Alterations in Cortical Sensorimotor Connectivity following Complete Cervical Spinal Cord Injury: A Prospective Resting-State fMRI Study

Functional magnetic resonance imaging (fMRI) studies have demonstrated alterations during task-induced brain activation in spinal cord injury (SCI) patients. The interruption to structural integrity of the spinal cord and the resultant disrupted flow of bidirectional communication between the brain and the spinal cord might contribute to the observed dynamic reorganization (neural plasticity). However, the effect of SCI on brain resting-state connectivity patterns remains unclear. We undertook a prospective resting-state fMRI (rs-fMRI) study to explore changes to cortical activation patterns following SCI. With institutional review board approval, rs-fMRI data was obtained in eleven patients with complete cervical SCI (>2 years post injury) and nine age-matched controls. The data was processed using the Analysis of Functional Neuroimages software. Region of interest (ROI) based analysis was performed to study changes in the sensorimotor network using pre- and post-central gyri as seed regions. Two-sampled t-test was carried out to check for significant differences between the two groups. SCI patients showed decreased functional connectivity in motor and sensory cortical regions when compared to controls. The decrease was noted in ipsilateral, contralateral, and interhemispheric regions for left and right precentral ROIs. Additionally, the left postcentral ROI demonstrated increased connectivity with the thalamus bilaterally in SCI patients. Our results suggest that cortical activation patterns in the sensorimotor network undergo dynamic reorganization following SCI. The presence of these changes in chronic spinal cord injury patients is suggestive of the inherent neural plasticity within the central nervous system.     

颞叶癫痫脑“默认模式”的fMRI研究

功能磁共振成像(functional magnetic resonance imaging,fMRI)被用于检测静息时脑功能神经网络.作者运用静息fMRI检测海马硬化颞叶癫痫(temporal lobe epilepsy,TLE)脑"默认模式",采用感兴趣区域功能连接分析检测16例TLE患者和16名正常对照静息时脑的"默认模式",并进行组内和组间分析.研究发现,与正常对照相比,TLE静息时海马、颞极、额叶、颞叶、壳核及楔前叶等脑区与后扣带回的功能连接增强.研究结果表明TLE患者的固有脑功能组织模式有可能出现紊乱.这一研究将有助于从脑功能的角度了解癫痫患者某些临床症状的发病机理,为今后癫痫诊治的发展提供一定的帮助.     

Disrupted functional brain connectivity in partial epilepsy: a resting-state fMRI study

Examining the spontaneous activity to understand the neural mechanism of brain disorder is a focus in recent resting-state fMRI. In the current study, to investigate the alteration of brain functional connectivity in partial epilepsy in a systematical way, two levels of analyses (functional connectivity analysis within resting state networks (RSNs) and functional network connectivity (FNC) analysis) were carried out on resting-state fMRI data acquired from the 30 participants including 14 healthy controls(HC) and 16 partial epilepsy patients. According to the etiology, all patients are subdivided into temporal lobe epilepsy group (TLE, included 7 patients) and mixed partial epilepsy group (MPE, 9 patients). Using group independent component analysis, eight RSNs were identified, and selected to evaluate functional connectivity and FNC between groups. Compared with the controls, decreased functional connectivity within all RSNs was found in both TLE and MPE. However, dissociating patterns were observed within the 8 RSNs between two patient groups, i.e, compared with TLE, we found decreased functional connectivity in 5 RSNs increased functional connectivity in 1 RSN, and no difference in the other 2 RSNs in MPE. Furthermore, the hierarchical disconnections of FNC was found in two patient groups, in which the intra-system connections were preserved for all three subsystems while the lost connections were confined to intersystem connections in patients with partial epilepsy. These findings may suggest that decreased resting state functional connectivity and disconnection of FNC are two remarkable characteristics of partial epilepsy. The selective impairment of FNC implicated that it is unsuitable to understand the partial epilepsy only from global or local perspective. We presumed that studying epilepsy in the multi-perspective based on RSNs may be a valuable means to assess the functional changes corresponding to specific RSN and may contribute to the understanding of the neuro-pathophysiological mechanism of epilepsy.     

