Predicting the efficacy of donepezil intervention in Alzheimer's disease patients using regional homogeneity in the inferior orbitofrontal cortex.

BACKGROUND: Although donepezil is a commonly used drug for treating Alzheimer's disease (AD), the mechanisms by which it affects patients' functional brain activity, and thus modulates clinical symptoms, remain unclear. METHODS: In the present study, we used resting-state functional magnetic resonance imaging (MRI) and regional homogeneity (ReHo) to investigate the effects of donepezil on local brain activity in AD patients. Resting-state functional MRI data were collected from 32 subjects: 16 healthy controls and 16 AD patients. All 16 AD patients underwent 6 months of donepezil treatment and received two MRI scans (pre- and post-intervention). Analysis of covariance and post hoc analyses were used to compare ReHo differences among the healthy controls, pre-intervention AD patients, and post-intervention AD patients. Pearson correlation analysis was used to examine relationships between ReHo values in differential brain regions and clinical symptoms. RESULTS: Compared with healthy controls, post-intervention AD patients had reduced ReHo in the orbital part of the inferior frontal gyrus, and pre-intervention AD patients had reduced ReHo in the orbital part of the right inferior frontal gyrus. Pattern recognition models revealed that pre-intervention ReHo values in abnormal brain regions of AD patients were 76% accurate for predicting the efficacy of donepezil on cognitive function and 65% accurate for predicting its efficacy on depressive symptoms. CONCLUSIONS: These findings deepen our understanding of the brain mechanisms underlying the clinical efficacy of donepezil in AD patients, and provide a novel way to predict its clinical efficacy in such patients.

Abnormalities in spontaneous brain activity and functional connectivity are associated with cognitive impairments in children with type 1 diabetes mellitus.

BACKGROUND: It remains unclear whether alterations in brain function occur in the early stage of pediatric type 1 diabetes mellitus(T1DM). We aimed to examine changes in spontaneous brain activity and functional connectivity (FC) in children with T1DM using resting-state functional magnetic resonance imaging (rs-fMRI), and to pinpoint potential links between neural changes and cognitive performance. METHODS: In this study, 22 T1DM children and 21 age-, sex-matched healthy controls underwent rs-fMRI. The amplitude of low frequency fluctuations (ALFF) and seed-based FC analysis were performed to examine changes in intrinsic brain activity and functional networks in T1DM children. Partial correlation analyses were utilized to explore the correlations between ALFF values and clinical parameters. RESULTS: The ALFF values were significantly lower in the lingual gyrus (LG) and higher in the left medial superior frontal gyrus (MSFG) in T1DM children compared to controls. Subsequent FC analysis indicated that the LG had decreased FC with bilateral inferior occipital gyrus, and the left MSFG had decreased FC with right precentral gyrus, right inferior parietal gyrus and right postcentral gyrus in children with T1DM. The ALFF values of LG were positively correlated with full-scale intelligence quotient and age at disease onset in T1DM children, while the ALFF values of left MSFG were positively correlated with working memory scores. CONCLUSION: Our findings revealed abnormal spontaneous activity and FC in brain regions related to visual, memory, default mode network, and sensorimotor network in the early stage of T1DM children, which may aid in further understanding the mechanisms underlying T1DM-associated cognitive dysfunction.

Altered gray matter volume in children with newly diagnosed type 1 diabetes mellitus.

BACKGROUND: Type 1 diabetes mellitus (T1DM) affects the development of cognitive function in children, which may be due to deficits in brain structures or functions. It is unclear whether children with T1DM experience alterations in the gray matter (GM) structure at the initial stages of the disease. This study investigated GM structure alterations in children with newly diagnosed T1DM. METHODS: Based on 3D T1-weighted MR images, we investigated the gray matter volume (GMV) of 35 newly diagnosed T1DM children and 35 age- and sex-matched healthy controls using voxel-based morphometry. The brain regions with significant differences in GMV between the newly diagnosed T1DM children and the controls were extracted and the correlation with clinical data was assessed. RESULTS: Compared with the control group, children with newly diagnosed T1DM had a lower GMV in the right inferior and middle temporal gyri, right lingual gyrus, and left superior frontal gyrus. In T1DM subjects, the GMV of the right middle temporal gyrus was positively correlated with IQ but was negatively correlated with HbA1c. CONCLUSIONS: Our findings provide compelling evidence that GM abnormalities occur during early disease stages in T1DM children, which may be a potential neurobiological mechanism underlying cognitive deficits. IMPACT: Using an efficient method to analyze gray matter changes in T1DM is very important. The anterior, posterior, and temporal brain regions are susceptible to T1DM in children. Recent glucose variability may affect regional gray matter volume in children with newly diagnosed T1DM. Structural changes were documented in the gray matter of the brain even at the early stages of the disease in children with T1DM.

