Psychiatry, 164, 459–468.CrossRefGoogle ScholarPubMed
Mega, M. & Cummings, J. L. (1994) Frontal-subcortical circuits and neuropsychiatric disorders. Journal of Neuropsychiatry and Clinical Neuroscience, 6, 358–380.Google ScholarPubMed
Mindus, P., Nyman, H., Mogard, J., et al (1991) Orbital and caudate glucose metabolism studied by positron emission tomography (PET) in patients undergoing capsulotomy for obsessive-compulsive disorder. In Understanding Obsessive-Compulsive Disorder (OCD) (eds Jenike, M. A. & Asberg, M.), pp. 52–57. Hogrefe and Huber Publishers.Google Scholar
Modell, J. G., Mountz, J. M., Curtis, G. C., et al (1989) Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder Journal of Neuropsychiatry and Clinical Neurosciences, 1, 27–36.Google ScholarPubMed
Mogenson, G. J. & Wu, M. (1988) Disruption of food hoarding by injections of procaine into mediodorsal thalamus, GABA into subpallidal regions, and haloperidol into accumbens. Brain Research Bulletin, 20, 247–251.CrossRefGoogle ScholarPubMed
Nauta, W. J. H. (1989) Reciprocal links of the corpus striatum with cortex and limbic system: a common substrate for movement and thought? In Neurology and Psychiatry: a Meeting of Minds (ed. Muleller, J.), pp. 43–63. New York: Karger.Google Scholar
Nordahl, T. E., Benkelfat, C., Semple, W. E., et al (1989) Cerebral glucose metabolic rates in obsessive-compulsive disorder. Neuropsychopharmacology, 2, 23–28.CrossRefGoogle ScholarPubMed
Parent, A. (1986) Comparative Neurobiology of the Basal Ganglia. New York: John Wiley & Sons.Google Scholar
Parent, A. & Hazrati, L.-N. (1995a) Functional anatomy of the basal ganglia I. The cortico-basal ganglia-thalamo-cortico loop. Brain Research Reviews, 20, 91–127.Google Scholar
Parent, A. & Hazrati, L.-N. (1995b) Functional anatomy of the basal ganglia II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Research Reviews, 20, 128–154.Google Scholar
Perani, D., Colombo, C., Bressi, S., et al (1995) [18FJFDG PET Study in obsessive-compulsive disorder: A clinical/metabolic correlation study after treatment. British Journal of Psychiatry, 166, 244–250.CrossRefGoogle ScholarPubMed
Peterson, B., Riddle, M. A., Cohen, D. J., et al (1993) Reduced basal ganglia volumes inTourette's syndrome using three-dimensional reconstruction techniques from magnetic resonance images. Neurology, 43, 941–949.CrossRefGoogle ScholarPubMed
Phillips, A. G. & Carr, G. D. (1987) Cognition and the basal ganglia: A possible substrate for procedural knowledge. Canadian Journal of Neurological Sciences, 14, 381–385.CrossRefGoogle ScholarPubMed
Rapoport, J. L. & Wise, S. P. (1988) Obsessive–compulsive disorder: Is it a basal ganglia dysfunction? Psychopharmacological Bulletin, 24, 380–384.Google Scholar
Rauch, S. L., Jenike, M. A., Alpert, N. M., et al (1994) Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. Archives of General Psychiatry, 51, 62–70.CrossRefGoogle ScholarPubMed
Rauch, S. L., Savage, C. R., Alpert, N. M., et al (1997) Probing striatal function in obsessive-compulsive disorder: a PET study of implicit sequence learning. Journal of Neuropsychiatry and Clinical Neurosciences, 9, 568–573.Google ScholarPubMed
Robinson, D., Wu, H., Munne, R. A., et al (1995) Reduced caudate nucleus volume in obsessive-compulsive disorder. Archives of General Psychiatry, 52, 393–398.CrossRefGoogle ScholarPubMed
Rosenberg, D. R., Keshavan, M. S., O'Hearn, K. M., et al (1997) Frontostriatal measurement in treatment-naive children with obsessive-compulsive disorder. Archives of General Psychiatry, 54, 824–830.CrossRefGoogle ScholarPubMed
Rubin, R. T., Villanueva-Meyer, J., Ananth, J., et al (1992) Regional 133Xe cerebral blood flow and cerebral 99m-HMPO uptake in unmedicated obsessive-compulsive disorder patients and matched normal control subjects: Determination by high-resolution single-photon emission computed tomography Archives of General Psychiatry, 49, 695–702.CrossRefGoogle ScholarPubMed
