Altered functional connectivity strength of primary visual cortex in subjects with thyroid-associated ophthalmopathy.

Our objective was to explore the disparities in the intrinsic functional connectivity (FC) patterns of primary visual cortex (V1) between patients with thyroid-associated ophthalmopathy (TAO) and healthy controls (HCs) utilizing resting-state functional MRI. Twenty-one patients with TAO (14 males and 7 females; mean age: 54.17 ±â€…4.83 years) and 21 well-matched HCs (14 males and 7 females; mean age: 55.17 ±â€…5.37 years) underwent functional MRI scans in the resting-state. We assessed modifications in the intrinsic FC patterns of the V1 in TAO patients using the FC method. Subsequently, the identified alterations in FC regions in the analysis were selected as classification features to distinguish TAO patients from HCs through the support vector machine (SVM) method. The results indicated that, in comparison to HCs, patients with TAO exhibited notably reduced FC values between the left V1 and the bilateral calcarine (CAL), lingual gyrus (LING) and superior occipital gyrus, as well as between the right V1 and the bilateral CAL/LING and the right cerebellum. Furthermore, the SVM classification model based on FC maps demonstrated effective performance in distinguishing TAO patients from HCs, achieving an accuracy of 61.9% using the FC of the left V1 and 64.29% using the FC of the right V1. Our study revealed that patients with TAO manifested disruptions in FC between the V1 and higher visual regions during rest. This might indicate that TAO patients could present with impaired top-down modulations, visual imagery and vision-motor function. These insights could be valuable in understanding the underlying neurobiological mechanisms of vision impairment in individuals with TAO.

A2AR antagonist treatment for multiple sclerosis: Current progress and future prospects.

Emerging evidence suggests that both selective and non-selective Adenosine A2A receptor (A2AR) antagonists could effectively protect mice from experimental autoimmune encephalomyelitis (EAE), which is the most commonly used animal model for multiple sclerosis (MS) research. Meanwhile, the recent FDA approval of Nourianz® (istradefylline) in 2019 as an add-on treatment to levodopa in Parkinson's disease (PD) with "OFF" episodes, along with its proven clinical safety, has prompted us to explore the potential of A2AR antagonists in treating multiple sclerosis (MS) through clinical trials. However, despite promising findings in experimental autoimmune encephalomyelitis (EAE), the complex and contradictory role of A2AR signaling in EAE pathology has raised concerns about the feasibility of using A2AR antagonists as a therapeutic approach for MS. This review addresses the potential effect of A2AR antagonists on EAE/MS in both the peripheral immune system (PIS) and the central nervous system (CNS). In brief, A2AR antagonists had a moderate effect on the proliferation and inflammatory response, while exhibiting a potent anti-inflammatory effect in the CNS through their impact on microglia, astrocytes, and the endothelial cells/epithelium of the blood-brain barrier. Consequently, A2AR signaling remains an essential immunomodulator in EAE/MS, suggesting that A2AR antagonists hold promise as a drug class for treating MS.

Targeted Knockdown of Genes in the Choroid Plexus.

The choroid plexus (ChP) serves as a critical gateway for immune cell infiltration into the central nervous system (CNS) under both physiological and pathological conditions. Recent research has shown that regulating ChP activity may offer protection against CNS disorders. However, studying the biological function of the ChP without affecting other brain regions is challenging due to its delicate structure. This study presents a novel method for gene knockdown in ChP tissue using adeno-associated viruses (AAVs) or cyclization recombination enzyme (Cre) recombinase protein consisting of TAT sequence (CRE-TAT). The results demonstrate that after injecting AAV or CRE-TAT into the lateral ventricle, the fluorescence was exclusively concentrated in the ChP. Using this approach, the study successfully knocked down the adenosine A2A receptor (A2AR) in the ChP using RNA interference (RNAi) or Cre/locus of X-overP1 (Cre/LoxP) systems, and showed that this knockdown could alleviate the pathology of experimental autoimmune encephalomyelitis (EAE). This technique may have important implications for future research on the ChP's role in CNS disorders.