Reduced Functional Connectivity of Default Mode and Set-Maintenance Networks in Ornithine Transcarbamylase Deficiency

Background and Purpose

Ornithine transcarbamylase deficiency (OTCD) is an X-chromosome linked urea cycle disorder (UCD) that causes hyperammonemic episodes leading to white matter injury and impairments in executive functioning, working memory, and motor planning. This study aims to investigate differences in functional connectivity of two resting-state networks—default mode and set-maintenance—between OTCD patients and healthy controls.

Methods

Sixteen patients with partial OTCD and twenty-two control participants underwent a resting-state scan using 3T fMRI. Combining independent component analysis (ICA) and region-of-interest (ROI) analyses, we identified the nodes that comprised each network in each group, and assessed internodal connectivity.

Results

Group comparisons revealed reduced functional connectivity in the default mode network (DMN) of OTCD patients, particularly between the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) node and bilateral inferior parietal lobule (IPL), as well as between the ACC/mPFC node and the posterior cingulate cortex (PCC) node. Patients also showed reduced connectivity in the set-maintenance network, especially between right anterior insula/frontal operculum (aI/fO) node and bilateral superior frontal gyrus (SFG), as well as between the right aI/fO and ACC and between the ACC and right SFG.

Conclusion

Internodal functional connectivity in the DMN and set-maintenance network is reduced in patients with partial OTCD compared to controls, most likely due to hyperammonemia-related white matter damage. Because several of the affected areas are involved in executive functioning, it is postulated that this reduced connectivity is an underlying cause of the deficits OTCD patients display in this cognitive domain.     

Aberrant hippocampal subregion networks associated with the classifications of aMCI subjects: a longitudinal resting-state study

Background

Altered hippocampal structure and function is a valuable indicator of possible conversion from amnestic type mild cognitive impairment (aMCI) to Alzheimer''s disease (AD). However, little is known about the disrupted functional connectivity of hippocampus subregional networks in aMCI subjects.

Methodology/Principal Findings

aMCI group-1 (n = 26) and controls group-1 (n = 18) underwent baseline and after approximately 20 months follow up resting-state fMRI scans. Integrity of distributed functional connectivity networks incorporating six hippocampal subregions (i.e. cornu ammonis, dentate gyrus and subicular complex, bilaterally) was then explored over time and comparisons made between groups. The ability of these extent longitudinal changes to separate unrelated groups of 30 subjects (aMCI-converters, n = 6; aMCI group-2, n = 12; controls group-2, n = 12) were further assessed. Six longitudinal hippocampus subregional functional connectivity networks showed similar changes in aMCI subjects over time, which were mainly associated with medial frontal gyrus, lateral temporal cortex, insula, posterior cingulate cortex (PCC) and cerebellum. However, the disconnection of hippocampal subregions and PCC may be a key factor of impaired episodic memory in aMCI, and the functional index of these longitudinal changes allowed well classifying independent samples of aMCI converters from non-converters (sensitivity was 83.3%, specificity was 83.3%) and controls (sensitivity was 83.3%, specificity was 91.7%).

Conclusions/Significance

It demonstrated that the functional changes in resting-state hippocampus subregional networks could be an important and early indicator for dysfunction that may be particularly relevant to early stage changes and progression of aMCI subjects.     

Altered Default Network Resting-State Functional Connectivity in Adolescents with Internet Gaming Addiction

Purpose

Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA).

Methods

Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute resting-state fMRI scan. Posterior cingulate cortex (PCC) connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between IGA symptom severity and PCC connectivity, contrast images representing areas correlated with PCC connectivity were correlated with the scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS) and Barratt Impulsiveness Scale-11 (BIS-11) and their hours of Internet use per week.