Alterations in Resting-State Interhemispheric Coordination With Refractory Auditory Verbal Hallucinations in Schizophrenia.

OBJECTIVE: The purpose of this study was to investigate resting-state interhemispheric functional connectivity in patients with schizophrenia and refractory auditory verbal hallucinations (RAVHs) by using voxel-mirrored homotopic connectivity (VMHC). METHODS: Thirty-four patients with schizophrenia and RAVHs (RAVH group), 23 patients with schizophrenia but no auditory verbal hallucinations (non-AVH group), and 28 matched healthy volunteers (healthy control group) were recruited in China. VMHC analyses were used to identify brain areas with significant differences in functional connectivity among the three groups, and correlations between symptom scores and neurological measures were examined. RESULTS: VMHC analyses showed aberrant bilateral connectivity between several homotopic brain regions: the RAVH and non-AVH groups showed differences in bilateral connectivity of the superior and middle temporal gyri, and the RAVH and healthy control groups showed differences in bilateral connectivity of the gyrus rectus, inferior frontal gyrus, and putamen. In addition, interhemispheric connectivity of the superior and middle temporal gyri correlated with patients' positive symptom scores. CONCLUSIONS: These findings may help to elucidate the pathophysiological mechanisms underlying auditory verbal hallucinations. The results revealed interhemispheric functional dysconnectivity among patients with schizophrenia and suggest that the dysconnectivity of homotopic brain regions may play an important role in the development of auditory verbal hallucinations.

Abnormal functional connectivity of the habenula in mild cognitive impairment patients with depression symptoms revealed by resting-state functional magnetic resonance imaging.

BACKGROUND: Recent research suggests that abnormalities in the habenula (HB), a core area of the brain that transmits reward information, may be a determinant of depression. However, it is not clear whether the functional connectivity (FC) pattern of the mild cognitive impairment (MCI) with and without depression symptoms is abnormal. METHODS: In this study, we used resting-state functional magnetic resonance imaging (fMRI) to examine the FC pattern of the HB in MCI patients with depression symptoms (D-MCI). We acquired fMRI data from 54 subjects on a 3T MRI. Subjects collected included 16 patients with D-MCI, 18 patients with MCI with no depression, and 20 healthy controls. One way ANCOVA and post hoc t-test were used to compare the difference in FC strength between the three groups. RESULTS: The D-MCI group had altered FC between the left HB and the right superior temporal gyrus, right inferior frontal gyrus/opercular part, and right middle frontal gyrus. The D-MCI group had increased FC between the right HB and precuneus. CONCLUSIONS: These results suggest that the dysfunction of the HB-Default model network might be involved in the neural mechanism underlying depression in MCI.

Disruption of brain regional homogeneity and functional connectivity in male NAFLD: evidence from a pilot resting-state fMRI study.

