Voxel-mirrored Homotopic Connectivity Values Research Articles

Reduction of Interhemispheric Functional Connectivity in Sensorimotor and Visual Information Processing Pathways in Schizophrenia.

Background:Previous studies have demonstrated interhemispheric functional connectivity alterations in schizophrenia. However, the relationship between these alterations and the disease state of schizophrenia is largely unknown. Therefore, we aimed to investigate this relationship using voxel-mirrored homotopic connectivity (VMHC) method.Methods:This study enrolled 36 schizophrenia patients with complete remission, 58 schizophrenia patients with incomplete remission and 55 healthy controls. The VMHC was calculated based on resting-state functional magnetic resonance imaging data. Differences in VMHC among three groups were compared using one-way analysis of variance. A brain region with a significant difference in VMHC was defined as a region of interest (ROI), and the mean VMHC value in the ROI was extracted for the post hoc analysis, i.e., pair-wise comparisons across the three groups.Results:VMHC in the visual region (inferior occipital and fusiform gyri) and the sensorimotor region (paracentral lobule) showed significant differences among the three groups (P < 0.05, a false discovery rate method corrected). Pair-wise comparisons in the post hoc analysis showed that VMHC of the visual and sensorimotor regions in schizophrenia patients with complete remission and incomplete remission was lower than that in healthy controls (P < 0.05, Bonferroni corrected); however, there was no significant difference between the two patient subgroups.Conclusions:Interhemispheric functional connectivity in the sensorimotor and visual processing pathways was reduced in patients with schizophrenia, but this reduction was unrelated to the disease state; thus, this reduction may serve as a trait marker of schizophrenia.

Disrupted Interhemispheric Synchrony in Default Mode Network Underlying the Impairment of Cognitive Flexibility in Late-Onset Depression.

The intuitive association between cognitive impairment and aberrant functional activity in the brain network has prompted interest in exploring the role of functional connectivity in late-onset depression (LOD). The relationship of altered voxel-mirrored homotopic connectivity (VMHC) and cognitive dysfunction in LOD is not yet well understood. This study was designed to examine the implicit relationship between the disruption of interhemispheric functional coordination and cognitive impairment in LOD. LOD patients (N = 31) and matched healthy controls (HCs; N = 37) underwent neuropsychological tests and functional magnetic resonance imaging (fMRI) in this study. The intergroup difference of interhemispheric coordination was determined by calculating VMHC value in the whole brain. The neuro-behavioral relevancy approach was applied to explore the association between disrupted VMHC and cognitive measures. Receiver operating characteristic (ROC) curve analysis was used to determine the capability of disrupted regional VMHC to distinguish LOD. Compared to the HC group, significantly attenuated VMHC in the superior frontal gyrus (SFG), superior temporal gyrus (STG), posterior cerebellar lobe (CePL) and post- and precentral gyri were observed in the bilateral brain of LOD patients. The interhemispheric asynchrony in bilateral CePLs was positively correlated with the performance of trail making test B (TMT-B) in LOD patients (r = 0.367, P = 0.040). ROC analysis revealed that regions with abnormal VMHC could efficiently distinguish LOD from HCs (Area Under Curve [AUC] = 0.90, P < 0.001). Altered linkage patterns of intrinsic homotopic connectivity and impaired cognitive flexibility was first investigated in LOD, and it would provide a novel clue for revealing the neural substrates underlying cognitive impairment in LOD.

Prognostic value of imbalanced interhemispheric functional coordination in early therapeutic efficacy in major depressive disorder

This study aims to explore the early response of antidepressant therapy by measuring the voxel-mirrored homotopic connectivity (VMHC) in major depressive disorder (MDD). Eighty-two MDD patients [n=42 treatment-responsive depression (RD) and n=40 non-responding depression (NRD)] and n=50 normal controls (NC) underwent clinical measures and a magnetic resonance imaging scan, and the VMHC values were calculated. Receiver operating characteristic (ROC) curve analysis was applied to determine the capability of altered VMHC to distinguish NRD. The NRD showed significantly decreased VMHC in bilateral precuneus (PCU) and inferior temporal gyrus (ITG), and increased VMHC in middle frontal gyrus (MFG) and caudate nucleus as compared to RD. When compared with NC, the NRD exhibited reduced VMHC in bilateral cerebellum anterior lobe, thalamus and postcentral gyrus. Moreover, VHMC in medial frontal gyrus, postcentral gyrus and precentral gyrus were significantly decreased in RD. Correlation analysis showed that reduced VMHC in PCU was negatively correlated with the baseline HAMD score of the NRD group. The ROC curve indicated that the combined changes of the three regional VMHC (PCU, ITG and MFG) could effectively identify NRD. The current study suggests that interhemispheric asynchrony may represents a novel neural trait underlying the prediction of early therapeutic outcome in MDD.

