Homotopic Functional Connectivity Research Articles

Lateralisation of subcortical functional connectivity during and after general anaesthesia

BackgroundArousal and awareness are two important components of consciousness states. Functional neuroimaging has furthered our understanding of cortical and thalamocortical mechanisms of awareness. Investigating the relationship between subcortical functional connectivity and arousal has been challenging owing to the relatively small size of brainstem structures and thalamic nuclei, and their depth in the brain. MethodsResting state functional MRI scans of 72 healthy volunteers were acquired before, during, 1 h after, and 1 day after sevoflurane general anaesthesia. Functional connectivity of subcortical regions of interest vs whole brain and homotopic functional connectivity for assessment of left–right symmetry analyses of both cortical and subcortical regions of interest were performed. Both analyses used high resolution atlases generated from deep brain stimulation applications. ResultsFunctional connectivity in subcortical loci within the thalamus and of the ascending reticular activating system was sharply restricted under anaesthesia, featuring a general lateralisation of connectivity. Similarly, left–right homology was sharply reduced under anaesthesia. Subcortical bilateral functional connectivity was not fully restored after emergence from anaesthesia, although greater restoration was seen between ascending reticular activating system loci and specific thalamic nuclei thought to be involved in promoting and maintaining arousal. Functional connectivity was fully restored to baseline by the following day. ConclusionsFunctional connectivity in the subcortex is sharply restricted and lateralised under general anaesthesia. This restriction may play a part in loss and return of consciousness. Clinical trial registrationNCT02275026.

Abnormal interhemispheric homotopic functional connectivity is correlated with gastrointestinal symptoms in patients with major depressive disorder

The severity of major depressive disorder (MDD) can be aggravated by gastrointestinal (GI) symptoms, but the neuroimaging mechanism underlying GI symptoms still remains unclear. In this study, we recruited 52 medication-free and first-episode MDD patients (35 with GI symptoms and 17 without GI symptoms) and 28 age-, sex-, and education-matched healthy controls to explore the inter-group differences in neuroimaging findings. All the participants underwent resting-state functional magnetic resonance imaging (fMRI) scan, and the functional connectivities that were reported to be abnormal in MDD were our focus of exploration. Voxel-mirrored homotopic connectivity (VMHC) method was used to explore the interhemispheric homotopic functional connectivity of all the subjects. Patients with MDD showed significantly different VMHC in brain regions in the default mode network (DMN), including the middle frontal gyrus, precuneus, inferior parietal lobule, and posterior cingulate cortex. Patients with GI symptoms exhibited significantly decreased interhemispheric homotopic functional connectivity in the middle frontal gyrus and superior frontal gyrus, compared with patients without GI symptoms. These results suggested that the DMN is involved in the neuropathology of MDD. Interhemispheric homotopic connectivity in specific regions could be applied as a biomarker to distinguish MDD patients with GI symptoms from those without GI symptoms.

Altered Homotopic Functional Connectivity Within White Matter in the Early Stages of Alzheimer's Disease.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with memory loss and cognitive impairment. The white matter (WM) BOLD signal has recently been shown to provide an important role in understanding the intrinsic cerebral activity. Although the altered homotopic functional connectivity within gray matter (GM-HFC) has been examined in AD, the abnormal HFC to WM remains unknown. The present study sought to identify changes in the WM-HFC and anatomic characteristics by combining functional magnetic resonance imaging with diffusion tensor imaging (DTI). Resting-state and DTI magnetic resonance images were collected from the OASIS-3 dataset and consisted of 53 mild cognitive impairment (MCI) patients, 90 very MCI (VMCI), and 100 normal cognitive (NC) subjects. Voxel-mirrored HFC was adopted to examine whether WM-HFC was disrupted in VMCI and MCI participants. Moreover, the DTI technique was used to investigate whether specific alterations of WM-HFC were associated with anatomic characteristics. Support vector machine analyses were used to identify the MCI and VMCI participants using the abnormal WM-HFC as the features. Compared with NC, MCI, and VMCI participants showed significantly decreased GM-HFC in the middle occipital gyrus and inferior parietal gyrus and decreased WM-HFC in the bilateral middle occipital and parietal lobe-WM. In addition, specific WM-functional network alteration for the bilateral sub-lobar-WM was found in MCI subjects. MCI subjects showed abnormal anatomic characteristics for bilateral sub-lobar and parietal lobe-WM. Results of GM-HFC mainly showed common neuroimaging features for VMCI and MCI subjects, whereas analysis of WM-HFC showed specific clinical neuromarkers and effectively compensated for the lack of GM-HFC to distinguish NC, VMCI, and MCI subjects.