Reduction of Interhemispheric Homotopic Connectivity in Cognitive and Visual Information Processing Pathways in Patients With Thyroid-Associated Ophthalmopathy.

Purpose: Thyroid-associated ophthalmopathy (TAO) is a vision threatening autoimmune and inflammatory orbital disease, and has been reported to be associated with a wide range of structural and functional abnormalities of bilateral hemispheres. However, whether the interhemisphere functional connectivity (FC) of TAO patients is altered still remain unclear. A new technique called voxel-mirrored homotopic connectivity (VMHC) combined with support vector machine (SVM) method was used in the present study to explore interhemispheric homotopic functional connectivity alterations in patients with TAO. Methods: A total of 21 TAO patients (14 males and 7 females) and 21 wellmatched healthy controls (HCs, 14 males and 7 females), respectively, underwent functional magnetic resonance imaging (fMRI) scanning in the resting state. We evaluated alterations in the resting state functional connectivity between hemispheres by applying VMHC method and then selected these abnormal brain regions as seed areas for subsequent study using FC method. Furthermore, the observed changes of regions in the VMHC analysis were chosen as classification features to differentiate patients with TAO from HCs through support vector machine (SVM) method. Results: The results showed that compared with HCs, TAO patients showed significantly lower VMHC values in the bilateral postcentral gyrus, lingual gyrus, calcarine, middle temporal gyrus, middle occipital gyrus and angular. Moreover, significantly decreased FC values were found between the right postcentral gyrus/lingual gyrus/calcarine and left lingual gyrus/cuneus/superior occipital gyrus, left postcentral gyrus/lingual gyrus/calcarine and right lingual gyrus/ middle temporal gyrus, right middle temporal gyrus and left cerebellum-8/lingual gyrus/middle occipital gyrus/supplementary motor area, left middle temporal gyrus and right middle occipital gyrus, right middle occipital gyrus/angular and left middle temporal pole (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). The SVM classification model achieved good performance in differentiating TAO patients from HCs (total accuracy: 73.81%; area under the curve: 0.79). Conclusion: The present study revealed that the altered interhemisphere interaction and integration of information involved in cognitive and visual information processing pathways including the postcentral gyrus, cuneus, cerebellum, angular, widespread visual cortex and temporal cortex in patients with TAO relative to HC group. VMHC variability had potential value for accurately and specifically distinguishing patients with TAO from HCs. The new findings may provide novel insights into the neurological mechanisms underlying visual and cognitive disorders in patients with TAO.

Local-to-Remote Brain Functional Connectivity in Patients with Thyroid-Associated Ophthalmopathy and Assessment of Its Predictive Value Using Machine Learning.

Purpose: To explore the alterations in both local and remote brain connectivity in patients with thyroid-associated ophthalmopathy (TAO) and to investigate whether the alterations of local neural function could be used to distinguish patients with TAO from healthy controls (HCs) using support vector machine (SVM) classifier. Materials and Methods: In total, 21 patients with TAO and 21 well-matched HCs were enrolled in our study and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We employed regional homogeneity (ReHo) algorithm to evaluate local neural function and selected significantly altered brain regions as seed areas for subsequent study of the remote functional connectivity (FC). Moreover, we chose the observed alterations in the ReHo analysis as classification features to differentiate patients with TAO from HCs through SVM classification method. Results: Compared with the HCs, TAO patients showed significantly lower ReHo values in the right middle occipital gyrus (MOG) and right angular (ANG). In contrast, TAO patients displayed higher ReHo values in the left hippocampus (Hipp). We further found TAO patients exhibited decreased FC between the left and right Hipp, right MOG and left cerebellum (CER), right ANG and left rectus, right superior temporal pole gyrus (PSTG) (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). The alterations in local neural function exhibited an accuracy of 78.57% and area under curve of 0.81 for distinguishing the patients from HCs. Conclusion: We mainly found the results that patients with TAO showed significantly dysfunctional local and remote brain functional connectivity in several brain regions associated with visual and cognitive functions. The ReHo variability has potential value in differentiating patients with TAO from HCs. These findings may provide novel insights into the neurological mechanisms underlying visual and cognitive disorders in patients with TAO.

