The increased effective connectivity from left middle occipital gyrus to right medial septum/diagonal bands in AD patients after donepezil intervention.

Introduction: Donepezil enhances the function of cholinergic nerves by increasing the concentration of acetylcholine, thereby improving clinical symptoms in patients with Alzheimer's disease (AD). However, the neural mechanisms of how donepezil modulates the effective connectivity (EC) network of cholinergic system in AD patients remain unknown. We speculated that the effective network of the cholinergic system changes in AD patients after donepezil intervention. Methods: We employed resting-state functional magnetic resonance imaging and Granger causality analysis approach to explore changes in the effective connectivity network of the basal forebrain in AD patients before and after donepezil intervention. This study included 32 participants, including 16 healthy controls (HCs) and 16 AD patients. In a 3T MRI scanner, the 16 AD patients were scanned before and after the donepezil intervention. To compare EC differences between the three groups of participants, ANOVA and post-hoc t-tests analysis were employed. Results: Compared to baseline status, AD patients after donepezil intervention had an increased EC from left middle occipital gyrus to right medial septum/diagonal bands. Compared to HCs, AD patients after donepezil intervention had an increased EC from right inferior frontal gyrus/orbit part to right medial septum/diagonal bands, AD patients before donepezil intervention had a reduced EC from right precuneus to right medial septum/diagonal bands. A significant positive correlation was found between EC values in right precuneus and Mini-Mental State Examination in pre-intervention AD patients (r = 0.7338, p = 0.0012). Discussion: Our study showed that effective connectivity of brain regions associated with the default mode network in the cholinergic pathway was enhanced after donepezil intervention. The results of this study will help us to better understand the neural mechanisms of donepezil intervention in AD and to find clinical targets for intervention.

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.

Abnormally decreased functional connectivity of the right nucleus basalis of Meynert in Alzheimer's disease patients with depression symptoms.

Dysfunction of the basal forebrain is the main pathological feature in patients with Alzheimer's disease (AD). The aim of this study was to explore whether depressive symptoms cause changes in the functional network of the basal forebrain in AD patients. We collected MRI data from depressed AD patients (n = 24), nondepressed AD patients (n = 14) and healthy controls (n = 20). Resting-state functional magnetic resonance imaging data and functional connectivity analysis were used to study the characteristics of the basal forebrain functional network of the three groups of participants. The functional connectivity differences among the three groups were compared using ANCOVA and post hoc analyses. Compared to healthy controls, depressed AD patients showed reduced functional connectivity between the right nucleus basalis of Meynert and the left supramarginal gyrus and the supplementary motor area. These results increase our understanding of the neural mechanism of depressive symptoms in AD patients.

Metabolic heterogeneity in cancer.

Cancer cells rewire their metabolism to survive during cancer progression. In this context, tumour metabolic heterogeneity arises and develops in response to diverse environmental factors. This metabolic heterogeneity contributes to cancer aggressiveness and impacts therapeutic opportunities. In recent years, technical advances allowed direct characterisation of metabolic heterogeneity in tumours. In addition to the metabolic heterogeneity observed in primary tumours, metabolic heterogeneity temporally evolves along with tumour progression. In this Review, we summarize the mechanisms of environment-induced metabolic heterogeneity. In addition, we discuss how cancer metabolism and the key metabolites and enzymes temporally and functionally evolve during the metastatic cascade and treatment.

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.

Altered functional connectivity of the locus coeruleus in Alzheimer's disease patients with depression symptoms.

Studies have shown that functional abnormalities in the locus coeruleus (LC) are strongly associated with depressive symptoms, but the pattern of LC functional connectivity in Alzheimer's disease patients with depressive symptoms (D-AD) remains unclear. The current study aimed to investigate the characteristics of LC functional connectivity (FC) in D-AD using resting-state functional magnetic resonance imaging (rsfMRI). We obtained rsfMRI data in 24 D-AD patients (aged 66-76 years), 14 non-depressive AD patients (nD-AD) (aged 69-79 years) and 20 normal controls (aged 67-74 years) using a 3 T scanner. We used the FC approach to investigate abnormalities in the LC brain network of D-AD patients. One-way ANCOVA and post-hoc two-sample t-tests were performed to compare the strength of functional connectivity from the LC among the three groups. Our results showed that, compared with normal controls, D-AD showed decreased left LC FC with the right caudate and left fusiform gyrus, whereas nD-AD showed decreased left LC FC with the right caudate, right middle frontal gyrus and left fusiform gyrus. Compared to nD-AD, D-AD showed increased left LC FC with right superior frontal gyrus and right precentral gyrus. These findings contribute to our understanding of the neural mechanisms of D-AD.