Disrupted resting-state interhemispheric functional connectivity in systemic lupus erythematosus patients with and without neuropsychiatric lupus.

The aim of the study is to explore interhemispheric homotopic functional connectivity alterations in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric lupus (NPSLE and non-NPSLE, respectively) and their potential correlations with clinical characteristics and neuropsychological performance. Based on resting-state functional MRI (rs-fMRI) data collected from SLE patients and matched healthy controls (HCs), the voxel-mirrored homotopic connectivity (VMHC) analysis was conducted to measure functional homotopy. Subsequently, correlations between altered functional homotopy and clinical/neuropsychological data were analyzed. Compared with the HC group, both NPSLE and non-NPSLE groups showed attenuated homotopic connectivity in middle temporal gyrus (MTG), cuneus (CUN), middle occipital gyrus (MOG), angular gyrus (ANG), and postcentral gyrus (PoCG). NPSLE patients also exhibited decreased homotopic connectivity in inferior parietal gyrus (IPG) and middle frontal gyrus (MFG). Compared with non-NPSLE patients, NPSLE patients showed weaker interhemispheric homotopic functional connectivity in MOG. Decreased homotopic functional connectivity in PoCG, IPG, and MOG were associated with the anxiety state of SLE patients. Our findings revealed attenuated functional homotopy in both NPSLE and non-NPSLE groups compared to the HC group, which appeared to be more severe in patients with comorbid neuropsychiatric lupus. Interhemispheric homotopy dysconnectivity may participate in the neuropathology of anxiety symptoms in SLE.

Fronto-parietal homotopy in resting-state functional connectivity predicts task-switching performance

Homotopic functional connectivity reflects the degree of synchrony in spontaneous activity between homologous voxels in the two hemispheres. Previous studies have associated increased brain homotopy and decreased white matter integrity with performance decrements on different cognitive tasks across the life-span. Here, we correlated functional homotopy, both at the whole-brain level and specifically in fronto-parietal network nodes, with task-switching performance in young adults. Cue-to-target intervals (CTI: 300 vs. 1200 ms) were manipulated on a trial-by-trial basis to modulate cognitive demands and strategic control. We found that mixing costs, a measure of task-set maintenance and monitoring, were significantly correlated to homotopy in different nodes of the fronto-parietal network depending on CTI. In particular, mixing costs for short CTI trials were smaller with lower homotopy in the superior frontal gyrus, whereas mixing costs for long CTI trials were smaller with lower homotopy in the supramarginal gyrus. These results were specific to the fronto-parietal network, as similar voxel-wise analyses within a control language network did not yield significant correlations with behavior. These findings extend previous literature on the relationship between homotopy and cognitive performance to task-switching, and show a dissociable role of homotopy in different fronto-parietal nodes depending on task demands.

Corpus callosum size and homotopic connectivity in Autism spectrum disorder

By examining how morphology of the corpus callosum (CC) in autism spectrum disorder (ASD) may affect functional communication across hemispheres, we hope to provide new insights into the structure-function relationship in the brain. We used a sample of 94 participants from the Autism Brain Imaging Data Exchange (ABIDE) database (55 typically-developing (TD) and 39 with ASD). The CC was segmented into five sub-regions (anterior, mid-anterior, central, mid-posterior, posterior) using FreeSurfer software, which were further examined for group differences. The total volume and specific sub-region volumes of the CC, and interhemispheric (homotopic) functional connectivity were calculated, along with the relationship between volume and connectivity. These measures were correlated with social ability assessed by the Social Responsiveness Scale (SRS). The central sub-region of CC was significantly smaller in ASD, although there was no group difference in total CC volume. ASD participants also showed stronger homotopic connectivity in the superior frontal gyrus. SRS scores were negatively correlated with the CC central sub-region volumes in ASD. The findings of this study add to the body of research showing morphological differences in the CC in ASD as well as connectivity differences. The absence of a significant relationship between structure and homotopic functional connectivity aligns with previous findings.