BACKGROUND: The neurophysiological mechanisms underlying cognitive deficits in non-alcoholic fatty liver disease (NAFLD) remain unknown. Cognitive changes may be caused by brain alterations in neural activity and functional connectivity (FC). AIM: This study aims to investigate the alterations between spontaneous brain neural activity and FC in male NAFLD patients and the relationship of neural activity with cognitive performance. METHODS: In this prospective study, 33 male pre-cirrhosis NAFLD subjects and 20 male controls matched for age, education level, and body mass index. All participants underwent resting-state functional magnetic resonance imaging scans and neuropsychological examinations. Regional homogeneity (ReHo) analysis was used to investigate the brain function in NAFLD, and regions with significantly altered ReHo were selected as seeds for subsequent FC analysis. Partial correlation analysis was used to assess the relationships between altered ReHo measures and cognitive performance indicators. RESULTS: Compared with the controls, the NAFLD patients showed increased ReHo in the opercular part of the right inferior frontal gyrus (IFGoperc) and decreased ReHo in the right middle frontal gyrus (MFG) and left superior parietal gyrus (SPG). The subsequent FC analysis showed increased FC between these regions (right IFGoperc, right MFG, and left SPG) and nodes of the default mode network (DMN) (such as left supraMarginal, left median cingulate and paracingulate gyri, left precuneus, orbital part of left medial frontal gyrus, and bilateral posterior cingulate gyrus). In addition, significant positive correlations were observed between NAFLD patients' clock drawing test scores and altered ReHo in prefrontal cortices (right IFGoperc and right MFG). CONCLUSION: Before developing cirrhosis, NAFLD patients showed altered neural activity in several brain regions and altered FC between the salience network and DMN. These alterations could potentially be a compensatory mechanism to maintain cognitive function in pre-cirrhosis NAFLD patients.

Disrupted topological organization of functional brain networks in Alzheimer's disease patients with depressive symptoms.

BACKGROUND: Depression is a common symptom of Alzheimer's disease (AD), but the underlying neural mechanism is unknown. The aim of this study was to explore the topological properties of AD patients with depressive symptoms (D-AD) using graph theoretical analysis. METHODS: We obtained 3-Tesla rsfMRI data from 24 D-AD patients, 20 non-depressed AD patients (nD-AD), and 20 normal controls (NC). Resting state networks were identified using graph theory analysis. ANOVA with a two-sample t-test post hoc analysis in GRETNA was used to assess the topological measurements. RESULTS: Our results demonstrate that the three groups show characteristic properties of a small-world network. NCs showed significantly larger global and local efficiency than D-AD and nD-AD patients. Compared with nD-AD patients, D-AD patients showed decreased nodal centrality in the pallidum, putamen, and right superior temporal gyrus. They also showed increased nodal centrality in the right superior parietal gyrus, the medial orbital portion of the right superior frontal gyrus, and the orbital portion of the right superior frontal gyrus. Compared with nD-AD patients, NC showed decreased nodal betweenness in the right superior temporal gyrus, and increased nodal betweenness in medial orbital part of the right superior frontal gyrus. CONCLUSIONS: These results indicate that D-AD is associated with alterations of topological structure. Our study provides new insights into the brain mechanisms underlying D-AD.

Abnormal Functional Connectivity Density in Patients with Dysthyroid Optic Neuropathy.

OBJECTIVE: Functional connectivity density (FCD) mapping was used to investigate abnormalities and factors related to brain functional connectivity in cortical regions of patients with dysthyroid optic neuropathy (DON) and to analyze the pathogenesis of DON further. METHODS: Patients diagnosed with thyroid-associated opthalmology (TAO) in the Eye Hospital were enrolled. All patients underwent comprehensive eye examinations and best-corrected visual acuity, visual field (VF) test. MRI data collection and analysis were completed in the 2nd Affiliated Hospital of Wenzhou Medical University. The patients were divided into 2 groups: the DON group, with an average VF, mean deviation (MD) of both eyes < -5 dB, and the non-DON group (nDON group), with an average VF MD of both eyes ≥ -2 dB. RESULTS: A total of 30 TAO patients (14 men, 16 women) with complete data who met the experimental requirements were enrolled. The average age was 48.79 (40-57) years. There were 16 patients in the DON group and 14 patients in the nDON group. No significant differences in age, gender, education level, and the maximum horizontal diameter of either medial rectus muscle were found between the 2 groups. The difference of brain FCD between the 2 groups showed significant abnormal connectivity in the right orbital gyri of the frontal lobe (Frontal_Inf_Orb_R) and the left precuneus in the DON group compared with the nDON group. As demonstrated by decreased FCD values in the right inferior frontal gyrus/orbital part, the relevant brain regions were the left middle temporal gyrus, left precuneus, left middle frontal gyrus, right postcentral gyrus, and brain gyri (excluding the supramarginal gyrus and angular gyrus) below the left parietal bone. The FCD associated with the left precuneus was increased, and the relevant brain areas were the left middle temporal gyrus, right cuneus, superior occipital gyrus, and right fusiform gyrus. A significant correlation was identified between the MD of the binocular VF and brain FCD. CONCLUSION: The abnormal FCD in the cortex of DON patients suggests that a central nervous system mechanism may be related to the pathogenesis of the DON.

