Alterations of homotopic functional connectivity and correlates with core neuropsychological impairments in mild cognitive impairment: a resting-state fMRI study.

Previous studies have demonstrated that functional connectivity (FC) of different brain regions in resting state function MRI were abnormal in patients suffering from mild cognitive impairment (MCI) and Alzheimer’s disease (AD) when comparing to healthy controls (HC) using seed based, independent component analysis (ICA) or small world network techniques. A new technique called voxel-mirrored homotopic connectivity (VMHC) was used in the current study to evaluate the value of interhemispheric functional connectivity (IFC) as a diagnostic tool to differentiate vascular dementia (VD) from other Alzheimer’s related neurodegenerative diseases. Eighty-three participants were recruited from the university hospital memory clinic. A multidisciplinary panel formed by a neuroradiologist and two geriatricians classified the participants into VD (13), AD (16), MCI (29), and HC (25) based on clinical history, Montreal Cognitive Assessment Hong Kong version (HK-MoCA) neuropsychological score, structural MRI, MR perfusion, and 18-F Flutametamol (amyloid) PET-CT findings of individual subjects. We adopted the calculation method used by Kelly et al. (2011) and Zuo et al. (2010) in obtaining VMHC maps. Specific patterns of VMHC maps were obtained for VD, AD, and MCI to HC comparison. VD showed significant reduction in VMHC in frontal orbital gyrus and gyrus rectus. Increased VMHC was observed in default mode network (DMN), executive control network (ECN), and the remaining salient network (SN) regions. AD showed a reduction of IFC in all DMN, ECN, and SN regions; whereas MCI showed VMHC reduction in vSN, and increased VMHC in DMN and ECN. When combining VMHC values of relevant brain regions, the accuracy was improved to 87%, 92%, and 83% for VD, AD, and MCI from HC, respectively, in receiver operating characteristic (ROC) analysis. Through studying the VMHC maps and using VMHC values in relevant brain regions, VMHC can be considered as a reliable diagnostic tool for VD, AD, and MCI from HC.

Abnormal postcentral gyrus voxel-mirrored homotopic connectivity as a biomarker of mild cognitive impairment: A resting-state fMRI and support vector machine analysis

Background: Recent studies have discovered that functional connections are impaired among patients with Alzheimer's disease (AD), even at the preclinical stage. The cerebellum has been implicated as playing a role in cognitive processes. However, functional connectivity (FC) among cognitive sub-regions of the cerebellum in patients with AD and mild cognitive impairment (MCI) remains to be further elucidated.Objective: Our study aims to investigate the FC changes of the cerebellum among patients with AD and MCI, compared to healthy controls (HC). Additionally, we explored the role of cerebellum FC changes in the cognitive performance of all subjects.Materials: Resting-state functional magnetic resonance imaging (rs-fMRI) data from three different groups (28 AD patients, 26 MCI patients, and 30 HC) was collected. We defined cerebellar crus II and lobule IX as seed regions to assess the intragroup differences of cortico-cerebellar connectivity. Bias correlational analysis was performed to investigate the relationship between changes in FC and neuropsychological performance.Results: Compared to HC, AD patients had decreased FC within the caudate, limbic lobe, medial frontal gyrus (MFG), middle temporal gyrus, superior frontal gyrus, parietal lobe/precuneus, inferior temporal gyrus, and posterior cingulate gyrus. Interestingly, MCI patients demonstrated increased FC within inferior parietal lobe, and MFG, while they had decreased FC in the thalamus, inferior frontal gyrus, and superior frontal gyrus. Further analysis indicated that FC changes between the left crus II and the right thalamus, as well as between left lobule IX and the right parietal lobe, were both associated with cognitive decline in AD. Disrupted FC between left crus II and right thalamus, as well as between left lobule IX and right parietal lobe, was associated with attention deficit among subjects with MCI.Conclusion: These findings indicate that cortico-cerebellar FC in MCI and AD patients was significantly disrupted with different distributions, particularly in the default mode networks (DMN) and fronto-parietal networks (FPN) region. Increased activity within the fronto-parietal areas of MCI patients indicated a possible compensatory role for the cerebellum in cognitive impairment. Therefore, alterations in the cortico-cerebellar FC represent a novel approach for early diagnosis and a potential therapeutic target for early intervention.

