Gaussian Random Field Correction Research Articles

Aberrant functional connectivity associated with drug response in patients with newly diagnosed epilepsy.

To analyze the local functional activity and connectivity features of the brain associated with drug response inpatients newly diagnosed with epilepsy (NDE) who are naïve to anti-seizure medication (ASM). Recruited patients, underwent functional magnetic resonance imaging at baseline, and were assigned to the well-controlled (WC, n = 28) or uncontrolled (UC, n = 11) groups based on their response to ASM. Healthy participants were included in the control group (HC, n = 29). The amplitudes of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were used to measure local functional activity, and voxel-wise degree centrality (DC) and seed-based functional connectivity (FC) were used to evaluate the connecting intensity of the brain areas. Compared to the HC and WC groups, the UC group had higher ALFF values in the left posterior central gyrus (PoCG.L) and left inferior temporal gyrus (ITG.L) and higher DC in the bilateral PoCG (Gaussian random field correction, voxel-level P < 0.001, and cluster-level P < 0.05). Both PoCG and ITG.L in the UC group showed stronger FC with multiple brain regions, mainly located in the occipital and temporal lobes, compared to the HC or WC group, while the WC group showed decreased or similar FC compared to the HC group. Excessive enhancement of brain functional activity or connecting intensity in ASM-naïve patients with NDE may be associated with a higher risk of poor drug response.

Altered brain texture features in end-stage renal disease patients: a voxel-based 3D brain texture analysis study.

Cognitive impairment in patients with end-stage renal disease (ESRD) is associated with brain structural damage. However, no prior studies have investigated the relationship between brain texture features and the cognitive function in ESRD patients. This study aimed to investigate changes in brain texture features in ESRD patients and their relationships with cognitive function using voxel-based 3D brain texture analysis (TA), and further predict individual cognitive-related brain damage in ESRD patients. Forty-seven ESRD patients and 45 control subjects underwent whole-brain high-resolution 3D T1-weighted imaging scans and neuropsychological assessments. The voxel-based 3D brain TA was performed to examine inter-group differences in brain texture features. Additionally, within the ESRD group, the relationships of altered texture features with neuropsychological function and clinical indicators were analyzed. Finally, receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of brain texture features for cognitive-related brain damage in ESRD patients. Compared to the control group, the ESRD group exhibited altered texture features in several brain regions, including the insula, temporal lobe, striatum, cerebellum, and fusiform gyrus (p < 0.05, Gaussian random-field correction). Some of these altered texture features were associated with scores from the Digit Symbol Substitution Test and the Trail Making Test Parts A (p < 0.05), and showed significant correlations with serum creatinine and calcium levels within the ESRD group (p < 0.05). Notably, ROC curve analysis revealed that the texture features in the right insula and left middle temporal gyrus could accurately predict cognitive-related brain damage in ESRD patients, with the area under the curve values exceeding 0.90. Aberrant brain texture features may be involved in the neuropathological mechanism of cognitive decline, and have high accuracy in predicting cognitive-related brain damage in ESRD patients. TA offers a novel neuroimaging marker to explore the neuropathological mechanisms of cognitive impairment in ESRD patients, and may be a valuable tool to predict cognitive decline.

Cerebral hypometabolism mediates the effect of stroke volume on cognitive impairment in heart failure patients.

The present study aimed to phenotype the cerebral structural and glucose metabolic alterations in patients with heart failure (HF) using simultaneous positron emission tomography (PET)/magnetic resonance (MR) and to investigate their relationship to cardiac biomarkers and cognitive performance. Forty-two HF patients caused by ischaemic heart disease (mean age 67.2±10.4, 32 males) and 32 age- and sex-matched healthy volunteers (mean age 61.3±4.8, 18 males) were included in this study. Participants underwent simultaneous cerebral fluorine-18 (18 F) fluorodeoxyglucose PET/MR followed by cardiac MR scan, and neuropsychological scores were obtained to assess cognitive performance. The grey matter volume (GMV) and standardized uptake value ratio (SUVR) were calculated to examine cerebral structural and metabolic alterations. Cardiac biomarkers included cardiac MR parameters and cardiac serum laboratory tests. Mediation analysis was performed to explore the associations among cerebral alterations, cardiac biomarkers, and cognitive performance. HF patients demonstrated notable cognitive impairment compared with normal controls (P<0.001). Furthermore, HF patients exhibited regional brain hypometabolism in the bilateral calcarine cortex, caudate nucleus, thalamus, hippocampus, precuneus, posterior cingulate cortex, lingual and olfactory cortex, and GMV reduction in bilateral thalamus and hippocampus (cluster level at P<0.05, Gaussian random field correction). The SUVR of the hypometabolic brain regions was correlated with the Montreal Cognitive Assessment (MoCA) scores (r=0.55, P = 0.038) and cardiac stroke volume (r=0.49, P=0.002). Cerebral hypometabolism played a key role in the relationship between the decreased stroke volume and MoCA scores, with a mediation effect of 33.2%. HF patients suffered cerebral metabolic and structural alterations in regions associated with cognition. The observed correlation between cardiac stroke volume and cognitive impairment underscored the potential influence of cerebral hypometabolism, suggesting that cerebral hypometabolism due to chronic systemic hypoperfusion may significantly contribute to cognitive impairment in HF patients.

