Mayumi Tomita

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.

fMRI of patients with social anxiety disorder during a social situation task

Previous functional neuroimaging studies found that the amygdala and other limbic regions may play a substantial role in social anxiety disorder (SAD). However, more widely distributed large-scale brain systems may be involved in cognitive processing in SAD patients when confronted with social situations. We employed functional MRI (fMRI) to investigate local brain activation of patients with SAD (n=6) and healthy controls (HC, n=9) during cognitive work. During fMRI scanning, subjects performed a social situation task using a block design paradigm in which the task and control trials were performed by turn. The patients with SAD showed higher anxiety levels during scanning in all social situations. The HC group showed greater common activation in the posterior cingulate cortex (PCC), cuneus, occipital gyrus, and cerebellum. Although the patients with SAD showed activation patterns similar to that of the HC group, they showed comparatively significant decreased activation in the left cerebellum, left precuneus, and bilateral PCC. The present study demonstrates that SAD may involve dysfunction of a broad neuronal network including the limbic system, parieto-posterior cortex and cerebellum. The findings contribute to previous findings that revealed abnormal activities of emotion-related regions including the amygdala and insular cortex during facial perception in SAD.

Predictors of treatment response to fluvoxamine in obsessive–compulsive disorder: An fMRI study

Recent neuroimaging studies suggest that the pathophysiology of obsessive-compulsive disorder (OCD) may involve more widely distributed large-scale brain systems, including the parietal, occipital, and cerebellar areas, rather than the conventional orbitofronto-striatal model. We hypothesized that not only orbitofrontal cortex and caudate nucleus activities but also posterior brain regions might be associated with subsequent treatment response to serotonin reuptake inhibitors in OCD. The participants were 17 patients with OCD. Each patient was required to undergo fluvoxamine pharmacotherapy for 12 weeks. Before treatment, fMRI images of the subjects were obtained in the context of a symptom-provocation paradigm. The percentage changes in total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores, from pre- to post-treatment, served as the index of treatment response. Statistical Parametric Mapping was used to identify brain loci where pre-treatment brain activation significantly correlated with the subsequent treatment response. Fifteen of 17 patients completed the 12-week treatment. During the symptom provocation task, patients showed brain activation in the left superior temporal gyrus (STG), left precuneus, left frontal cortices, right cerebellum, and right frontal cortices. We found that pre-treatment activation in the right cerebellum (Z-score=5.10, x,y,z=22,-84,-18) and the left STG (Z-score=4.95, x,y,z=-62,-22,0) was positively correlated with the improvement in the Y-BOCS score. Our results suggest that pre-treatment activation in the right cerebellum and in the left STG predict subsequent reduction in OCD symptom severity. There is every possibility that fMRI can be used as a tool to predict treatment response.

Differential neural network of checking versus washing symptoms in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is clinically heterogeneous. The aim of this study was to investigate differential neural responses to a symptom provocation task in drug-free patients who have predominantly aggression/checking symptoms (Checkers) and patients with contamination/washing symptoms (Washers). We compared the Checkers (n=10) and the Washers (n=12) separately to normal controls during the symptom provocation tasks using fMRI (functional magnetic resonance imaging). Moreover, we performed correlative analysis in each OCD group between brain activation and symptom severity. The Checkers showed hypoactivation in the left caudate and left anterior cingulate cortex (ACC) compared to the normal controls and a positive correlation between activated brain areas and symptom severity in the left ACC. The Washers showed hyperactivation in several bilateral cortico-cerebellar regions and a positive correlation between symptom severity and the bilateral fronto-temporal gyrus. We suggest that the caudate and ACC are associated with checking rituals and that large cortical brain regions are related to washing rituals.

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.

Biological heterogeneity of obsessive-compulsive disorder: A voxel-based morphometric study based on dimensional assessment.

Although many neuroimaging studies of obsessive–compulsive disorder (OCD) have reported broad abnormalities in gray matter (GM), their results remain inconsistent. One reason for this inconsistency could be the heterogeneity of OCD. In the present study, we aimed to classify alterations in brain anatomy by OCD subtype.

A pilot study exploring the association of morphological changes with 5-HTTLPR polymorphism in OCD patients

BackgroundClinical and pharmacological studies of obsessive-compulsive disorder (OCD) have suggested that the serotonergic systems are involved in the pathogenesis, while structural imaging studies have found some neuroanatomical abnormalities in OCD patients. In the etiopathogenesis of OCD, few studies have performed concurrent assessment of genetic and neuroanatomical variables.MethodsWe carried out a two-way ANOVA between a variable number of tandem repeat polymorphisms (5-HTTLPR) in the serotonin transporter gene and gray matter (GM) volumes in 40 OCD patients and 40 healthy controls (HCs).ResultsWe found that relative to the HCs, the OCD patients showed significant decreased GM volume in the right hippocampus, and increased GM volume in the left precentral gyrus. 5-HTTLPR polymorphism in OCD patients had a statistical tendency of stronger effects on the right frontal pole than those in HCs.ConclusionsOur results showed that the neuroanatomical changes of specific GM regions could be endophenotypes of 5-HTTLPR polymorphism in OCD.

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.).