The Evaluation of Longitudinal Strain of Large and Small Abdominal Aortic Aneurysm by Two-Dimensional Speckle-Tracking Ultrasound.

OBJECTIVES: Abdominal aortic aneurysm (AAA) is a dangerous and lethal vascular disease. Non-invasive two-dimensional speckle-tracking imaging (2D STI) plays an important role in assessing aortic biomechanical properties. Our study aimed to evaluate the alterations of biomechanical characteristics using 2D STI in 91 AAA patients with different size. METHODS: Aneurysm strain, elastic modulus, stiffness index ß, and aortic distensibility determined by M-Mode ultrasound (US), and longitudinal strain (LS) derived from 2D STI were compared in 40 large AAA patients (diameter ≥ 55 mm) and 51 small AAA patients (diameter < 55 mm). RESULTS: Compared with small AAA group, anterior wall longitudinal strain (ALS) and posterior wall longitudinal strain (PLS) were significantly decreased in large AAA group (all P < .05) and not affected by age, symptom, hypertension, and thrombus. Meanwhile, ALS and PLS correlated negatively with maximal aneurysm diameters (r = -0.628 and -0.469, respectively, all P < .001). And only ALS was associated with M-Mode US parameters (all P < .05). Based on receiver operating characteristic (ROC) analysis, ALS and PLS had strong diagnostic values for large AAA with the area under the curve (AUC) of 0.82 and 0.72, and cut-off points of 1.71 and 1.64% with a sensitivity of 78 and 72%, and a specificity of 75 and 70%, respectively. CONCLUSIONS: LS measured by 2D STI could evaluate the biomechanical properties of aneurysm wall with different size, and add additional diagnostic value in distinguishing between small and large AAA.

Zearalenone affects the growth of endometriosis via estrogen signaling and inflammatory pathways.

Endometriosis is a chronic, inflammatory, estrogen-dependent gynecological disease characterized by the growth of endometrial stromal cells and glands outside the uterine cavity in response to hormones, which commonly occurs in reproductive-age women. Zearalenone (ZEA) is a toxic metabolite produced by Fusarium, which acts as estrogen activity because of the similarity of its structure to estrogen. In this study, we used an endometriosis mouse model: 15 days after ovariectomy, endometrial fragments were sutured on the pelvic wall, and exogenous estrogen was supplied using an estrogen-releasing silicone tube embedded subcutaneously. Mice were treated with different doses of ZEA by gavage for 21 days. The results show that ZEA significantly inhibited the growth of ectopic endometrium in a dose-dependent manner. The proliferation of cells decreased while apoptosis increased in the ectopic tissues of ZEA-treated mice compared to the vehicle group. The expression of estrogen receptor-α and its downstream targets MUC1 and p-AKT decreased, indicating an impaired estrogen signaling activity by ZEA treatment. In addition, the decreased expression of pro-inflammatory cytokine Tnf-α, Il-1ß, and Il-6, the lower number of macrophages and neutrophils cells, and the inhibited NF-κB signaling pathway suggest the inflammatory response in the ectopic endometrium was also suppressed by ZEA treatment. However, when the exogenous estrogen supply is removed, ZEA, in turn, plays an estrogen-like role that promotes cell proliferation in the ectopic endometrium. In summary, our data suggest ZEA acts as an antagonist in endometriotic tissue when estrogen is sufficient but turns to estrogenic activity in the absence of estrogen in the development of endometriosis. ZEA also inhibits ectopic tissue growth by inhibiting inflammatory response in the endometriosis model.