BOLD frequency-dependent alterations in resting-state functional connectivity by pallidal deep brain stimulation in patients with Parkinson's disease.

Functional MRI (fMRI) has been used to investigate the therapeutic mechanisms underlying deep brain stimulation (DBS) for Parkinson's disease (PD). However, the alterations in stimulation site-seeded functional connectivity induced by DBS at the internal globus pallidus (GPi) remain unclear. Furthermore, whether DBS-modulated functional connectivity is differentially affected within particular frequency bands remains unknown. The present study aimed to reveal the alterations in stimulation site-seeded functional connectivity induced by GPi-DBS and to examine whether there exists a frequency band effect in blood oxygen level-dependent (BOLD) signals related to DBS. Patients with PD receiving GPi-DBS (n = 28) were recruited for resting-state fMRI with DBS on and DBS off under a 1.5-T MR scanner. Age- and sex-matched healthy controls (n = 16) and DBS-naïve PD patients (n = 24) also received fMRI scanning. The alterations in stimulation site-seeded functional connectivity in the stimulation-on state versus stimulation-off state, as well as the relationship between alterations in connectivity and improvement in motor function induced by GPi-DBS, were examined. Furthermore, the modulatory effect of GPi-DBS on the BOLD signals within the 4 frequency subbands (slow-2 to slow-5) was investigated. Finally, the functional connectivity of the motor-related network, consisting of multiple cortical and subcortical regions, was also examined among the groups. In this study, p < 0.05 with Gaussian random field correction indicates statistical significance. Functional connectivity seeding from the stimulation site (i.e., the volume of tissue activated [VTA]) increased in the cortical sensorimotor areas and decreased in the prefrontal regions with GPi-DBS. Alterations in connectivity between the VTA and the cortical motor areas were correlated with motor improvement by pallidal stimulation. The alterations in connectivity were dissociable between the frequency subbands in the occipital and cerebellar areas. The motor network analysis indicated decreased connectivity among most cortical and subcortical regions but increased connectivity between the motor thalamus and the cortical motor area in patients with GPi-DBS compared with those in DBS-naïve patients. The DBS-induced decrease in several cortical-subcortical connectivities within the slow-5 band correlated with motor improvement with GPi-DBS. These findings indicate that the alterations in functional connectivity from the stimulation site to the cortical motor areas, as well as multiple connectivities among the motor-related network, were associated with the efficacy of GPi-DBS for PD. Furthermore, the changing pattern of functional connectivity within the 4 BOLD frequency subbands is partially dissociable.

Aberrant spontaneous brain activity in patients with thyroid-associated ophthalmopathy with and without optic neuropathy: a resting-state functional MRI study.

