Brain morphological changes and functional neuroanatomy related to cognitive and emotional distractors during working memory maintenance in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is associated with abnormalities in the processing and regulation of emotion as well as cognitive deficits. This study evaluated the differential brain activation patterns associated with cognitive and emotional distractors during working memory (WM) maintenance for human faces between patients with PTSD and healthy controls (HCs) and assessed the relationship between changes in the activation patterns by the opposing effects of distraction types and gray matter volume (GMV). Twenty-two patients with PTSD and twenty-two HCs underwent T1-weighted magnetic resonance imaging (MRI) and event-related functional MRI (fMRI), respectively. Event-related fMRI data were recorded while subjects performed a delayed-response WM task with human face and trauma-related distractors. Compared to the HCs, the patients with PTSD showed significantly reduced GMV of the inferior frontal gyrus (IFG) (p < 0.05, FWE-corrected). For the human face distractor trial, the patients showed significantly decreased activities in the superior frontal gyrus and IFG compared with HCs (p < 0.05, FWE-corrected). The patients showed lower accuracy scores and slower reaction times for the face recognition task with trauma-related distractors compared with HCs as well as significantly increased brain activity in the STG during the trauma-related distractor trial was observed (p < 0.05, FWE-corrected). Such differential brain activation patterns associated with the effects of distraction in PTSD patients may be linked to neural mechanisms associated with impairments in both cognitive control for confusable distractors and the ability to control emotional distraction.

Altered brain morphology and functional connectivity in postmenopausal women: automatic segmentation of whole-brain and thalamic subnuclei and resting-state fMRI.

The transition to menopause is associated with various physiological changes, including alterations in brain structure and function. However, menopause-related structural and functional changes are poorly understood. The purpose of this study was not only to compare the brain volume changes between premenopausal and postmenopausal women, but also to evaluate the functional connectivity between the targeted brain regions associated with structural atrophy in postmenopausal women. Each 21 premenopausal and postmenopausal women underwent magnetic resonance imaging (MRI). T1-weighted MRI and resting-state functional MRI data were used to compare the brain volume and seed-based functional connectivity, respectively. In statistical analysis, multivariate analysis of variance, with age and whole brain volume as covariates, was used to evaluate surface areas and subcortical volumes between the two groups. Postmenopausal women showed significantly smaller cortical surface, especially in the left medial orbitofrontal cortex (mOFC), right superior temporal cortex, and right lateral orbitofrontal cortex, compared to premenopausal women (p < 0.05, Bonferroni-corrected) as well as significantly decreased functional connectivity between the left mOFC and the right thalamus was observed (p < 0.005, Monte-Carlo corrected). Although postmenopausal women did not show volume atrophy in the right thalamus, the volume of the right pulvinar anterior, which is one of the distinguished thalamic subnuclei, was significantly decreased (p < 0.05, Bonferroni-corrected). Taken together, our findings suggest that diminished brain volume and functional connectivity may be linked to menopause-related symptoms caused by the lower sex hormone levels.

Early Detection of Alzheimer's Disease in Postmenopausal Women Using Thalamic Subnuclear Volumetry.

Alzheimer's disease (AD) and aging are intrinsically interconnected with each other and are mediated by molecular, cellular, and biological systems. In particular, a specific pattern of brain volume atrophy is the most profound risk factor for cognitive impairment, including AD, that is directly linked to aging. Thus, this study aimed to investigate knowledge on the early detection of AD in postmenopausal women, focusing on the volume changes of the subcortical regions, including the thalamic subnuclei, in women with AD vs. postmenopausal women. Twenty-one women with AD and twenty-one postmenopausal women without AD underwent magnetic resonance imaging (MRI). Women with AD showed significantly reduced volumes in the hippocampus, thalamus, and amygdala compared with postmenopausal women (p < 0.05, FWE-corrected). After adjustments for age, the right hippocampal volume was found to be significantly lower in the women with AD, but the volumes of the thalamus and amygdala were relatively unaffected. The women with AD exhibited significantly reduced volume in the right laterodorsal nucleus of the thalamus compared with the postmenopausal women (p < 0.05, Bonferroni-corrected). Our findings suggest that the reduced volume of both the right laterodorsal thalamic nucleus and right hippocampus may serve as a potential biomarker for the early detection of AD in postmenopausal women.

