Kazuko Yoshioka

Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement: A functional magnetic resonance imaging study

BACKGROUND Functional neuroimaging studies have implicated hyperactivity of the frontal cortex in obsessive-compulsive disorder (OCD); however, relationships between abnormal brain activity, clinical improvement, and neuropsychological function have not been clarified in OCD. To clarify the pathophysiology of this disorder, regional changes in brain function were examined during administration of cognitive and symptom provocation tasks in patients with OCD before and after treatment. METHODS Ten outpatients with OCD participated in the study. Functional magnetic resonance imaging (fMRI) was performed before and after treatment. Stroop and symptom provocation tasks were administered during fMRI. Each patient was randomly allocated to receive either pharmacotherapy with fluvoxamine 200 mg/day (n = 4) or behavior therapy (n = 6) for 12 weeks. RESULTS After 12-week treatment, mean (+/- SD) total score on the Yale-Brown Obsessive-Compulsive Scale decreased from 29.00 +/- 3.59 to 14.60 +/- 9.22, representing symptomatic improvement from moderate to mild. After symptom improvement, symptom provocation-related activation in the orbitofrontal, dorsolateral-prefrontal, and anterior cingulate cortices decreased. Conversely, Stroop task-related activation in the parietal cortex and cerebellum increased. CONCLUSIONS After improvement of OCD with either fluvoxamine or behavioral therapy, hyperactivation of the frontal lobe related to a symptom-provocative state decreases, and posterior brain activity related to action-monitoring function increases.

Functional MRI study of brain activation alterations in patients with obsessive–compulsive disorder after symptom improvement

Dysfunction of the frontal-subcortical circuits has been the most common finding in the pathophysiology of obsessive-compulsive disorder (OCD), and recent neuropsychological studies have shown cognitive impairments in OCD. To clarify the pathophysiology of OCD without the confounding effects of medication, we investigated the alterations of brain function in OCD patients and changes after clinical improvement due solely to behavior therapy. The participants were 11 outpatients with OCD and 19 normal controls. The patients received 12 weeks of behavior therapy. We investigated the differences in the behavioral performance and functional magnetic resonance imaging results during the Stroop test in the patients and normal controls, and their changes after treatment in the patients. The patients showed less activation in the anterior cingulate gyrus and cerebellum than control subjects. Following significant improvement in OC symptoms, the cerebellum and parietal lobe showed increased activation, and the orbitofrontal cortex, middle frontal gyrus, and temporal regions showed decreased activation during the Stroop task, and performance of the task itself improved. Our findings suggest that dysfunction of the posterior brain regions, especially the cerebellum, is involved in the pathogenesis of OCD, and that normalization in function can occur with improvement of OC symptoms.

Working memory dysfunction in obsessive–compulsive disorder: A neuropsychological and functional MRI study

Previous neuropsychological studies indicate that OCD subtypes such as checking rituals might be associated with a working memory deficit. On the other hand, functional neuroimaging studies found functional abnormalities of the frontal cortex and subcortical structures in OCD. Combined with functional imaging method, we applied neuropsychological batteries to demonstrate a working memory deficit in OCD by comparison with normal controls. In addition, working memory and brain activation were further examined with symptom-based analysis. Forty patients with OCD and 25 normal controls were examined using neuropsychological tests including the WAIS-R, WCST, WMS-R, and R-OCFT and functional MRI (fMRI) during the N-back task including 0- and 2-back task. On fMRI, the brain regions activated during the performance and the differences in the activation between patients and controls were identified. Additional analyses of severity and subtypes were conducted by using Y-BOCS severity score, symptom-checklist and Leckmans four-factor model, respectively. On the neuropsychological tests, the OCD patients had significantly lower scores on the delayed recall section of the WMS-R and the immediate recall section of the R-OCFT compared to the controls. On fMRI, the patients showed greater activation in the right dorsolateral prefrontal cortex (DLPFC), left superior temporal gyrus (STG), left insula, and cuneus during two-back task compared to the controls. Right orbitofrontal cortex activity showed a significant positive correlation with Y-BOCS scores in OCD. Furthermore, patients with obsessions/checking rituals (n=10) showed severer memory deficits and decreased activity in the postcentral gyrus than patients with cleanliness/washing rituals (n=14). In conclusion, we found neuropsychological dysfunction and brain abnormalities in OCD. Furthermore, our results suggested that symptom severity and symptom subtype such as obsessions/checking might affect neuropsychological dysfunction and related brain activities.