To investigate the brain functional alterations in dysthyroid optic neuropathy (DON) by evaluating spontaneous neural activity, using functional magnetic resonance imaging (fMRI) with regional homogeneity (ReHo), and its relationship with ophthalmologic performance. Forty-seven patients with thyroid-associated ophthalmopathy (TAO; 20 with DON, 27 with non-DON) and 33 age-, sex-, and education-matched healthy controls (HCs) underwent fMRI. ReHo values were compared using one-way analysis of variance (ANOVA) with post hoc pairwise comparisons (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). Correlations between ReHo values and ophthalmological metrics were assessed for DONs, with Bonferroni correction for multiple comparisons (p < 0.004). ROC curves were applied to evaluate the diagnostic performance of ReHo metrics. ReHo values were significantly lower in the left insula and right superior temporal gyrus, and higher in the left posterior cingulate cortex (LPCC), of DON than of non-DON patients. ReHo values were also significantly lower in the right middle temporal, left insula, and left precentral gyrus in DON than in HCs. Meanwhile, ReHo values were higher in LPCC in non-DON than in HCs. ReHo values correlated with ophthalmic examinations to varying degrees in DON. For distinguishing DON, the ReHo values in LPCC showed optimal individually (AUC = 0.843), the combination of the ReHo in both the left insula and LPCC performed better (AUC = 0.915). Spontaneous brain activity differed between TAO with and without DON, which may reflect the underlying pathological mechanism of DON. The ReHo index can be considered a diagnostic biomarker. Spontaneous brain activity in DON differed from that in TAO without DON, which may reflect the underlying pathological mechanism of DON. The ReHo index can be considered a diagnostic biomarker for early detection of DON. • Dysthyroid optic neuropathy (DON) affects brain activity, which contributes in the understanding of its visual dysfunction. • Regional homogeneity values differ between thyroid-associated ophthalmopathy with and without DON in various brain regions. • Regional homogeneity values can be used as a biomarker in the differential diagnosis of DON.

Distinct resting-state functional connectivity patterns of Anterior Insula affected by smoking in mild cognitive impairment

Smoking is a modifiable risk factor for Alzheimer’s disease (AD). The insula plays a vital role in both smoking and cognition. However, the smoking effects on insula-related networks in cognitively normal controls (CN) and mild cognitive impairment (MCI) patients remain unknown. We identified 129 CN (85 non-smokers and 44 smokers) and 83 MCI (54 non-smokers and 29 smokers). Each underwent neuropsychological assessment and MRI (structural and resting-state functional). Seed-based functional analyses in the anterior and posterior insula were performed to calculate the functional connectivity (FC) with voxels in the whole brain. Mixed-effect analyses were performed to explore the interactive effects on smoking and cognitive status. Associations between FC and neuropsychological scales were assessed. Mixed-effect analyses revealed the FC differences between the right anterior insula (RAI) with the left middle temporal gyrus (LMTG) and that with the right inferior parietal lobule (RIPL) (p < 0.01, cluster level < 0.05, two-tailed, gaussian random field correction). The FC of RAI in both LMTG and RIPL sees a significant decrease in MCI smokers (p < 0.01). Smoking affects insula FC differently between MCI and CN, and could decrease the insula FC in MCI patients. Our study provides evidence of neural mechanisms between smoking and AD.

Functional connectivity alterations in reward-related circuits associated with non-suicidal self-injury behaviors in drug-naïve adolescents with depression

Non-suicidal self-injury (NSSI) behaviors are a major public health concern among adolescents with depression. Such behaviors may be associated with the reward system. However, the underlying mechanism in patients with depression and NSSI still remains unclear. A total of 56 drug-naïve adolescents with depression, including 23 patients with NSSI (the NSSI group) and 33 patients without NSSI (the nNSSI group), and 25 healthy controls (HCs) were recruited in this study. Seed-based functional connectivity (FC) was used to explore the NSSI-related FC alterations in the reward circuit. Correlation analysis was conducted between the altered FCs and clinical data. Compared with the nNSSI group, the NSSI group showed greater FC between left nucleus accumbens (NAcc) and right lingual gyrus and between right putamen accumbens and right angular gyrus (ANG). The NSSI group also had declined FC between right NAcc and left inferior cerebellum, between left cingulate gyrus (CG) and right ANG, between left CG and left middle temporal gyrus (MTG), and between right CG and bilateral MTG (voxel-wise p < 0.01, cluster-wise p < 0.05, Gaussian random field correction). The FC between right NAcc and left inferior cerebellum was found positively correlated with the score of addictive features of NSSI (r = 0.427, p = 0.042). Our findings indicated that the regions in the reward circuit with NSSI-related FC alterations included bilateral NAcc, right putamen and bilateral CG, which may provide new evidence on the neural mechanisms of NSSI behaviors in adolescents with depression.

Association Between MRI-Assessed Patterns of Connectome Gradient and Gene-Expression Profiles in Two Independent Patient Cohorts With Hepatitis B Virus-Related Cirrhosis.