Endothelial ether lipids link the vasculature to blood pressure, behavior, and neurodegeneration

Vascular disease contributes to neurodegeneration, which is associated with decreased blood pressure in older humans. Plasmalogens, ether phospholipids produced by peroxisomes, are decreased in Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders. However, the mechanistic links between ether phospholipids, blood pressure, and neurodegeneration are not fully understood. Here, we show that endothelium-derived ether phospholipids affect blood pressure, behavior, and neurodegeneration in mice. In young adult mice, inducible endothelial-specific disruption of PexRAP, a peroxisomal enzyme required for ether lipid synthesis, unexpectedly decreased circulating plasmalogens. PexRAP endothelial knockout (PEKO) mice responded normally to hindlimb ischemia but had lower blood pressure and increased plasma renin activity. In PEKO as compared with control mice, tyrosine hydroxylase was decreased in the locus coeruleus, which maintains blood pressure and arousal. PEKO mice moved less, slept more, and had impaired attention to and recall of environmental events as well as mild spatial memory deficits. In PEKO hippocampus, gliosis was increased, and a plasmalogen associated with memory was decreased. Despite lower blood pressure, PEKO mice had generally normal homotopic functional connectivity by optical neuroimaging of the cerebral cortex. Decreased glycogen synthase kinase-3 phosphorylation, a marker of neurodegeneration, was detected in PEKO cerebral cortex. In a co-culture system, PexRAP knockdown in brain endothelial cells decreased glycogen synthase kinase-3 phosphorylation in co-cultured astrocytes that was rescued by incubation with the ether lipid alkylglycerol. Taken together, our findings suggest that endothelium-derived ether lipids mediate several biological processes and may also confer neuroprotection in mice.

Homotopic functional connectivity disruptions in glioma patients are associated with tumor malignancy and overall survival.

BackgroundGliomas exhibit widespread bilateral functional connectivity (FC) alterations that may be associated with tumor grade. Limited studies have examined the connection-level mechanisms responsible for these effects. Given the typically strong FC observed between mirroring/homotopic brain regions in healthy subjects, we hypothesized that homotopic connectivity (HC) is altered in low-grade and high-grade glioma patients and the extent of disruption is associated with tumor grade and predictive of overall survival (OS) in a cohort of de novo high-grade glioma (World Health Organization [WHO] grade 4) patients.MethodsWe used a mirrored FC-derived cortical parcellation to extract blood-oxygen-level-dependent (BOLD) signals and to quantify FC differences between homotopic pairs in normal-appearing brain in a retrospective cohort of glioma patients and healthy controls.ResultsFifty-nine glioma patients (WHO grade 2, n = 9; grade 4 = 50; mean age, 57.5 years) and 30 healthy subjects (mean age, 65.9 years) were analyzed. High-grade glioma patients showed lower HC compared with low-grade glioma patients and healthy controls across several cortical locations and resting-state networks. Connectivity disruptions were also strongly correlated with hemodynamic lags between homotopic regions. Finally, in high-grade glioma patients with known survival times (n = 42), HC in somatomotor and dorsal attention networks were significantly correlated with OS.ConclusionsThese findings demonstrate an association between tumor grade and HC alterations that may underlie global FC changes and provide prognostic information.

Functional Integration Between the Two Brain Hemispheres: Evidence From the Homotopic Functional Connectivity Under Resting State.

