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Brain Imaging In Obsessive-Compulsive Disorder: Evidence for the Involvement of Frontal-Subcortical Circuitry in the Mediation of Symptomatology

Published online by Cambridge University Press:  07 November 2014

Arthur L. Brody  and
Sanjaya Saxena
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Abstract

Recent brain-imaging studies have examined the neuroanatomy and pathophysiology of obsessive-compulsive disorder (OCD). Researchers have used computed tomography and magnetic resonance imaging to look at brain structure and single-photon emission computed tomography and positron emission tomography scanning to look at brain function in OCD subjects. In this article, we review these studies and discuss their methodology. We then present a theoretical model derived from these studies for how the brain mediates OCD symptomatology.

Functional neuroimaging studies have pointed to hyperactivity of orbitofrontal-basal ganglionic–thalamic circuitry in patients with OCD. Our model posits an imbalance between the classical “direct” and “indirect” orbitofrontal–basal ganglionic–thalamic pathways in OCD subjects. The direct circuit appears to function as a positive feedback loop and may “capture” or “lock in” symptomatic OCD subjects. The indirect circuit, which usually provides tonic inhibition to the direct circuit, may be relatively weak.

Finally, we discuss how frontal-subcortical brain circuitry may be involved in other neuropsychiatric illnesses, and we describe how monoamines, such as serotonin and dopamine, may be involved in regulating these circuits in OCD and other illnesses.

Type
Feature Articles
Information
CNS Spectrums , Volume 1 , Issue 1: Special Academic Supplement: 2nd International OCD Conference , September 1996 , pp. 27 - 41
Copyright
Copyright © Cambridge University Press 1996