Patients with hepatitis B virus-related cirrhosis (HBV-RC) exhibit progressive neurologic dysfunction from primary sensorimotor to high-order cognition, as their disease advances. However, the exact neurobiologic mechanisms and the potential association with gene-expression profiles are not fully understood. To explore the hierarchical disorganization in the large-scale functional connectomes in HBV-RC patients and to investigate its potential underlying molecular basis. Prospective. Fifty HBV-RC patients and 40 controls (Cohort 1) and 30 HBV-RC patients and 38 controls (Cohort 2). Gradient-echo echo-planar and fast field echo sequences at 3.0 T (Cohort 1) and 1.5 T (Cohort 2). Data were processed with Dpabi and the BrainSpace package. Gradient scores were evaluated from global to voxel level. Cognitive measurement and patients grouping were based on psychometric hepatic encephalopathy scores. The whole-brain microarray-based gene-expression data were obtained from the AIBS website. One-way ANOVA, chi-square test, two-sample t-test, Kruskal-Wallis test, Spearman's correlation coefficient (r), the gaussian random field correction, false discovery rate (FDR) correction and the Bonferroni correction. Significance level: P < 0.05. HBV-RC patients exhibited a robust and replicable connectome gradient dysfunction, which was significantly associated with the gene-expression profiles in both cohorts (r = 0.52 and r = 0.56, respectively). The most correlated genes were enriched in γ-aminobutyric acid (GABA) and GABA-related receptor genes (FDR q value <0.05). Moreover, the connectome gradient dysfunction at network level observed in HBV-RC patients correlated with their poor cognitive performance (Cohort 2: visual network, r = -0.56; subcortical network, r = 0.66; frontoparietal network, r = 0.51). HBV-RC patients had hierarchical disorganization in the large-scale functional connectomes, which may underly their cognitive impairment. In addition, we showed the potential molecular mechanism of the connectome gradient dysfunction, which suggested the importance of GABA and GABA-related receptor genes. 2 TECHNICAL EFFICACY: Stage 2.

Exploration of static functional connectivity and dynamic functional connectivity alterations in the primary visual cortex among patients with high myopia via seed-based functional connectivity analysis.

This study was conducted to explore differences in static functional connectivity (sFC) and dynamic functional connectivity (dFC) alteration patterns in the primary visual area (V1) among high myopia (HM) patients and healthy controls (HCs) via seed-based functional connectivity (FC) analysis. Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 82 HM patients and 59 HCs who were closely matched for age, sex, and weight. Seed-based FC analysis was performed to identify alterations in the sFC and dFC patterns of the V1 in HM patients and HCs. Associations between mean sFC and dFC signal values and clinical symptoms in distinct brain areas among HM patients were identified via correlation analysis. Static and dynamic changes in brain activity in HM patients were investigated by assessments of sFC and dFC via calculation of the total time series mean and sliding-window analysis. In the left anterior cingulate gyrus (L-ACG)/left superior parietal gyrus (L-SPG) and left V1, sFC values were significantly greater in HM patients than in HCs. In the L-ACG and right V1, sFC values were also significantly greater in HM patients than in HCs [two-tailed, voxel-level P < 0.01, Gaussian random field (GRF) correction, cluster-level P < 0.05]. In the left calcarine cortex (L-CAL) and left V1, dFC values were significantly lower in HM patients than in HCs. In the right lingual gyrus (R-LING) and right V1, dFC values were also significantly lower in HM patients than in HCs (two-tailed, voxel-level P < 0.01, GRF correction, cluster-level P < 0.05). Patients with HM exhibited significantly disturbed FC between the V1 and various brain regions, including L-ACG, L-SPG, L-CAL, and R-LING. This disturbance suggests that patients with HM could exhibit impaired cognitive and emotional processing functions, top-down control of visual attention, and visual information processing functions. HM patients and HCs could be distinguished from each other with high accuracy using sFC and dFC variabilities. These findings may help to identify the neural mechanism of decreased visual performance in HM patients.

Regional activity alterations in Parkinson's disease patients with anxiety disorders: A resting-state functional magnetic resonance imaging study.