Results

There were no significant differences in the distributions of the age, gender, and years of education between the two groups. The subjects with IGA showed longer Internet use per week (hours) (p<0.0001) and higher CIAS (p<0.0001) and BIS-11 (p = 0.01) scores than the controls. Compared with the control group, subjects with IGA exhibited increased functional connectivity in the bilateral cerebellum posterior lobe and middle temporal gyrus. The bilateral inferior parietal lobule and right inferior temporal gyrus exhibited decreased connectivity. Connectivity with the PCC was positively correlated with CIAS scores in the right precuneus, posterior cingulate gyrus, thalamus, caudate, nucleus accumbens, supplementary motor area, and lingual gyrus. It was negatively correlated with the right cerebellum anterior lobe and left superior parietal lobule.

Conclusion

Our results suggest that adolescents with IGA exhibit different resting-state patterns of brain activity. As these alterations are partially consistent with those in patients with substance addiction, they support the hypothesis that IGA as a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders.     

Abnormal Resting-State Activities and Functional Connectivities of the Anterior and the Posterior Cortexes in Medication-Na?ve Patients with Obsessive-Compulsive Disorder

Background

Obsessive-compulsive disorder (OCD) is a mental illness characterized by the loss of control. Because the cingulate cortex is believed to be important in executive functions, such as inhibition, we used functional magnetic resonance imaging (fMRI) techniques to examine whether and how activity and functional connectivity (FC) of the cingulate cortex were altered in drug-naïve OCD patients.

Methods

Twenty-three medication-naïve OCD patients and 23 well-matched healthy controls received fMRI scans in a resting state. Functional connectivities of the anterior cingulate (ACC) and the posterior cingulate (PCC) to the whole brain were analyzed using correlation analyses based on regions of interest (ROI) identified by the fractional amplitude of low-frequency fluctuation (fALFF). Independent Component Analysis (ICA) was used to identify the resting-state sub-networks.

Results

fALFF analysis found that regional activity was increased in the ACC and decreased in the PCC in OCD patients when compared to controls. FC of the ACC and the PCC also showed different patterns. The ACC and the PCC were found to belong to different resting-state sub-networks in ICA analysis and showed abnormal FC, as well as contrasting correlations with the severity of OCD symptoms.

Conclusions

Activity of the ACC and the PCC were increased and decreased, respectively, in the medication-naïve OCD patients compared to controls. Different patterns in FC were also found between the ACC and the PCC with respect to these two groups. These findings implied that the cardinal feature of OCD, the loss of control, may be attributed to abnormal activities and FC of the ACC and the PCC.     

Structural and Functional Abnormalities of Default Mode Network in Minimal Hepatic Encephalopathy: A Study Combining DTI and fMRI

Background and Purpose

Live failure can cause brain edema and aberrant brain function in cirrhotic patients. In particular, decreased functional connectivity within the brain default-mode network (DMN) has been recently reported in overt hepatic encephalopathy (HE) patients. However, so far, little is known about the connectivity among the DMN in the minimal HE (MHE), the mildest form of HE. Here, we combined diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) to test our hypothesis that both structural and functional connectivity within the DMN were disturbed in MHE.

Materials and Methods

Twenty MHE patients and 20 healthy controls participated in the study. We explored the changes of structural (path length, tracts count, fractional anisotropy [FA] and mean diffusivity [MD] derived from DTI tractography) and functional (temporal correlation coefficient derived from rs-fMRI) connectivity of the DMN in MHE patients. Pearson correlation analysis was performed between the structural/functional indices and venous blood ammonia levels/neuropsychological tests scores of patients. All thresholds were set at P<0.05, Bonferroni corrected.

Results

Compared to the healthy controls, MHE patients showed both decreased FA and increased MD in the tract connecting the posterior cingulate cortex/precuneus (PCC/PCUN) to left parahippocampal gyrus (PHG), and decreased functional connectivity between the PCC/PCUN and left PHG, and medial prefrontal cortex (MPFC). MD values of the tract connecting PCC/PCUN to the left PHG positively correlated to the ammonia levels, the temporal correlation coefficients between the PCC/PCUN and the MPFC showed positive correlation to the digital symbol tests scores of patients.

