Neural correlates of clinical symptoms and cognitive dysfunctions in obsessive–compulsive disorder

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Abstract

Although results from neuropsychological and neuroimaging studies have postulated the involvement of the frontal lobe and the subcortical brain regions in the pathophysiology of obsessive–compulsive disorder (OCD), neuroimaging studies have provided little evidence that cognitive abnormalities in patients with OCD are related to dysfunctions in these areas. This study was designed to determine whether the clinical features and cognitive deficits of OCD might be taken to reflect frontal-subcortical dysfunction. Fourteen patients with OCD and 14 case-matched normal subjects completed clinical and cognitive evaluation, including four sets of neuropsychological tests that assessed the executive functions and visual memory. Cerebral glucose metabolic rates were measured by using positron emission tomography (PET) with 18F-fluorodeoxyglucose. Behavioral and PET data were analyzed using statistical parametric mapping for group differences and behavioral–metabolic correlates. The right orbitofrontal cortex showed increased metabolic activity and the left parieto-occipital junction showed decreased metabolic activity in patients. Metabolism in the right hippocampus, the left putamen and the right parietal region was associated with the severity of obsessive–compulsive symptoms. Correlations between metabolic rates and neuropsychological test scores in the prefrontal cortex and the putamen occurred only in the patient group. These results suggest that patients with OCD have distinct features of brain metabolic activities for performing cognitive tasks as well as presenting obsessive–compulsive symptoms. In particular, the frontal–subcortical circuits might mediate not only symptomatic expression but also cognitive expression in patients with OCD.

Introduction

Although obsessive-compulsive disorder (OCD) is still the subject of an etiologic controversy, a number of studies over the last 20 years have provided strong evidence that a wide variety of neural dysfunctions are implicated in the pathophysiology of this illness. In the majority of studies using positron emission tomography (PET), hypermetabolic rates have been found in the orbitofrontal cortex and/or the basal ganglia in a resting state (Baxter et al., 1987, Baxter et al., 1988, Nordahl et al., 1989, Swedo et al., 1989, Benkelfat et al., 1990, Sawle et al., 1991, Baxter et al., 1992). Interventions that provoke OCD symptoms have also been found to activate similar brain regions (McGuire et al., 1994, Rauch et al., 1994, Breiter et al., 1996, Cottraux et al., 1996). Furthermore, metabolic rates in these areas were demonstrated to be lower after pharmacotherapy, especially amongst drug responders (Baxter et al., 1987, Swedo et al., 1989, Saxena et al., 1999), and after behavioral therapy (Baxter et al., 1992, Schwartz et al., 1996). Accordingly, it has been hypothesized that frontal-subcortical circuitry may mediate the symptomatology of OCD (Insel, 1992, Saxena et al., 1998).

A number of neuropsychological studies have indicated that some cognitive deficits, including executive and visual memory dysfunctions, are associated with OCD (Christensen et al., 1992, Purcell et al., 1998, Savage et al., 1999). In general, researchers have also interpreted abnormal neuropsychological performance in OCD to reflect circuital dysfunction, including the frontal lobe and subcortical brain regions (Savage et al., 1999, Galderisi et al., 1995, Veale et al., 1996, Schmidtkek et al., 1998). However, to date neuroimaging studies have presented little evidence that defective cognitive functions as identified by neuropsychological studies are related to dysfunctions in the circuit. Martinot et al. (1990) studied correlations between regional cerebral glucose metabolic rates and neuropsychological tests that revealed impairments in memory and attention, but only the Stroop test subscores were observed to be negatively correlated with regional metabolic activities in some cerebral areas, including the prefrontal lateral cortex. It is believed likely that such limited findings are a result of the region of interest (ROI) approach adopted.

In fact, most of the earlier functional imaging studies employed the ROI approach and thus suffered from some methodological limitations. For example, the arbitrarily defined ROIs might be generally too large to reflect the functional unit of brain activities and, therefore, significantly increased metabolic activity in some neuronal field is likely to be obscured if surrounding areas within the same ROI show no changes or decreases in activity. There is a report that there existed both hyper- and hypo-functioning regions in the prefrontal area of patients with schizophrenia, which might account for the inconsistent findings of functional imaging studies using the ROI approach regarding so-called ‘hypofrontality’ in schizophrenia (Kim et al., 2000b).

Based on the consistent reports regarding the functional abnormalities of the frontal and subcortical regions in OCD, it can be hypothesized that the voxel-based approach, in which tiny functional units are examined without arbitrary delineation, would further highlight more precise localized positions of the abnormalities. In addition, we hypothesized that we could find evidence of the close relationship between cognitive dysfunctions and frontal-subcortical circuits in OCD if a voxel-based approach were applied. In the current study, we examined symptom severity and cognitive performance on tasks anticipated to be defective in patients with OCD, and measured regional brain metabolic activity using [18F]-2-fluoro-2-deoxyglucose (FDG) PET. Subsequently, results were analyzed using statistical parametric mapping (SPM) to examine the group differences in the metabolic activity between OCD and normal control subjects as well as the presence of any correlations between neuropsychological performance and frontal-subcortical activity.

Section snippets

Subjects

We studied 14 patients with OCD (10 men and 4 women) who were recruited from an OCD outpatient clinic at Seoul National University Hospital and who fulfilled DSM-IV criteria (American Psychiatric Association, 1994) for OCD as diagnosed using the Structured Clinical Interview for DSM-IV (SCID-IV) (First et al., 1996). Exclusion criteria were the presence of significant medical illness and other major psychiatric disorders, such as substance abuse, schizophrenia and bipolar disorder. One of the

Neuropsychological performance

Mean IQ estimated by the KWIS was 114.1±7.8 for the patients and 116.4±8.2 for the normal subjects (t=0.74, d.f.=26, P=0.47), demonstrating no significant difference in general function between the two groups. As shown in Table 1, however, in the cognitive tests selected to evaluate executive functions and visual memory, the patient group had poorer performances than the comparison group. The total numbers of words starting with three different Korean letters were significantly fewer in the

Discussion

To confirm the a priori functional changes in the frontal-subcortical regions in patients with OCD, we analyzed data using a voxel-based approach rather than an ROI approach. Consistent with previous findings obtained with ROI-based methods, the patients with OCD in the current study were found to have a hypermetabolic area in the central portion of the right orbitofrontal cortex when compared with the normal subjects. The orbitofrontal cortex, particularly on the right side, had been found to

Acknowledgements

This study was supported by a Korean Public Health Research and Development Grant (HMP-98-N-2-0029).

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