Spontaneous brain activity alterations in thyroid-associated ophthalmopathy patients using amplitude of low-frequency fluctuation: A resting-state fMRI study.

OBJECTIVES: Previous studies demonstrated that thyroid-associated ophthalmopathy (TAO) patients were accompanied by cognitive decline. However, The exact neural mechanisms of cognitive decline in TAO patients remain unclear. Our study aimed to investigate the spontaneous brain activity alterations using amplitude of low-frequency fluctuation (ALFF) method and their relationships with clinical features in TAO patients. MATERIALS AND METHODS: In total, twenty-one patients with TAO (14 men and 7 women) and 21 healthy control (HC) subjects (14 men and 7 women) were enrolled in this study. The ALFF method was used to assess the spontaneous brain activity changes. Meanwhile, receiver operating characteristic (ROC) curve was used to distinguish TAO group and HCs group. And Pearson correlation was performed to calculate the relationship between the observed mean ALFF values of the altered regions in patients with TAO and their clinical features. RESULTS: Compared with the HCs, TAO patients had significantly lower ALFF values in the right superior occipital gyrus (SOG) and bilateral precuneus (preCUN). In contrast, TAO patients showed higher ALFF values in the left cerebellum (CER) and left insula (INS). CONCLUSION: our result highlighted that TAO patients showed altered intrinsic brain activities in the preCUN, left CER, left INS and right SOG, which might provide useful information for explaining neural mechanisms in patients with TAO.

Mapping Regional Homogeneity and Functional Connectivity of the Visual Cortex in Resting-State fMRI.

A combined regional homogeneity (ReHo) and functional connectivity (FC) method, a type of noninvasive functional magnetic resonance imaging (fMRI) method, has been used to evaluate synchronous neuronal activity changes in retinitis pigmentosa (RP). The purpose of this study is to describe our method for analysis of intra- and interregional synchronizations of changes in neuronal activity in RP patients. The advantages of the combined ReHo and FC method are that it is both noninvasive and sufficiently sensitive to investigate changes in cerebral synchronous neuronal activity changes in vivo. Here, 16 RP patients and 14 healthy controls closely matched in age, sex, and education underwent resting-state fMRI scans. Two sample t-tests were conducted to compare ReHo and FC across groups. Our results showed that visual network disconnection and reorganization of the retino-thalamocortical pathway and dorsal visual stream occurred in the RP patients. Here, we describe the details of this method, its use, and the impact of its key parameters in a step-by-step manner.

Altered Functional Connectivity Strength of Primary Visual Cortex in Subjects with Diabetic Retinopathy.

OBJECTIVE: The purpose of the study was to find the differences in intrinsic functional connectivity (FC) patterns of the primary visual area (V1) among diabetic retinopathy (DR), diabetes mellitus (DM), and healthy controls (HCs) applying resting-state functional magnetic resonance imaging (rs-fMRI). PATIENTS AND METHODS: Thirty-five subjects with DR (18 males and 17 females), 22 DM (10 males and 12 females) and 38 HCs (16 males and 22 females) matched for sex, age, and education underwent rs-fMRI scanning. Seed-based FC analysis was performed to find the alterations in the intrinsic FC patterns of V1 in DR compared with DM and HCs. RESULTS: The study found that DR patients had a significant lower FC between the bilateral calcarine (CAL)/left lingual gyrus (LING) (BA 17/18) and the left V1, and between the bilateral CAL/left LING (BA 17/18) and the right V1 compared with the HCs. Meanwhile, patients with DR exhibited higher FC strength between the left V1 and the bilateral Caudate/Olfactory/Orbital superior frontal gyrus (OSFG), and between the bilateral Caudate/Olfactory/OSFG (BA 3/4/6) and the right V1. Compared with DM group, patients with DR showed increased FC strength between the right CAL (BA 17/18) and the right V1. DM group exhibited lower FC strength between the left fusiform and the left V1, and between the bilateral CAL and the right V1 when compared with HCs. Moreover, DM group was observed to have higher FC strength between the left superior frontal gyrus and the left V1. CONCLUSION: Our findings indicated that DR patients exhibited FC disruptions between V1 and higher visual regions at rest, which may reflect the aberrant information communication in the V1 area of DR individuals. The findings offer important insights into the neuromechanism of vision disorder in DR patients.