Objective To investigate the inter-hemispheric resting-state functional connectivity and its relation with cognitive function in patients with end-stage renal disease (ESRD) by using resting-state functional magnetic resonance imaging (rs-fMRI) based on voxel-mirrored homotopic connectivity (VMHC). Methods A total of 52 patients with ESRD (ESRD group), admitted to our hospital from July 2018 to January 2019, were enrolled; 36 age-, gender-, and education level-matched healthy controls (HCs group) were collected at the same time period. The cognitive function of all subjects was assessed by Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT)-A, TMT-B and Symbol Digit Modalities Test (SDMT). The rs-fMRI and 3D-T1WI data were acquired from all subjects; after image preprocessing, VMHC values between brain hemispheres were calculated and the regions with significantly different VMHC values were obtained. The correlations between VMHC values in significant regions and cognitive scale scores were analyzed. Results MMSE, MoCA and SDMT scores of ESRD patients were significantly lower than those of the HCs group (P<0.05), and ESRD patients took longer time to complete TMT-A and TMT-B tests than the HCs group (P<0.05). As compared with that of the HCs group, significant decrease of VMHC values of ESRD patients was found in the hippocampus, lingual gyrus, superior temporal gyrus, caudate nucleus and anterior cingulate gyrus (P<0.01, AlphaSim correction); the VMHC values of the anterior cingulate gyrus and hippocampus were positively correlated with MMSE and MoCA scores (P<0.05). Conclusion Significant abnormal inter-hemisphere functional connectivity is found in patients with ESRD, which is associated with cognitive function. Key words: End-stage renal disease; Cognitive impairment; Resting-state functional magnetic resonance imaging; Voxel-mirrored homotopic connectivity

ObjectivesChemotherapy induces cognitive impairments including memory impairment attention deficit and executive dysfunction in patients with breast cancer (BC) during or after chemotherapy. Previous studies identified brain structural and functional changes in BC patients receiving chemotherapy; however, there are no studies assessing functional connectivity (FC) between homotopic brain regions in BC patients using a voxel-mirrored homotopic connectivity (VMHC) method. In the present study, we explored cognitive function and whole brain homotopic FC in BC patients receiving chemotherapy compared with healthy controls using the VMHC method.MethodsThe present cross-sectional study included 35 premenopausal women with breast cancer who received chemotherapy, as well as 32 age- and sex-matched healthy controls (HC). All subjects underwent resting-state functional magnetic resonance imaging, which measured homotopic brain FC, and cognitive neuropsychological assessments evaluating attention, memory, and executive function domains.ResultsThe BC group had lower VMHC than the HC group in the cingulated posterior, insular and postcentral regions. No region exhibited higher VMHC in the BC group than in HC group. Correlation analysis in the BC group indicated that VMHC values in the cingulated posterior were significantly correlated with executive function tests, and that the VMHC values in the insular were significantly correlated with memory tests.ConclusionThe present study showed that VMHC decreased in different brain regions including cingulated posterior, insular and postcentral regions. A significant correlation was observed between the VMHC values in the brain regions and neuropsychological tests. These results suggested that changes in VMHC values in different brain regions may underlie cognitive changes in BC patients receiving chemotherapy.

Abnormalities in structural and functional brain connectivity have been increasingly reported in patients with bipolar disorder (BD) by recent neuroimaging studies. However, relatively little is known about the changes in functional interaction between the cerebral hemispheres in BD. The present study aimed to examine the interhemispheric functional connectivity of the whole brain in patients with BD II during resting state. Twenty-six patients with unmedicated BD II depression and 40 normal controls underwent the resting-state functional magnetic resonance imaging. The functional connectivity between any pair of symmetrical interhemispheric voxels (i.e., functional homotopy) was measured by voxel-mirrored homotopic connectivity (VMHC). The patients with BD II showed lower VMHC than normal controls in the medial prefrontal cortex and inferior temporal gyrus. No regions of increased VMHC were detected in patients. There were no significant correlations between the VMHC values in these regions and clinical severity of BD symptoms. These findings suggest substantial impairment of interhemispheric coordination in BD II.