Long-term acclimatization to high-altitude hypoxia modifies interhemispheric functional and structural connectivity in the adult brain.

BackgroundStructural and functional networks can be reorganized to adjust to environmental pressures and physiologic changes in the adult brain, but such processes remain unclear in prolonged adaptation to high‐altitude (HA) hypoxia. This study aimed to characterize the interhemispheric functionally and structurally coupled modifications in the brains of adult HA immigrants.MethodsWe performed resting‐state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) in 16 adults who had immigrated to the Qinghai‐Tibet Plateau (2300–4400 m) for 2 years and in 16 age‐matched sea‐level (SL) controls. A recently validated approach of voxel‐mirrored homotopic connectivity (VMHC) was employed to examine the interhemispheric resting‐state functional connectivity. Areas showing changed VMHC in HA immigrants were selected as regions of interest for follow‐up DTI tractography analysis. The fiber parameters of fractional anisotropy and fiber length were obtained. Cognitive and physiological assessments were made and correlated with the resulting image metrics.ResultsCompared with SL controls, VMHC in the bilateral visual cortex was significantly increased in HA immigrants. The mean VMHC value extracted within the visual cortex was positively correlated with hemoglobin concentration. Moreover, the path length of the commissural fibers connecting homotopic visual areas was increased in HA immigrants, covarying positively with VMHC.ConclusionsThese observations are the first to demonstrate interhemispheric functional and structural connectivity resilience in the adult brain after prolonged HA acclimatization independent of inherited and developmental effects, and the coupled modifications in the bilateral visual cortex indicate important neural compensatory mechanisms underlying visual dysfunction in physiologically well‐acclimatized HA immigrants. The study of human central adaptation to extreme environments promotes the understanding of our brain's capacity for survival.

Impaired interhemispheric synchrony in Parkinson's disease with depression.

The alterations of interhemispheric resting-state functional connectivity (FC) in Parkinson’s disease (PD) with depression remain unclear, so we aimed to explore the differences of interhemispheric FC between PD with and without depression. Twenty-one depressed PD (DPD) patients, 49 non-depressed PD (NDPD) patients and 50 matched healthy controls (HC) participated in this study. Resting-state functional magnetic resonance imaging (fMRI) data were analyzed with the voxel-mirrored homotopic connectivity (VMHC) approach. The DPD patients showed lower VMHC values in the bilateral dorsolateral prefrontal cortex (DLPFC) and calcarine cortex compared to both NDPD and HC groups, and further receiver operating characteristic curves (ROC) analyses revealed that the VMHC in these two brain areas could be used as biomarkers to distinguish DPD from NDPD and from HC. The pooled PD patients (both DPD and NDPD) exhibited decreased VMHC in the bilateral putamen, middle occipital gyrus (MOG), postcentral gyrus (PoCG), paracentral lobule (PCL) and cerebellum posterior lobe when compared with HC. Decreased VMHC values within the DLPFC and calcarine cortex appeared to be unique features for DPD and might be used as potential neuroimaging markers to distinguish DPD patients from NDPD and HC groups. These findings may underlie the neural mechanisms of depression in PD.

Interhemispheric resting state functional connectivity abnormalities in unipolar depression and bipolar depression

Depression in the context of bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatment and poor clinical outcomes. However, little is known about the similarities and differences in interhemispheric functional connectivity between BD and UD. Patients with bipolar II disorder (n=36) and UD (n=32) during a depressive episode as well as 40 healthy controls underwent resting-state functional magnetic resonance imaging. The functional connectivity between any pair of symmetric interhemispheric voxels (i.e., functional homotopy) was measured by voxel-mirrored homotopic connectivity (VMHC). The three groups showed significant VMHC differences in the posterior cingulate cortex (PCC), fusiform and lingual gyrus, anterior lobe of the cerebellum (CeAL), and posterior lobe of the cerebellum (CePL). In the BD group, the VMHC decreases in the fusiform/lingual gyrus, CeAL, and CePL were shown relative to controls. In the UD group, the VMHC decreases in the PCC, fusiform/lingual gyrus, and CePL were shown relative to controls. No regions of increased VMHC were detected in either patient group. There was no significant difference in the VMHC values in any brain region between the BD group and the UD group. Depressive episodes in BD and UD have similar impairments of interhemispheric coordination, which might imply an overlap in the neuropathology of depression.

