EEG-MEG Integration Enhances the Characterization of Functional and Effective Connectivity in the Resting State Network

At the sensor level many aspects, such as spectral power, functional and effective connectivity as well as relative-power-ratio ratio (RPR) and spatial resolution have been comprehensively investigated through both electroencephalography (EEG) and magnetoencephalography (MEG). Despite this, differences between both modalities have not yet been systematically studied by direct comparison. It remains an open question as to whether the integration of EEG and MEG data would improve the information obtained from the above mentioned parameters. Here, EEG (64-channel system) and MEG (275 sensor system) were recorded simultaneously in conditions with eyes open (EO) and eyes closed (EC) in 29 healthy adults. Spectral power, functional and effective connectivity, RPR, and spatial resolution were analyzed at five different frequency bands (delta, theta, alpha, beta and gamma). Networks of functional and effective connectivity were described using a spatial filter approach called the dynamic imaging of coherent sources (DICS) followed by the renormalized partial directed coherence (RPDC). Absolute mean power at the sensor level was significantly higher in EEG than in MEG data in both EO and EC conditions. At the source level, there was a trend towards a better performance of the combined EEG+MEG analysis compared with separate EEG or MEG analyses for the source mean power, functional correlation, effective connectivity for both EO and EC. The network of coherent sources and the spatial resolution were similar for both the EEG and MEG data if they were analyzed separately. Results indicate that the combined approach has several advantages over the separate analyses of both EEG and MEG. Moreover, by a direct comparison of EEG and MEG, EEG was characterized by significantly higher values in all measured parameters in both sensor and source level. All the above conclusions are specific to the resting state task and the specific analysis used in this study to have general conclusion multi-center studies would be helpful.     

Escitalopram Decreases Cross-Regional Functional Connectivity within the Default-Mode Network

The default-mode network (DMN), which comprises medial frontal, temporal and parietal regions, is part of the brain’s intrinsic organization. The serotonergic (5-HT) neurotransmitter system projects to DMN regions from midbrain efferents, and manipulation of this system could thus reveal insights into the neurobiological mechanisms of DMN functioning. Here, we investigate intrinsic functional connectivity of the DMN as a function of activity of the serotonergic system, through the administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram. We quantified DMN functional connectivity using an approach based on dual-regression. Specifically, we decomposed group data of a subset of the functional time series using spatial independent component analysis, and projected the group spatial modes to the same and an independent resting state time series of individual participants. We found no effects of escitalopram on global functional connectivity of the DMN at the map-level; that is, escitalopram did not alter the global functional architecture of the DMN. However, we found that escitalopram decreased DMN regional pairwise connectivity, which included anterior and posterior cingulate cortex, hippocampal complex and lateral parietal regions. Further, regional DMN connectivity covaried with alertness ratings across participants. Our findings show that escitalopram altered intrinsic regional DMN connectivity, which suggests that the serotonergic system plays an important role in DMN connectivity and its contribution to cognition. Pharmacological challenge designs may be a useful addition to resting-state functional MRI to investigate intrinsic brain functional organization.     

Aberrant Functional Connectivity of Resting State Networks in Transient Ischemic Attack

Background

Transient ischemic attack (TIA) is usually defined as a neurologic ischemic disorder without permanent cerebral infarction. Studies have showed that patients with TIA can have lasting cognitive functional impairment. Inherent brain activity in the resting state is spatially organized in a set of specific coherent patterns named resting state networks (RSNs), which epitomize the functional architecture of memory, language, attention, visual, auditory and somato-motor networks. Here, we aimed to detect differences in RSNs between TIA patients and healthy controls (HCs).

Methods

Twenty one TIA patients suffered an ischemic event and 21 matched HCs were enrolled in the study. All subjects were investigated using cognitive tests, psychiatric tests and functional magnetic resonance imaging (fMRI). Independent component analysis (ICA) was adopted to acquire the eight brain RSNs. Then one-sample t-tests were calculated in each group to gather the spatial maps of each RSNs, followed by second level analysis to investigate statistical differences on RSNs between twenty one TIA patients and 21 controls. Furthermore, a correlation analysis was performed to explore the relationship between functional connectivity (FC) and cognitive and psychiatric scales in TIA group.