Rubin, R. T., Ananth, J., Villanueva-Meyer, J., et al (1995) Regional 133Xenon cerebral blood flow and cerebral Tc-HMPAO uptake in patients with obsessive-compulsive disorder before and after treatment. Biological Psychiatry, 38, 429–437.CrossRefGoogle Scholar
Saint-Cyr, J. A. & Taylor, A. E. (1992) The mobilization of procedural learning: the “key signature” of the basal ganglia. In Neuropsychology of Memory (2nd edn) (eds Squire, L. R. & Butters, N.), pp. 188–202. New York: Guilford Press.Google Scholar
Sawle, G. V., Hymas, N. F., Lees, A. J., et al (1991) Obsessional slowness: Functional studies with positron emission tomography. Brain, 114, 2191–2202.Google Scholar
Saxena, S., Brody, A. L., Colgan, M. E., et al (1995) Cerebral metabolic changes with successful paroxetine treatment of obsessive-compulsive disorder versus unipolar depression. Journal of Neuropsychiatry and Clinical Neurosciences, 7, 422.Google Scholar
Saxena, S., Brody, A. L., Colgan, M. E., et al (1998) Localized frontal and subcortical metabolic changes and predictors of response to paroxetine treatment of obsessive-compulsive disorder. Neuropsychopharmacology, in press.CrossRefGoogle Scholar
Scarone, S., Colombo, C., Livian, S., et al (1992) Increased right caudate nucleus size in obsessive-compulsive disorder: detection with magnetic resonance imaging. Psychiatry Research, 45, 115–121.CrossRefGoogle ScholarPubMed
Schwartz, J. M., Stoessel, P. W., Baxter, L. R., et al (1996) Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder. Archives of General Psychiatry, 53, 109–113.CrossRefGoogle ScholarPubMed
Sizer, A. R., Long, S. K. & Roberts, M. H. T. (1992) A modulatory function of 5-hydroxytrypamine in the central nervous system. In Serotonin, CNS Receptors, and Brain Function (eds Bradley, P. B., Handley, S. L., Cooper, S. J., et al), pp. 124–138. Oxford: Pergamon Press.Google Scholar
Sorenson, J. A. & Phelps, M. E. (1987) Physics in Nuclear Medicine. Philadelphia, PA: W B. Saunders Co.Google Scholar
Squire, L. R. (1992) Memory and the hippocampus: a synthesis of findings from rats, monkeys and humans. Psychology Reviews, 99, 195–231.CrossRefGoogle ScholarPubMed
Stein, D. J., Hollander, E., Chan, S., et al (1993) Computed tomography and neurological soft signs in obsessive–compulsive disorder. Psychiatry Research, 50, 143–150.Google Scholar
Swedo, S. E., Schapiro, M. G., Grady, C. L., et al (1989) Cerebral glucose metabolism in childhood onset obsessive-compulsive disorder. Archives of General Psychiatry, 46, 518–523.CrossRefGoogle ScholarPubMed
Swedo, S. E., Pietrini, P., Leonard, H. L., et al (1992) Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder: Revisualization during pharmacotherapy. Archives of General Psychiatry, 49, 690–694.CrossRefGoogle ScholarPubMed
Swerdlow, N. R. (1995) Serotonin, obsessive-compulsive disorder, and the basal ganglia. International Review of Psychiatry, 7, 115–129.CrossRefGoogle Scholar
Waeber, C. & Palacios, J. C. (1994) Binding sites for 5-hydroxytryptamine-2 receptor agonists are predominantly located in striosomes in the human basal ganglia. Molecular Brain Research, 24, 199–209.CrossRefGoogle ScholarPubMed
Zald, D. H. & Kim, S. W. (1996) Anatomy and function of the orbital frontal cortex, I: Anatomy, neurocircuitry, and obsessive-compulsive disorder. Journal of Neuropsychiatry and Clinical Neurosciences, 8, 125–138.Google Scholar
Zohar, J., Insel, T. R., Berman, K. F., et al (1989) Anxiety and cerebral blood flow during behavioral challenge: Dissociation of central from peripheral and subjective measures. Archives of General Psychiatry, 46, 505–510.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.