There has been a considerable focus on the changes of functional connections between brain regions in patients with type 2 diabetes mellitus (T2DM) by previous resting-state functional magnetic resonance imaging (rs-fMRI) studies. However, little is known about the function of brain information integration between the two hemispheres of the brain. This study explores differences in interhemispheric coordination between T2DM patients and normal control (NC) subjects using the voxel-mirrored homotopic connectivity (VMHC) method. We also assess whether differences in VMHC were relevant to cognitive dysfunction in T2DM patients. Sixty-nine T2DM patients and 69 NC subjects were enrolled (matched for age, sex and education level). All participants underwent cognitive assessments. VMHC between brain regions was obtained by rs-fMRI analysis. Partial correlation analysis (after controlling for age, sex and education level) was used to explore the correlation between VMHC value and neuropsychological tests. Compared with NC subjects, T2DM patients exhibited significantly lower VMHC in the medial orbitofrontal gyrus cortex (mOFC), anterior cingulate gyrus, inferior parietal lobe, superior and middle temporal gyrus (MTG), middle occipital gyrus, and superior occipital gyrus. Moreover, after applying Bonferroni correction, the Montreal Cognitive Assessment (MoCA) score and VMHC value for the MTG were significantly positively correlated in T2DM patients. In contrast, T2DM patients exhibited higher VMHC in the cerebellum posterior lobe and tonsil and inferior temporal gyrus than the NCs. Our study indicates that functional coordination between homotopic brain regions is generally impaired in T2DM patients. In brain regions with decreased VMHC in the default mode network (DMN), MTG impairment could serve as a critical node for T2DM-related cognitive dysfunction. Furthermore, the increased VMHC observed in the cerebellum and inferior temporal gyrus might indicate a functional coordination mechanism.

PurposePrevious research suggests that diabetic optic neuropathy (DON) can cause marked anatomical and functional variations in the brain, but to date altered functional synchronization between two functional hemispheres remains uncharacterized in DON patients. Voxel mirrored homotopic connectivity (VMHC) is a voxel-based method to evaluate the synchronism between two mirrored hemispheric by determining the functional connectivity between each voxel in one hemisphere and its counterpart. In this study, we aim to assess abnormal changes in interhemispheric functional connectivity in DON patients via the VMHC method.MethodsThe study included 28 adult DON patients (12 male, 16 female) and 28 healthy controls (12 male, 16 female) who were closely matched for sex and age. Participants were examined using resting-state functional magnetic resonance imaging. The VMHC method was applied to investigate the abnormal state in bilateral hemispheres in DON patients and the same regions in healthy controls, as well as the receiver operating characteristic (ROC) curves were used to evaluate characteristics. Associations between altered VMHC values in distinct cerebral regions and clinical features were assessed via correlational analysis.ResultsMarkedly lower VMHC values were evident in the right temporal inferior, the left temporal inferior, the right mid-cingulum, the left mid-cingulum, the right supplementary motor region, and the left supplementary motor region in DON patients compared with healthy controls. ROC curve analysis suggested that the application of VMHC is reliable for the diagnosis of DON.ConclusionAnomalous interhemispheric functional connectivity in specific brain areas caused by DON may indicate neuropathologic mechanisms of vision loss and blurry vision in patients with DON.