TLR4 rs1927914 polymorphism contributes to serum TLR4 levels in patients with aortic aneurysm.

Toll-like receptor 4 (TLR4) is a crucial regulator of inflammatory reactions and vascular remodeling. Elevated TLR4 expression has been proved to be correlated with an increased risk of aortic aneurysm (AA). This study aimed to explore the influence of TLR4 gene polymorphisms on TLR4 expression levels and its probable functional significance in AA disease. A total of 294 AA patients and 285 controls were enrolled in the study and serum TLR4 levels were detected by ELISA. All the participants were genotyped for two tag-SNPs in TLR4 (rs1927914 in the promoter region and rs11536889 in the 3'-untranslated region) using the KASP method. Relative luciferase activity was measured by the dual-luciferase reporter assay system. The rs1927914 TC, TC/CC genotypes and C allele showed associations with increased serum TLR4 levels in the total population and AA patients (all P<0.05). Further stratified analysis demonstrated that AA subjects with TC or TC/CC genotype of rs1927914 had significantly higher serum levels of TLR4 than those with TT genotype in male, age>60y, hypertension, diabetes, TAA type and size>5.0 cm subgroups (all P<0.05). In binary logistic analysis, rs1927914 TC genotype and dominant model presented significant associations with high TLR4 levels (OR = 1.579 and 1.431, P = 0.020 and 0.049, respectively) after adjusting age, hypertension and diabetes. However, rs11536889 polymorphism had no significant influence on serum TLR4 levels. Regarding rs1927914, luciferase activity of the C allele construct was significantly increased in comparison with the T allele construct (0.589 ± 0.004 vs. 0.340 ± 0.014, P<0.001). Our results provided evidence that rs1927914 polymorphism contributed to serum TLR4 levels, possibly by influencing promoter activity of TLR4, and could be a novel genetic factor in the formation of AA.

The elevated expression of TLR4 and MMP9 in human abdominal aortic aneurysm tissues and its implication.

BACKGROUND: Toll-like receptor 4 (TLR4) and matrix metalloproteinase 9 (MMP9) have been investigated to play significant roles in the formation of abdominal aortic aneurysm (AAA). But the reports on the expression pattern of TLR4 and MMP9 in human AAA specimens were relatively scant. The aim of this study was to make a detailed analysis of TLR4 and MMP9 expression in situ and their association with clinical parameters involved in human AAA. METHODS: 40 AAA specimens were obtained from full-thickness aneurysmal tissues at the maximal dilation area during the open surgical repair, and 8 non-aneurysmal abdominal aortas from transplant donors served as controls. Expression of TLR4 and MMP9 protein was determined by immunohistochemistry. RESULTS: There were increased levels of TLR4 and MMP9 expression in human AAA tissues. Compared with macrophages or SMCs, lymphocytes showed a higher positive rate of TLR4 and MMP9 staining, and an elevated ratio of high MMP9 expression (all P < 0.05). There existed a significant association between TLR4 and MMP9 expression (r = 0.767, P < 0.001), and both TLR4 and MMP9 levels were statistically related to circulating CRP. Moreover, TLR4 expression in situ indicated a positive correlation with its serum level (r = 0.654, P = 0.006). Multiple analysis revealed that high TLR4 expression in situ was associated with the risk of large AAA (OR = 6.211, 95%CI = 1.226-31.480, P = 0.027), while high MMP9 expression was correlated to the presence of thrombus within AAA (OR = 5.494, 95%CI = 1.181-25.562, P = 0.030), separately compared with their low expression. CONCLUSIONS: This study confirmed the overexpression of TLR4 and MMP9 in human AAA tissues, and their close relationship implying in the pathogenesis of AAA. We further provided evidence that TLR4 had a potential effect on AAA size and MMP9 could influence the occurrence of thrombus within AAA.

Assessment of the Global and Regional Circumferential Strain of Abdominal Aortic Aneurysm with Different Size by Speckle-Tracking Echocardiography.