Previous studies have revealed alteration of functional connectivity (FC) in Parkinson's disease patients with anxiety (PD-A), but local brain activities associated with anxiety in Parkinson's disease (PD) patients remain to be elucidated. Regional homogeneity (ReHo) analysis was employed to investigate alterations of regional brain activities in PD-A patients. Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 42 PD-A patients, 41 PD patients without anxiety (PD-NA), and 40 age-and gender-matched healthy control (HC) subjects. ReHo analysis was used to investigate the synchronization of neuronal activities in brain regions in the three groups. The relationship between ReHo value and anxiety score in the PD-A group was also investigated. Parkinson's disease patients with anxiety showed increased ReHo values in the bilateral frontal lobes, caudate nucleus, and anterior cingulate gyrus [Gaussian random field (GRF) correction, voxel size p < 0.01, cluster size p < 0.05], compared with PD-NA patients and HC subjects, but the ReHo values of the right cerebellar hemisphere and posterior cerebellar lobe decreased (GRF correction, voxel size p < 0.01, cluster size p < 0.05). The increased ReHo values of the right superior frontal gyrus (r = 0.633, p = 0.001) and anterior cingulate gyrus (r = 0.45, p = 0.01) were positively correlated with anxiety scores in PD-A patients. The development of PD-A may be associated with dysfunctional local activities in multiple brain regions, including the frontal cortex, cerebella, basal ganglia, and limbic system. Abnormal ReHo values in these brain regions may serve as neuroimaging markers for the early diagnosis of PD-A. The results suggest that using ReHo analysis to identify functional changes in core regions may advance our understanding of the pathophysiological mechanisms underlying PD-A.

Alteration of whole-brain amplitude of low-frequency fluctuation and degree centrality in patients with mild to moderate depression: A resting-state functional magnetic resonance imaging study.

Mild to moderate depressive disorder has a high risk of progressing to major depressive disorder. Low-frequency amplitude and degree centrality were calculated to compare 49 patients with mild to moderate depression and 21 matched healthy controls. Correlation analysis was conducted to explore the correlation between the amplitude of low-frequency fluctuation (ALFF) and the degree centrality (DC) of altered brain region and the scores of clinical scale. Receiver operating characteristic (ROC) curves were further analyzed to evaluate the predictive value of above altered ALFF and DC areas as image markers for mild to moderate depression. Compared with healthy controls, patients with mild to moderate depression had lower ALFF values in the left precuneus and posterior cingulate gyrus [voxel p < 0.005, cluster p < 0.05, Gaussian random field correction (GRF) corrected] and lower DC values in the left insula (voxel p < 0.005, cluster p < 0.05, GRF corrected). There was a significant negative correlation between DC in the left insula and scale scores of Zung's Depression Scale (ZungSDS), Beck Self-Rating Depression Scale (BDI), Toronto Alexithymia Scale (TAS26), and Ruminative Thinking Response Scale (RRS_SUM, RRS_REFLECTION, RRS_DEPR). Finally, ROC analysis showed that the ALFF of the left precuneus and posterior cingulate gyrus had a sensitivity of 61.9% and a specificity of 79.6%, and the DC of the left insula had a sensitivity of 81% and a specificity of 85.7% in differentiating mild to moderate depression from healthy controls. Intrinsic abnormality of the brain was mainly located in the precuneus and insular in patients with mild to moderate depression, which provides insight into potential neurological mechanisms.

Correlations between Hippocampus and Cognitive Score in Patients with Carotid Artery Stenosis Based on Resting State Functional Magnetic Resonance Imaging

