Jun Iwatani

Microstructural abnormalities in anterior callosal fibers and their relationship with cognitive function in major depressive disorder and bipolar disorder: A tract-specific analysis study

BACKGROUND The corpus callosum modulates interhemispheric communication and cognitive processes. It has been suggested that white matter abnormalities in the corpus callosum are related to the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). The aim of this study was to examine microstructural abnormalities in callosal fibers separated by their connection to functional brain regions and determine the relationship of these abnormalities with cognitive function in MDD and BD. METHODS The subjects were 18 patients with MDD, 20 patients with BD, and 21 healthy controls. The callosal fibers were divided into 6 segments based on their cortical projection using tract-specific analysis of diffusion tensor imaging. We examined differences in the fractional anisotropy (FA) of callosal fibers in six segments among the three subject groups and examined the correlation between the FA in each segment and cognitive performance in the 3 groups. RESULTS The FA of anterior callosal fibers were reduced significantly in the MDD and BD groups compared to those in the HC group, and the FA of anterior callosal fibers correlated significantly with the raw scores of the digit sequencing task and symbol coding in the MDD group. LIMITATIONS The patients were medicated at the time of scanning, and the MDD and BD groups were not matched for symptom severity. CONCLUSIONS Our results suggest that MDD and BD have similar microstructural abnormalities in anterior callosal fibers connecting bilateral frontal cortices, and these abnormalities may be related to impairment of working memory and attention in MDD.

Reduction of cortical GABAergic inhibition correlates with working memory impairment in recent onset schizophrenia.

BACKGROUND Cognitive impairments are present during the early course of schizophrenia, and the contribution of GABAergic dysfunction to these cognitive impairments has received increasing attention. Cortical GABAergic inhibition can be assessed using short-interval intracortical inhibition (SICI) in a paired-pulse transcranial magnetic stimulation (ppTMS). The aim of this study was to examine the relationship between cortical GABAergic inhibition and cognitive function in recent onset schizophrenia patients using ppTMS and a neuropsychological battery. METHODS The subjects were 20 healthy controls (HC group) and 20 patients with schizophrenia whose duration of illness was less than three years (SZ group). All subjects underwent ppTMS measurements of SICI and intracortical facilitation (ICF), and cognitive performance of the SZ group was assessed using the Brief Assessment of Cognition in Schizophrenia Japanese-language version. We examined group differences in ppTMS measurements (resting motor threshold, SICI, and ICF). In the SZ group, we assessed the relationship between SICI and cognitive performance, and the relationships between SICI and age, duration of illness, medications, and psychopathology. RESULTS The SZ group showed a significant reduction of SICI compared to the HC group, and demonstrated a significant correlation between the reduction of SICI and impaired performance of a working memory task. The HC and the SZ groups did not differ significantly in resting motor threshold and ICF. The SZ group did not show any significant correlations between SICI and age, duration of illness, medications, or psychopathology. CONCLUSIONS Our results suggest that the reduction of cortical GABAergic inhibition is related to impairment of working memory in patients with recent onset schizophrenia.

Variance and Autocorrelation of the Spontaneous Slow Brain Activity

Slow (<0.1 Hz) oscillatory activity in the human brain, as measured by functional magnetic imaging, has been used to identify neural networks and their dysfunction in specific brain diseases. Its intrinsic properties may also be useful to investigate brain functions. We investigated the two functional maps: variance and first order autocorrelation coefficient (r 1). These two maps had distinct spatial distributions and the values were significantly different among the subdivisions of the precuneus and posterior cingulate cortex that were identified in functional connectivity (FC) studies. The results reinforce the functional segregation of these subdivisions and indicate that the intrinsic properties of the slow brain activity have physiological relevance. Further, we propose a sample size (degree of freedom) correction when assessing the statistical significance of FC strength with r 1 values, which enables a better understanding of the network changes related to various brain diseases.

Use of T1-weighted/T2-weighted magnetic resonance ratio images to elucidate changes in the schizophrenic brain.

One leading hypothesis suggests that schizophrenia (SZ) is a neurodevelopmental disorder caused by genetic defects in association with environmental risk factors that affect synapse and myelin formation. Recent magnetic resonance imaging (MRI) studies of SZ brain showed both gray matter (GM) reduction and white matter (WM) fractional anisotropy reduction. In this study, we used T1‐weighted (T1w)/T2‐weighted (T2w) MRI ratio images, which increase myelin‐related signal contrast and reduce receiver‐coil bias.

