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Structural Abnormalities of Frontal Neocortex in Obsessive-compulsive Disorder

Structural Abnormalities of Frontal Neocortex in Obsessive-compulsive Disorder In the July 1996 issue of the ARCHIVES, Jenike et al1 presented results from a morphometric magnetic resonance imaging (MRI)–based brain segmentation study of obsessive-compulsive disorder (OCD). Compared with normal controls, patients with OCD had significantly less total white matter (extending previous findings of decreased posterior white matter in a separate cohort of patients2), greater total neocortex, and greater opercular volumes. Furthermore, clinical severity of OCD and nonverbal immediate memory correlated with opercular cortical volume.1 Several morphometric studies have found caudate volumetric abnormalities in OCD1,3,4; however, comprehensive parcellation of neocortex has not been reported. Functional neuroimaging studies of OCD have primarily implicated orbitofrontal and anterior cingulate cortex, as well as striatum, with reports of hyperactivity during neutral states that is accentuated during symptom provocation and attenuated with treatment.5 As a complement to these imaging findings, a recent neuropsychological study has reported evidence of a nonverbal memory retrieval deficit with normal verbal and nonverbal memory storage in OCD.6 To our knowledge, there have been no morphometric studies to date linking prefrontal cortex to behavioral or neuropsychological indices in OCD. We reanalyzed the original MRI data of Jenike et al,1 using methods of neocortical parcellation,7-9 to determine (1) whether, in comparison with matched controls, patients with OCD exhibited volumetric differences in orbitofrontal or anterior cingulate cortex; (2) which cortical subterritories contributed to the opercular volumetric differences reported in the original segmentation study1; and (3) whether cortical volumetric differences in OCD correlated with measures of symptom severity or nonverbal memory. The study sample was as previously described.1 Ten right-handed female subjects with OCD by DSM-III-R criteria and 10 female normal controls were matched for age (patients with OCD, 31.6±8.7 years; controls, 28.5±11.4 years [mean±SD]), handedness, and education. All subjects were without Tourette syndrome, psychosis, major depression, substance abuse, or significant medical or neurological illnesses. The MRI-based brain segmentation method,10-12 using well-characterized semiautomated intensity and differential contour algorithms by signal intensity and frequency histograms, was blindly used to segment the principal gray and white matter structures. The neocortical ribbon was subdivided into 48 parcellation units (PUs) per hemisphere.7-9 The absolute volume of each PU was summed from all outlines in all planes by multiplying the total number of voxels by each voxel volume. Statistical analyses were performed with SAS statistical analysis software (SAS Institute Inc, Cary, NC) using the Student t test. We found no difference in anterior cingulate, orbitofrontal, or opercular cortical volumes in patients with OCD compared with matched normal control subjects (all P>.1). The total cerebral neocortical volume was larger for patients with OCD (t=3.59, df=18, P=.002), which is consistent with our previously published results.1 Specifically, the cerebral neocortical volume for patients with OCD was larger for the right (t=3.67, df=18, P=.001) and for the left (t=3.36, df=18, P=.003) hemispheres. Opercular volumetric differences by segmentation1 were not evident by neocortical parcellation.7-9 In comparison with the opercular territory defined by segmentation, the volume by parcellation was smaller by 27%. Further evaluation revealed that subterritories of 11 (mostly frontal) neocortical PUs were included within the opercular volume defined by segmentation. Thus, the volumetric differences attributed to opercular volume by segmentation may more precisely be reflective of differences within frontal PUs. Hence, we compared the 14 frontal PUs per hemisphere and found 10 (6 on the right and 4 on the left) for which the OCD group showed significantly greater volumes than controls (P<.05). In our previous study,1 a complex relationship between total opercular volume and behavioral measures was suggested. Thus, we wanted to determine which subregions of operculum or frontal neocortex might