Metabolic alterations in a rat model of hepatic ischaemia reperfusion injury: In vivo hyperpolarized 13 C MRS and metabolic imaging.

BACKGROUND & AIMS: Despite a number of studies addressing the pathophysiology of hepatic IRI, a gold standard test for early diagnosis and evaluation of IRI remains elusive. This study investigated the metabolic alterations in a rat model of hepatic IRI using the in vivo hyperpolarized ¹³C MRS and metabolic imaging. METHODS: Hyperpolarized 13 C MRS with IVIM-DWI was performed on the liver of 7 sham-operated control rats and 7 rats before and after hepatic IRI. RESULTS: The hepatic IRI-induced rats showed significantly higher ratios of [1-13 C] alanine/pyruvate, [1-13 C] alanine/tC, [1-13 C] lactate/pyruvate and [1-13 C] lactate/tC compared with both sham-operated controls and rats before IRI, whereas [1-13 C] pyruvate/tC ratio was decreased in IRI-induced rats. In IVIM-DWI study, apparent diffusion coefficient (ADC), f and D values in rats after hepatic IRI were significantly lower than those of rats before IRI and sham-operated controls. The levels of [1-13 C] alanine and [1-13 C] lactate were negatively correlated with ADC, f and D values, whereas the level of [1-13 C] pyruvate was positively correlated with these values. CONCLUSIONS: The levels of [1-13 C] alanine, [1-13 C] lactate and [1-13 C] pyruvate in conjunction with IVIM-DWI will be helpful to evaluate the hepatic IRI as well as these findings can be useful in understanding the biochemical mechanism associated with hepatic damage.

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.

Metabolic biomarkers for non-alcoholic fatty liver disease induced by high-fat diet: In vivo magnetic resonance spectroscopy of hyperpolarized [1-13C] pyruvate.

Hyperpolarized 13C magnetic resonance spectroscopy (MRS) to assess hepatic metabolism in non-alcoholic fatty liver disease (NAFLD) has not been reported. This study searched for cellular metabolism-based biomarkers for NAFLD induced by a high-fat diet (HFD) in rats. Also, correlations of the biomarkers with enzyme levels and histopathology were identified during a 6-week follow-up. Six rats were fed a control diet (CD) and seven rats were fed the HFD for 6 weeks. Hyperpolarized 13C dynamic MRS was performed on rat liver following an injection of hyperpolarized [1-13C] pyruvate. Compared with CD-fed rats, HFD-fed rats showed significant increases in the levels of serum alanine aminotransferase and low-density lipoprotein cholesterol at weeks 4 and 6 of follow-up. After the 6-week HFD, the ratios of [1-13C] alanine/pyruvate and [1-13C] lactate/pyruvate were significantly increased, as were the levels of alanine aminotransferase and lactate dehydrogenase, which are potentially associated with hepatosteatosis. The results implicate [1-13C] alanine and [1-13C] lactate as potentially useful noninvasive biomarkers of hepatosteatosis occurring in NAFLD.

Abnormalities in gray and white matter volumes associated with explicit memory dysfunction in patients with generalized anxiety disorder.

Background The neuroanatomical abnormalities associated with behavioral dysfunction on explicit memory in patients generalized anxiety disorder (GAD) have not yet been clearly identified. Purpose To investigate the regional gray matter (GM) and white matter (WM) volume alterations over the whole brain in patients with GAD, as well as the correlation between the brain structural abnormality and explicit memory dysfunction. Material and Methods Twenty patients with GAD and 20 healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted magnetic resonance imaging (MRI). The participants performed the explicit memory tasks with the neutral and anxiety-inducing words. Results Patients with GAD showed significantly reduced GM volumes in the midbrain (MB), thalamus, hippocampus (Hip), insula, and superior temporal gyrus (STG); and reduced WM volumes in the MB, anterior limb of the internal capsule (ALIC), dorsolateral prefrontal cortex (DLPFC), and precentral gyrus (PrG). It is important to note that the GM volume of the Hip and the WM volume of the DLPFC were positively correlated with the recognition accuracy (%) in the explicit memory tasks with neutral and anxiety-inducing words, respectively. On the other hand, the WM volume of the PrG was negatively correlated with the reaction time in the same memory tasks. Conclusion This study demonstrated the regional volume changes on whole-brain GM and WM and the correlation between the brain structural alteration and explicit memory dysfunction in GAD patients. These findings would be helpful to understand the association between the brain structure abnormality and the functional deficit in the explicit memory in GAD.