Elucidating the aberrant brain regions in bipolar disorder using T1-weighted/T2-weighted magnetic resonance ratio images

Although diffusion tensor imaging (DTI) have revealed brain abnormalities in bipolar disorder (BD) subjects, DTI methods might not detect disease-related abnormalities in the white matter (WM) where nerve fibers are crossing. We investigated BD myelin-related abnormal brain regions in both gray matter and WM for 29 BD and 33 healthy control (HC) participants using T1-weighted (T1w)/T2-weighted (T2w) ratio images that increase myelin-related contrast irrespective of nerve fiber orientation. To check effect of the brain volume, the results were compared with those of voxel-based morphometry (VBM). We found significantly lower T1w/T2w signal intensity in broad WM regions in BD subjects, including the corpus callosum, corona radiata, internal capsule, middle cerebellar peduncle and cerebellum. Regional volume reduction was found in the WM bilateral posterior thalami and retrolenticular part of the internal capsules of BD subjects. We also performed tract-based spatial statistics (TBSS) in 25 BD and 24 HC participants and compared those for the T1w/T2w ratio images. Both methods detected the BD corpus callosum abnormality. Further, the ratio images detected the corona radiata and the cerebellar abnormality in BD. These results suggest that T1w/T2w ratio image analysis could take a complementary role with the DTI method in elucidating myelin-related abnormalities in BD.

Interhemispheric disconnectivity in the sensorimotor network in bipolar disorder revealed by functional connectivity and diffusion tensor imaging analysis

Background Little is known regarding interhemispheric functional connectivity (FC) abnormalities via the corpus callosum in subjects with bipolar disorder (BD), which might be a key pathophysiological basis of emotional processing alterations in BD. Methods We performed tract-based spatial statistics (TBSS) using diffusion tensor imaging (DTI) in 24 healthy control (HC) and 22 BD subjects. Next, we analyzed the neural networks with independent component analysis (ICA) in 32HC and 25 BD subjects using resting-state functional magnetic resonance imaging. Results In TBSS analysis, we found reduced fractional anisotropy (FA) in the corpus callosum of BD subjects. In ICA, functional within-connectivity was reduced in two clusters in the sensorimotor network (SMN) (right and left primary somatosensory areas) of BD subjects compared with HCs. FC between the two clusters and FA values in the corpus callosum of BD subjects was significantly correlated. Further, the functional within-connectivity was related to Young Mania Rating Scale (YMRS) total scores in the right premotor area in the SMN of BD subjects. Limitations Almost all of our BD subjects were taking several medications which could be a confounding factor. Conclusions Our findings suggest that interhemispheric FC dysfunction in the SMN is associated with the impaired nerve fibers in the corpus callosum, which could be one of pathophysiological bases of emotion processing dysregulation in BD patients.

Increased libido during fluvoxamine treatment

We treated an 80‐year‐old man with vascular dementia who developed increased libido induced by fluvoxamine. Sexual stimulation associated with fluvoxamine administration has been rarely reported and the present findings suggest that organic brain dysfunction could be a risk factor for the development of the condition.

EPA-0443 – Changes of white matter integrity in the corpus callosum by rtms for treatment-resistant depression: a preliminary dti tractography study

Background Reduced white matter integrity in the corpus callosum (CC) has been reported in treatment-resistant depression (TRD). rTMS is assumed to have remote effect on interconnected area with the stimulation site, and this effect is speculated to be one of the therapeutic mechanisms of rTMS treatment. In this preliminary study, we examined changes of callosal fiber integrity in 5 segments of the CC before and after rTMS treatment for TRD. Methods The subjects were 2 patients with treatment-resistant unipolar depression and 1 patient with treatment-resistant bipolar depression, and 24 healthy controls (HC group). The patients underwent 4-week high frequency rTMS to their left DLPFC. In diffusion tensor imaging (DTI) tractography, the CC was divided into 5 segments (orbital, frontal, parietal, temporal, and occipital) based on their cortical projection zones, and fractional anisotropy (FA) value of each segment was estimated. We compared FA in the CC between the patients and the HC groups, and examined changes of FA in the CC after rTMS treatment in the patients. Results The patients showed reduced FA in the frontal, parietal, temporal, and occipital-callosal segments compared to the HC group. All patients responded to the rTMS treatment, and FA in the orbital, frontal, parietal, temporal-callosal segments increased after the rTMS treatment. Conclusions Our results suggest that white matter integrity in the CC is reduced in TRD and that increased white matter integrity in the CC might be related with the therapeutic mechanisms of rTMS treatment.

A five-times repeated verbal memory test revealed difference between bipolar disorder and major depressive disorder

P2-p16 The mood stabilizer valproic acid activates the cytohesin-2-Arf6 signaling unit and induces abnormal neuritogenesis Junji Yamauchi 1,2,3 , Tomohiro Torii 1, Yuki Miyamoto 1, Akito Tanoue 1 1 Department of Pharmacology, National Research Institute for Child Health and Development 2 Department of Biological Sciences, Tokyo Institute of Technology, Midori, Yokohama, Japan 3 The Human Science Foundation, Chuo, Tokyo, Japan