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References

1.Hoehn-Saric, R, Benkelfat, C. Structural and functional brain imaging in obsessive compulsive disorder. In: Hollander, E, Zohar, J, Marazzati, D, and Olivier, B, eds. Current Insights in Obsessive Compulsive Disorder. John Wiley & Sons Ltd; 1995:183–211.Google Scholar
2.Baxter, LR. PET studies of cerebral function in major depression and obsessive-compulsive disorder: the emerging prefrontal consensus. Ann Clin Psychiatry. 1991;3:103–109.CrossRefGoogle Scholar
3.Baxter, LR, Schwartz, JM, Guze, BH, et al. Neuroimaging in obsessive-compulsive disorder: seeking the mediating neuroanatomy. In: Jenicke, MA, Baer, L, Minichiello, WE, eds. Obsessive-Compulsive Disorders: Theory and Management. 2nd ed. Chicago: Year Book Medical Publishers; 1990:167–188.Google Scholar
4.Baxter, LR, Schwartz, JM, Guze, BH, et al. PET imaging in obsessive-compulsive disorder with and without depression. J Clin Psychiatry. 1990:51 (suppl):61–69.Google ScholarPubMed
5.Baxter, LR, Schwartz, JM. Guze, BH. Brain imaging: toward a neuroanatomy of OCD. In: Zohar, Y, Insel, TR, Rasmussen, S, eds. The Psychobiology of Obsessive-Compulsive Disorder. New York: Springer Verlag; 1991:101–125.Google Scholar
6.Insel, TR, Winslow, JT. Neurobiology of obsessive-compul- sive disorder. In: Jenicke, MA, Baer, L, Minichiello, WE, eds. Obsessive-Compulsive Disorders: Theory and Management, 2nd ed. Chicago: Year Book Medical Publishers; 1990:116–131.Google Scholar
7.Insel, TR, Donnelly, EF, Lalakea, ML, et al. Neurological and neuropsychological studies of patients with obsessive-compulsive disorder. Biol Psychiatry. 1983:18:741–751.Google ScholarPubMed
8.Behar, D, Rapoport, JL, Berg, CJ, et al. Computerized tomography and neuropsychological test measures in adolescents with obsessive-compulsive disorder. Am J Psychiatry. 1984:141:363–369.Google ScholarPubMed
9.Luxenberg, JS, Swedo, SE, Flamant, MF, et al. Neuroanatomical abnormalities in obsessive-compulsive disorder determined with quantitative x-ray computed tomography. Am J Psychiatry. 1988;145:1089–1093.Google Scholar
10.Garber, HJ, Ananth, JV, Chiu, LC, et al. Nuclear magnetic resonance study of obsessive-compulsive disorder. Am J Psychiatry. 1989:146:1001–1005.Google ScholarPubMed
11.Kellner, CH, Jolley, RR, Holgate, RC, et al. Brain MRI in obsessive-compulsive disorder. Psychiatry Res. 1991:36:45–49.CrossRefGoogle ScholarPubMed
12.Scarone, S, Colombo, C, Livian, S, et al. Increased right caudate nucleus size in obsessive-compulsive disorder: detection with magnetic resonance imaging. Psychiatry Res. 1992:45:115–121.CrossRefGoogle ScholarPubMed
13.Zohar, J, Insel, TR, Berman, KF, et al. Anxiety and cerebral blood flow during behavioral challenge: dissociation of central from peripheral and subjective measures. Arch Gen Psychiatry. 1989:46:505–510.CrossRefGoogle ScholarPubMed
14.Rubin, RT, Villanueva-Meyer, J, Ananth, J, et al. Regional 133Xe cerebral blood flow and cerebral 99m- HMPAO uptake in unmedicated obsessive-compulsive disorder patients and matched normal control subjects: determination by high-resolution single-photon emission computed tomography. Arch Gen Psychiatry. 1992;49:695–702.CrossRefGoogle ScholarPubMed
15.Hollander, E, Prohovnik, I, Stein, DJ. Increased cerebral blood flow during m-CPP exacerbation of obsessive-compulsive disorder. J Neuropsychiatry. 1995;7:485–490.Google ScholarPubMed
16.Machlin, SR, Harris, GJ, Pearlson, GD, et al. Elevated medial-frontal cerebral blood flow in obsessive-compulsive patients: a SPECT study. Am J Psychiatry. 1991;148:1240–1242.Google ScholarPubMed
17.Hoehn-Saric, R, Pearlson, GD, Harris, GJ, et al. Effects of fluoxetine on regional cerebral blood flow in obsessive-compulsive patients. Am J Psychiatry. 1991;48:1243–1245.Google Scholar
18.Adams, BL, Warneke, LB, McEwan, AJB, et al. Single photon emission computerized tomography in obsessive-compulsive disorder: a preliminary study. J Psychiatr Neurosci. 1993:18:109–112.Google ScholarPubMed
19.Sorenson, JA, Phelps, ME. Physics in nuclear medicine. Philadelphia Pa: WB Saunders Co; 1987.Google Scholar