be associated with nonverbal immediate memory impairment or severity of OCD. We conducted secondary analyses correlating scores from the Yale-Brown Obsessive Compulsive Scale13,14 and the Rey-Osterrieth Complex Figure Test.15,16 Volumes of the 10 frontal cortical PUs were found to be significantly different between groups. Two of these 10 structures were found to be correlated with behavioral measures. Right inferior frontal pars triangularis and right midfrontal cortical volumes were negatively related to Rey-Osterrieth Complex Figure Test immediate recall (r=−0.69, P<.001 and r=−0.56, P=.01, respectively), suggesting that OCD patients with greater right frontal volumes had worse memory performance. None of these frontal volumes were significantly related to OCD clinical severity. This preliminary cortical parcellation study in OCD suggests volumetric abnormalities involving the frontal lobes and structural neuroanatomical differences involving right frontal neocortex, which may represent a substrate of nonverbal immediate memory impairment in OCD. Especially given the small number of subjects and the problem of multiple comparisons, our findings require further investigation. References 1. Jenike MABreiter HCBaer LKennedy DNSavage CROlivares NJO'Sullivan RLShera DMRauch SLKeuthen NRosen BRCaviness VSFilipek PA Cerebral structural abnormalities in obsessive-compulsive disorder: a quantitative morphometric magnetic resonance imaging study. Arch Gen Psychiatry. 1996;53625- 632Google Scholar 2. Breiter HCRFilipek PAKennedy DNBaer LPitcher DOlivares MRenshaw PCaviness VSJenike MA Retrocallosal white matter abnormalities in patients with obsessive-compulsive disorder. Arch Gen Psychiatry. 1994;51663- 664Google Scholar 3. Scarone SColombo CLivian SAbbruzzese MRonchi PLocatelli MScotti GSmeraldi E Increased right caudate nucleus size in obsessive compulsive disorder: detection with magnetic resonance imaging. Psychiatry Res. 1992;45115- 121Google Scholar 4. Robinson DWu HMunne RAAshtari MAlvir JMJLerner GKoreen ACole KBogerts B Reduced caudate nucleus volume in obsessive-compulsive disorder. Arch Gen Psychiatry. 1995;52393- 398Google Scholar 5. Hoehn-Saric RBenkelfat C Structural and functional brain imaging in obsessive compulsive disorder. Hollander EZohar JMarazziti Deds Current Insights in Obsessive Compulsive Disorder. New York, NY John Wiley & Sons Inc1994;183- 214Google Scholar 6. Savage CRKeuthen NJJenike MABrown HDBaer LKendrick ADMiguel ECRauch SLAlbert MS Recall and recognition memory in obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci. 1996;899- 103Google Scholar 7. Rademacher JGalaburda AMKennedy DNFilipek PACaviness VS Human cerebral cortex: localization, parcellation, and morphometry with magnetic resonance imaging. J Cogn Neurosci. 1992;4352- 374Google Scholar 8. Caviness VSMeyer JMakris NKennedy N MRI-based topographic parcellation of human neocortex: an anatomically specified method with estimate of reliability. J Cogn Neurosci. 1996;8566- 587Google Scholar 9. Grachev IDJenike MABaer LRauch RLO'Sullivan RLBreiter HCKennedy DNKeuthen NJSavage CRCaviness VS Magnetic resonance imaging study of the brain's neocortex. Neuroimage. 1996;3132Abstract.Google Scholar 10. Kennedy DNFilipek PACaviness VS Anatomic segmentation and volumetric calculations in nuclear magnetic resonance imaging. IEEE Trans Med Imaging. 1989;81- 7Google Scholar 11. Kennedy DNMeyer JWFilipek PACaviness VS MRI-based topographic segmentation. Thatcher RHallett MZeffiro TJohn RHuerta Meds Functional Neuroimaging. New York, NY Academic Press1994;201- 208Google Scholar 12. Filipek PARichelme CKennedy DNCaviness VS The young adult human brain: an MRI-based morphometric analysis. Cereb Cortex. 1994;4344- 360Google Scholar 13. Goodman WKPrice LHRasmussen SAMazure CFleischmann RHill CHenninger GRCharney DS The Yale-Brown Obsessive Compulsive Scale, I: development, use, and reliability. Arch Gen Psychiatry. 1989;461006- 1011Google Scholar 14. Goodman WKPrice LHRasmussen SAMazure CDelgado PHenninger GRCharney DS The Yale-Brown Obsessive Compulsive Scale, II: validity. Arch Gen Psychiatry. 1989;461012- 1016Google Scholar 15. Osterrieth PRey A Le test de copie d'une figure complex. Arch Psychol. 1944;30205- 221Google Scholar 16. Lezak MD Neuropsychological Assessment. 2nd ed. New York, NY Oxford University Press1983; http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