Altered Functional Connectivity of the Primary Visual Cortex in Patients With Iridocyclitis and Assessment of Its Predictive Value Using Machine Learning.

Purpose: To explore the intrinsic functional connectivity (FC) alteration of the primary visual cortex (V1) between individuals with iridocyclitis and healthy controls (HCs) by the resting-state functional magnetic resonance imaging (fMRI) technique, and to investigate whether FC findings be used to differentiate patients with iridocyclitis from HCs. Methods: Twenty-six patients with iridocyclitis and twenty-eight well-matched HCs were recruited in our study and underwent resting-state fMRI examinations. The fMRI data were analyzed by Statistical Parametric Mapping (SPM12), Data Processing and Analysis for Brain Imaging (DPABI), and Resting State fMRI Data Analysis Toolkit (REST) software. Differences in FC signal values of the V1 between the individuals with iridocyclitis and HCs were compared using independent two-sample t-tests. Significant differences in FC between two groups were chosen as classification features for distinguishing individuals with iridocyclitis from HCs using a support vector machine (SVM) classifier that involved machine learning. Classifier performance was evaluated using permutation test analysis. Results: Compared with HCs, patients with iridocyclitis displayed significantly increased FC between the left V1 and left cerebellum crus1, left cerebellum 10, bilateral inferior temporal gyrus, right hippocampus, and left superior occipital gyrus. Moreover, patients with iridocyclitis displayed significantly lower FC between the left V1 and both the bilateral calcarine and bilateral postcentral gyrus. Patients with iridocyclitis also exhibited significantly higher FC values between the right V1 and left cerebellum crus1, bilateral thalamus, and left middle temporal gyrus; while they displayed significantly lower FC between the right V1 and both the bilateral calcarine and bilateral postcentral gyrus (voxel-level P<0.01, Gaussian random field correction, cluster-level P<0.05). Our results showed that 63.46% of the participants were correctly classified using the leave-one-out cross-validation technique with an SVM classifier based on the FC of the left V1; and 67.31% of the participants were correctly classified based on the FC of the right V1 (P<0.001, non-parametric permutation test). Conclusion: Patients with iridocyclitis displayed significantly disturbed FC between the V1 and various brain regions, including vision-related, somatosensory, and cognition-related regions. The FC variability could distinguish patients with iridocyclitis from HCs with substantial accuracy. These findings may aid in identifying the potential neurological mechanisms of impaired visual function in individuals with iridocyclitis.

Assessment of spontaneous brain activity patterns in patients with iridocyclitis: a resting-state study.

Several studies demonstrated that patients with iridocyclitis were associated with vision loss and cognitive decline, whereas alterations in spontaneous brain activity occur in iridocyclitis patients remains unknown. The study aimed to explore spontaneous brain activity changes in iridocyclitis patients. Twenty-six patients with iridocyclitis and 26 healthy controls were finally included in our study. Resting-state MRI (rs-MRI) scan was conducted on both groups and the whole brain amplitude of low-frequency fluctuations (ALFFs) value was collected to assess differences in spontaneous brain activity. A receiver operating characteristic (ROC) curve was analyzed to distinguish between the fMRI data of patients with iridocyclitis and healthy controls. Patients with iridocyclitis showed significantly lower ALFF values in the right inferior parietal lobule, right calcarine, right superior temporal gyrus and right precentral gyrus compared to healthy controls and significantly higher ALFF values in the left superior frontal gyrus (P < 0.01, false discovery rate correction). The ROC curve analysis of different brain areas showed that the accuracies of ALFF value specificity between the iridocyclitis and healthy controls of the area under the curve were over 0.8. Our study highlighted an altered spontaneous activity in multiple brain regions, including the visual cortex, default-mode network, auditory area and sensorimotor areas in iridocyclitis. This may provide valuable information about underlying pathogenic mechanisms of iridocyclitis. These findings also indicate that rs-fMRI serves as a potential tool in the disease detection and evaluation of neurologic impairment in iridocyclitis.