Functional integration among neural units is one of the fundamental principles in brain organization that could be examined using resting-state functional connectivity (rs-FC). Interhemispheric functional integration plays a critical role in human cognition. Homotopic functional connectivity (HoFC) under resting state provide an avenue to investigate functional integration between the two brain hemispheres, which can improve the present understanding of how interhemispheric interactions affect cognitive processing. In this review, we summarize the progress of HoFC studies under resting state and highlight how these findings have enhanced our understanding of interhemispheric functional organization of the human brain. Future studies are encouraged to address particular methodological issues and to further ascertain behavioral correlates, brain disease’s modulation, task influence, and genetic basis of HoFC.

Differential early predictive factors for upper and lower extremity motor recovery after ischaemic stroke.

Various clinical and neuroimaging predictive factors have been identified for the recovery of upper extremity (UE) motor function after stroke. However, few studies have addressed factors related to the recovery of lower extremity (LE) motor function after stroke or performed direct comparisons of UE and LE motor recovery in the same set of patients. In this study, predictive factors for UE and LE motor recovery after stroke were investigated using clinical and neuroimaging characteristics. Forty-two subacute ischaemic stroke patients underwent structural and functional magnetic resonance imaging data acquisition and cognitive/behavioral assessments using the Fugl-Meyer assessment, the National Institutes of Health Stroke Scale (NIHSS) and the Mini-Mental State Examination (MMSE) 2 weeks after stroke onset. Neuroimaging factors, including corticospinal tract (CST) fractional anisotropy, lesion volume, CST lesion load and interhemispheric homotopic functional connectivity, were extracted. The outcome of motor function was assessed by Fugl-Meyer assessment scores 3 months after onset. Early clinical and neuroimaging factors for predicting motor recovery were noticeably different for UE and LE. UE motor function recovery was related to age, NIHSS, MMSE, CST lesion load, lesion volume, ipsilesional CST integrity and interhemispheric homotopic functional connectivity. In contrast, LE motor recovery was related to ipsilesional and contralesional CST integrity and MMSE. Specifically, LE recovery showed a strong relationship to the preservation of cognitive function compared with motor impairment. Our results indicate that different mechanisms underlie UE and LE motor recovery after stroke. LE motor recovery seems to be more intensively modulated by cognitive functions than UE.

Increased functional homotopy of the prefrontal cortex is associated with corpus callosum degeneration and working memory decline

Functional homotopy reflects the link between spontaneous activity in a voxel and its counterpart in the opposite hemisphere. Alterations in homotopic functional connectivity (FC) are seen in normal aging, with highest and lowest homotopy being present in sensory-motor and higher-order regions, respectively. Homotopic FC relates to underlying structural connections, but its neurobiological underpinnings remain unclear. The genu of the corpus callosum joins symmetrical parts of the prefrontal cortex (PFC) and is susceptible to age-related degeneration, suggesting that PFC homotopic connectivity is linked to changes in white-matter integrity. We investigated homotopic connectivity changes and whether these were associated with white-matter integrity in 338 individuals. In addition, we examined whether PFC homotopic FC was related to changes in the genu over 10 years and working memory over 5 years. There were increases and decreases in functional homotopy, with the former being prevalent in subcortical and frontal regions. Increased PFC homotopic FC was partially driven by structural degeneration and negatively associated with working memory, suggesting that it reflects detrimental age-related changes.

Modulation of Interhemispheric Functional Coordination in Breast Cancer Patients Receiving Chemotherapy.

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.

How functional network connectivity changes as a result of lesion and recovery: An investigation of the network phenotype of stroke

This study, through a series of univariate and multivariate (classification) analyses, investigated fMRI task-based functional connectivity (FC) at pre- and post-treatment time-points in 18 individuals with chronic post-stroke dysgraphia. The investigation examined the effects of lesion and treatment-based recovery on functional organization, focusing on both inter-hemispheric (homotopic) and intra-hemispheric connectivity. The work confirmed, in the chronic stage, the “network phenotype of stroke injury” proposed by Siegel et al. (2016) consisting of abnormally low inter-hemispheric connectivity as well as abnormally high intra-hemispheric (ipsilesional) connectivity. In terms of recovery-based changes in FC, this study found overall hyper-normalization of these abnormal inter and intra-hemispheric connectivity patterns, suggestive of over-correction. Specifically, treatment-related homotopic FC increases were observed between left and right dorsal frontal-parietal regions. With regard to intra-hemispheric connections, recovery was dominated by increased ipsilateral connectivity between frontal and parietal regions along with decreased connectivity between the frontal regions and posterior parietal-occipital-temporal areas. Both inter and intra-hemispheric changes were associated with treatment-driven improvements in spelling performance. We suggest an interpretation according to which, with treatment, as posterior orthographic processing areas become more effective, executive control from frontal-parietal networks becomes less necessary.