Objective To investigate the correlations among brain functional connectivity,hippocampal subregion volume and cognitive score in the patients with carotid artery stenosis(CAS)based on resting state functional magnetic resonance imaging.Methods Forty CAS patients treated in the Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University from January to December in 2019 and 31 healthy volunteers were enrolled in this study.All the participants underwent cognitive assessment,structural MRI for the measurement of hippocampal volume,and resting state functional magnetic resonance imaging for the examination of brain functional connectivity(FC).We compared the cognitive function,hippocampal subregion volumes,and brain functional connectivity between the two groups and investigated the correlations between the three indicators.Results The CAS patients had lower mini-mental state examination(MMSE)(F=13.346,P=0.001)and Montreal cognitive assessment(MoCA)(F=52.005,P<0.001)scores than the healthy volunteers.Compared with healthy volunteers,CAS patients showed small whole hippocampus(right side:t=2.176,P=0.033;left side:t=2.881,P=0.005;especially on the left side),small hippocampal tail(right side:t=2.394,P=0.019;left side:t=3.158,P=0.002),small hippocampal body(right side:t=2.336,P=0.022;left side:t=3.165,P=0.002),small subiculum(right side:t=2.211,P=0.030;left side:t=2.430;P=0.018),and small molecular layer(right side:t=2.103,P=0.039;left side:t=2.702,P=0.009).The whole hippocampal volume was positively correlated with MoCA and MMSE scores(left MoCA:r=0.289,P=0.015;right MMSE:r=0.249,P=0.038;left MMSE:r=0.316,P=0.008).The volume changes in the subiculum,presubiculum,and left molecular layer were positively correlated with MoCA(right subiculum:r=0.290,P=0.015;left subiculum:r=0.382,P=0.001;right presubiculum:r=0.293,P=0.014;left presubiculum:r=0.440,P<0.001;left molecular layer:r=0.259,P=0.031)and MMSE scores(right subiculum:r=0.278,P=0.020;left subiculum:r=0.419,P<0.001;right presubiculum:r=0.296,P=0.013;left presubiculum:r=0.506,P<0.001;left molecular layer:r=0.298,P=0.012),while the volume changes in the remaining hippocampal subregions were not correlated with cognitive scores(all P>0.05).Compared with healthy volunteers,the CAS patients presented low FC values of the left hippocampus to the occipital lobe and frontal lobe and of right hippocampus to the occipital lobe,temporal lobe,prefrontal lobe,and middle frontal gyrus(Gaussian random field correction,voxel P<0.01,cluster P<0.05).The volume changes of the left whole hippocampus,hippocampal head,and cornu ammonis 1(CA1)were positively correlated with the FC value of right hippocampus to the temporal lobe(left whole hippocampus:r=0.358,P=0.025;right hippocampal head:r=0.325,P=0.044;left hippocampal head:r=0.360,P=0.024;right CA1:r=0.326,P=0.043;left CA1:r=0.341,P=0.034).MoCA and MMSE scores were positively correlated with the FC value of right hippocampus to the frontal lobe(MoCA middle frontal gyrus:r=0.389,P=0.014;MoCA prefrontal lobe:r=0.363,P=0.023;MMSE prefrontal lobe:r=0.321,P=0.046).Conclusions CAS patients have different levels of cognitive impairment.Hippocampal atrophy and a decline in the FC value of hippocampus to the occipital lobe may play a role in cognitive impairment in CAS patients.This discovery lays a foundation for the future research on the mechanism of cognitive dysfunction in CAS patients.

Changed cerebral function and morphology serve as neuroimaging evidence for subclinical type 2 diabetic polyneuropathy.

Central and peripheral nervous systems are all involved in type 2 diabetic polyneuropathy mechanisms, but such subclinical changes and associations remain unknown. This study aims to explore subclinical changes of the central and peripheral and unveil their association. A total of 55 type-2 diabetes patients consisting of symptomatic (n = 23), subclinical (n = 12), and no polyneuropathy (n = 20) were enrolled in this study. Cerebral morphology, function, peripheral electrophysiology, and clinical information were collected and assessed using ANOVA and post-hoc analysis. Gaussian random field correction was used for multiple comparison corrections. Pearson/Spearman correlation analysis was used to evaluate the association of the cerebral with the peripheral. When comparing the subclinical group with no polyneuropathy groups, no statistical differences were shown in peripheral evaluations except amplitudes of tibial nerves. At the same time, functional connectivity from the orbitofrontal to bilateral postcentral and middle temporal cortex increased significantly. Gray matter volume of orbitofrontal and its functional connectivity show a transient elevation in the subclinical group compared with the symptomatic group. Besides, gray matter volume in the orbitofrontal cortex negatively correlated with the Neuropathy Symptom Score (r = -0.5871, p < 0.001), Neuropathy Disability Score (r = -0.3682, p = 0.009), and Douleur Neuropathique en 4 questions (r = -0.4403, p = 0.003), and also found correlated positively with bilateral peroneal amplitude (r > 0.4, p < 0.05) and conduction velocities of the right sensory sural nerve(r = 0.3181, p = 0.03). Similarly, functional connectivity from the orbitofrontal to the postcentral cortex was positively associated with cold detection threshold (r = 0.3842, p = 0.03) and negatively associated with Neuropathy Symptom Score (r = -0.3460, p = 0.01). Function and morphology of brain changes in subclinical type 2 diabetic polyneuropathy might serve as an earlier biomarker. Novel insights from subclinical stage to investigate the mechanism of type 2 diabetic polyneuropathy are warranted.

Aberrant gray matter volume and functional connectivity in Parkinson's disease with minor hallucination.