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Publisher
American Medical Association
Copyright
Copyright © 1998 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.55.2.181
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Abstract

In the July 1996 issue of the ARCHIVES, Jenike et al1 presented results from a morphometric magnetic resonance imaging (MRI)–based brain segmentation study of obsessive-compulsive disorder (OCD). Compared with normal controls, patients with OCD had significantly less total white matter (extending previous findings of decreased posterior white matter in a separate cohort of patients2), greater total neocortex, and greater opercular volumes. Furthermore, clinical severity of OCD and nonverbal immediate memory correlated with opercular cortical volume.1 Several morphometric studies have found caudate volumetric abnormalities in OCD1,3,4; however, comprehensive parcellation of neocortex has not been reported. Functional neuroimaging studies of OCD have primarily implicated orbitofrontal and anterior cingulate cortex, as well as striatum, with reports of hyperactivity during neutral states that is accentuated during symptom provocation and attenuated with treatment.5 As a complement to these imaging findings, a recent neuropsychological study has reported evidence of a nonverbal memory retrieval deficit with normal verbal and nonverbal memory storage in OCD.6 To our knowledge, there have been no morphometric studies to date linking prefrontal cortex to behavioral or neuropsychological indices in OCD. We reanalyzed the original MRI data of Jenike et al,1 using methods of neocortical parcellation,7-9 to determine (1) whether, in comparison with matched controls, patients with OCD exhibited volumetric differences in orbitofrontal or anterior cingulate cortex; (2) which cortical subterritories contributed to the opercular volumetric differences reported in the original segmentation study1; and (3) whether cortical volumetric differences in OCD correlated with measures of symptom severity or nonverbal memory. The study sample was as previously described.1 Ten right-handed female subjects with OCD by DSM-III-R criteria and 10 female normal controls were matched for age (patients with OCD, 31.6±8.7 years; controls, 28.5±11.4 years [mean±SD]), handedness, and education. All subjects were without Tourette syndrome, psychosis, major depression, substance abuse, or significant medical or neurological illnesses. The MRI-based brain segmentation method,10-12 using well-characterized semiautomated intensity and differential contour algorithms by signal intensity and frequency histograms, was blindly used to segment the principal gray and white matter structures. The neocortical ribbon was subdivided into 48 parcellation units (PUs) per hemisphere.7-9 The absolute volume of each PU was summed from all outlines in all planes by multiplying the total number of voxels by each voxel volume. Statistical analyses were performed with SAS statistical analysis software (SAS Institute Inc, Cary, NC) using the Student t test. We found no difference in anterior cingulate, orbitofrontal, or opercular cortical volumes in patients with OCD compared with matched normal control subjects (all P>.1). The total cerebral neocortical volume was larger for patients with OCD (t=3.59, df=18, P=.002), which is consistent with our previously published results.1 Specifically, the cerebral neocortical volume for patients with OCD was larger for the right (t=3.67, df=18, P=.001) and for the left (t=3.36, df=18, P=.003) hemispheres. Opercular volumetric differences by segmentation1 were not evident by neocortical parcellation.7-9 In comparison with the opercular territory defined by segmentation, the volume by parcellation was smaller by 27%. Further evaluation revealed that subterritories of 11 (mostly frontal) neocortical PUs were included within the opercular volume defined by segmentation. Thus, the volumetric differences attributed to opercular volume by segmentation may more precisely be reflective of differences within frontal PUs. Hence, we compared the 14 frontal PUs per hemisphere and found 10 (6 on the right and 4 on the left) for which the OCD group showed significantly greater volumes than controls (P<.05). In our previous study,1 a complex relationship between total opercular volume and behavioral measures was suggested. Thus, we wanted to determine which subregions of operculum or frontal neocortex