OBJECTIVES: We aimed to use speckle-tracking echocardiography (STE) to quantify circumferential aortic strain of abdominal aortic aneurysms (AAA) with different size. METHODS: A total of 87 AAA patients were included. The morphological variables, including aortic maximum diameter (MD), end systolic area (ESA), end diastolic area (EDA), and thickness and area of intraluminal thrombus (ILT), were measured by ultrasound. STE was applied to calculate circumferential strain (CS) at 6 equally divided segments of the aorta at MD. We evaluated the mean value of peak strain along the 6 segments as global circumferential strain (GCS). RESULTS: Large AAA (≥5.5 cm) patients had higher MD, ESA, EDA, AAA length, ILT thickness, and area, but lower fractional area change, GCS, and segmental CSs than small AAA (<5.5 cm) subjects (all P < .05). Compared with AAA <4.5 cm group, AAA patients ≥4.5 cm possessed increased MD, ESA, EDA, AAA length, ILT thickness, and area, which results were also reflected in the comparison between AAA <6.5 and ≥6.5 cm group. In small AAA patients, GCS and regional strains in CS1, CS3, and CS5 segments were lower in AAA subjects ≥4.5 cm than those <4.5 cm (all P<.05). However, no significant differences in the GCS and regional CS between ≥6.5 and <6.5 cm group were found. Correlation analysis revealed a significant negative association of GCS with MD, ESA, and EDA, even after adjusting the potential confounding factors (all P < .05). CONCLUSIONS: Our findings may yield insight into the structural strain characteristics of AAA wall with different size, which adds the benefit of using simple echocardiography-derived biomechanics to stratify AAA patients.

Influence of the hypothalamus-pituitary-gonadal axis reactivation and pubertal hormones on gray matter volume in early pubertal girls.

OBJECTIVE: Puberty is a sensitive period of brain development accompany with pubertal hormones fluctuation. However, the underlying mechanisms of the impact of hypothalamus-pituitary-gonadal (HPG) axis reactivation and associated elevated pubertal hormones on brain structure are still unclear. Here, we investigated the brain structure differences between girls with and without HPG axis reactivation and the influence of pubertal hormones on these brain regions. METHODS: 126 girls aged 8-9.5 years underwent a gonadotropin-releasing hormone (GnRH) stimulation test to identify the HPG axis status and categorized into HPG+ group (n = 80) and HPG- group (n = 46). T1-weighted gradient echo three dimensional MRI was performed using a 3.0-Tesla scanner to assess the difference in GMV between the two groups. Correlation analyses were conducted to explore the relations between the brain regions showing significant GMV differences and serum hormone concentrations. RESULT: The HPG+ group showed significantly higher GMV in the bilateral lingual gyrus and lower GMV within the right orbital inferior frontal gyrus compare to the HPG - group. Furthermore, GMV in the right orbital inferior frontal gyrus was positively associated with plasma concentrations of follicle stimulating hormone (FSH) in HPG+ group. CONCLUSION: The present study suggests that the reactivated HPG axis could affects regional structural brain changes in early pubertal girls. FSH production play an important role in bilateral lingual gyrus, which are involved in vision processing, semantic processing and emotional expression.

Disrupted Regional Spontaneous Neural Activity in Mild Cognitive Impairment Patients with Depressive Symptoms: A Resting-State fMRI Study.

Depressive symptoms are common in individuals with mild cognitive impairment (MCI) who have an increased risk of dementia. It is currently unclear whether the pattern of spontaneous brain activity in patients with MCI differs between subjects with and without depressive symptoms. The current study sought to investigate the features of spontaneous brain activity in MCI patients with depressive symptoms (D-MCI) using coherence regional homogeneity (CReHo) analysis with resting-state functional magnetic resonance imaging (rsfMRI). We obtained rsfMRI data in 16 MCI patients with depressive symptoms and 18 nondepressed MCI patients (nD-MCI) using a 3 T scanner. Statistical analyses were performed to determine the regions in which ReHo differed between the two groups in specific frequency bands, slow-4 (0.027-0.073 Hz) and slow-5 (0.010-0.027 Hz), and typical bands (0.01-0.08 Hz). Correlation analyses were performed between the CReHo index of these regions and clinical variables to evaluate the relationship between CReHo and pathophysiological measures in the two groups. Our results showed that D-MCI patients exhibited significantly higher CReHo in the left Heschl's gyrus and left thalamus and lower CReHo in the left postcentral gyrus in the typical frequency band. In the slow-4 frequency band, D-MCI patients showed significantly higher CReHo in the left Heschl's gyrus and left thalamus. In the slow-5 frequency band, D-MCI patients exhibited significantly lower CReHo in the superior medial prefrontal gyrus. In addition, the results revealed that CReHo values in the left thalamus were positively correlated with Hamilton Depression Rating Scale (HAMD) scores in D-MCI patients. These results suggest that the sensorimotor network may be one of the main pathophysiological factors in D-MCI.