Portable, field-based neuroimaging using high-density diffuse optical tomography

Behavioral and cognitive tests in individuals who were malnourished as children have revealed malnutrition-related deficits that persist throughout the lifespan. These findings have motivated recent neuroimaging investigations that use highly portable functional near-infrared spectroscopy (fNIRS) instruments to meet the demands of brain imaging experiments in low-resource environments and enable longitudinal investigations of brain function in the context of long-term malnutrition. However, recent studies in healthy subjects have demonstrated that high-density diffuse optical tomography (HD-DOT) can significantly improve image quality over that obtained with sparse fNIRS imaging arrays. In studies of both task activations and resting state functional connectivity, HD-DOT is beginning to approach the data quality of fMRI for superficial cortical regions. In this work, we developed a customized HD-DOT system for use in malnutrition studies in Cali, Colombia. Our results evaluate the performance of the HD-DOT instrument for assessing brain function in a cohort of malnourished children. In addition to demonstrating portability and wearability, we show the HD-DOT instrument’s sensitivity to distributed brain responses using a sensory processing task and measurements of homotopic functional connectivity. Task-evoked responses to the passive word listening task produce activations localized to bilateral superior temporal gyrus, replicating previously published work using this paradigm. Evaluating this localization performance across sparse and dense reconstruction schemes indicates that greater localization consistency is associated with a dense array of overlapping optical measurements. These results provide a foundation for additional avenues of investigation, including identifying and characterizing a child’s individual malnutrition burden and eventually contributing to intervention development.

Aberrant inter-hemispheric coordination characterizes the progression of minimal hepatic encephalopathy in patients with HBV-related cirrhosis.

Patients with hepatitis B virus (HBV)-related cirrhosis (HBV-RC) and minimal hepatic encephalopathy (MHE) exhibit alterations in homotopic inter-hemispheric functional connectivity (FC) and corpus callosum (CC) degeneration. However, the progression of inter-hemispheric dysconnectivity in cirrhotic patients from no MHE (NMHE) to MHE and its association with the progression of diseased-related cognitive impairment remain uncharacterized. We hypothesized that inter-hemispheric dysconnectivity exists in NMHE patients and further deteriorates at the MHE stage, which is associated with performance measured by psychometric hepatic encephalopathy scores (PHES) that can characterize cirrhotic patients with NMHE and MHE. Using inter-hemispheric homotopic FC and CC (and its subfields) volumetric measurements in 31 patients with HBV-RC (17 with NMHE and 14 with MHE) and 37 healthy controls, we verified that MHE patients had significant attenuated inter-hemispheric homotopic FC in the bilateral cuneus, post-central gyrus, inferior parietal lobule, and superior temporal gyms, as well as CC degeneration in total CC, CC2, CC3, and CC4 (each comparison had a corrected P < 0.05). In contrast, NMHE patients had relatively less severe inter-hemispheric homotopic FC and no CC degeneration. In addition, the degeneration of the CC and inter-hemispheric homotopic functional disconnections correlated with poor PHES performances in all cirrhotic patients (NMHE and MHE). Furthermore, impairment of inter-hemispheric homotopic FC partially mediated the association between CC degeneration and worse PHES performance. Notably, a combination of inter-hemispheric homotopic FC and CC volumes had higher discriminative values according to the area under the curve (AUC) score (AUC=0.908, P < 0.001) to classify patients into MHE or NMHE groups when compared with either alone. Our findings shed light on the progression of inter-hemispheric dysconnectivity in relation to the progression of disease-related cognitive impairment in patients with HBV-RC.