Altered brain functional connectivity has been reported in patients with amblyopia by recent neuroimaging studies. However, relatively little is known about the alterations in interhemispheric functional connectivity in amblyopia. The present study aimed to investigate the functional connectivity patterns between homotopic regions across hemispheres in patients with anisometropic and strabismic amblyopia under resting state. Nineteen monocular anisometropic amblyopia (AA), 18 strabismic amblyopia (SA), and 20 normal-sight controls (NC) were enrolled in this study. After a comprehensive ophthalmologic examination, resting-state fMRI scanning was performed in all participants. The pattern of the interhemispheric functional connectivity was measured with the voxel-mirrored homotopic connectivity (VMHC) approach. VMHC values differences within and between three groups were compared, and correlations between VMHC values and each the clinical variable were also analyzed. Altered VMHC was observed in AA and SA patients in lingual gyrus and fusiform gyrus compared with NC subjects. The altered VMHC of lingual gyrus showed a pattern of AA > SA > NC, while the altered VMHC of fusiform gyrus showed a pattern of AA > NC > SA. Moreover, the VMHC values of lingual gyrus were positively correlated with the stereoacuity both in AA and SA patients, and the VMHC values of fusiform gyrus were positively correlated with the amount of anisometropia just in AA patients. These findings suggest that interhemispheric functional coordination between several homotopic visual-related brain regions is impaired both in AA and SA patients under resting state and revealed the similarities and differences in interhemispheric functional connectivity between the anisometropic and strabismic amblyopia.

Objective To investigate the resting-state functional connectivity between the two hemispheres in primary insomnia(PI) using voxel-mirrored homotopic connectivity(VMHC) based on restingstate functional MRI(fMRI).Methods Eighteen PI patients and 19 healthy volunteers matched for age and sex underwent resting-state fMRI scans in a 1.5T scanner.Pittsburgh sleep quality index(PSQI) was performed for all subjects.The data was pre-processed by SPM 8 and then the VMHC values were calculated by REST software.The VMHC values between the two groups were compared by two-sample t-test.The statistical map with significant differences of VMHC value was obtained.Results Compared to the controls,PI patients showed significant VMHC decreases in the middle frontal gyrus(MFG),superior frontal gyrus(SFG),orbitofrontal cortex(OFC),hippocampus,thalamus,insula and a few occipital regions including cuneus and lingual gyrus(voxel size 1 269-7 425 mm3,t=-4.47-2.74 P＜ 0.05,Alphasim corrected).Negative correlation was observed between VMHC coefficients(0.324±0.247) of OFC and the PSQI score (10.1 ± 1.7) in PI patients(r=-0.69,P＜0.01).The other regions showing significant VMHC changes had no correlation with the PSQI score(P＞0.05).Conclusions These findings suggest that the functional coordination between homotopic brain regions is impaired in PI patients.Interhemispheric RSFC may serve as a useful method for evaluating PI where neural connectivity is implicated in the pathophysiology. Key words: Sleep initiation and maintenance disorders; Magnetic resonance imaging; Neural networks(computer)

Suicidal ideation (SI) is a major cause of death in patients with major depressive disorder (MDD). Although current clinical tools can assess suicide risk, objective neurobiological markers based on research remain lacking. Clinical evidence suggests that resting-state functional magnetic resonance imaging (rs-fMRI) studies utilizing voxel-mirrored homotopic connectivity (VMHC) analysis can uncover the neural mechanisms underlying mental disorders. This study explores differences in interhemispheric connectivity between MDD patients with and without SI, aiming to identify imaging biomarkers for suicide risk. This study included 48 SI patients and 44 non-SI patients. VMHC values were calculated to assess interhemispheric functional connectivity. Brain regions with significant differences between the groups were identified. A support vector machine (SVM) model was applied to evaluate the utility of VMHC values in distinguishing SI patients from non-SI patients with MDD. Patients with suicidal ideation exhibited significantly increased VMHC values in the superior frontal gyrus, putamen, inferior temporal gyrus, and cerebellum compared to those without suicidal ideation. The SVM model achieved an accuracy of 77.2%, sensitivity of 83.3%, specificity of 70.5%, and an area under the curve (AUC) of 0.81. When combining VMHC values from multiple brain regions, classification accuracy improved to 86.8%. MDD patients with SI exhibit abnormal interhemispheric connectivity, with VMHC abnormalities in specific brain regions serving as potential biomarkers for suicide risk. The integration of machine learning and neuroimaging highlights the clinical relevance of VMHC as a tool for early detection and targeted intervention in suicide prevention.