Functional and morphological alterations associated with working memory dysfunction in patients with generalized anxiety disorder.

Background Generalized anxiety disorder (GAD) has been related to functional brain activities and structural brain abnormalities. Purpose To investigate the neural mechanism on working memory dysfunction in patients with GAD in terms of the combined functional and morphological brain abnormalities. Material and Methods Patients with GAD and healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted (T1W) magnetic resonance imaging (MRI) and functional MRI (fMRI). In this study, fMRI and voxel-based morphometry (VBM) were used for assessing the differential brain activation patterns, as well as for comparing the morphological alterations between the two groups. Results In response to the neutral distractors, the patients showed significantly lower activities in the regions of the fusiform gyrus (FuG), superior parietal gyrus (SPG), precuneus (PCu), superior occipital gyrus (SOG), lingual gyrus (LiG), cuneus (Cun), calcarine cortex (CaC), parahippocampal gyrus (PHG) and cerebellar cortex (Cb) compared to the controls. In response to the anxiety-inducing distractors, the patients showed significantly higher activity in the hippocampus and lower activities in the regions of the dorsolateral prefrontal cortex (DLPFC), FuG, SPG, PCu, SOG, and Cb. Also, the patients showed a significant reduction of the white matter volumes in the DLPFC, anterior limb of the internal capsule (ALIC) and midbrain. Conclusion This study provides the first evidence for the association between the morphometric alterations and functional deficit in the working memory processing with the neutral and anxiety-inducing distractors in GAD patients. These findings would be helpful to understand the neural mechanisms on working memory impairment in connection with GAD symptoms.

Functional neuroanatomy associated with the interaction between emotion and cognition in explicit memory tasks in patients with generalized anxiety disorder.

BACKGROUND: The functional neuroanatomy for explicit memory in conjunction with the major anxiety symptoms in patients with generalized anxiety disorder (GAD) has not yet been clearly identified. PURPOSE: To investigate the brain activation patterns on the interaction between emotional and cognitive function during the explicit memory tasks, as well as its correlation with clinical characteristics in GAD. MATERIAL AND METHODS: The participants comprised GAD patients and age-matched healthy controls. The fMR images were obtained while the participants performed an explicit memory task with neutral and anxiety-inducing words. RESULTS: Patients showed significantly decreased functional activities in the putamen, head of the caudate nucleus, hippocampus, and middle cingulate gyrus during the memory tasks with the neutral and anxiety-inducing words, whereas the precentral gyrus and ventrolateral prefrontal cortex were significantly increased only in the memory tasks with the anxiety-inducing words. Also, the blood oxygenation level-dependent (BOLD) signal changes in the hippocampus were positively correlated with the recognition accuracy for both neutral and anxiety-inducing words. CONCLUSION: This study identified the brain areas associated with the interaction between emotional regulation and cognitive function in the explicit memory tasks in patients with GAD. These findings would be helpful to understand the neural mechanism on the explicit memory-related cognitive deficits and emotional dysfunction with GAD symptoms.

Alterations in white matter volume and its correlation with neuropsychological scales in patients with Alzheimer's disease: a DARTEL-based voxel-based morphometry study.