20.Andreasen, NC. Brain Imaging: Applications in Psychiatry. Washington, DC: American Psychiatric Press; 1989.Google Scholar
21.Baxter, LR, Phelps, ME, Mazziotta, JC, et al. Local cerebral glucose metabolic rates in obsessive-compulsive disorder—a comparison with rates in unipolar depression and in normal controls. Arch Gen Psychiatry. 1987;44:211–218.CrossRefGoogle ScholarPubMed
22.Baxter, LR, Schwartz, JM, Mazziotta, JC, et al. Cerebral glucose metabolic rates in non-depressed obsessive-compulsives. Am J Psychiatry. 1988;145:1560–1563.Google Scholar
23.Nordahl, TE, Benkelfat, C, Semple, WE. et al. Cerebral glucose metabolic rates in obsessive-compulsive disorder. Neuropsychopharmacology. 1989:2:23–28.CrossRefGoogle ScholarPubMed
24.Swedo, SE, Schapiro, MG, Grady, CL, et al. Cerebral glucose metabolism in childhood onset obsessive-compulsive disorder. Arch Gen Psychiatry. 1989:46:518–523.CrossRefGoogle ScholarPubMed
25.Horwitz, B, Swedo, SE, Grady, CL, et al. Cerebral metabolic pattern in obsessive-compulsive disorder: altered intercorrelations between regional rates of glucose utilization. Psychiatry Res. 1991:40:221–237.CrossRefGoogle ScholarPubMed
26.Martinot, JL, Allilaire, JF, Mazoyer, BM, et al. Obsessive-compulsive disorder: a clinical, neuropsychological and positron emission tomography study. Acta Psychiatr Scand. 1990:82:233–242.CrossRefGoogle ScholarPubMed
27.Martinot, JL, Hardy, P, Feline, A, et al. Left prefrontal glucose hypometabolism in the depressed state: a confirmation. Am J Psychiatry. 1990;147:1313–1317.Google ScholarPubMed
28.Sawle, GV, Hymas, NF, Lees, AJ, et al. Obsessional slowness: functional studies with positron emission tomography. Brain. 1991:114:2191–2202.CrossRefGoogle ScholarPubMed
29.Mindus, P, Nyman, H, Mogard, J, et al. Orbital and caudate glucose metabolism studied by positron emission tomography (PET) in patients undergoing capsulotomy for obsessive-compulsive disorder. In: Jenicke, MA, Asberg, M, eds. Understanding Obsessive-Compulsive Disorder (OCD). Toronto: Hogrefe and Huber Publishers; 1991:52–57.Google Scholar
30.Swedo, SE, Pietrini, P, Leonard, HL, et al. Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder: revlsualization during pharmacotherapy. Arch Gen Psychiatry. 1992;49:690–694.CrossRefGoogle ScholarPubMed
31.Benkelfat, C, Nordahl, TE, Semple, WE, et al. Local cerebral glucose metabolic rates in obsessive-compulsive disorder: patients treated with clomipramine. Arch Gen Psychiatry. 1990:47:840–848.CrossRefGoogle ScholarPubMed
32.Baxter, LR, Schwartz, JM, Bergman, KS, et al. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry. 1992;49:681–689.CrossRefGoogle ScholarPubMed
33.Perani, D, Colombo, C, Bressi, S, et al. [18F]FDG PET Study in obsessive-compulsive disorder: a clinical/metabolic correlation study after treatment. Br J Psychiatry. 1995;166:244–250.CrossRefGoogle ScholarPubMed
34.Schwartz, JM, Stoessel, PW, Baxter, LR, et al. Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder. Arch Gen Psychiatry. 1996:53:109–113.CrossRefGoogle ScholarPubMed
35.Rauch, SL, Jenike, MA, Alpert, NM, et al. Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. Arch Gen Psychiatry. 1994;51:62–70.CrossRefGoogle ScholarPubMed
36.McGuire, PK, Bench, CJ, Frith, CD, et al. Functional anatomy of obsessive-compulsive phenomena. Br J Psychiatry. 1994:164:459–468.CrossRefGoogle ScholarPubMed
37.Rapoport, JL, Wise, SP. Obsessive-compulsive disorder: is it a basal ganglia dysfunction? Psychopharmacol Bull. 1988:24:380–384.Google ScholarPubMed
38.Insel, TR. Obsessive-compulsive disorder: a neuroethological perspective. Psychopharmacol Bull. 1988:24:365–369.Google ScholarPubMed
39.Modell, JG, Mountz, JM, Curtis, GC, et al. Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder. J Neumpsychiatry. 1989:1:27–36.Google ScholarPubMed
40.Alexander, GE, DeLong, MR, Strick, PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci. 1986:9:357–381.CrossRefGoogle ScholarPubMed
41.Cummings, JL. Frontal-subcortical circuits and human behavior. Arch Neurol. 1993:50:873–880.CrossRefGoogle ScholarPubMed