BackgroundMinor hallucination (MH) is the most common psychotic symptom in Parkinson’s disease (PD); it can develop into well-structured visual hallucination (VH), suggesting that MH may be a staccato form of well-structured VH. However, it remains unclear whether the pathogenesis is the same. Therefore, the aim of this study was to investigate the altered gray matter volume (GMV) and functional connectivity (FC) of MH in PD to further understand the complex mechanisms.Materials and methodsWe included 67 PD patients who attended the outpatient clinic of Nanjing Medical University Affiliated Brain Hospital and recruited 31 healthy controls (HC). Demographic data and clinical characteristics of all subjects were recorded, and cranial structural magnetic resonance imaging (MRI) and resting-state functional MRI data were acquired. Patients were classified into the PD with MH (PD-MH) group and PD without hallucinations or delusions (PD-NH) group. Voxel-based morphometry was used to analyze the differences in GMV in the structural pattern. Seed-based FC was used to analyze the functional pattern. Gaussian random field correction was used, with voxel level P < 0.001 and cluster level P < 0.05 representing statistically significant differences. Finally, the correlation between FC values and scores on the clinical characteristics assessment scale was analyzed.ResultsIn the GMV analysis, compared to the PD-NH group, the PD-MH group had reduced GMV in the medial superior frontal gyrus (SFGmed). In the FC analysis, the FC between the SFGmed and the left middle occipital gyrus and right calcarine sulcus decreased in the PD-MH group compared with the PD-NH group, while the FC between SFGmed and the left middle temporal gyrus increased. Correlation analysis revealed that the FC values of the SFGmed and right calcarine sulcus were correlated with the assessment scores for anxiety and sleep symptoms. The FC values of the SFGmed and left middle occipital gyrus were correlated with assessment scores for rapid eye movement disorder.ConclusionThe aberrant structure and function of the default mode network and visual processing areas seems to facilitate the generation of MH in PD, as the alteration was previously found in well-structured VH, suggesting that the two hallucinations have similar pathophysiological mechanisms.

Disrupted interhemispheric functional connectivity in primary angle-closure glaucoma: a functional MRI study: voxel-mirrored homotopic connectivity in primary angle-closure glaucoma patients.

The purpose of the study is to use the voxel-mirrored homotopic connectivity (VMHC) technique to explore the pattern of the interhemispheric functional connectivity in patients with primary angle-closure glaucoma (PACG). The interhemispheric functional connectivity was compared between 31 individuals with PACG and 31 healthy controls closely matched with sex, age, and educational level using the VMHC technique. Significant differences in VMHC between two groups were selected to be classification features for classifying individuals with PACG from healthy controls using the support vector machine algorithm of the machine learning. We used the permutation test analysis to assess the classification performance. In addition, the Pearson analysis was applied to explore the relationship between changed VMHC and clinical varieties in patients with PACG. Compared with healthy controls, individuals with PACG exhibited significantly lower VMHC signal values in the right calcarine, right cuneus, right superior occipital gyrus, and right postcentral gyrus [voxel level: P < 0.001, Gaussian random field correction, cluster level: P < 0.05]. Moreover, the results displayed that the total accuracy, sensitivity, and specificity of the machine learning classification were 0.758, 0.710, and 0.807, respectively (P < 0.001, nonparametric permutation test). The findings demonstrated that there is disturbed interhemispheric resting-state functional connectivity in the vision-related brain areas of individuals with PACG; and the VMHC variability can classify individuals with PACG from healthy controls with high accuracy, which provided novel evidence for understanding the neuropathological mechanism of PACG.

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

PurposeThyroid-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.MethodsA 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.ResultsThe 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).ConclusionThe 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.

Abnormal Functional Connectivity Between Cerebral Hemispheres in Patients With High Myopia: A Resting FMRI Study Based on Voxel-Mirrored Homotopic Connectivity.