Disrupted Neural Activity in Individuals With Iridocyclitis Using Regional Homogeneity: A Resting-State Functional Magnetic Resonance Imaging Study.

Objective: This study used the regional homogeneity (ReHo) technique to explore whether spontaneous brain activity is altered in patients with iridocyclitis. Methods: Twenty-six patients with iridocyclitis (14 men and 12 women) and 26 healthy volunteers (15 men and 11 women) matched for sex and age were enrolled in this study. The ReHo technique was used to comprehensively assess changes in whole-brain synchronous neuronal activity. The diagnostic ability of the ReHo method was evaluated by means of receive operating characteristic (ROC) curve analysis. Moreover, associations of average ReHo values in different brain areas and clinical characteristics were analyzed using correlation analysis. Result: Compared with healthy volunteers, reduced ReHo values were observed in patients with iridocyclitis in the following brain regions: the right inferior occipital gyrus, bilateral calcarine, right middle temporal gyrus, right postcentral gyrus, left superior occipital gyrus, and left precuneus. In contrast, ReHo values were significantly enhanced in the right cerebellum, left putamen, left supplementary motor area, and left inferior frontal gyrus in patients with iridocyclitis, compared with healthy volunteers (false discovery rate correction, P < 0.05). Conclusion: Patients with iridocyclitis exhibited disturbed synchronous neural activities in specific brain areas, including the visual, motor, and somatosensory regions, as well as the default mode network. These findings offer a novel image-guided research strategy that might aid in exploration of neuropathological or compensatory mechanisms in patients with iridocyclitis.

Dynamic Changes of Amplitude of Low-Frequency Fluctuations in Patients With Diabetic Retinopathy.

Background: Growing evidence demonstrate that diabetic retinopathy (DR) patients have a high risk of cognitive decline and exhibit abnormal brain activity. However, neuroimaging studies thus far have focused on static cerebral activity changes in DR patients. The characteristics of dynamic cerebral activity in patients with DR are poorly understood. Purpose: The purpose of the study was to investigate the dynamic cerebral activity changes in patients with DR using the dynamic amplitude of low-frequency fluctuation (dALFF) method. Materials and methods: Thirty-four DR patients (18 men and 16 women) and 38 healthy controls (HCs) (18 males and 20 females) closely matched in age, sex, and education were enrolled in this study. The dALFF method was used to investigate dynamic intrinsic brain activity differences between the DR and HC groups. Results: Compared with HCs, DR patients exhibited increased dALFF variability in the right brainstem, left cerebellum_8, left cerebellum_9, and left parahippocampal gyrus. In contrast, DR patients exhibited decreased dALFF variability in the left middle occipital gyrus and right middle occipital gyrus. Conclusion: Our study highlighted that DR patients showed abnormal variability of dALFF in the visual cortices, cerebellum, and parahippocampal gyrus. These findings suggest impaired visual and motor and memory function in DR individuals. Thus, abnormal dynamic spontaneous brain activity might be involved in the pathophysiology of DR.

Abnormal intrinsic functional network hubs in diabetic retinopathy patients.