Increased Hippocampal-Inferior Temporal Gyrus White Matter Connectivity following Donepezil Treatment in Patients with Early Alzheimer's Disease: A Diffusion Tensor Probabilistic Tractography Study.

The incidence of Alzheimer's disease (AD) has been increasing each year, and a defective hippocampus has been primarily associated with an early stage of AD. However, the effect of donepezil treatment on hippocampus-related networks is unknown. Thus, in the current study, we evaluated the hippocampal white matter (WM) connectivity in patients with early-stage AD before and after donepezil treatment using probabilistic tractography, and we further determined the WM integrity and changes in brain volume. Ten patients with early-stage AD (mean age = 72.4 ± 7.9 years; seven females and three males) and nine healthy controls (HC; mean age = 70.7 ± 3.5 years; six females and three males) underwent a magnetic resonance (MR) examination. After performing the first MR examination, the patients received donepezil treatment for 6 months. The brain volumes and diffusion tensor imaging scalars of 11 regions of interest (the superior/middle/inferior frontal gyrus, the superior/middle/inferior temporal gyrus, the amygdala, the caudate nucleus, the hippocampus, the putamen, and the thalamus) were measured using MR imaging and DTI, respectively. Seed-based structural connectivity analyses were focused on the hippocampus. The patients with early AD had a lower hippocampal volume and WM connectivity with the superior frontal gyrus and higher mean diffusivity (MD) and radial diffusivity (RD) in the amygdala than HC (p < 0.05, Bonferroni-corrected). However, brain areas with a higher (or lower) brain volume and WM connectivity were not observed in the HC compared with the patients with early AD. After six months of donepezil treatment, the patients with early AD showed increased hippocampal-inferior temporal gyrus (ITG) WM connectivity (p < 0.05, Bonferroni-corrected).

Diminished frontal pole size and functional connectivity in young adults with high suicidality.

BACKGROUND: Suicide rates among young people have been increasing in recent years, yet no validated methods are available for identifying those who are at greatest risk for suicide. Abnormalities in the medial prefrontal cortex have been previously observed in suicidal individuals, but confounding factors such as treatment and chronic illness may have contributed to these findings. Thus, in this study we tested whether the size of the medial prefrontal cortex is altered in suicidal young adults who have received no treatment with psychotropic medications. METHODS: Suicidality was evaluated using the Suicide Behaviors Questionnaire-Revised (SBQ-R) and surface areas of four regions-of-interest (ROIs) within the medial prefrontal cortex were measured using magnetic resonance imaging (MRI) in a cohort of college students (n = 102). In addition, a secondary seed-based functional connectivity analysis was conducted using resting-state functional MRI data. Areas and functional connectivity of the medial prefrontal cortex of young adults with high suicidality (HS; SBQ-R score > 7; n = 20) were compared to those with low suicidality (LS; SBQ-R score = 3, n = 37). RESULTS: Compared to the LS group, the HS group had a significantly lower surface area of the right frontal pole (p < 0.05, Bonferroni-corrected) and significantly lower functional connectivity of the right frontal pole with the bilateral inferior frontal cortex (p < 0.001, Monte-Carlo corrected). LIMITATION: These findings require replication in a larger sample and extension in younger (adolescent) populations. CONCLUSION: Diminished frontal pole surface area and functional connectivity may be linked to elevated levels of suicidality in young people.

Neural Correlates of Emotion-Cognition Interaction During Working Memory Maintenance in Obsessive-Compulsive Disorder: The Role of the Dorsolateral Prefrontal Cortex.