Conclusion

MHE patients have both disturbed structural and functional connectivity within the DMN. The decreased functional connectivity was also detected between some regions without abnormal structural connectivity, suggesting that the former may be more sensitive in detecting the early abnormalities of MHE. This study extends our understanding of the pathophysiology of MHE.     

fMRI Resting Slow Fluctuations Correlate with the Activity of Fast Cortico-Cortical Physiological Connections

Recording of slow spontaneous fluctuations at rest using functional magnetic resonance imaging (fMRI) allows distinct long-range cortical networks to be identified. The neuronal basis of connectivity as assessed by resting-state fMRI still needs to be fully clarified, considering that these signals are an indirect measure of neuronal activity, reflecting slow local variations in de-oxyhaemoglobin concentration. Here, we combined fMRI with multifocal transcranial magnetic stimulation (TMS), a technique that allows the investigation of the causal neurophysiological interactions occurring in specific cortico-cortical connections. We investigated whether the physiological properties of parieto-frontal circuits mapped with short-latency multifocal TMS at rest may have some relationship with the resting-state fMRI measures of specific resting-state functional networks (RSNs). Results showed that the activity of fast cortico-cortical physiological interactions occurring in the millisecond range correlated selectively with the coupling of fMRI slow oscillations within the same cortical areas that form part of the dorsal attention network, i.e., the attention system believed to be involved in reorientation of attention. We conclude that resting-state fMRI ongoing slow fluctuations likely reflect the interaction of underlying physiological cortico-cortical connections.     

Interictal functional connectivity of human epileptic networks assessed by intracerebral EEG and BOLD signal fluctuations

In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal derived from resting state functional magnetic resonance imaging (fMRI) reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG) and resting-state functional MRI (fMRI) in 5 patients suffering from intractable temporal lobe epilepsy (TLE). Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions) during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband) and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal). This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional connectivity measured by iEEG and BOLD signals give complementary but sometimes inconsistent information in TLE.     

Aberrant Default-Mode Functional and Structural Connectivity in Heroin-Dependent Individuals

Background

Little is known about connectivity within the default mode network (DMN) in heroin-dependent individuals (HDIs). In the current study, diffusion-tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) were combined to investigate both structural and functional connectivity within the DMN in HDIs.

Methods

Fourteen HDIs and 14 controls participated in the study. Structural (path length, tracts count, (fractional anisotropy) FA and (mean diffusivity) MD derived from DTI tractography)and functional (temporal correlation coefficient derived from rs-fMRI) DMN connectivity changes were examined in HDIs. Pearson correlation analysis was performed to compare the structural/functional indices and duration of heroin use/Iowa gambling task(IGT) performance in HDIs.

Results

HDIs had lower FA and higher MD in the tract connecting the posterior cingulate cortex/precuneus (PCC/PCUN) to right parahippocampal gyrus (PHG), compared to the controls. HDIs also had decreased FA and track count in the tract connecting the PCC/PCUN and medial prefrontal cortex (MPFC), as well as decreased functional connectivity between the PCC/PCUN and bilateral PHG and MPFC, compared to controls. FA values for the tract connecting PCC/PCUN to the right PHG and connecting PCC/PCUN to the MPFC were negatively correlated to the duration of heroin use. The temporal correlation coefficients between the PCC/PCUN and the MPFC, and the FA values for the tract connecting the PCC/PCUN to the MPFC were positively correlated to IGT performance in HDIs.

Conclusions

Structural and functional connectivity within the DMN are both disturbed in HDIs. This disturbance progresses as duration of heroin use increases and is related to deficits in decision making in HDIs.     

Functional and Anatomical Connectivity Abnormalities in Cognitive Division of Anterior Cingulate Cortex in Schizophrenia

Introduction

Current pathophysiological theories of schizophrenia highlight the role of altered brain functional and anatomical connectivity. The cognitive division of anterior cingulate cortex (ACC-cd) is a commonly reported abnormal brain region in schizophrenia for its importance in cognitive control process. The aim of this study was to investigate the functional and anatomical connectivity of ACC-cd and its cognitive and clinical manifestation significance in schizophrenia by using the resting-state functional magnetic resonance imaging (fMRI) and the diffusion tensor imaging (DTI).