A functional MRI comparison of patients with obsessive–compulsive disorder and normal controls during a Chinese character Stroop task

Recent functional neuroimaging and neuropsychological studies have suggested that abnormal activity in the anterior cingulate cortex (ACC) might cause an action-monitoring dysfunction in obsessive-compulsive disorder (OCD). To identify the relationship between brain dysfunction and cognitive dysfunction, we examined regional brain changes in OCD with functional magnetic resonance imaging (fMRI) during the performance of a cognitive task. Participants comprised 24 patients with OCD and 14 normal controls. First, we compared the cognitive function in the two groups as assessed by several neuropsychological tests. Then we used fMRI to explore brain correlates of their performance during the Chinese character version of the Stroop test, a task that is strongly related to action-monitoring function. The two groups did not differ on the neuropsychological tests. Both groups also showed similar activation pattern on fMRI. The patients, however, showed weaker activation than the normal controls in the ACC and the right caudate nucleus.

A Randomized Controlled Trial of Japanese Patients with Obsessive-Compulsive Disorder – Effectiveness of Behavior Therapy and Fluvoxamine

Background: The aim of this study was to confirm and compare the efficacy of fluvoxamine (the only licensed SSRI for treatment for OCD in Japan) and behavior therapy in treating Japanese patients with OCD. In addition, we investigated predictors of these treatments. Methods: Thirty-one outpatients meeting the DSM-III-R criteria for OCD without any axis I disorder were randomly assigned to one of three treatment conditions: BT (behavior therapy ± pill placebo), FLV [autogenic training (a psychological placebo for OCD) ± fluvoxamine] and control group [autogenic training (psychological placebo) ± pill placebo] for 12 weeks of treatment. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression-Improvement Scale (CGI-I) were administered blindly at baseline and week 4, 8 and 12. Results: Twenty-eight patients completed this study. Patients in the BT and FLV groups showed significantly more improvement than those in the control group in the mean score of total Y-BOCS; moreover, the BT group showed significantly more reduction in total Y-BOCS score at the end of treatment than the FLV group (BT > FLV, p < 0.01). Patients with lower baseline total Y-BOCS, past history of a major depressive episode and absence of cleaning compulsion improved more with fluvoxamine. Conclusions: We confirmed the effectiveness of behavior therapy and fluvoxamine for Japanese patients with OCD. Behavior therapy improved the condition of OCD patients more than fluvoxamine.

Duration effect of obsessive-compulsive disorder on cognitive function: A functional MRI study

Background: The inconsistency of previous reports examining cognitive function in obsessive–compulsive disorder (OCD) suggests its heterogeneity. In this study, we examined the effect of illness duration on cognitive function in OCD. Methods: We examined the cognitive function of 32 OCD patients and 16 healthy volunteers by neuropsychological tests and functional magnetic resonance imaging while they performed the Stroop and N‐back tasks to assess attention and nonverbal memory. The patients were divided into two groups by illness duration: a short‐term group (n=17, 5.5±3.1 years) and a long‐term group (n=15, 20.3±6.1 years). Statistical analysis was performed to determine the differences between these two groups and the normal control group (n=16). Results: The long‐term group showed attention deficit and nonverbal memory dysfunction on the neuropsychological tests. In contrast, on functional magnetic resonance imaging, the short‐term group showed weaker activation of the right caudate during the Stroop task and stronger activation of the right dorso‐lateral prefrontal cortex during the N‐back task than the long‐term and normal control groups. Conclusions: The results suggested that abnormal brain activation occurs in the early phase of OCD and that the long‐term persistence of OCD might involve a decline in cognitive function. Depression and Anxiety, 2009.

Effect of illness duration on cognitive function of OCD: a neuropsychological and functional neuroimaging study

Materials and methods Thirty-two OCD patients whose diagnoses were confirmed by SCID-IIIR participated in the study. We administered them neuropsychological tests including WAIS-R, Stroop test, WCST, WMS-R and R-OCFT. We also examined them using functional MRI (fMRI) during the Chinese character version Stroop task that is strongly related with attention. Then the patients were divided into two groups by duration of illness; short-term illness group (Group S, n = 17, 5.5 ± 3.1 years) and long-term illness group (Group L, n = 15, 20.3 ± 6.1 years). There was no significant group difference in background and clinical characteristics but for the mean age of onset (Group S; 25.5 ± 10.2 y.o., Group L; 15.3 ± 7.1 y.o.).