Brain Homotopic Connectivity in Mild Cognitive Impairment APOE-ε4 Carriers

Disrupted interhemispheric functional and structural connectivity in patients with major depressive disorder.

In the spectrum of Alzheimer's Disease (AD) and related disorders, the resting-state functional magnetic resonance imaging (rs-fMRI) signals within the cerebral cortex may exhibit distinct characteristics across various frequency ranges. Nevertheless, this hypothesis has not yet been substantiated within the broader context of whole-brain functional connectivity. This study aims to explore potential modifications in degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) among individuals with amnestic mild cognitive impairment (aMCI) and AD, while assessing whether these alterations differ across distinct frequency bands. This investigation encompassed a total of 53 AD patients, 40 aMCI patients, and 40 healthy controls (HCs). DC and VMHC values were computed within three distinct frequency bands: classical (0.01-0.08 Hz), slow-4 (0.027-0.073 Hz), and slow-5 (0.01-0.027 Hz) for the three respective groups. To discern differences among these groups, ANOVA and subsequent post hoc two-sample t-tests were employed. Cognitive function assessment utilized the mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA). Pearson correlation analysis was applied to investigate the associations between MMSE and MoCA scores with DC and VMHC. Significant variations in degree centrality (DC) were observed among different groups across diverse frequency bands. The most notable differences were identified in the bilateral caudate nucleus (CN), bilateral medial superior frontal gyrus (mSFG), bilateral Lobule VIII of the cerebellar hemisphere (Lobule VIII), left precuneus (PCu), right Lobule VI of the cerebellar hemisphere (Lobule VI), and right Lobule IV and V of the cerebellar hemisphere (Lobule IV, V). Likewise, disparities in voxel-mirrored homotopic connectivity (VMHC) among groups were predominantly localized to the posterior cingulate gyrus (PCG) and Crus II of the cerebellar hemisphere (Crus II). Across the three frequency bands, the brain regions exhibiting significant differences in various parameters were most abundant in the slow-5 frequency band. This study enhances our understanding of the pathological and physiological mechanisms associated with AD continuum. Moreover, it underscores the importance of researchers considering various frequency bands in their investigations of brain function.

The current study evaluated whether the functional connectivity pattern of the thalamo-cortical network in patients with Alzheimer' s disease (AD) and mild cognitive impairment (MCI) would show disease severityrelated alterations. Resting-state functional magnetic resonance imaging (MRI) data were obtained from 35 patients with AD, 27 patients with MCI and 27 subjects with normal cognition (NC). First, the altered functional connectivity pattern in AD patients was evaluated in comparison to NC subjects. Second, the MCI subjects were included to evaluate how different stages of disease affect the functional connectivity pattern of the thalamus. Finally, a correlation analysis was performed between the strength of the functional connectivity of the identified regions and various clinical variables to evaluate the relationship between the strength of functional connectivity and the cognitive abilities of MCI and AD patients. When compared to NC subjects, AD patients showed decreased functional connectivity between the left thalamus and brain regions including the precuneus/posterior cingulate cortex, right middle frontal gyrus and left inferior frontal gyrus. Decreased functional connectivity was also found between the right thalamus and right middle frontal gyrus and left inferior parietal lobule/angular gyrus. In addition, increased functional connectivity was observed between the bilateral thalamus and brain regions including the middle frontal gyrus, middle temporal gyrus, inferior temporal gyrus, superior parietal lobule, postcentral gyrus and precuneus. Functional connectivity between the bilateral thalamus and the identified brain regions of MCI subjects was intermediate in comparison to the functional connectivity of AD and NC subjects. A significant correlation between the fitted functional connectivity strength and the clinical variables was also detected. Our results revealed disease severity-related alterations of the thalamo-default mode network and thalamocortical connectivity in AD and MCI patients. These results support the hypothesis of network disconnection in AD.