Background Non-invasive imaging markers can be used to diagnose Alzheimer's disease (AD) in its early stages, but an optimized quantification analysis to measure the brain integrity has been less studied. Purpose To evaluate white matter volume change and its correlation with neuropsychological scales in patients with AD using a diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL)-based voxel-based morphometry (VBM). Material and Methods The 21 participants comprised 11 patients with AD and 10 age-matched healthy controls. High-resolution magnetic resonance imaging (MRI) data were processed by VBM analysis based on DARTEL algorithm. Results The patients showed significant white matter volume reductions in the posterior limb of the internal capsule, cerebral peduncle of the midbrain, and parahippocampal gyrus compared to healthy controls. In correlation analysis, the parahippocampal volume was positively correlated with the Korean-mini mental state examination score in AD. Conclusion This study provides an evidence for localized white matter volume deficits in conjunction with cognitive dysfunction in AD. These findings would be helpful to understand the neuroanatomical mechanisms in AD and to robust the diagnostic accuracy for AD.

Metabolic abnormality in the right dorsolateral prefrontal cortex in patients with obsessive-compulsive disorder: proton magnetic resonance spectroscopy.

OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) was used to evaluate metabolic changes in the dorsolateral prefrontal cortex (DLPFC) in patients with obsessive-compulsive disorder (OCD). METHODS: In total, 14 OCD patients (mean age 28.9±7.2 years) and 14 healthy controls (mean age 32.6±7.1 years) with no history of neurological and psychiatric illness participated in this study. Brain metabolite concentrations were measured from a localised voxel on the right DLPFC using a 3-Tesla 1H-MRS. RESULTS: The metabolic concentration of myo-inositol in patients with OCD increased significantly by 52% compared with the healthy controls, whereas glutamine/glutamate was decreased by 11%. However, there were no significant differences in N-acetylaspartate, choline, lactate and lipid between the two groups. CONCLUSION: These findings would be helpful to understand the pathophysiology of OCD associated with the brain metabolic abnormalities in the right DLPFC.

Neural activation-based sexual orientation and its correlation with free testosterone level in postoperative female-to-male transsexuals: preliminary study with 3.0-T fMRI.

PURPOSE: The purpose of this study was to evaluate the brain activation pattern associated with sexual orientation and its correlation with the level of the free testosterone (free T) in postoperative female-to-male (FtM) transsexuals using a 3.0-Tesla functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: Eleven postoperative FtM transsexuals with sex reassignment surgery underwent fMRI on a 3.0-T MR scanner. Brain activity was measured while viewing erotic male and female nude pictures. RESULTS: The average level of free T in the FtM transsexuals was in the normal range of heterosexual men. The brain areas with predominant activities during viewing female nude pictures in contrast to male pictures included the hippocampus, parahippocampal gyrus, anterior cingulate gyrus, putamen, amygdala, hypothalamus, and insula (p < 0.005). The free T levels were positively correlated with the BOLD signal changes in the parahippocampal gyrus (Spearman's rho = 0.91, p < 0.001), hippocampus (rho = 0.90, p < 0.001), insula (rho = 0.68, p < 0.05), putamen (rho = 0.66, p < 0.05), and amygdala (rho = 0.64, p < 0.05). Compared to FtM transsexuals with deficient level of free T, the FtM transsexuals with normal range of free T showed significantly higher activities in the parahippocampal gyrus, hippocampus, insula, putamen, and amygdala during viewing female nude pictures (p < 0.005). CONCLUSION: This study revealed the specific brain activation pattern associated with sexual orientation and its correlation with free T in the postoperative FtM transsexuals. These findings are applicable in understanding the neural mechanism on sexual arousal in FtM transsexuals and their sexual orientation in connection with the free T levels.