The neural correlates for the effect of emotional distraction on working memory (WM) function in obsessive-compulsive disorder (OCD) have not been clearly identified. This study utilized functional magnetic resonance imaging (fMRI) to investigate the effect of emotional distraction during WM maintenance in OCD patients and to determine if the frontoparietal region was involved during the task. Patients with OCD tried to maintain WM during the task-irrelevant anxiety-provoking distractions, which induced interruption and needed attention. Compared with healthy controls, the patients with OCD showed significantly increased activities in the dorsolateral prefrontal cortex (DLPFC) supplementary motor area during the delayed-response WM task with anxiety-provoking distractors. An increase in the activity of the DLPFC and SMA reflects compensatory efforts of neural circuits to perform cognitive tasks by controlling emotions and inhibiting the interference of anxiety provoking distractors during WM tasks. In addition, the brain areas showed significantly decreased activities during the delayed-response WM task with neutral distractors were superior parietal gyrus and fusiform gyrus. The parietal cortex, along with the DLPFC is the main structure for frontoparietal network and is involved in cognitive control. Therefore, parietal dysfunction in OCD patients prevents them from paying appropriate attention to visual processing for picture distractors during the WM task. Our findings might be helpful for further understanding of the neural correlates that are associated with the effects of emotional distraction on cognitive function in OCD.

A pilot study of brain morphometry following donepezil treatment in mild cognitive impairment: volume changes of cortical/subcortical regions and hippocampal subfields.

The efficacy of donepezil is well known for improving the cognitive performance in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Most of the recent neuroimaging studies focusing on the brain morphometry have dealt with the targeted brain structures, and thus it remains unknown how donepezil treatment influences the volume change over the whole brain areas including the cortical and subcortical regions and hippocampal subfields in particular. This study aimed to evaluate overall gray matter (GM) volume changes after donepezil treatment in MCI, which is a prodromal phase of AD, using voxel-based morphometry. Patients with MCI underwent the magnetic resonance imaging (MRI) before and after 6-month donepezil treatment. The cognitive function for MCI was evaluated using the questionnaires of the Korean version of the mini-mental state examination (K-MMSE) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog). Compared with healthy controls, patients with MCI showed significantly lower GM volumes in the hippocampus and its subfields, specifically in the right subiculum and left cornu ammonis (CA3). The average scores of K-MMSE in patients with MCI improved by 8% after donepezil treatment. Treated patients showed significantly higher GM volumes in the putamen, globus pailldus, and inferior frontal gyrus after donepezil treatment (p < 0.001). However, whole hippocampal volume in the patients decreased by 0.6% after 6-month treatment, and the rate of volume change in the left hippocampus was negatively correlated with the period of treatment. These findings will be useful for screening and tracking MCI, as well as understanding of the pathogenesis of MCI in connection with brain morphometric change.

White Matter Connectivity and Gray Matter Volume Changes Following Donepezil Treatment in Patients With Mild Cognitive Impairment: A Preliminary Study Using Probabilistic Tractography.

The donepezil treatment is associated with improved cognitive performance in patients with mild cognitive impairment (MCI), and its clinical effectiveness is well-known. However, the impact of the donepezil treatment on the enhanced white matter connectivity in MCI is still unclear. The purpose of this study was to evaluate the thalamo-cortical white matter (WM) connectivity and cortical thickness and gray matter (GM) volume changes in the cortical regions following donepezil treatment in patients with MCI using probabilistic tractography and voxel-based morphometry. Patients with MCI underwent magnetic resonance examinations before and after 6-month donepezil treatment. Compared with healthy controls, patients with MCI showed decreased WM connectivity of the thalamo-lateral prefrontal cortex, as well as reduced thickness in the medial/lateral orbitofrontal cortices (p < 0.05). The thalamo-lateral temporal cortex connectivity in patients with MCI was negatively correlated with Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) (r = -0.76, p = 0.01). The average score of the Korean version of the mini-mental state examination (K-MMSE) in patients with MCI was improved by 7.9% after 6-months of donepezil treatment. However, the patterns of WM connectivity and brain volume change in untreated and treated patients were not significantly different from each other, resulting from multiple comparison corrections. These findings will be valuable in understanding the neurophysiopathological mechanism on MCI as a prodromal phase of Alzheimer's disease in connection with brain functional connectivity and morphometric change.

Brain Morphological Changes With Functional Deficit Associated With Sexual Arousal in Postmenopausal Women.