Results

Compared with the controls, TIA patients exhibited both decreased and increased functional connectivity in default mode network (DMN) and self-referential network (SRN), and decreased functional connectivity in dorsal attention network (DAN), central-executive network (CEN), core network (CN), somato-motor network (SMN), visual network (VN) and auditory network (AN). There was no correlation between neuropsychological scores and functional connectivity in regions of RSNs.

Conclusions

We observed selective impairments of RSN intrinsic FC in TIA patients, whose all eight RSNs had aberrant functional connectivity. These changes indicate that TIA is a disease with widely abnormal brain networks. Our results might put forward a novel way to look into neuro-pathophysiological mechanisms in TIA patients.     

Acute Effects of Modafinil on Brain Resting State Networks in Young Healthy Subjects

Background

There is growing debate on the use of drugs that promote cognitive enhancement. Amphetamine-like drugs have been employed as cognitive enhancers, but they show important side effects and induce addiction. In this study, we investigated the use of modafinil which appears to have less side effects compared to other amphetamine-like drugs. We analyzed effects on cognitive performances and brain resting state network activity of 26 healthy young subjects.

Methodology

A single dose (100 mg) of modafinil was administered in a double-blind and placebo-controlled study. Both groups were tested for neuropsychological performances with the Raven’s Advanced Progressive Matrices II set (APM) before and three hours after administration of drug or placebo. Resting state functional magnetic resonance (rs-FMRI) was also used, before and after three hours, to investigate changes in the activity of resting state brain networks. Diffusion Tensor Imaging (DTI) was employed to evaluate differences in structural connectivity between the two groups. Protocol ID: Modrest_2011; {"type":"clinical-trial","attrs":{"text":"NCT01684306","term_id":"NCT01684306"}}NCT01684306; http://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT01684306","term_id":"NCT01684306"}}NCT01684306.

Principal Findings

Results indicate that a single dose of modafinil improves cognitive performance as assessed by APM. Rs-fMRI showed that the drug produces a statistically significant increased activation of Frontal Parietal Control (FPC; p<0.04) and Dorsal Attention (DAN; p<0.04) networks. No modifications in structural connectivity were observed.

Conclusions and Significance

Overall, our findings support the notion that modafinil has cognitive enhancing properties and provide functional connectivity data to support these effects.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01684306","term_id":"NCT01684306"}}NCT01684306 http://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT01684306","term_id":"NCT01684306"}}NCT01684306.     

Motor Imagery Learning Modulates Functional Connectivity of Multiple Brain Systems in Resting State

Background

Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning.

Methodology/Principal Findings

We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN.

Conclusions/Significance

These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning.     

Resting State fMRI Reveals Diminished Functional Connectivity in a Mouse Model of Amyloidosis

Introduction

Functional connectivity (FC) studies have gained immense popularity in the evaluation of several neurological disorders, such as Alzheimer’s disease (AD). AD is a complex disorder, characterised by several pathological features. The problem with FC studies in patients is that it is not straightforward to focus on a specific aspect of pathology. In the current study, resting state functional magnetic resonance imaging (rsfMRI) is applied in a mouse model of amyloidosis to assess the effects of amyloid pathology on FC in the mouse brain.

Methods

Nine APP/PS1 transgenic and nine wild-type mice (average age 18.9 months) were imaged on a 7T MRI system. The mice were anesthetized with medetomidine and rsfMRI data were acquired using a gradient echo EPI sequence. The data were analysed using a whole brain seed correlation analysis and interhemispheric FC was evaluated using a pairwise seed analysis. Qualitative histological analyses were performed to assess amyloid pathology, inflammation and synaptic deficits.