Reduced interhemispheric resting-state functional connectivity in unmedicated bipolar II disorder.

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.

Increased interhemispheric functional connectivity in college students with non-clinical depressive symptoms in resting state

The underlying neural basis of non-clinical depressive symptoms (nCDSs) remains unclear. Interhemispheric functional connectivity has been suggested as one of the most robust characteristics of brain’s intrinsic functional architecture. Here, we investigated the functional connectivity between homotopic points in the brain using the voxel-mirrored homotopic connectivity (VMHC) approach. We performed VMHC analysis on resting-state functional magnetic resonance imaging (rs-fMRI) data from 17 individuals with nCDSs and 20 healthy controls (HCs) who were enrolled from a sample of 1105 college students. We found increased VMHCs in the bilateral posterior cerebellum and fusiform gyrus in nCDSs subjects compared with HCs. Furthermore, receiver operating characteristic (ROC) curves indicated that VMHC values in the posterior cerebellum lobes could use to differente nCDSs from HCs [area under the curve (AUC), 0.756; p<0.01]. We suggest increased VMHCs indicate a possible compensatory mechanism involved in the pathophysiology of nCDSs. VMHC values of the posterior cerebellum lobes might serve as a reliable biomarker for identifying nCDSs.

Decreased interhemispheric functional connectivity in subtypes of Parkinson's disease.

Parkinson's disease (PD) can be classified into tremor-dominant (TD) subtype and akinetic-rigid (AR) subtype, which exhibit different clinical courses and prognoses. However, the neural mechanisms underlying different subtypes of PD are not well understood. Using voxel-mirrored homotopic connectivity (VMHC), we examined the homotopic resting-state functional connectivity patterns in akinetic-rigid PD (AR-PD) and tremor-dominant PD (TD-PD) to study the neural basis for these disparate manifestations of PD. Twenty-one TD-PD patients, 29 AR-PD patients and 26 normal control subjects participated in this study. Resting-state fMRI data were analyzed using VMHC. Correlations between VMHC values and each clinical characteristic were also calculated. Compared with normal control subjects and subjects with AR-PD, subjects with TD-PD exhibited significantly lower VMHC values in the posterior lobe of the cerebellum. Moreover, tremor scores and VMHC values for the cerebellum were found to be significantly negatively correlated in TD-PD patients. By contrast, subjects with AR-PD exhibited lower VMHC values in the precentral gyrus compared with normal control subjects. These findings suggest that functional coordination between homotopic brain regions is impaired in AR-PD and TD-PD patients. This study provides evidence of both cerebellum-related connectivity deficits in TD-PD. The finding that VMHC values and tremor scores were significantly correlated suggests that VMHC measurements may be of potential clinical relevance in TD-PD.

Modulation of interhemispheric functional coordination in electroconvulsive therapy for depression.

Considerable evidence suggests that depression is related to interhemispheric functional coordination deficits. For depression, electroconvulsive therapy (ECT) is the most rapid and effective therapy, but its underlying mechanism remains unknown. The aim of this study was to explore the impact of ECT on the interhemispheric functional coordination in depression patients. We used resting-state functional magnetic resonance imaging to observe the change of interhemispheric functional coordination with the method of voxel-mirrored homotopic connectivity (VMHC) in 11 depressed patients before and after ECT, compared with 15 healthy controls. The results showed that, compared with depression patients before ECT, VMHC was significantly increased in superior frontal gyri (BA 8), middle frontal gyri (two clusters: BA 8/9 and BA 10) and angular gyri (BA 39) in depression patients after ECT. Compared with healthy controls, VMHC in those areas was significantly lower in the middle frontal gyri (BA 8/9) and angular gyri (BA 39) in depression patients before ECT, but no significant difference was observed in the superior frontal gyri (BA 8) and middle frontal gyri (BA 10). There was no significant correlation between the changes of Hamilton Depression Rating Scale scores and changed VMHC values in those four areas in depression patients. The results suggest that ECT selectively modulated interhemispheric functional coordination in depression patients. Such may play an important mechanistic role in the treatment of depression, and may afford a useful avenue for optimizing treatment.