Altered Brain Structure and Functional Connectivity Associated with Pubertal Hormones in Girls with Precocious Puberty.

Pubertal hormones play an important role in brain and psychosocial development. However, the role of abnormal HPG axis states in altering brain function and structure remains unclear. The present study is aimed at determining whether there were significant differences in gray matter volume (GMV) and resting state (RS) functional connectivity (FC) patterns in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP). We further explored the correlation between these differences and serum pubertal hormone levels. To assess this, we recruited 29 idiopathic CPP girls and 38 age-matched PPP girls. A gonadotropin-releasing hormone (GnRH) stimulation test was performed, and pubertal hormone levels (including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin, and cortisol) were assessed. All subjects underwent multimodal magnetic resonance imaging of brain structure and function. Voxel-based morphometry (VBM) analysis was paired with seed-to-voxel whole-brain RS-FC analysis to calculate the GMV and RS-FC in idiopathic CPP and PPP girls. Correlation analyses were used to assess the effects of pubertal hormones on brain regions with structural and functional differences between the groups. We found that girls with CPP exhibited decreased GMV in the left insula and left fusiform gyrus, while connectivity between the left and right insula and the right middle frontal gyrus (MFG), as well as the left fusiform gyrus and right amygdala, was reduced in girls with CPP. Furthermore, the GMV of the left insula and peak FSH levels were negatively correlated while higher basal and peak E2 levels were associated with increased bilateral insula RS-FC. These findings suggest that premature activation of the HPG axis and pubertal hormone fluctuations alter brain structure and function involved in the cognitive and emotional process in early childhood. These findings provide vital insights into the early pathophysiology of idiopathic CPP.

Abnormal changes in functional connectivity between the amygdala and frontal regions are associated with depression in Alzheimer's disease.

PURPOSE: The aim of the present study was to investigate the functional connectivity (FC) of Alzheimer's disease patients with depression (D-AD) based on an amygdalar seed using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Twenty-one non-depressed AD (nD-AD) patients and 21 D-AD patients underwent rs-fMRI. The Hamilton Depression Rating Scale and Neuropsychiatric Inventory were used to evaluate the severity of depression. The amygdala was used as the seed for FC analysis. The FC differences between the two groups were evaluated by two-sample t tests, and the correlation of FC changes with depressive severity was analyzed by Pearson correlational analysis. RESULTS: Compared with the nD-AD patients, D-AD patients had increased FC values between the amygdala and orbitofrontal cortex and decreased FC values among the amygdala, medial prefrontal cortex, and inferior frontal gyrus. CONCLUSION: These data suggest that abnormal amygdala-prefrontal FC may be an important characteristic of AD patients with depression.

Altered Intrinsic Coupling between Functional Connectivity Density and Amplitude of Low-Frequency Fluctuation in Mild Cognitive Impairment with Depressive Symptoms.