BACKGROUND: However, whether the whole-brain functional network hub changes occur in diabetic retinopathy patients remains unknown. PURPOSE: The purpose of the study was to investigate the function network centrality and connectivity changes in diabetic retinopathy patients using the voxel-wise degree centrality method. MATERIALS AND METHODS: Thirty-four diabetic retinopathy patients (18 male and 16 female) and 38 healthy controls (18 male and 20 female) closely matched in age, sex, and education were enrolled in the study. Graph theory-based network analysis was performed to investigate the degree centrality between two groups. RESULTS: Compared with healthy controls, diabetic retinopathy patients had significantly higher degree centrality values in the pons and bilateral caudate and had significantly lower degree centrality values in the left lingual and right lingual, and right angular/middle occipital gyrus (MOG). Moreover, diabetic retinopathy patients exhibited increased functional connectivity between the bilateral lingual and right cerebellum lobe and right fusiform/bilateral caudate and increased functional connectivity between the right angular/MOG and bilateral anterior cingulum and right cuneus/bilateral precuneus and increased functional connectivity between the bilateral caudate and right lingual and right superior occipital gyrus. In contrast, diabetic retinopathy patients showed decreased functional connectivity between bilateral lingual and left lingual and right lingual and left superior occipital gyrus and decreased functional connectivity between the angular/MOG and right inferior occipital gyrus/right fusiform and left MOG/inferior occipital gyrus and decreased functional connectivity between the bilateral caudate and bilateral cerebellum crus1. CONCLUSION: Our results highlight that reorganization of the hierarchy of the cortical connectivity network related to visual network.

Altered resting cerebral blood flow specific to patients with diabetic retinopathy revealed by arterial spin labeling perfusion magnetic resonance imaging.

BACKGROUND: Previous neuroimaging studies have shown that patients with diabetic retinopathy (DR) were accompanied by abnormalities in cerebral functional and structural architecture, whereas the resting cerebral blood flow (CBF) alterations in patients with DR are not well understood. PURPOSE: To explore CBF alterations in patients with DR using pseudo-continuous arterial spin labeling (pCASL) imaging. MATERIAL AND METHODS: Thirty-one individuals with DR (15 men, 16 women; mean age = 53.38 ± 9.12 years) and 33 healthy controls (HC) (12 men, 21 women; mean age = 51.61 ± 9.84 years) closely matched for age, sex, and education, underwent pCASL imaging scans. Two-sample T test was conducted to compare different CBF values between two groups. RESULTS: Patients with DR exhibited significantly increased CBF values in the left middle temporal gyrus (Brodmann's area, BA 22) and the bilateral supplementary motor area (BA3) and decreased CBF values in the bilateral calcarine (BA17,18) and bilateral caudate relative to HC group (two-tailed, voxel level at P < 0.01, Gaussian random field (GRF), cluster level at P < 0.05). Moreover, the HbA1c (%) level showed a positive correlation with CBF values in the bilateral caudate (r = 0.473, P = 0.007) in patients with DR. CONCLUSION: Our results highlighted that patients with DR had abnormal CBF values in the visual cortices, caudate, middle temporal gyrus, and supplementary motor area, which might reflect vision and sensorimotor and cognition dysfunction in patients with DR. These findings might help us to understanding the neural mechanism of patients with DR.

Altered Intrinsic Brain Activities in Patients with Diabetic Retinopathy Using Amplitude of Low-frequency Fluctuation: A Resting-state fMRI Study.

OBJECTIVE: The current study aimed to apply the amplitude of low-frequency fluctuation (ALFF) method for investigating the spontaneous brain activity alterations and their relationships with clinical features in patients with diabetic retinopathy (DR). PATIENTS AND METHODS: In total, 35 patients with DR (18 males and 17 females) and 38 healthy control (HC) subjects (18 males and 20 females) were enrolled in this study. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning, respectively. The ALFF method was used to assess the spontaneous brain activity, while the mean ALFF signal values of patients with DR and HCs were classified by the receiver operating characteristic (ROC) curve. Correlation analysis was performed to calculate the relationship between the observed mean ALFF values of the altered regions in patients with DR and their clinical features. RESULTS: Compared with the HCs, patients with DR had significantly lower ALFF values in the left and right middle occipital gyrus (MOG). In contrast, patients with DR showed higher ALFF values in the left cerebellum (CER), left inferior temporal gyrus (ITG) and left hippocampus (Hipp). However, no relationship was observed between the mean ALFF signal values of the altered regions and clinical manifestations in the patients with DR. CONCLUSION: We mainly found that patients with DR showed abnormal intrinsic brain activities in the left and right MOG, left CER, left ITG and left Hipp, which might provide useful information for explaining neural mechanisms in patients with DR.