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.

Limiting mitochondrial plasticity by targeting DRP1 induces metabolic reprogramming and reduces breast cancer brain metastases.

Disseminated tumor cells with metabolic flexibility to utilize available nutrients in distal organs persist, but the precise mechanisms that facilitate metabolic adaptations remain unclear. Here we show fragmented mitochondrial puncta in latent brain metastatic (Lat) cells enable fatty acid oxidation (FAO) to sustain cellular bioenergetics and maintain redox homeostasis. Depleting the enriched dynamin-related protein 1 (DRP1) and limiting mitochondrial plasticity in Lat cells results in increased lipid droplet accumulation, impaired FAO and attenuated metastasis. Likewise, pharmacological inhibition of DRP1 using a small-molecule brain-permeable inhibitor attenuated metastatic burden in preclinical models. In agreement with these findings, increased phospho-DRP1 expression was observed in metachronous brain metastasis compared with patient-matched primary tumors. Overall, our findings reveal the pivotal role of mitochondrial plasticity in supporting the survival of Lat cells and highlight the therapeutic potential of targeting cellular plasticity programs in combination with tumor-specific alterations to prevent metastatic recurrences.

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.

Abnormally Increased Effective Connectivity of the Periaqueductal Gray in Migraine Without Aura Patients.

OBJECTIVES: The periaqueductal gray (PAG) is a key region in the descending pain modulatory system. We applied a Granger causality analysis-based approach to examine resting-state effective connectivity of the bilateral PAG regions in migraine patients without aura (MwoA). MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging data were obtained from 28 MwoA patients and 17 healthy controls. The effective connectivity of the bilateral PAG was characterized using a voxel-wised Granger causality analysis method. The resulting effective connectivity measurements were assessed for correlations with other clinical features. RESULTS: Compared with the healthy controls, MwoA patients showed increased effective connectivity from the left PAG to the left anterior cingulate gyrus and right postcentral gyrus. Meanwhile, MwoA patients also showed increased effective connectivity from the right PAG to the left precentral gyrus and increased effective connectivity from the left caudate and right middle occipital gyrus to the right PAG. DISCUSSION: Abnormally increased effective connectivity between PAG and limbic system, primary sensorimotor cortex, and visual cortex may play a key role in neuropathological features, perception, and affection of MwoA. The current study provides further insights into the complex scenario of MwoA mechanisms.

The Characteristics of Entorhinal Cortex Functional Connectivity in Alzheimer's Disease Patients with Depression.

BACKGROUND: Depression is one of the most common neuropsychiatric symptoms of Alzheimer's disease (AD) which decreases the life quality of both patients and caregivers. There are currently no effective drugs. It is therefore important to explore the pathogenesis of depression in AD patients. OBJECTIVE: The present study aimed to investigate the characteristics of the entorhinal cortex (EC) functional connectivity (FC) in the whole brain neural network of AD patients with depression (D-AD). METHODS: Twenty-four D-AD patients, 14 AD patients without depression (nD-AD), and 20 healthy controls underwent resting-state functional magnetic resonance imaging. We set the EC as the seed and used FC analysis. One-way analysis of variance was used to examine FC differences among the three groups. RESULTS: Using the left EC as the seed point, there were FC differences among the three groups in the left EC-inferior occipital gyrus. Using the right EC as the seed point, there were FC differences among the three groups in the right EC-middle frontal gyrus, -superior parietal gyrus, -superior medial frontal gyrus, and -precentral gyrus. Compared with the nD-AD group, the D-AD group had increased FC between the right EC and right postcentral gyrus. CONCLUSION: Asymmetry of FC in the EC and increased FC between the EC and right postcentral gyrus may be important in the pathogenesis of depression in AD.