PurposeTo study the changes in functional connections between the left and right hemispheres of patients with high myopia (HM) and healthy controls (HCs) by resting functional magnetic resonance imaging (fMRI) based on voxel-mirrored homotopic connectivity (VMHC). To study the changes in resting-state functional connectivity (rsFC) between the left and right hemispheres of patients with HM and healthy controls (HCS) at rest by using resting functional magnetic resonance imaging (fMRI) based on voxel-mirror homotopy connectivity (VMHC).Patients and MethodsA total of 89 patients with HM (41 men and 48 women) and 59 HCs (24 men and 35 women) were collected and matched according to gender, age, and education level. The VMHC method was used to evaluate the changes in rsFC between cerebral hemispheres, and a correlation analysis was carried out to understand the differences in brain functional activities between the patients with HM and the HCs.ResultsCompared with the HCs, the VMHC values of the putamen and fusiform in the HM group were significantly lower (voxel-level p < 0.01, Gaussian random field correction cluster level p < 0.05).ConclusionThis study preliminarily confirmed the destruction of interhemispheric functional connection in some brain regions of the patients with HM and provided effective information for clarifying the neural mechanism of patients with HM.

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

PurposeTo 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 MethodsIn 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.ResultsCompared 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.ConclusionWe 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.

Altered Spontaneous Brain Activity in Left-Behind Children: A Resting-State Functional MRI Study.

BackgroundParental migration has been associated with a higher risk of cognitive and behavioral abnormalities in left-behind children (LBC). This study aimed to explore the spontaneous brain activity in LBC and reveal the mechanisms underlying behavioral and cognitive abnormalities.MethodsInvolved LBC (n = 36) and non-LBC (n = 22) underwent resting-state functional MRI (fMRI) examination and cognitive and behavioral assessment. The fMRI-based amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were assessed to analyze the spontaneous brain activity pattern. The relationships among abnormal spontaneous brain activity, behavioral and cognitive deficits and altered family environment were assessed by partial correlation analysis.ResultsCompared with non-LBC, LBC exhibited increased amplitude of low-frequency fluctuations in the right lingual gyrus (LING), while a decreased ALFF was observed in the bilateral insula and right orbital part of the middle frontal gyrus (ORBmid) (two-tailed voxel-level p < 0.01 and cluster-level p <0.05, Gaussian Random Field (GRF) correction). The fALFF in LBC were significantly increased in the left cerebellum 9 (Cbe9) and right cerebellum Crus2 (CbeCru2), while it decreased in the right hippocampus and left superior temporal gyrus (STG) (two-tailed voxel-level p < 0.01 and cluster-level p < 0.05, GRF correction). The ALFF and fALFF values in abnormal brain regions were found to be correlated with the learning ability, except for the right insula, while the fALFF values of the left STG were positively correlated with the full-scale IQ scores (p < 0.05). Moreover, the ALFF and fALFF values in all abnormal brain regions correlated with the education level of caregivers (p < 0.05).ConclusionsOur study provided empirical evidence that the lack of direct parental care during early childhood could affect brain function development involving cognition, behavior, and emotion. Our findings emphasized that intellectual and emotional cares are essential for LBC.

Enhancement of Impaired Olfactory Neural Activation and Cognitive Capacity by Liraglutide, but Not Dapagliflozin or Acarbose, in Patients With Type 2 Diabetes: A 16-Week Randomized Parallel Comparative Study

The comparative neuroprotective effects of different antidiabetes drugs have not been characterized in randomized controlled trials. Here, we investigated the therapeutic effects of liraglutide, dapagliflozin, or acarbose treatment on brain functional alterations and cognitive changes in patients with type 2 diabetes. Thirty-six patients with type 2 diabetes inadequately controlled with metformin monotherapy were randomized to receive liraglutide, dapagliflozin, or acarbose treatment for 16 weeks. Brain functional MRI (fMRI) scan and a battery of cognitive assessments were evaluated pre- and postintervention in all subjects. The 16-week treatment with liraglutide significantly enhanced the impaired odor-induced left hippocampal activation with Gaussian random field correction and improved cognitive subdomains of delayed memory, attention, and executive function (all P < 0.05), whereas dapagliflozin or acarbose did not. Structural equation modeling analysis demonstrated that such improvements of brain health and cognitive function could be partly ascribed to a direct effect of liraglutide on left hippocampal activation (β = 0.330, P = 0.022) and delayed memory (β = 0.410, P = 0.004) as well as to the metabolic ameliorations of reduced waist circumference, decreased body fat ratio, and elevated fasting insulin (all P < 0.05). Our head-to-head study demonstrated that liraglutide enhanced impaired brain activation and restored impaired cognitive domains in patients with type 2 diabetes, whereas dapagliflozin and acarbose did not. The results expand the clinical application of liraglutide and provide a novel treatment strategy for individuals with diabetes and a high risk of cognitive decline.