INTRODUCTION: We have not known how menopause synchronously influences brain morphology and function associated with visually stimulated sexual arousal in postmenopausal women. AIM: This study used a combination of functional magnetic resonance imaging and voxel-based morphometry to evaluate menopause-related brain morphological and functional changes in postmenopausal women. METHODS: Nineteen premenopausal women and 19 postmenopausal women underwent functional and structural magnetic resonance imaging. Brain function activity was measured while the subjects viewed an erotic video clip. MAIN OUTCOME MEASURES: A 2-sample t-test was used for cross-analysis of the 2 groups for comparison of gray matter volumes (corrected P < .05) and brain activation (uncorrected P < .01). RESULTS: Our study revealed a relationship between sexual function and morphological changes in postmenopausal women. Compared with premenopausal women, the postmenopausal group showed significantly lower brain activations in the major parts of the limbic system and basal ganglia, including the parahippocampal gyrus, head of caudate nucleus, insula, putamen, hippocampus, hypothalamus, amygdala, and globus pallidus, which are involved in sexual behavior and emotional responses. In morphometric analyses, postmenopausal women showed significantly decreased gray matter volumes of the insula, putamen, parahippocampal gyrus, amygdala, and anterior cingulate gyrus, most of which were associated with decreased functional activity during visual sexual arousal in postmenopausal women. In addition, the premenopausal group alone showed a positive correlation between the activity of the insula and the level of estradiol (Pearson correlation r = 0.588; P = .008). CONCLUSION: This study demonstrates an association between menopause-related brain function and morphological changes in postmenopausal women. This finding provides insight into the neural mechanisms associated with the sexual functional deficit in postmenopausal women. Baek H-S, Kim G-W, Sundaram T, et al. Brain Morphological Changes with Functional Deficit Associated with Sexual Arousal in Postmenopausal Women. Sex Med 2019;7:480-488.

Brain Activation Patterns Associated with the Effects of Fearful Distractors during Working Memory Maintenance in Patients with Schizophrenia.

OBJECTIVE: The neural correlates underlying the effects of emotional distraction during working memory (WM) tasks in patients with schizophrenia have yet to be clearly identified. Thus, the present study employed functional magnetic resonance imaging (fMRI) to investigate the effects of emotional distraction involving fear during WM maintenance in patients with schizophrenia. METHODS: This study included 17 patients with schizophrenia who were diagnosed based on Diagnostic and Statistical Manual of Mental Disorders fourth edition, text revision (DSM-IV-TR) criteria and 17 matched healthy controls. Event-related fMRI data were acquired while the participants performed a delayed-response WM task that included neutral and fearful distractors. RESULTS: Patients with schizophrenia may have tried to maintain WM function during the presentation of task-irrelevant fearful distractors that induced interruption and required attention. Compared to healthy controls, the schizophrenia patients exhibited significantly increased activity in the dorsolateral prefrontal cortex, medial prefrontal cortex, superior temporal gyrus, middle temporal gyrus, insula, hippocampus, caudate nucleus, and postcentral gyrus in a delayed-response WM task when presented with fearful relative to neutral distractors. In addition to its series of increased brain activations, prefrontal areas exhibited interconnections with more caudal brain regions, including temporal areas and the hippocampus and insula. CONCLUSION: The present study identified specific brain areas associated with the interaction between emotional regulation and cognitive functioning during fearful distractors presented while patients with schizophrenia performed a WM maintenance task. These findings further the current understanding of the neural correlates underlying the effects of emotional distraction on cognitive functioning in patients with schizophrenia.

A comparative study of white matter volume between postoperative female-to-male transsexuals and healthy female.