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

OBJECTIVE: We performed functional magnetic resonance imaging (fMRI) to discriminate the differential brain activation patterns in patients with obsessive compulsive disorder (OCD) and healthy controls during implicit retrieval tasks with emotionally neutral and unpleasant words. METHODS: Sixteen patients with OCD (mean age: 31.4±10.1 years) and 16 healthy controls (mean age: 32.6±5.8 years) with no history of neurological or psychiatric illness underwent 3-T fMRI. The stimulation paradigm consisted of the following cycle: rest, encoding of a string of two-syllable words, rest, and retrieval of the previously encoded words with the first consonant omitted. RESULTS: During the implicit retrieval task with emotionally neutral words, no distinct brain activity was observed in either the patients with OCD or healthy controls. On the other hand, during the retrieval task with unpleasant words, the patients with OCD showed predominant activity in the superior/middle temporal pole, medial superior frontal gyrus, and orbitofrontal cortex (uncorrected p<0.001, extent threshold: 30 voxels), whereas the healthy controls did not show any distinct regions of activation. CONCLUSION: This study revealed the differential brain activation patterns between patients with OCD and healthy controls during implicit memory tasks with unpleasant words. Our results suggest that the impact of negative emotion on implicit memory task may be associated with the symptomatology of OCD. This finding may be helpful for understanding the neural mechanisms that underlie implicit memory retrieval, particularly the interaction between emotion and cognition, in patients with OCD.

Neuroanatomical mechanism on the effect of distraction in working memory maintenance in patients with schizophrenia.

This study utilized functional magnetic resonance imaging (fMRI) to discriminate brain activation patterns associated with the effect of distraction during working memory (WM) maintenance for human faces in healthy controls and patients with schizophrenia. Event-related fMRI data were obtained while the subjects performed WM maintenance in a delayed-response WM task with task-irrelevant distracters. Compared with healthy controls, patients showed significantly decreased activities in the superior frontal gyrus, dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex, anterior cingulate cortex, inferior parietal gyrus, and fusiform gyrus during the delayed-response WM task with human face distracters. The blood-oxygen-level-dependent signal changes in the DLPFC were negatively correlated with both of the scores of the Positive Subscale and General Psychopathology Subscale under the Positive and Negative Syndrome Scale during the WM maintenance for the human faces in the patients. This study will be helpful in understanding the neural mechanisms in the general impairment of the inhibition control in schizophrenia.

Alterations in white matter volume and its correlation with clinical characteristics in patients with generalized anxiety disorder.

INTRODUCTION: Only a few morphological studies have focused on changes in white matter (WM) volume in patients with generalized anxiety disorder (GAD). We evaluated alterations in WM volume and its correlation with symptom severity and duration of illness in adults with GAD. METHODS: The 44 subjects were comprised of 22 patients with GAD (13 males and nine females) diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and 22 age-matched healthy controls (13 males and nine females). High-resolution magnetic resonance imaging (MRI) data were processed by voxel-based morphometry (VBM) analysis based on diffeomorphic anatomical registration using the exponentiated Lie algebra (DARTEL) algorithm in SPM8. RESULTS: Patients with GAD showed significantly reduced WM volume, particularly in the dorsolateral prefrontal cortex (DLPFC), anterior limb of the internal capsule (ALIC), and midbrain. In addition, DLPFC volume was negatively correlated with GAD-7 score and illness duration. ALIC volume was negatively correlated with GAD-7 score. Female patients had significantly less orbitofrontal cortex volume compared to that in male patients. CONCLUSION: The findings demonstrate localized changes in WM volume associated with cognitive and emotional dysfunction in patients with GAD. The finding will be helpful for understanding the neuropathology in patients with GAD.

Cerebral white matter volume changes in patients with obsessive-compulsive disorder: Voxel-based morphometry.