Frequency-dependent alterations in regional homogeneity associated with puberty hormones in girls with central precocious puberty: A resting-state fMRI study.

OBJECTIVE: Central precocious puberty (CPP) patients are at significantly higher risk of emotional, mental, and behavioral disorders than those normal pubertal population. However, to date, the definite mechanism of how puberty hormones affect patients with CPP remains unclear. This regional homogeneity (ReHo) study aimed to explore the impact of premature hypothalamus-pituitary-gonadal (HPG) axis activation on brain function alteration in girls with CPP, meanwhile, to explore the relationship between gonadotropin and gonadal hormones levels, abnormal brain activity and cognitive function. METHODS: In this prospective study, a total of 85 girls who were suspected of having CPP were enrolled from the Child Healthcare Department of the Second Affiliated Hospital of Wenzhou Medical University Hospital from June 2018 to May 2021, including 41 CPP girls and 44 non-CPP girls. All participants collected the 0, 30, 60 min blood luteinizing hormone (LH), follicle-stimulating hormone (FSH), 0, 30 min estradiol (E2) and baseline cortisol (COR) and prolactin (PRL) concentrations after gonadotrophin-releasing hormone (GnRH) stimulating test. Resting-state magnetic resonance imaging (rs-MRI) scans were performed for all participants at 2 weeks before the GnRH stimulating test, voxel-wise ReHo was calculated in the standard frequency band (0.01-0.10 Hz), and in slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz). Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV) was also collected. Independent-sample t-test or Mann-Whitney U test was used to compare the differences between two groups. The correlation analysis among abnormal brain regions, serum hormone levels and WISC-IV scores were performed by Spearman or partial correlation analysis. RESULTS: Compared to the non-CPP group, the CPP group showed higher regional homogeneity (ReHo) values in the left inferior temporal gyrus (ITG.L), as well as lower ReHo values in left superior temporal gyrus (STG.L), left superior occipital gyrus (SOG.L) and the right middle gyrus (MTG.R) in slow4.in slow5 frequency band, CPP group demonstrated decreased ReHo values in bilateral orbital part of superior frontal gyrus and medial superior frontal gyrus. LIMITATION: Due to the cross-section design of this study, further research is needed to explore the relationships between age, premature activation HPG axis and brain function changes. CONCLUSION: Our findings demonstrate that premature HPG axis activation and alterations in puberty hormones, may lead to changes in brain activity and cognitive function. This rs-fMRI study may enhance our understanding of the neuroendocrine mechanisms of mood, behavior, and cognitive function alterations in patients with CPP.

A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling.

Metabolic rewiring is often considered an adaptive pressure limiting metastasis formation; however, some nutrients available at distant organs may inherently promote metastatic growth. We find that the lung and liver are lipid-rich environments. Moreover, we observe that pre-metastatic niche formation increases palmitate availability only in the lung, whereas a high-fat diet increases it in both organs. In line with this, targeting palmitate processing inhibits breast cancer-derived lung metastasis formation. Mechanistically, breast cancer cells use palmitate to synthesize acetyl-CoA in a carnitine palmitoyltransferase 1a-dependent manner. Concomitantly, lysine acetyltransferase 2a expression is promoted by palmitate, linking the available acetyl-CoA to the acetylation of the nuclear factor-kappaB subunit p65. Deletion of lysine acetyltransferase 2a or carnitine palmitoyltransferase 1a reduces metastasis formation in lean and high-fat diet mice, and lung and liver metastases from patients with breast cancer show coexpression of both proteins. In conclusion, palmitate-rich environments foster metastases growth by increasing p65 acetylation, resulting in a pro-metastatic nuclear factor-kappaB signaling.

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.

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.

Altered dynamic intrinsic brain activity of the default mode network in Alzheimer's disease: A resting-state fMRI study.