Decreased interhemispheric functional connectivity rather than corpus callosum volume as a potential biomarker for autism spectrum disorder

Previous studies have implicated both structural and interhemispheric functional connectivity alterations in autism spectrum disorder (ASD) although findings are inconsistent. There is evidence that connectivity between corresponding regions in each hemisphere (homotopic) may be of particular importance and therefore the present study used the Autism Brain Imaging Data Exchange data to investigate ASD-related resting-state and structural alterations as well as associations with symptom severity (Autism Diagnostic Observation Schedule – ADOS). We employed a voxel-mirrored homotopic connectivity analysis to compare interhemispheric functional connectivity in 409 ASD and 455 typically developing subjects. Additionally, voxel-based morphology was used to investigate volumetric differences in the corpus callosum, the major commissure for interhemispheric communication. ASD subjects demonstrated significant reductions in interhemispheric functional connections between regions in the default mode network (medial prefrontal, posterior cingulate and precuneus), salience network (anterior cingulate and insula), mirror neuron/motor systems (inferior frontal gyrus, inferior parietal lobule, precentral gyrus, supplementary motor area), thalamus and auditory (superior temporal gyrus) and visual systems (lingual, fusiform and inferior occipital gyri). A support vector machine analysis based on interhemispheric connectivity (but not all homotopic) revealed an average classification accuracy of 88.70% for distinguishing ASD from controls across different sites. In ASD subjects symptom severity as measured by ADOS was negatively associated with posterior cingulate, insula and superior temporal gyrus homotopic functional connectivity. While ASD subjects displayed reduced anterior and posterior callosal volumes they were not associated with either ADOS scores or functional connectivity changes. Our findings suggest that reduced interhemispheric connectivity involving homotopic regions may be a potential biomarker for ASD with bilateral posterior cingulate, insula and superior temporal gyrus connections being associated with symptom severity.

Interhemispheric functional connectivity in the zebra finch brain, absent the corpus callosum in normal ontogeny

Bilaterally symmetric intrinsic brain activity (homotopic functional connectivity; FC) is a fundamental feature of the mammalian brain's functional architecture. In mammals, homotopic FC is primarily mediated by the corpus callosum (CC), a large interhemispheric white matter tract thought to balance the bilateral coordination and hemispheric specialization critical for many complex brain functions, including human language. The CC first emerged with the Eutherian (placental) mammals ∼160 MYA and is not found among other vertebrates. Despite this, other vertebrates also exhibit complex brain functions requiring hemispheric specialization and coordination. For example, the zebra finch (Taeniopygia guttata) songbird learns to sing from tutors much as humans acquire speech and must balance hemispheric specialization and coordination to successfully learn and produce song. We therefore tested whether the zebra finch also exhibits homotopic FC, despite lacking the CC. Resting-state fMRI analyses demonstrated widespread homotopic FC throughout the zebra finch brain across development, including within a network required for learned song that lacks direct interhemispheric structural connectivity. The presence of homotopic FC in a non-Eutherian suggests that ancestral pathways, potentially including indirect connectivity via the anterior commissure, are sufficient for maintaining a homotopic functional architecture, an insight with broad implications for understanding interhemispheric coordination across phylogeny.

Severe asymptomatic carotid stenosis is associated with robust reductions in homotopic functional connectivity.