Altered Temporal Dynamic Intrinsic Brain Activity in Late Blindness.

Previous neuroimaging studies demonstrated that visual deprivation triggers significant crossmodal plasticity in the functional and structural architecture of the brain. However, prior neuroimaging studies focused on the static brain activity in blindness. It remains unknown whether alterations of dynamic intrinsic brain activity occur in late blindness (LB). This study investigated dynamic intrinsic brain activity changes in individuals with late blindness by assessing the dynamic amplitude of low-frequency fluctuations (dALFFs) using sliding-window analyses. Forty-one cases of late blindness (LB) (29 males and 12 females, mean age: 39.70 ± 12.66 years) and 48 sighted controls (SCs) (17 males and 31 females, mean age: 43.23 ± 13.40 years) closely matched in age, sex, and education level were enrolled in this study. The dALFF with sliding-window analyses was used to compare the difference in dynamic intrinsic brain activity between the two groups. Compared with SCs, individuals with LB exhibited significantly lower dALFF values in the bilateral lingual gyrus (LING)/calcarine (CAL) and left thalamus (THA). LB cases also showed considerably decreased dFC values between the bilateral LING/CAL and the left middle frontal gyrus (MFG) and between the left THA and the right LING/cerebelum_6 (CER) (two-tailed, voxel-level P < 0.01, Gaussian random field (GRF) correction, cluster-level P < 0.05). Our study demonstrated that LB individuals showed lower-temporal variability of dALFF in the visual cortices and thalamus, suggesting lower flexibility of visual thalamocortical activity, which might reflect impaired visual processing in LB individuals. These findings indicate that abnormal dynamic intrinsic brain activity might be involved in the neurophysiological mechanisms of LB.

Large-Scale Neuronal Network Dysfunction in Diabetic Retinopathy.

Diabetic retinopathy (DR) patients are at an increased risk of cognitive decline and dementia. There is accumulating evidence that specific functional and structural architecture changes in the brain are related to cognitive impairment in DR patients. However, little is known regarding whether the functional architecture of resting-state networks (RSNs) changes in DR patients. The purpose of this study was to investigate the intranetwork functional connectivity (FC) and functional network connectivity (FNC) of RSN changes in DR patients using independent component analysis (ICA). Thirty-four DR patients (18 men and 16 women; mean age, 53.53 ± 8.67 years) and 38 nondiabetic healthy controls (HCs) (15 men and 23 women; mean age, 48.63 ± 11.83 years), closely matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. ICA was applied to extract the nine RSNs. Then, two-sample t-tests were conducted to investigate different intranetwork FCs within nine RSNs between the two groups. The FNC toolbox was used to assess interactions among RSNs. Pearson correlation analysis was conducted to explore the relationship between intranetwork FCs and clinical variables in the DR group. A receiver operating characteristic (ROC) curve was conducted to assess the ability of the intranetwork FCs of RSNs in discriminating between the two groups. Compared to the HC group, DR patients showed significant decreased intranetwork FCs within the basal ganglia network (BGN), visual network (VN), ventral default mode network (vDMN), right executive control network (rECN), salience network (SN), left executive control network (lECN), auditory network (AN), and dorsal default mode network (dDMN). In addition, FNC analysis showed increased VN-BGN, VN-vDMN, VN-dDMN, vDMN-lECN, SN-BGN, lECN-dDMN, and AN-BGN FNCs in the DR group, relative to the HC group. Furthermore, altered intranetwork FCs of RSNs were significantly correlated with the glycosylated hemoglobin (HbA1c) level in DR patients. A ROC curve showed that these specific intranetwork FCs of RSNs discriminated between the two groups with a high degree of sensitivity and specificity. Our study highlighted that DR patients had widespread deficits in both low-level perceptual and higher-order cognitive networks. Our results offer important insights into the neural mechanisms of visual loss and cognitive decline in DR patients.