Results

The whole brain seed analysis revealed an overall decrease in FC in the brains of transgenic mice compared to wild-type mice. The results showed that interhemispheric FC was relatively preserved in the motor cortex of the transgenic mice, but decreased in the somatosensory cortex and the hippocampus when compared to the wild-type mice. The pairwise seed analysis confirmed these results. Histological analyses confirmed the presence of amyloid pathology, inflammation and synaptic deficits in the transgenic mice.

Conclusions

In the current study, rsfMRI demonstrated decreased FC in APP/PS1 transgenic mice compared to wild-type mice in several brain regions. The APP/PS1 transgenic mice had advanced amyloid pathology across the brain, as well as inflammation and synaptic deficits surrounding the amyloid plaques. Future studies should longitudinally evaluate APP/PS1 transgenic mice and correlate the rsfMRI findings to specific stages of amyloid pathology.     

Abnormalities of Resting State Functional Connectivity Are Related to Sustained Attention Deficits in MS

Objectives

Resting state (RS) functional MRI recently identified default network abnormalities related to cognitive impairment in MS. fMRI can also be used to map functional connectivity (FC) while the brain is at rest and not adhered to a specific task. Given the importance of the anterior cingulate cortex (ACC) for higher executive functioning in MS, we here used the ACC as seed-point to test for differences and similarities in RS-FC related to sustained attention between MS patients and controls.

Design

Block-design rest phases of 3 Tesla fMRI data were analyzed to assess RS-FC in 31 patients (10 clinically isolated syndromes, 16 relapsing-remitting, 5 secondary progressive MS) and 31 age- and gender matched healthy controls (HC). Participants underwent extensive cognitive testing.

Observations

In both groups, signal changes in several brain areas demonstrated significant correlation with RS-activity in the ACC. These comprised the posterior cingulate cortex (PCC), insular cortices, the right caudate, right middle temporal gyrus, angular gyri, the right hippocampus, and the cerebellum. Compared to HC, patients showed increased FC between the ACC and the left angular gyrus, left PCC, and right postcentral gyrus. Better cognitive performance in the patients was associated with increased FC to the cerebellum, middle temporal gyrus, occipital pole, and the angular gyrus.

Conclusion

We provide evidence for adaptive changes in RS-FC in MS patients compared to HC in a sustained attention network. These results extend and partly mirror findings of task-related fMRI, suggesting FC may increase our understanding of cognitive dysfunction in MS.     

Resting State BOLD Functional Connectivity at 3T: Spin Echo versus Gradient Echo EPI

Previous evidence showed that, due to refocusing of static dephasing effects around large vessels, spin-echo (SE) BOLD signals offer an increased linearity and promptness with respect to gradient-echo (GE) acquisition, even at low field. These characteristics suggest that, despite the reduced sensitivity, SE fMRI might also provide a potential benefit when investigating spontaneous fluctuations of brain activity. However, there are no reports on the application of spin-echo fMRI for connectivity studies at low field. In this study we compared resting state functional connectivity as measured with GE and SE EPI sequences at 3T. Main results showed that, within subject, the GE sensitivity is overall larger with respect to that of SE, but to a less extent than previously reported for activation studies. Noteworthy, the reduced sensitivity of SE was counterbalanced by a reduced inter-subject variability, resulting in comparable group statistical connectivity maps for the two sequences. Furthermore, the SE method performed better in the ventral portion of the default mode network, a region affected by signal dropout in standard GE acquisition. Future studies should clarify if these features of the SE BOLD signal can be beneficial to distinguish subtle variations of functional connectivity across different populations and/or treatments when vascular confounds or regions affected by signal dropout can be a critical issue.     