Cross-sex hormones in female-to-male (FtM) transsexuals play a crucial role in brain plasticity. Morphological study associated with white matter (WM) volume in postoperative FtM transsexuals receiving cross-sex hormones has not been published yet. This study was performed to discriminate the regional WM volume differences between postoperative FtM transsexuals and female controls using voxel-based morphometry (VBM) and further to assess the correlations between regional volume variations and cross-sex hormones. WM volume was assessed in 12 postoperative FtM transsexuals receiving cross-sex hormones with 16 age-matched female controls. WM volume was processed using SPM8 software with diffeomorphic anatomical registration via an exponentiated Lie algebra (DARTEL) algorithm. Serum sex hormones, including estriol, free testosterone (free-T), estradiol, follicle-stimulating hormone, and luteinizing hormone were measured. Postoperative FtM transsexuals showed significantly (p < 0.05) larger WM volumes in the inferior parietal lobule, postcentral gyrus, and middle temporal gyrus compared with female controls. However, there were no brain areas with larger WM volume in female controls compared with FtM transsexuals. WM volumes of the inferior parietal lobule and middle temporal gyrus in FtM transsexuals were positively correlated with the levels of free-T. This study revealed WM volume change and its correlation with free-T level in postoperative FtM transsexuals. These findings will improve our understanding of the morphometric changes in FtM transsexuals under cross-sex hormone therapy.

Effects of Sex Hormones and Age on Brain Volume in Post-Menopausal Women.

BACKGROUND: Investigation of the effect of sex hormones on the brain volume in women provides a unique opportunity to examine menopause-related morphometric alterations. AIM: To evaluate brain morphological alterations in post-menopausal women using voxel-based morphometry and its correlations with sex hormone levels. METHODS: 20 Pre-menopausal women and 20 post-menopausal women underwent structural MRI. OUTCOMES: T1-weighted magnetic resonance data were acquired and serum sex hormones including total estrogen, estriol, estradiol (E2), follicle-stimulating hormone, free testosterone, SHBG, and luteinizing hormone were measured. RESULTS: Post-menopausal women showed decreased gray matter (GM) in the supplementary motor area (SMA), inferior frontal gyrus, olfactory cortex, and superior temporal gyrus as contrasted with pre-menopausal women using analysis of covariance (P < .05). The GM volume (GMV) values of the SMA, inferior frontal gyrus, and superior temporal gyrus were positively correlated with the levels of E2 in the pre-menopausal and post-menopausal women, in which the volume of the SMA was negatively correlated with the duration of time after menopause in post-menopausal women. CLINICAL TRANSLATION: This finding is potentially applicable to assess the brain dysfunction with morphological changes in post-menopausal women. CONCLUSIONS: Our study is the first to evaluate a direct relationship between the level of E2 and GMV change. We directly compared pre-menopausal and menopausal women un-matched in age. This study highlights the menopause-related morphological alterations in post-menopausal women, suggesting that the reduced GMV were closely associated with the symptoms of menopause caused by the decreased levels of E2. Kim G-W, Park K, Jeong G-W. Effects of Sex Hormones and Age on Brain Volume in Post-Menopausal Women. J Sex Med 2018;15:662-670.

Whole-brain volume alteration and its correlation with anxiety severity in patients with obsessive-compulsive disorder and generalized anxiety disorder.

PURPOSE: To evaluate the differential gray matter (GM) and white matter volume alterations between healthy controls and patients with obsessive-compulsive disorder (OCD) and generalized anxiety disorder (GAD) using voxel-based morphometry (VBM). METHOD: Patients with OCD and GAD, and healthy controls underwent MR. RESULTS: Patients with GAD showed significantly decreased GM volume in the medial prefrontal cortex (mPFC) compared with patients with OCD (p < 0.001). The GM volumes of the mPFC in patients with GAD were negatively correlated with Hamilton Anxiety Rating Scales. CONCLUSION: Our findings indicate that the mPFC volume abnormality may be associated with anxiety disorder in patients with GAD rather than OCD.

Whole brain volume changes and its correlation with clinical symptom severity in patients with schizophrenia: A DARTEL-based VBM study.