Neuroimaging studies have demonstrated that major depressive disorder increases the risk of dementia in older individuals with mild cognitive impairment. We used resting-state functional magnetic resonance imaging to explore the intrinsic coupling patterns between the amplitude and synchronisation of low-frequency brain fluctuations using the amplitude of low-frequency fluctuations (ALFF) and the functional connectivity density (FCD) in 16 patients who had mild cognitive impairment with depressive symptoms (D-MCI) (mean age: 69.6 ± 6.2 years) and 18 patients with nondepressed mild cognitive impairment (nD-MCI) (mean age: 72.1 ± 9.7 years). Coupling was quantified as the correlations between the ALFF values and their associated FCDs. The results showed that the ALFF values in the D-MCI group were higher in the left medial prefrontal cortex (mPFC) and lower in the right precentral gyrus (preCG), and the FCD values were higher in the left medial temporal gyrus (MTG) than those in the nD-MCI group. Further, correlation analyses demonstrated that, in the D-MCI group, the mPFC was negatively correlated with the MTG. These findings may relate to the characteristics of mood disorders in patients with MCI, and they offer further insight into the neuropathophysiology of MCI with depressive symptoms.

Abnormal baseline brain activity in Alzheimer's disease patients with depression: a resting-state functional magnetic resonance imaging study.

PURPOSE: As one of the most common mental disorders and the most important precursor of suicide in Alzheimer's disease (AD), depression is associated with a decline in both well-being and daily functioning. At present, the diagnosis of AD patients with depression (D-AD) is largely dependent on clinical signs and symptoms, and the precise neural correlate underlying D-AD is still not fully understood. METHODS: The current study sought to investigate low-frequency oscillations at the voxel level in D-AD patients based on the amplitude of low-frequency fluctuations (ALFF) measured using resting-state functional magnetic resonance imaging. We examined 22 D-AD patients and 21 non-depressed AD (nD-AD) patients. RESULTS: The results revealed that D-AD patients exhibited increased ALFF values in the left caudate and thalamus and decreased ALFF values in the left middle temporal pole compared with nD-AD patients. CONCLUSION: These findings may provide further insight into the underlying neuropathophysiology of AD with depression.

Common 1H-MRS Characteristics in Patients With Alzheimer's Disease and Vascular Dementia Diagnosed With Kidney Essence Deficiency Syndrome: A Preliminary Study.

Context • Traditional Chinese medicine (TCM) indicates that both Alzheimer's disease (AD) and vascular dementia (VD) should be categorized as dementia and that they have a common etiology and pathogenesis under TCM classification of syndromes, such as with kidney essence deficiency syndrome (KEDS). The pathological location is mainly in the brain. However, it remains unclear whether AD and VD patients with KEDS exhibit a metabolic commonality in the same region of the brain. Objective • The study intended to investigate the metabolic characteristics of the brain using proton magnetic resonance spectroscopy (1H-MRS) in patients with AD and VD who had been diagnosed with KEDS. Design • The research team designed a pilot study, with the participants being allocated to 3 groups: (1) an AD group, (2) a VD group, and (3) a control group. All data analysis was carried out by a trained radiologist who was blinded to each participant's diagnosis. Setting • The study took place at the Tongde Hospital of Zhejiang Province (Zhejiang Sheng, China). Participants • Participants were patients at the Tongde Hospital with mild AD or VD who had been diagnosed with KEDS. The normal controls were patients' spouses or guardians with normal cognitive function. Outcome Measures • All participants underwent 1H-MRS. The N-acetyl aspartate (NAA)/myo-inositol (mI), NAA/creatine (Cr), choline (Cho)/Cr, and mI/Cr ratios were bilaterally measured in the posterior cingulate gyrus (PCG) and anterior cingulate gyrus (ACG) by the Syngo spectroscopy postprocessing package. Demographic characteristics and 1H-MRS data were assessed across the AD, VD, and normal control groups. Results • Thirteen patients with mild AD with KEDS, 15 patients with mild VD with KEDS, and 18 normal controls were recruited from May 2013 through May 2014. The AD and VD groups did not significantly differ in the NAA/mI, NAA/Cr, Cho/Cr, and mI/Cr ratios in either the PCG or the ACG, with the exception being the Cho/Cr ratio in the right ACG, for which the ratio of the AD group was significantly lower when compared with that of the VD group (P < .05). Conclusions • Mild AD and VD with KEDS showed similar patterns for the 1H-MRS on the cingulate cortex, providing evidence for a common pathogenesis for the KEDS that is associated with AD and VD, providing a modern biological basis for the philosophy of providing the same treatment for different diseases.