Decreased Functional Connectivity of Homotopic Brain Regions in Chronic Stroke Patients: A Resting State fMRI Study

The recovery of motor functions is accompanied by brain reorganization, and identifying the inter-hemispheric interaction post stroke will conduce to more targeted treatments. However, the alterations of bi-hemispheric coordination pattern between homologous areas in the whole brain for chronic stroke patients were still unclear. The present study focuses on the functional connectivity (FC) of mirror regions of the whole brain to investigate the inter-hemispheric interaction using a new fMRI method named voxel-mirrored homotopic connectivity (VMHC). Thirty left subcortical chronic stroke patients with pure motor deficits and 37 well-matched healthy controls (HCs) underwent resting-state fMRI scans. We employed a VMHC analysis to determine the brain areas showed significant differences between groups in FC between homologous regions, and we explored the relationships between the mean VMHC of each survived area and clinical tests within patient group using Pearson correlation. In addition, the brain areas showed significant correlations between the mean VMHC and clinical tests were defined as the seed regions for whole brain FC analysis. Relative to HCs, patients group displayed lower VMHC in the precentral gyrus, postcentral gyrus, inferior frontal gyrus, middle temporal gyrus, calcarine gyrus, thalamus, cerebellum anterior lobe, and cerebellum posterior lobe (CPL). Moreover, the VMHC of CPL was positively correlated with the Fugl–Meyer Score of hand (FMA-H), while a negative correlation between illness duration and the VMHC of this region was also detected. Furthermore, we found that when compared with HCs, the right CPL exhibited reduced FC with the left precentral gyrus, inferior frontal gyrus, inferior parietal lobule, middle temporal gyrus, thalamus and hippocampus. Our results suggest that the functional coordination across hemispheres is impaired in chronic stroke patients, and increased VMHC of the CPL is significantly associated with higher FMA-H scores. These findings may be helpful in understanding the mechanism of hand deficit after stroke, and the CPL may serve as a target region for hand rehabilitation following stroke.     

Disruptions in Resting State Functional Connectivity and Cerebral Blood Flow in Mild Traumatic Brain Injury Patients

Mild traumatic brain injury (mTBI) is often occult to conventional imaging techniques. However, there is growing evidence that mTBI patients who lack evidence of structural intracranial injury may develop post-concussive syndrome (PCS). We investigated longitudinal alterations in resting state functional connectivity (rs-FC) in brain networks in a population of 28 patients compared to 28 matched control participants. Rs-FC and cerebral blood flow (CBF) within the nodes of the Default Mode Network (DMN) and Task Positive Network (TPN) were assessed at three time points including acute, sub-acute, and chronic stages following mTBI. Participants received the Automated Neuropsychological Assessment Metrics (ANAM) to assess cognitive performance. Main findings indicate that despite normalized cognitive performance, chronic mTBI patients demonstrate increased rs-FC between the DMN and regions associated with the salience network (SN) and TPN compared to the control populations, as well as reduced strength of rs-FC within the DMN at the acute stage of injury. In addition, chronic mTBI patients demonstrate an imbalance in the ratio of CBF between nodes of the DMN and TPN. Furthermore, preliminary exploratory analysis suggests that compared to those without chronic PCS, patients with chronic PCS reveal an imbalance in the ratio of CBF between the DMN nodes and TPN nodes across multiple stages of recovery. Findings suggest that the altered network perfusion with the associated changes in rs-FC may be a possible predictor of which mTBI patients will develop chronic PCS.     

Modafinil Alters Intrinsic Functional Connectivity of the Right Posterior Insula: A Pharmacological Resting State fMRI Study

Background

Modafinil is employed for the treatment of narcolepsy and has also been, off-label, used to treat cognitive dysfunction in neuropsychiatric disorders. In a previous study, we have reported that single dose administration of modafinil in healthy young subjects enhances fluid reasoning and affects resting state activity in the Fronto Parietal Control (FPC) and Dorsal Attention (DAN) networks. No changes were found in the Salience Network (SN), a surprising result as the network is involved in the modulation of emotional and fluid reasoning. The insula is crucial hub of the SN and functionally divided in anterior and posterior subregions.

Methodology

Using a seed-based approach, we have now analyzed effects of modafinil on the functional connectivity (FC) of insular subregions.

Principal Findings

Analysis of FC with resting state fMRI (rs-FMRI) revealed increased FC between the right posterior insula and the putamen, the superior frontal gyrus and the anterior cingulate cortex in the modafinil-treated group.

