Skip to main content Accessibility help
×
Home

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

  • Arthur L. Brody and Sanjaya Saxena

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.

Copyright

References

Hide All
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; 1995:183211.
2.Baxter, LR. PET studies of cerebral function in major depression and obsessive-compulsive disorder: the emerging prefrontal consensus. Ann Clin Psychiatry. 1991;3:103109.
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; 1990:167188.
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):6169.
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; 1991:101125.
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; 1990:116131.
7.Insel, TR, Donnelly, EF, Lalakea, ML, et al. Neurological and neuropsychological studies of patients with obsessive-compulsive disorder. Biol Psychiatry. 1983:18:741751.
8.Behar, D, Rapoport, JL, Berg, CJ, et al. Computerized tomography and neuropsychological test measures in adolescents with obsessive-compulsive disorder. Am J Psychiatry. 1984:141:363369.
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;145:10891093.
10.Garber, HJ, Ananth, JV, Chiu, LC, et al. Nuclear magnetic resonance study of obsessive-compulsive disorder. Am J Psychiatry. 1989:146:10011005.
11.Kellner, CH, Jolley, RR, Holgate, RC, et al. Brain MRI in obsessive-compulsive disorder. Psychiatry Res. 1991:36:4549.
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. 1992:45:115121.
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. 1989:46:505510.
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;49:695702.
15.Hollander, E, Prohovnik, I, Stein, DJ. Increased cerebral blood flow during m-CPP exacerbation of obsessive-compulsive disorder. J Neuropsychiatry. 1995;7:485490.
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;148:12401242.
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;48:12431245.
18.Adams, BL, Warneke, LB, McEwan, AJB, et al. Single photon emission computerized tomography in obsessive-compulsive disorder: a preliminary study. J Psychiatr Neurosci. 1993:18:109112.
19.Sorenson, JA, Phelps, ME. Physics in nuclear medicine. Philadelphia Pa: WB Saunders Co; 1987.
20.Andreasen, NC. Brain Imaging: Applications in Psychiatry. Washington, DC: American Psychiatric Press; 1989.
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;44:211218.
22.Baxter, LR, Schwartz, JM, Mazziotta, JC, et al. Cerebral glucose metabolic rates in non-depressed obsessive-compulsives. Am J Psychiatry. 1988;145:15601563.
23.Nordahl, TE, Benkelfat, C, Semple, WE. et al. Cerebral glucose metabolic rates in obsessive-compulsive disorder. Neuropsychopharmacology. 1989:2:2328.
24.Swedo, SE, Schapiro, MG, Grady, CL, et al. Cerebral glucose metabolism in childhood onset obsessive-compulsive disorder. Arch Gen Psychiatry. 1989:46:518523.
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. 1991:40:221237.
26.Martinot, JL, Allilaire, JF, Mazoyer, BM, et al. Obsessive-compulsive disorder: a clinical, neuropsychological and positron emission tomography study. Acta Psychiatr Scand. 1990:82:233242.
27.Martinot, JL, Hardy, P, Feline, A, et al. Left prefrontal glucose hypometabolism in the depressed state: a confirmation. Am J Psychiatry. 1990;147:13131317.
28.Sawle, GV, Hymas, NF, Lees, AJ, et al. Obsessional slowness: functional studies with positron emission tomography. Brain. 1991:114:21912202.
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; 1991:5257.
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;49:690694.
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. 1990:47:840848.
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;49:681689.
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;166:244250.
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. 1996:53:109113.
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;51:6270.
36.McGuire, PK, Bench, CJ, Frith, CD, et al. Functional anatomy of obsessive-compulsive phenomena. Br J Psychiatry. 1994:164:459468.
37.Rapoport, JL, Wise, SP. Obsessive-compulsive disorder: is it a basal ganglia dysfunction? Psychopharmacol Bull. 1988:24:380384.
38.Insel, TR. Obsessive-compulsive disorder: a neuroethological perspective. Psychopharmacol Bull. 1988:24:365369.
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. 1989:1:2736.
40.Alexander, GE, DeLong, MR, Strick, PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci. 1986:9:357381.
41.Cummings, JL. Frontal-subcortical circuits and human behavior. Arch Neurol. 1993:50:873880.
42.Gerfen, CR. The neostriatal mosaic: multiple levels of compartmental organization in the basal ganglia. Annu Rev Neurosci. 1992:15:285320.
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.
44.Joel, D, Weinger, J. the organization of the basal ganglia thalamocortical circuits: open interconnected rather than closed segregated. Neuroscience. 1994:63:363379.
45.Nauta, WJH, Domesick, VB. Afferent and efferent relationships of the basal ganglia. Functions of the Basal Ganglia. London: Pitman (CIBA Foundation Symposium #107); 1984:329.
46.Parent, A. Comparative Neumbiology of the Basal Ganglia. New York: John Wiley & Sons; 1986.
47.Parent, A, Hazrati, L-N. Functional anatomy of the basal ganglia. I: the cortico-basal ganglia-thalamo-cortico loop. Brain Res Rev. 1995:20:91127.
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;20:128154.
49.Swerdlow, NR, Koob, GF. Dopamine, schizophrenia, mania and depression: toward a unified hypothesis of cortico-striato-pallido-thalamic function. Behav Brain Sci. 1987:10:197245.
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; 1990:167188.
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;46:243250.
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;11:245256.
53.Gerfen, CR, Engber, TM, Mahan, LC, et al. D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science. 1990:250:14291432.
54.Baxter, LR, Phelps, ME, Mazziotta, JC, et al. Cerebral metabolic rates for glucose in mood disorders. Arch Gen Psychiatry. 1985:42:441447.
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; 1993:289304.
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. 1995:13:151168.
57.Insel, TR. Toward a neuroanatomy of obsessive-compulsive disorder. Arch Gen Psychiatry. 1992:49:739744.
58.Lavoie, B, Parent, A. Immunohistochemical study of the serotoninergic innervation of the basal ganglia in the squirrel monkey. J Comp Neurology. 1990:299:116.
59.Palacios, JM, Wawber, C, Hoyer, D, Mengod, G. Distribution of serotonin receptors. Ann N Y Acad Sci. 1990;600:3652.
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; 1991:71101
61.Mansari, ME, Bouchard, C, Blier, P. Alteration of serotonin release in the guinea pig orbito-frontal cortex by selective serotonin reuptake inhibitors. Neuropsychopharmacology. 1995:13:117127.
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. 1996:1:3247.

Related content

Powered by UNSILO

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

  • Arthur L. Brody and Sanjaya Saxena

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.