Severe (>70% narrowing) asymptomatic carotid stenosis (SACS) is associated with cognitive impairment and future strokes, and connectivity basis for the remote brain consequences is poorly understood. Here we explored homotopic connectivity and parenchymal lesions measured by multimodal magnetic resonance imaging (MRI) parameters in patients with SACS. Twenty-four patients with SACS (19 males/5 females; 64.25±7.18 years), 24 comorbidities-matched controls (19 males/5 females; 67.16±6.10 years), and an independent sample of elderly healthy controls (39 females/45 males; 57.92±4.94 years) were included. Homotopic functional connectivity (FC) of resting-state functional MRI and structural connectivity (SC) of deterministic tractography were assessed. Arterial spin labeling based cerebral perfusion, susceptibility weighted imaging based microhemorrhagic lesions, and T2-weighted white matter hyperintensities were also quantified. Significant and robust homotopic reductions (validated by the independent dataset and support vector machine-based machine learning) were identified in the Perisylvian fissure in patients with SACS (false discovery rate corrected, voxel p<0.05). These involved regions span across several large-scale brain systems, which include the somatomotor, salience, dorsal attention, and orbitofrontal-limbic networks. This significantly reduced homotopic FC can be partially explained by the corrected white matter hyperintensity size. Further association analyses suggest that the decreased homotopic FC in these brain regions is most closely associated with delayed memory recall, sensorimotor processing, and other simple cognitive functions. Together, these results suggest that SACS predominately affects the lower-order brain systems, while higher-order systems, especially the topographies of default mode network, are least impacted initially, but may serve as a hallmark precursor to vascular dementia. Thus, assessment of homotopic FC may provide a means of noninvasively tracking the progression of downstream brain damage following asymptomatic carotid stenosis.

Focal epilepsy caused by single cerebral cavernous malformation (CCM) is associated with regional and global resting state functional connectivity (FC) disruption.

Epilepsy, including the type with focal onset, is increasingly viewed as a disorder of the brain network. Here we employed the functional connectivity (FC) metrics estimated from the resting state functional MRI (rsfMRI) to investigate the changes of brain network associated with focal epilepsy caused by single cerebral cavernous malformation (CCM). Eight CCM subjects and 21 age and gender matched controls were enrolled in the study. Seven of 8 CCM subjects underwent surgical resection of the CCM and became seizure free and 4 of the surgical subjects underwent a repeat rsfMRI study. We showed that there was both regional and global disruption of the FC values among the CCM subjects including decreased in homotopic FC (HFC) and global FC (GFC) in the regions of interest (ROIs) where the CCMs were located. There was also the disruption of the default mode network (DMN) especially the FC between the middle prefrontal cortex (MPFC) and the right lateral parietal cortex (LPR) among these individuals. We observed the trend of alleviation of these disruptions after the individual has become seizure free from the surgical resection of the CCM. Using a voxel-based approach, we found the disruption of the HFC and GFC in the brain tissue immediately adjacent to the CCM and the severity of the disruption appeared inversely proportional to the distance of the brain tissue to the lesion. Our findings confirm the disruption of normal brain networks from focal epilepsy, a process that may be reversible with successful surgical treatments rendering patients seizure free. Some voxel-based metrics may help identify the epileptogenic zone and guide the surgical resection.

Nicotine in action: cigarette smoking modulated homotopic functional connectivity in schizophrenia.

Cigarette smoking is intimately associated with both early onset and increased severity of schizophrenia. The self-medication hypothesis suggests that nicotine can relieve or restore neurocognitive deficits and symptoms associated with schizophrenia. Schizophrenia patients and healthy subjects who smoked showed deficits in communication between their hemispheres. These homotopic connectivity mechanisms associated with both schizophrenia and smoking comorbidity were largely unknown until now. A mixed sample including patients with schizophrenia (22 smokers and 27 non-smokers) and healthy controls (22 smokers and 21 non-smokers) based on clinical diagnoses and cigarette dependence were recruited for the current study. All subjects underwent resting-state functional magnetic resonance imaging to determine possible interactions between schizophrenia and smoking, and to determine the main effects of schizophrenia and smoking on homotopic functional connectivity. Decreased homotopic functional connectivity of the subgenual anterior cingulate cortex suggested a main effect of schizophrenia and smoking-an additive effect. Furthermore, we found an antagonistic interaction effect between schizophrenia and smoking located in the ventrolateral prefrontal cortex (VLPFC). In addition, the connectivity strength of the bilateral VLPFC was negatively correlated with the Positive and Negative Syndrome Scale Negative scores and positively correlated with lifetime smoking. These results suggest that smoking has multiple effects on the modulation of interhemispheric connectivity in schizophrenia. Our findings provide valuable information underlying the pathophysiological mechanisms of schizophrenia and offer a potential target for future clinical treatment of schizophrenia and smoking comorbidity.