Conclusions

Modafinil is considered a putative cognitive enhancer. The rs-fMRI modifications that we have found are consistent with the drug cognitive enhancing properties and indicate subregional targets of action.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01684306","term_id":"NCT01684306"}}NCT01684306     

Altered Functional Connectivity between Emotional and Cognitive Resting State Networks in Euthymic Bipolar I Disorder Patients

Bipolar disorder is characterized by a functional imbalance between hyperactive ventral/limbic areas and hypoactive dorsal/cognitive brain regions potentially contributing to affective and cognitive symptoms. Resting-state studies in bipolar disorder have identified abnormal functional connectivity between these brain regions. However, most of these studies used a seed-based approach, thus restricting the number of regions that were analyzed. Using data-driven approaches, researchers identified resting state networks whose spatial maps overlap with frontolimbic areas such as the default mode network, the frontoparietal networks, the salient network, and the meso/paralimbic network. These networks are specifically engaged during affective and cognitive tasks and preliminary evidence suggests that functional connectivity within and between some of these networks is impaired in bipolar disorder. The present study used independent component analysis and functional network connectivity approaches to investigate functional connectivity within and between these resting state networks in bipolar disorder. We compared 30 euthymic bipolar I disorder patients and 35 age- and gender-matched healthy controls. Inter-network connectivity analysis revealed increased functional connectivity between the meso/paralimbic and the right frontoparietal network in bipolar disorder. This abnormal connectivity pattern did not correlate with variables related to the clinical course of the disease. The present finding may reflect abnormal integration of affective and cognitive information in ventral-emotional and dorsal-cognitive networks in euthymic bipolar patients. Furthermore, the results provide novel insights into the role of the meso/paralimbic network in bipolar disorder.     

Decreased Thalamocortical Functional Connectivity after 36 Hours of Total Sleep Deprivation: Evidence from Resting State fMRI

Objectives

The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections, which hold a key function in segregating internally and externally directed awareness information. Previous task-related studies have revealed altered activities of the thalamus after total sleep deprivation (TSD). However, it is still unclear how TSD impacts on the communication between the thalamus and cerebral cortex. In this study, we examined changes of thalamocortical functional connectivity after 36 hours of total sleep deprivation by using resting state function MRI (fMRI).

Materials and Methods

Fourteen healthy volunteers were recruited and performed fMRI scans before and after 36 hours of TSD. Seed-based functional connectivity analysis was employed and differences of thalamocortical functional connectivity were tested between the rested wakefulness (RW) and TSD conditions.

Results

We found that the right thalamus showed decreased functional connectivity with the right parahippocampal gyrus, right middle temporal gyrus and right superior frontal gyrus in the resting brain after TSD when compared with that after normal sleep. As to the left thalamus, decreased connectivity was found with the right medial frontal gyrus, bilateral middle temporal gyri and left superior frontal gyrus.

Conclusion

These findings suggest disruptive changes of the thalamocortical functional connectivity after TSD, which may lead to the decline of the arousal level and information integration, and subsequently, influence the human cognitive functions.     

Interhemispheric Functional Connectivity and Its Relationships with Clinical Characteristics in Major Depressive Disorder: A Resting State fMRI Study

Background

Abnormalities in large-scale, structural and functional brain connectivity have been increasingly reported in patients with major depressive disorder (MDD). However, MDD-related alterations in functional interaction between the cerebral hemispheres are still not well understood. Resting state fMRI, which reveals spontaneous neural fluctuations in blood oxygen level dependent signals, provides a means to detect interhemispheric functional coherence. We examined the resting state functional connectivity (RSFC) between the two hemispheres and its relationships with clinical characteristics in MDD patients using a recently proposed measurement named “voxel-mirrored homotopic connectivity (VMHC)”.