The purpose of this study was to evaluate gray matter (GM) and white matter (WM) volume alterations in whole-brain structures in patients with schizophrenia and healthy controls using voxel-based morphometry (VBM), and further to assess the correlation between GM and WM volume variations and symptom severity in schizophrenia. A total of 22 patients with schizophrenia and 22 age-matched healthy controls participated. Magnetic resonance image data were processed using SPM8 software with diffeomorphic anatomical registration via an exponentiated Lie algebra (DARTEL) algorithm. Patients with schizophrenia exhibited significantly decreased GM volumes of the insula, superior temporal gyrus (STG), gyrus rectus, and anterior cingulate cortex (ACC) compared with healthy controls. The GM volumes of the STG and gyrus rectus were negatively correlated with the positive scales on the Positive and Negative Syndrome Scale (PANSS) and those of the STG and ACC were negatively correlated with the negative scales. The durations of illness in schizophrenia were negatively correlated with the GM volumes of the insula, STG, and ACC. Patients with schizophrenia exhibited significantly decreased WM volumes of the superior frontal gyrus, inferior temporal gyrus, and STG. The WM volumes of the STG were negatively correlated with the duration of illness. Our findings suggest that GM and WM volume abnormalities in the STG are associated with the psychopathology of schizophrenia.

Comparative functional neuroanatomy between implicit and explicit memory tasks under negative emotional condition in schizophrenia.

PURPOSE: To evaluate the brain activation patterns in response to negative emotion during implicit and explicit memory in patients with schizophrenia. MATERIAL AND METHODS: Fourteen patients with schizophrenia and 14 healthy controls were included in this study. The 3.0T fMRI was obtained while the subjects performed the implicit and explicit retrievals with unpleasant words. RESULTS: The different predominant brain activation areas were observed during the implicit retrieval and explicit with unpleasant words. CONCLUSION: The differential neural mechanisms between implicit and explicit memory tasks associated with negative emotional processing in schizophrenia.

Menopause-related brain activation patterns during visual sexual arousal in menopausal women: An fMRI pilot study using time-course analysis.

The aging process and menopausal transition are important factors in sexual dysfunction of menopausal women. No neuroimaging study has assessed the age- and menopause-related changes on brain activation areas associated with sexual arousal in menopausal women. The purpose of this study was to evaluate the time course of regional brain activity associated with sexual arousal evoked by visual stimulation in premenopausal and menopausal women, and further to assess the effect of menopause on the brain areas associated with sexual arousal in menopausal women using functional magnetic resonance imaging (fMRI). Thirty volunteers consisting of 15 premenopausal and 15 menopausal women underwent the fMRI. For the activation condition, volunteers viewed sexually arousing visual stimulation. The brain areas with significantly higher activation in premenopausal women compared with menopausal women included the thalamus, amygdala, and anterior cingulate cortex (ACC) using analysis of covariance adjusting for age (p<0.005). Blood-oxygen-level-dependent signal changes in the amygdala while viewing erotic video were positively correlated with estrogen levels in the two groups. Our findings suggest that reduced brain activity of the thalamus, amygdala, and ACC in menopausal women may be associated with menopause-related decrease in sexual arousal. These findings might help elucidate the neural mechanisms associated with sexual dysfunction in menopausal women.

Neuroanatomical assessment of the impact of negative emotion on explicit memory in patients with obsessive-compulsive disorder.

The aim of this study was to identify the brain activation patterns associated with emotionally neutral or unpleasant words during explicit memory tasks in patients with obsessive-compulsive disorder (OCD) using a functional MRI. Sixteen patients with OCD (mean age=31.4±10.1 years) and 16 healthy controls (mean age=32.6±5.8 years) who had no history of neurological or psychiatric illness underwent functional MRI examinations on a 3-T Siemens MR Scanner. The stimulation paradigm consisted of five times rest-condition, two times encoding of two-syllable words, and two times explicit retrieval of the previously learned words. Six different words were presented for 3 s each in the encoding and retrieval tasks. In the retrieval task, the same words as those used at the encoding task were presented randomly. Brain activation maps were quantified and analyzed using SPM8 and MRIcron software. During the explicit retrieval tasks with emotionally neutral words, the predominant activation areas observed in patients with OCD included the angular gyrus and the supramarginal gyrus, whereas healthy controls showed significantly higher activity in the postcentral gyrus (P<0.005). During the explicit retrieval tasks with unpleasant words, patients with OCD showed significantly higher activity, compared with healthy controls, in the cerebellum, posterior cingulate gyrus, middle occipital gyrus, middle temporal gyrus, and inferior frontal gyrus (P<0.005); however, no predominant activation areas in healthy controls over patients with OCD were observed. This study showed differential brain activation patterns in response to emotionally neutral and unpleasant words in patients with OCD. This finding will be useful in assessing the neural mechanisms associated with emotional effect on the impairment of memory retrieval in OCD.