Assessment of cerebral low-frequency oscillations in patients with retinal vein occlusion: a preliminary functional MRI study.

BACKGROUND: There is increasing evidence that patients with retinal vein occlusion exhibit cerebral vascular changes and are at an increased risk of stroke. However, it remains unknown whether patients with retinal vein occlusion exhibit changes in intrinsic brain activity. PURPOSE: This study investigated intrinsic brain activity changes in patients with retinal vein occlusion by assessing the amplitude of low-frequency fluctuations. MATERIAL AND METHODS: Forty-five patients with retinal vein occlusion (22 men, 23 women, mean age 56.55 ± 6.97 years) and 43 healthy controls (13 men, 30 women; mean age 53.53 ± 8.19 years) closely matched in age, sex, and education level underwent resting-state MRI scans. The amplitude of low-frequency fluctuation method was used to compare intrinsic brain activity between the two groups. RESULTS: Compared with healthy controls, patients with retinal vein occlusion exhibited significantly lower amplitude of low-frequency fluctuation values in the left middle occipital gyrus, right middle occipital gyrus, and right calcarine. However, patients with retinal vein occlusion showed significantly higher amplitude of low-frequency fluctuations in the bilateral cerebellum 6, right hippocampus, left insula, and left fusiform (voxel-level P < 0.01, Gaussian random field correction, cluster-level P < 0.05). CONCLUSION: Our results demonstrated that patients with retinal vein occlusion showed abnormal spontaneous neural activities in the visual cortices, cerebellum, and Papez circuit, which might indicate impaired vision, cognition, and emotional function in patients with retinal vein occlusion. These findings offer important insights into the neural mechanism of retinal vein occlusion.

Disrupted topological organization of human brain connectome in diabetic retinopathy patients.

OBJECTIVE: There is increasing neuroimaging evidence that type 2 diabetes patients with retinal microvascular complications show abnormal brain functional and structural architecture and are at an increased risk of cognitive decline and dementia. However, changes in the topological properties of the functional brain connectome in diabetic retinopathy (DR) patients remain unknown. The aim of this study was to explore the topological organization of the brain connectome in DR patients using graph theory approaches. METHODS: Thirty-five DR patients (18 males and 17 females) and 38 healthy controls (HCs) (18 males and 20 females), matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. Graph theory analysis was performed to investigate the topological properties of brain functional connectome at both global and nodal levels. RESULTS: Both DR and HC groups showed high-efficiency small-world network in their brain functional networks. Notably, the DR group showed reduction in the clustering coefficient (P=0.0572) and local efficiency (P=0.0151). Furthermore, the DR group showed reduced nodal centralities in the default-mode network (DMN) and increased nodal centralities in the visual network (VN) (P<0.01, Bonferroni-corrected). The DR group also showed abnormal functional connections among the VN, DMN, salience network (SN), and sensorimotor network (SMN). Altered network metrics and nodal centralities were significantly correlated with visual acuity and fasting blood glucose level in DR patients. CONCLUSION: DR patients showed abnormal topological organization of the human brain connectome. Specifically, the DR group showed reduction in the clustering coefficient and local efficiency, relative to HC group. Abnormal nodal centralities and functional disconnections were mainly located in the DMN, VN, SN, and SMN in DR patients. Furthermore, the disrupted topological attributes showed correlations with clinical variables. These findings offer important insight into the neural mechanism of visual loss and cognitive deficits in DR patients.