Methodology/Principal Findings

We compared the interhemispheric RSFC, computed using the VMHC approach, of seventeen first-episode drug-naive patients with MDD and seventeen healthy controls. Compared to the controls, MDD patients showed significant VMHC decreases in the medial orbitofrontal gyrus, parahippocampal gyrus, fusiform gyrus, and occipital regions including the middle occipital gyrus and cuneus. In MDD patients, a negative correlation was found between VMHC of the fusiform gyrus and illness duration. Moreover, there were several regions whose VMHC showed significant negative correlations with the severity of cognitive disturbance, including the prefrontal regions, such as middle and inferior frontal gyri, and two regions in the cereballar crus.

Conclusions/Significance

These findings suggest that the functional coordination between homotopic brain regions is impaired in MDD patients, thereby providing new evidence supporting the interhemispheric connectivity deficits of MDD. The significant correlations between the VMHC and clinical characteristics in MDD patients suggest potential clinical implication of VMHC measures for MDD. Interhemispheric RSFC may serve as a useful screening method for evaluating MDD where neural connectivity is implicated in the pathophysiology.     

Reduced Fractional Anisotropy of Corpus Callosum Modulates Inter-Hemispheric Resting State Functional Connectivity in Migraine Patients without Aura

Background

Diffusion tensor imaging (DTI) study revealed reduced fractional anisotropy (FA) values in the corpus callosum (CC) in migraine patients without aura. Abnormalities in white matter integrity, particularly in the CC, may affect inter-hemispheric resting state functional connectivity (RSFC). Unfortunately, relatively little is known about the alterations in functional interactions between the cerebral hemispheres during resting state in migraine patients without aura, and even less about how the inter-hemispheric RSFC are affected by the abnormalities of the CC.

Methods and findings

Twenty-one migraine patients without aura and 21 healthy controls participated in this study, age-, sex-, and education-matched. Tract-based spatial statistics (TBSS) was employed to investigate the white matter alterations of the CC. Meanwhile, voxel-mirrored homotopic connectivity (VMHC) was used to compare the inter-hemispheric RSFC differences between the patients and controls. TBSS analysis revealed reduced FA values in the genu and the splenium of CC in patient group. VMHC analysis showed decreased inter-hemispheric RSFC of anterior cingulate cortex (ACC) in migraine patients without aura relative to that of the controls. Furthermore, in migraine patients without aura, the reduced FA values of the genu of CC correlated with the decreased inter-hemispheric RSFC of the ACC.

Conclusions

Our findings demonstrated that the migraine patients without aura showed reduced FA values of the genu of CC and decreased inter-hemispheric RSFC of the ACC. The correlation between the above structural and functional changes suggested that the reduced fractional anisotropy (FA) of CC modulates inter-hemispheric VMHC in migraine patients without aura. Our results demonstrated that the VMHC alterations of ACC can reflect the FA changes of the genu of CC in migraine patients without aura.     

Decreased Resting Functional Connectivity after Traumatic Brain Injury in the Rat

Traumatic brain injury (TBI) contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ) seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and contralateral parietal cortex and other regions. Our data provide the first evidence on abnormal functional connectivity after experimental TBI assessed with resting state BOLD-fMRI.     

Reproducibility of Resting State Connectivity in Patients with Stable Multiple Sclerosis

Given increasing efforts to use resting-state fMRI (rfMRI) as a biomarker of disease progression in multiple sclerosis (MS) we here explored the reproducibility of longitudinal rfMRI over three months in patients with clinically and radiologically stable MS. To pursue this aim, two approaches were applied in nine rfMRI networks: First, the intraclass correlation coefficient (ICC 3,1) was assessed for the mean functional connectivity maps across the entire network and a region of interest (ROI). Second, the ratio of overlap between Z-thresholded connectivity maps for each network was assessed. We quantified between-session functional reproducibility of rfMRI for 20 patients with stable MS and 14 healthy controls (HC). Nine rfMRI networks (RSNs) were examined at baseline and after 3 months of follow-up: three visual RSNs, the default-mode network, sensorimotor-, auditory-, executive control, and the left and right fronto-parietal RSN. ROI analyses were constrained to thresholded overlap masks for each individual (Z>0) at baseline and follow-up.In both stable MS and HC mean functional connectivity across the entire network did not reach acceptable ICCs for several networks (ICC<0.40) but we found a high reproducibility of ROI ICCs and of the ratio of overlap. ROI ICCs of all nine networks were between 0.98 and 0.99 for HC and ranged from 0.88 to 0.99 in patients with MS, respectively. The ratio of overlap for all networks was similar for both groups, ranging from 0.60 to 0.75.Our findings attest to a high reproducibility of rfMRI networks not only in HC but also in patients with stable MS when applying ROI analysis. This supports the utility of rfMRI to monitor functional changes related to disease progression or therapeutic interventions in MS.     