Homotopic connectivity in drug-naïve, first-episode, early-onset schizophrenia.

The disconnection hypothesis of schizophrenia has been extensively tested in adults. Recent studies have reported the presence of brain disconnection in younger patients, adding evidence to support the neurodevelopmental hypothesis of schizophrenia. Because of drug confounds in chronic and medicated patients, it has been extremely challenging for researchers to directly investigate abnormalities in the development of connectivity and their role in the pathophysiology of schizophrenia. The present study aimed to examine functional homotopy - a measure of interhemispheric connection - and its relevance to clinical symptoms in first-episode drug-naïve early-onset schizophrenia (EOS) patients. Resting-state functional magnetic resonance imaging was performed in 26 first-episode drug-naïve EOS patients (age: 14.5 ± 1.94, 13 males) and 25 matched typically developing controls (TDCs) (age: 14.4 ± 2.97, 13 males). We were mainly concerned with the functional connectivity between any pair of symmetric interhemispheric voxels (i.e., functional homotopy) measured by voxel-mirrored homotopic connectivity (VMHC). Early-onset schizophrenia patients exhibited both global and regional VMHC reductions in comparison with TDCs. Reduced VMHC values were observed within the superior temporal cortex and postcentral gyrus. These interhemispheric synchronization deficits were negatively correlated with negative symptom of the Positive and Negative Syndrome Scale. Moreover, regions of interest analyses based on left and right clusters of temporal cortex and postcentral gyrus revealed abnormal heterotopic connectivity in EOS patients. Our findings provide novel neurodevelopmental evidence for the disconnection hypothesis of schizophrenia and suggest that these alterations occur early in the course of the disease and are independent of medication status.

Decreased inter-hemispheric connectivity in anterior sub-network of default mode network and cerebellum: significant findings in major depressive disorder.

The issue of inter-hemispheric connectivity is an emerging new area in understanding the pathophysiology of depression. This study was designed to analyse the pattern of inter-hemispheric connectivity in patients with major depressive disorder (MDD). The resting-state functional magnetic resonance imaging (RFMRI) was acquired in all enrolled patients and controls. We used a method of voxel-mirrored homotopic connectivity (VMHC) to estimate the significant differences in inter-hemispheric connectivity between 44 patients with first-episode medication-naïve MDD and 27 normal controls. The patients and controls were matched for age and gender. The patients with first-episode medication-naïve MDD showed lower VMHC than normal controls in bilateral medial frontal cortex, anterior cingulate and cerebellar posterior lobe. The strength of inter-hemispheric connectivity VMHC value was negatively correlated with clinical severity of MDD. From the results, we suggested that decreased inter-hemispheric connectivity in the anterior sub-network of the default mode network and the cerebellar posterior lobe might represent an emerging finding in the pathophysiology for MDD.

Interhemispheric functional connectivity in primary insomnia: a resting-state funtional MRI study

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)

Decreased Interhemispheric Coordination in Treatment-Resistant Depression: A Resting-State fMRI Study

BackgroundPrevious studies have demonstrated that patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) differed at neural level. However, it remains unclear if these two subtypes of depression differ in the interhemispheric coordination. This study was undertaken for two purposes: (1) to explore the differences in interhemispheric coordination between these two subtypes by using the voxel-mirrored homotopic connectivity (VMHC) method; and (2) to determine if the difference of interhemispheric coordination can be used as a biomarker(s) to differentiate TRD from both TSD and healthy subjects (HS).MethodsTwenty-three patients with TRD, 22 with TSD, and 19 HS participated in the study. Data of these participants were analyzed with the VMHC and seed-based functional connectivity (FC) approaches.ResultsCompared to the TSD group, the TRD group showed significantly lower VMHC values in the calcarine cortex, fusiform gyrus, hippocampus, superior temporal gyrus, middle cingulum, and precentral gyrus. Lower VMHC values were also observed in the TRD group in the calcarine cortex relative to the HS group. However, the TSD group had no significant change in VMHC value in any brain region compared to the HS group. Receiver operating characteristic curves (ROC) analysis revealed that the VMHC values in the calcarine cortex had discriminatory function distinguishing patients with TRD from patients with TSD as well as those participants in the HS group.ConclusionsLower VMHC values of patients with TRD relative to those with TSD and those in the HS group in the calcarine cortex appeared to be a unique feature for patients with TRD and it may be used as an imaging biomarker to separate patients with TRD from those with TSD or HS.