AIMS: We carried out a voxel-based morphometry (VBM) study to evaluate cerebral white matter (WM) volume alteration in obsessive-compulsive disorder (OCD) and its correlation with the scores of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). METHODS: Fourteen patients with OCD, who were diagnosed using the DSM-IV-TR, and 14 age-matched healthy controls participated. The high-resolution magnetic resonance imaging data were analyzed by voxel-based morphometry and Statistical Parametric Mapping 8. RESULTS: There was no significant difference in the total intracranial volumes between OCD patients and healthy controls. However, patients with OCD showed significantly increased WM volumes in the right dorsolateral prefrontal cortex, middle frontal gyrus, precuneus, and inferior parietal lobule compared with healthy controls. In addition, the OCD patients showed a positive correlation between the WM volumes of the dorsolateral prefrontal cortex and Y-BOCS scores (r = 0.334, P = 0.03 and Pearson's correlation coefficient = 0.58) rating for the severity of OCD symptoms. CONCLUSIONS: WM volume variations of the specific brain regions in patients with OCD will be helpful to understand the neural connectivity associated with a symptom of OCD. Furthermore, the findings would be valuable to aid the diagnostic accuracy of OCD in connection with morphometric magnetic resonance imaging analysis.

Functional neuroanatomy on the working memory under emotional distraction in patients with generalized anxiety disorder.

AIMS: Patients with generalized anxiety disorder (GAD) suffer the symptoms of psychological distress, including excessive and uncontrollable anxiety. Until now, the functional neuroanatomy for working memory (WM) in conjunction with the major anxiety symptoms in GAD patients has not yet been clearly identified. This study investigated the neural activation patterns associated with the effect of neutral and anxiety-inducing distractors during the delayed-response WM task in GAD patients. METHODS: Eighteen patients with GAD and 18 age-matched healthy controls participated in this study. The functional magnetic resonance images were obtained while the subjects performed a delayed-response WM task with neutral and anxiety-inducing distractors. RESULTS: During the neutral distractor, GAD patients compared to controls showed significantly lower activities in the fusiform gyrus, superior parietal gyrus, precuneus, superior occipital gyrus, lingual gyrus, cuneus, calcarine gyrus, parahippocampal gyrus and cerebellar cortex. During the anxiety-inducing distractor, GAD patients showed significantly higher activity in the hippocampus, whereas they showed lower activities in the dorsolateral prefrontal cortex, fusiform gyrus, superior parietal gyrus, precuneus, superior occipital gyrus and cerebellar cortex. The blood-oxygen-level dependent signal changes in the dorsolateral prefrontal cortex in GAD patients during the anxiety-inducing distractor were negatively correlated with Anxiety Sensitivity Index-Revised scores. CONCLUSIONS: This study identified the specific brain areas associated with the interaction between emotional regulation and cognitive function associated with neutral and anxiety-inducing distractors during WM maintenance in GAD patients. These findings will be helpful for understanding the neural mechanism on the WM-related cognitive deficits and emotional dysfunction with typical anxiety symptoms in GAD.

Metabolic change in the right dorsolateral prefrontal cortex and its correlation with symptom severity in patients with generalized anxiety disorder: Proton magnetic resonance spectroscopy at 3 Tesla.

AIMS: A few neuroimaging studies have demonstrated the key brain areas associated with generalized anxiety disorder (GAD). However, the brain metabolic changes in the dorsolateral prefrontal cortex (DLPFC) of patients with GAD are unclear. This study utilized 3-Tesla proton magnetic resonance spectroscopy ((1) H-MRS) to assess the DLPFC metabolic change and its correlation with symptom severity in patients with GAD. METHODS: Patients with GAD diagnosed using the DSM-IV-TR and age-matched healthy controls participated in this study. Brain metabolite concentrations were measured from a localized voxel on the DLPFC using 3-Tesla (1) H-MRS. Also, the volumetric composition of the gray matter and white matter volumes was assessed using voxel-based morphometry. RESULTS: The choline/creatine and choline/N-acetylaspartate ratios were significantly lower in patients than in controls. However, there were no significant differences in other metabolite ratios between the two groups. Choline concentrations were negatively correlated with anxiety levels as measured by the Hamilton Anxiety Rating Scale and the Generalized Anxiety Disorder Scale 7. There was no significant difference in the gray matter and white matter volumes in the MRS voxel between the two groups. CONCLUSIONS: The present study demonstrates that GAD is associated with low a level of choline/N-acetylaspartate in the DLPFC, which is closely related with symptom severity and cognitive dysfunction. This finding will be useful for an understanding of the neural mechanism associated with GAD.