Objective: Static regional homogeneity (ReHo) based on the resting-state functional magnetic resonance imaging (rs-fMRI) has been used to study intrinsic brain activity (IBA) in Alzheimer's disease (AD). However, few studies have examined dynamic ReHo (dReHo) in AD. In this study, we used rs-fMRI and dReHo to investigate the alterations in dynamic IBA in patients with AD to uncover dynamic imaging markers of AD. Method: In total, 111 patients with AD, 29 patients with mild cognitive impairment (MCI), and 73 healthy controls (HCs) were recruited for this study ultimately. After the rs-fMRI scan, we calculated the dReHo values using the sliding window method. ANOVA and post hoc two-sample t-tests were used to detect the differences among the three groups. We used the mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate the cognitive function of the subjects. The associations between the MMSE score, MoCA score, and dReHo were assessed by the Pearson correlation analysis. Results: Significant dReHo variability in the right middle frontal gyrus (MFG) and right posterior cingulate gyrus (PCG) was detected in the three groups through ANOVA. In post hoc analysis, the AD group exhibited significantly greater dReHo variability in the right MFG than the MCI group. Compared with the HC group, the AD group exhibited significantly increased dReHo variability in the right PCG. Furthermore, dReHo variability in the right PCG was significantly negatively correlated with the MMSE and MoCA scores of patients with AD. Conclusion: Disrupted dynamic IBA in the DMN might be an important characteristic of AD and could be a potential biomarker for the diagnosis or prognosis of AD.

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.

Alterations of Regional Homogeneity in Parkinson's Disease: A Resting-State Functional Magnetic Resonance Imaging (fMRI) Study.

Objective The objective of this study is to investigate the regional homogeneity (ReHo) of spontaneous brain activities in Parkinson's disease (PD) patients. Methods In total, 20 PD patients and 20 matched normal controls (NCs) participants were recruited for this study. The regional homogeneity (ReHo) approach based on resting-state functional magnetic resonance imaging on a 3T MRI system was used to investigate local brain activity. We examined activity in two frequency bands, slow-4 (0.027-0.073 Hz) and slow-5 (0.010-0.027 Hz). Two-sample t-tests were used to determine the between-group differences in the ReHo data. Pearson correlation analysis was used to explore the relationships between the ReHo values and clinical indices in PD patients. Results Compared with NCs, PD patients showed decreased ReHo values in the right middle occipital gyrus, right cuneus, and left superior occipital gyrus, and increased ReHo values in the right middle frontal gyrus in slow-4. PD patients showed decreased ReHo values in the right calcarine, left calcarine, and right precentral gyrus compared with NCs in slow-5. Correlation analysis showed that disease duration was negatively correlated with ReHo values in the right precentral gyrus in PD patients. Conclusions These results indicate that several brain regions were altered in PD patients. The regions are associated with the visual network-related cortex, motor cortex, and default mode network. The findings provide new insights into the neuropathophysiology of PD.

Alterations in Spontaneous Neuronal Activity and Microvascular Density of the Optic Nerve Head in Active Thyroid-Associated Ophthalmopathy.

Purpose: To investigate changes in local spontaneous brain activity in patients with active thyroid-associated ophthalmopathy (TAO) and explore the relationship between such alterations and microvascular indices. Methods: Thirty-six active TAO patients with active phase and 39 healthy controls (HCs) were enrolled in this study. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI), neuropsychological tests, and ophthalmological examinations. The rs-fMRI-based fractional low-frequency fluctuation amplitude (fALFF) analysis methods were used to assess spontaneous brain activity in both groups. The structure (peripapillary retinal nerve fiber layer, pRNFL) and microvascular indices (the optic nerve head (ONH) whole image vessel density, ONH-wiVD, and peripapillary vessel density) were analyzed through optical coherence tomographic angiography imaging. The relationship between abnormal spontaneous brain activity and ophthalmological indices was analyzed using the Spearman's rank correlation analysis. Results: Compared with HCs, active TAO patients had increased fALFF in the right inferior temporal gyrus (R.ITG) and left posterior cingulate gyrus (L.PCC), but decreased fALFF in the right calcarine (R.CAL). The fALFF values in L.PCC were positively correlated with peripapillary vessel density, whereas fALFF values in R.CAL were negatively related to peripapillary vessel density. Conclusions: This study demonstrates that changes in spontaneous brain activity of active TAO are accompanied by peripapillary microvascular variations. These results provide insights into the pathophysiological mechanisms of active TAO. In addition, the combination of fALFF values and peripapillary vessel density may be served as important references for better clinical decision making.