An Evaluation of the Left-Brain vs. Right-Brain Hypothesis with Resting State Functional Connectivity Magnetic Resonance Imaging

Lateralized brain regions subserve functions such as language and visuospatial processing. It has been conjectured that individuals may be left-brain dominant or right-brain dominant based on personality and cognitive style, but neuroimaging data has not provided clear evidence whether such phenotypic differences in the strength of left-dominant or right-dominant networks exist. We evaluated whether strongly lateralized connections covaried within the same individuals. Data were analyzed from publicly available resting state scans for 1011 individuals between the ages of 7 and 29. For each subject, functional lateralization was measured for each pair of 7266 regions covering the gray matter at 5-mm resolution as a difference in correlation before and after inverting images across the midsagittal plane. The difference in gray matter density between homotopic coordinates was used as a regressor to reduce the effect of structural asymmetries on functional lateralization. Nine left- and 11 right-lateralized hubs were identified as peaks in the degree map from the graph of significantly lateralized connections. The left-lateralized hubs included regions from the default mode network (medial prefrontal cortex, posterior cingulate cortex, and temporoparietal junction) and language regions (e.g., Broca Area and Wernicke Area), whereas the right-lateralized hubs included regions from the attention control network (e.g., lateral intraparietal sulcus, anterior insula, area MT, and frontal eye fields). Left- and right-lateralized hubs formed two separable networks of mutually lateralized regions. Connections involving only left- or only right-lateralized hubs showed positive correlation across subjects, but only for connections sharing a node. Lateralization of brain connections appears to be a local rather than global property of brain networks, and our data are not consistent with a whole-brain phenotype of greater “left-brained” or greater “right-brained” network strength across individuals. Small increases in lateralization with age were seen, but no differences in gender were observed.     

Resting Brain Perfusion and Selected Vascular Risk Factors in Healthy Elderly Subjects

Background and Purpose

Both cerebral hypoperfusion and vascular risk factors have been implicated in early aging of the brain and the development of neurodegenerative disease. However, the current knowledge of the importance of cardiovascular health on resting brain perfusion is limited. The aim of the present study was to elucidate the relation between brain perfusion variability and risk factors of endothelial dysfunction and atherosclerosis in healthy aged subjects.

Methods

Thirty-eight healthy subjects aged 50–75 years old were included. Mean global brain perfusion was measured using magnetic resonance phase contrast mapping and regional brain perfusion by use of arterial spin labeling.

Results

Mean global brain perfusion was inversely correlated with caffeine and hematocrit, and positively with end-tidal P_CO2. Furthermore, the mean global brain perfusion was inversely correlated with circulating homocysteine, but not with asymmetric dimethylarginine, dyslipidemia or the carotid intima-media thickness. The relative regional brain perfusion was associated with circulating homocysteine, with a relative parietal hypoperfusion and a frontal hyperperfusion. No effect on regional brain perfusion was observed for any of the other risk factors. A multiple regression model including homocysteine, caffeine, hematocrit and end-tidal P_CO2, explained nearly half of the observed variability.

Conclusion

Both intrinsic and extrinsic factors influenced global cerebral perfusion variation between subjects. Further, the results suggest that the inverse relation between homocysteine and brain perfusion is owing to other mechanisms, than reflected by asymmetric dimethylarginine, and that homocysteine may be a marker of cerebral perfusion in aging brains.