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.

Assessment of brain metabolites change during visual sexual stimulation in healthy women using functional MR spectroscopy.

INTRODUCTION: Numerous functional magnetic resonance imaging (fMRI) studies demonstrated the key brain areas associated with visual sexual arousal. However, the changes in brain metabolites involved in sexual stimuli have not been reported. AIM: This study utilized functional MR spectroscopy (fMRS) to evaluate the changes in brain metabolites associated with sexual arousal induced by stimulation with erotic video clips in healthy women. METHODS: Twenty-three healthy, right-handed women (38.4 ± 10.0 years) participated in (1) H-fMRS and fMRI studies. T1 and T2 MR images were used for voxel localization of the anterior cingulate gyrus, which is one of the most important key centers associated with sexual arousal. MAIN OUTCOME MEASURES: The changes of brain metabolites were measured using (1) H-fMRS during time-course activation: "before," "during," and "after" visual sexual stimulation. The time-course variation of the brain metabolites was analyzed by the repeated-measures analysis of variance. RESULTS: The CVmean of all the metabolites had <30% (range, 9-29%). The ICCs of α-glutamine-glutamate (Glx), choline (Cho), ߷γ-Glx, N-acetylaspartate (NAA) and lactate (Lac) all exceeded 0.6. However, myo-inositol (mI) and lipid (Lip) were <0.6. The concentration of brain metabolites including α-Glx, ߷γ-Glx, Cho, and Lac comparatively increased significantly during visual sexual stimulation. CONCLUSIONS: (1) H-fMRS, for the first time, was applied to assess the brain metabolic changes during visually-evoked sexual arousal. The fMRS outcomes in relation to functional MRI data will be useful to understand the neural mechanism associated with sexual arousal.

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).

Comparative Functional Connectivity of Core Brain Regions between Implicit and Explicit Memory Tasks Underlying Negative Emotion in General Anxiety Disorder.

Objective: To investigate not only differential patterns of functional connectivity of core brain regions between implicit and explicit verbal memory tasks underlying negatively evoked emotional condition, but also correlations of functional connectivity (FC) strength with clinical symptom severity in patients with generalized anxiety disorder (GAD). Methods: Thirteen patients with GAD and 13 healthy controls underwent functional magnetic resonance imaging for memory tasks with negative emotion words. Results: Clinical symptom and its severities of GAD were potentially associated with abnormalities of task-based FC with core brain regions and distinct FC patterns between implicit vs. explicit memory processing in GAD were potentially well discriminated. Outstanding FC in implicit memory task includes positive connections of precentral gyus (PrG) to inferior frontal gyrus and inferior parietal gyrus (IPG), respectively, in encoding period; a positive connection of amygdala (Amg) to globus pallidus as well as a negative connection of Amg to cerebellum in retrieval period. Meanwhile, distinct FC in explicit memory included a positive connection of PrG to inferior temporal gyrus (ITG) in encoding period; a positive connection of the anterior cingulate gyrus to superior frontal gyrus in retrieval period. Especially, there were positive correlation between GAD-7 scores and FC of PrG-IPG (r2 = 0.324, p= 0.042) in implicit memory encoding, and FC of PrG-ITG (r2 = 0.378, p= 0.025) in explicit memory encoding. Conclusion: This study clarified differential patterns of brain activation and relevant FC between implicit and explicit verbal memory tasks underlying negative emotional feelings in GAD. These findings will be helpful for an understanding of distinct brain functional mechanisms associated with clinical symptom severities in GAD.