42.Gerfen, CR. The neostriatal mosaic: multiple levels of compartmental organization in the basal ganglia. Annu Rev Neurosci. 1992:15:285–320.CrossRefGoogle ScholarPubMed
43.Iversen, SD. Behavioral aspects of cortico-subcortical interaction with special reference to frontostriatal relations. In: Reinoso-Suarez, G, Ajmone-Marsan, C, eds. Cortical Integration. New York: Raven Press; 1984.Google Scholar
44.Joel, D, Weinger, J. the organization of the basal ganglia thalamocortical circuits: open interconnected rather than closed segregated. Neuroscience. 1994:63:363–379.CrossRefGoogle ScholarPubMed
45.Nauta, WJH, Domesick, VB. Afferent and efferent relationships of the basal ganglia. Functions of the Basal Ganglia. London: Pitman (CIBA Foundation Symposium #107); 1984:3–29.Google Scholar
46.Parent, A. Comparative Neumbiology of the Basal Ganglia. New York: John Wiley & Sons; 1986.Google Scholar
47.Parent, A, Hazrati, L-N. Functional anatomy of the basal ganglia. I: the cortico-basal ganglia-thalamo-cortico loop. Brain Res Rev. 1995:20:91–127.CrossRefGoogle Scholar
48.Parent, A, Hazrati, L-N. Functional anatomy of the basal ganglia: II. the place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Rev. 1995;20:128–154.CrossRefGoogle ScholarPubMed
49.Swerdlow, NR, Koob, GF. Dopamine, schizophrenia, mania and depression: toward a unified hypothesis of cortico-striato-pallido-thalamic function. Behav Brain Sci. 1987:10:197–245.CrossRefGoogle Scholar
50.Baxter, LR, Schwartz, JM, Guze, BH, Bergman, K, Szuba, MP. Neuroimaging in obsessive-compulsive disorders: seeking the mediating neuroanatomy. In: Jenike, MA, Baer, L, Minichiello, WE, eds. Obsessive-Compulsive Disorders: Theory and Management, 2nd ed., Chicago: Year Book; 1990:167–188.Google Scholar
51.Baxter, LR, Schwartz, JM, Phelps, ME, et al. Reduction of prefrontal cortex glucose metabolism common to three types of depression. Arch Gen Psychiatry. 1989;46:243–250.CrossRefGoogle ScholarPubMed
52.Hall, H, Sedvall, G, Magnusson, O, et al. Distribution of D1 and D2-dopamine receptors, and dopamine and its metaboltes in the human brain. Neuropsychopharmacology. 1994;11:245–256.CrossRefGoogle Scholar
53.Gerfen, CR, Engber, TM, Mahan, LC, et al. D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science. 1990:250:1429–1432.CrossRefGoogle ScholarPubMed
54.Baxter, LR, Phelps, ME, Mazziotta, JC, et al. Cerebral metabolic rates for glucose in mood disorders. Arch Gen Psychiatry. 1985:42:441–447.CrossRefGoogle ScholarPubMed
55.Baxter, LR, Guze, BH: Neuroimaging in Tourette's and related disorders. In: Kurland, R, ed. Handbook of Tourette's Syndrome and Related Tic and Behavioral Disorders. Paris: Marcel Dekker; 1993:289–304.Google Scholar
56.Braun, AR, Randolph, C, Stoetter, B, et al. The functional neuroanatomy of Tourette's syndrome: an FDG-PET study. I: relationships between regional cerebral metabolism and associated behavioral and cognitive features of the illness. Neuropsychopharmacology. 1995:13:151–168.CrossRefGoogle Scholar
57.Insel, TR. Toward a neuroanatomy of obsessive-compulsive disorder. Arch Gen Psychiatry. 1992:49:739–744.CrossRefGoogle Scholar
58.Lavoie, B, Parent, A. Immunohistochemical study of the serotoninergic innervation of the basal ganglia in the squirrel monkey. J Comp Neurology. 1990:299:1–16.Google ScholarPubMed
59.Palacios, JM, Wawber, C, Hoyer, D, Mengod, G. Distribution of serotonin receptors. Ann N Y Acad Sci. 1990;600:36–52.Google Scholar
60.Pazos, A, Gonzalez, AM, Waeber, C, Palacios, JM. Multiple serotonin receptors in the human brain. In: Receptors in the Human Nervous System. New York: Academic Press; 1991:71–101CrossRefGoogle Scholar
61.Mansari, ME, Bouchard, C, Blier, P. Alteration of serotonin release in the guinea pig orbito-frontal cortex by selective serotonin reuptake inhibitors. Neuropsychopharmacology. 1995:13:117–127.CrossRefGoogle ScholarPubMed
62.Baxter, LR, Saxena, S, Brody, AL, et al. Brain mediation of obsessive-compulsive disorder symptoms: evidence from functional brain imaging studies in the human and non-human primate. Semin Clin Neuropsychiatry. 1996:1:32–47.Google Scholar