might be associated with nonverbal immediate memory impairment or severity of OCD. We conducted secondary analyses correlating scores from the Yale-Brown Obsessive Compulsive Scale13,14 and the Rey-Osterrieth Complex Figure Test.15,16 Volumes of the 10 frontal cortical PUs were found to be significantly different between groups. Two of these 10 structures were found to be correlated with behavioral measures. Right inferior frontal pars triangularis and right midfrontal cortical volumes were negatively related to Rey-Osterrieth Complex Figure Test immediate recall (r=−0.69, P<.001 and r=−0.56, P=.01, respectively), suggesting that OCD patients with greater right frontal volumes had worse memory performance. None of these frontal volumes were significantly related to OCD clinical severity. This preliminary cortical parcellation study in OCD suggests volumetric abnormalities involving the frontal lobes and structural neuroanatomical differences involving right frontal neocortex, which may represent a substrate of nonverbal immediate memory impairment in OCD. Especially given the small number of subjects and the problem of multiple comparisons, our findings require further investigation. References 1. Jenike MABreiter HCBaer LKennedy DNSavage CROlivares NJO'Sullivan RLShera DMRauch SLKeuthen NRosen BRCaviness VSFilipek PA Cerebral structural abnormalities in obsessive-compulsive disorder: a quantitative morphometric magnetic resonance imaging study. Arch Gen Psychiatry. 1996;53625- 632Google Scholar 2. Breiter HCRFilipek PAKennedy DNBaer LPitcher DOlivares MRenshaw PCaviness VSJenike MA Retrocallosal white matter abnormalities in patients with obsessive-compulsive disorder. Arch Gen Psychiatry. 1994;51663- 664Google Scholar 3. Scarone SColombo CLivian SAbbruzzese MRonchi PLocatelli MScotti GSmeraldi E Increased right caudate nucleus size in obsessive compulsive disorder: detection with magnetic resonance imaging. Psychiatry Res. 1992;45115- 121Google Scholar 4. Robinson DWu HMunne RAAshtari MAlvir JMJLerner GKoreen ACole KBogerts B Reduced caudate nucleus volume in obsessive-compulsive disorder. Arch Gen Psychiatry. 1995;52393- 398Google Scholar 5. Hoehn-Saric RBenkelfat C Structural and functional brain imaging in obsessive compulsive disorder. Hollander EZohar JMarazziti Deds Current Insights in Obsessive Compulsive Disorder. New York, NY John Wiley & Sons Inc1994;183- 214Google Scholar 6. Savage CRKeuthen NJJenike MABrown HDBaer LKendrick ADMiguel ECRauch SLAlbert MS Recall and recognition memory in obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci. 1996;899- 103Google Scholar 7. Rademacher JGalaburda AMKennedy DNFilipek PACaviness VS Human cerebral cortex: localization, parcellation, and morphometry with magnetic resonance imaging. J Cogn Neurosci. 1992;4352- 374Google Scholar 8. Caviness VSMeyer JMakris NKennedy N MRI-based topographic parcellation of human neocortex: an anatomically specified method with estimate of reliability. J Cogn Neurosci. 1996;8566- 587Google Scholar 9. Grachev IDJenike MABaer LRauch RLO'Sullivan RLBreiter HCKennedy DNKeuthen NJSavage CRCaviness VS Magnetic resonance imaging study of the brain's neocortex. Neuroimage. 1996;3132Abstract.Google Scholar 10. Kennedy DNFilipek PACaviness VS Anatomic segmentation and volumetric calculations in nuclear magnetic resonance imaging. IEEE Trans Med Imaging. 1989;81- 7Google Scholar 11. Kennedy DNMeyer JWFilipek PACaviness VS MRI-based topographic segmentation. Thatcher RHallett MZeffiro TJohn RHuerta Meds Functional Neuroimaging. New York, NY Academic Press1994;201- 208Google Scholar 12. Filipek PARichelme CKennedy DNCaviness VS The young adult human brain: an MRI-based morphometric analysis. Cereb Cortex. 1994;4344- 360Google Scholar 13. Goodman WKPrice LHRasmussen SAMazure CFleischmann RHill CHenninger GRCharney DS The Yale-Brown Obsessive Compulsive Scale, I: development, use, and reliability. Arch Gen Psychiatry. 1989;461006- 1011Google Scholar 14. Goodman WKPrice LHRasmussen SAMazure CDelgado PHenninger GRCharney DS The Yale-Brown Obsessive Compulsive Scale, II: validity. Arch Gen Psychiatry. 1989;461012- 1016Google Scholar 15. Osterrieth PRey A Le test de copie d'une figure complex. Arch Psychol. 1944;30205- 221Google Scholar 16. Lezak MD Neuropsychological Assessment. 2nd ed. New York, NY Oxford University Press1983;

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Feb 1, 1998

References