Time-course metabolic changes in high-fat diet-induced obesity rats: A pilot study using hyperpolarized (13)C dynamic MRS.

The purpose of this study was to investigate the time-course metabolic changes based on hyperpolarized (13)C magnetic resonance spectroscopy (MRS) in high-fat diet (HFD)-induced obesity rats and the correlation between metabolic and serum enzyme levels. Sprague-Dawley rats were fed either HFD (60% fat) or normal diet (10% fat) for 6weeks. A HyperSense DNP was used to hyperpolarize [1-(13)C] pyruvic acid and the hyperpolarized (13)C MRS was examined every 2weeks in the course of 6weeks using a 3T GE MR750 scanner. The body weight of HFD-induced obese rats was significantly increased compared to normal rats at the 6th week after the onset of feeding (p=0.05). Simultaneously, the HFD-induced obese rats showed significantly increased levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and low-density lipoprotein (LDL)-cholesterol compared to normal rats (p≤0.05). In the dynamic (13)C MR spectra acquired at the 6th week, the obese rats showed significantly increased ratios of [1-(13)C] lactate/[1-(13)C] pyruvate and [1-(13)C] alanine/[1-(13)C] pyruvate (p=0.05). The (13)C spectral outcomes are positively correlated with the enzyme levels of ALT and LDH in the HFD-induced obesity. The [1-(13)C] lactate and [1-(13)C] alanine are potentially considered as noninvasive biomarkers for the HFD-induced obesity.

Brain Activation Patterns Associated with the Effects of Emotional Distracters during Working Memory Maintenance in Patients with Generalized Anxiety Disorder.

Few studies have assessed the neural mechanisms of the effects of emotion on cognition in generalized anxiety disorder (GAD) patients. In this functional MRI (fMRI), we investigated the effects of emotional interference on working memory (WM) maintenance in GAD patients. Fifteen patients with GAD participated in this study. Event-related fMRI data were obtained while the participants performed a WM task (face recognition) with neutral and anxiety-provoking distracters. The GAD patients showed impaired performance in WM task during emotional distracters and showed greater activation on brain regions such as DLPFC, VLPFC, amygdala, hippocampus which are responsible for the active maintenance of goal relevant information in WM and emotional processing. Although our results are not conclusive, our finding cautiously suggests the cognitive-affective interaction in GAD patients which shown interfering effect of emotional distracters on WM maintenance.

Noninvasive biomarkers for acute hepatotoxicity induced by 1,3-dichloro-2-propanol: hyperpolarized 13C dynamic MR spectroscopy.

The purpose of this study was to investigate the cellular metabolite change for acute hepatotoxicity induced by 1,3-dichloro-2-propanol (1,3-DCP) in rats and its correlations with the enzyme levels. In order to induce acute hepatotoxicity, a single subcutaneous injection of 1,3-DCP (80 mg/kg) was given to six male Sprague-Dawley rats. Hyperpolarized (13)C dynamic magnetic resonance spectroscopy (MRS) was performed on rat liver following injection of hyperpolarized [1-(13)C] pyruvate. The levels of serum aspartate am inotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in the 1,3-DCP treated rats were significantly increased as compared with those in normal rats. In the dynamic (13)C MR spectra, the ratios of [1-(13)C] lactate to the total carbon and [1-(13)C] alanine to the total carbon in the 1,3-DCP treated rats were significantly increased, and there were positive correlations between cellular metabolic changes and enzyme levels. The levels of [1-(13)C] lactate and [1-(13)C] alanine are potentially considered as important biomarkers for the 1,3-DCP-induced acute hepatotoxicity.