Methods

Thirty-three medicated schizophrenics and 30 well-matched health controls were recruited. Region-of-interest (ROI)-based resting-state functional connectivity analysis and Tract-Based Spatial Statistics (TBSS) were performed on 30 patients and 30 controls, and 24 patients and 29 controls, respectively. The Pearson correlation was performed between the imaging measures and the Stroop performance and scores of the Positive and Negative Syndrome Scale (PANSS), respectively.

Results

Patients with schizophrenia showed significantly abnormal in the functional connectivity and its hemispheric asymmetry of the ACC-cd with multiple brain areas, e.g., decreased positive connectivity with the bilateral putamen and caudate, increased negative connectivity with the left posterior cingulated cortex (PCC), increased asymmetry of connectivity strength with the contralateral inferior frontal gyrus (IFG). The FA of the right anterior cingulum was significantly decreased in patients group (p = 0.014). The abnormal functional and structural connectivity of ACC-cd were correlated with Stroop performance and the severity of the symptoms in patients.

Conclusions

Our results suggested that the abnormal connectivity of the ACC-cd might play a role in the cognitive impairment and clinical symptoms in schizophrenia.     

慢性疼痛患者静息态脑功能磁共振的默认网络研究

运用静息态功能磁共振成像技术(resting-state fMRI)研究慢性疼痛患者脑默认网络结构.通过选择双侧膝骨性关节炎(knee osteoarthritis,KOA)患者20例和正常志愿者20名,以后扣带回(posterior cingulated cortex,PCC)为种子点,分别进行fMRI扫描,分析配对两组受试者的脑功能连接情况.结果显示相对正常受试者,KOA患者存在异常脑功能连接,主要表现为PCC呈负激活,边缘叶、脑岛呈正激活.     

Early Altered Resting-State Functional Connectivity Predicts the Severity of Post-Traumatic Stress Disorder Symptoms in Acutely Traumatized Subjects

The goal of this study was to investigate the relationship between resting-state functional connectivity and the severity of post-traumatic stress disorder (PTSD) symptoms in 15 people who developed PTSD following recent trauma. Fifteen participants who experienced acute traumatic events underwent a 7.3-min resting functional magnetic resonance imaging scan within 2 days post-event. All the patients were diagnosed with PTSD within 1 to 6 months after trauma. Brain areas in which activity was correlated with that of the posterior cingulate cortex (PCC) were assessed. To assess the relationship between the severity of PTSD symptoms and PCC connectivity, contrast images representing areas positively correlated with the PCC were correlated with the subject’s Clinician-Administered PTSD Scale scores (CAPS) when they were diagnosed. Furthermore, the PCC, medial prefrontal cortex and bilateral amygdala were selected to assess the correlation of the strength of functional connectivity with the CAPS. Resting state connectivity with the PCC was negatively correlated with CAPS scores in the left superior temporal gyrus and right hippocampus/amygdala. Furthermore, the strength of connectivity between the PCC and bilateral amygdala, and even between the bilateral amygdala could predict the severity of PTSD symptoms later. These results suggest that early altered resting-state functional connectivity of the PCC with the left superior temporal gyrus, right hippocampus and amygdala could predict the severity of the disease and may be a major risk factor that predisposes patients to develop PTSD.     

Increased Intrinsic Connectivity of the Default Mode Network in Temporal Lobe Epilepsy: Evidence from Resting-State MEG Recordings

The electrophysiological signature of resting state oscillatory functional connectivity within the default mode network (DMN) during spike-free periods in temporal lobe epilepsy (TLE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in TLE, and we examined the effect of lateralized TLE on functional connectivity. Sixteen medically intractable TLE patients and 22 controls participated in this study. Whole-scalp 306-channel MEG epochs without interictal spikes generated from both MEG and EEG data were analyzed using a minimum norm estimate (MNE) and source-based imaginary coherence analysis. With this processing, we obtained the cortical activation and functional connectivity within the DMN. The functional connectivity was increased between DMN and the right medial temporal (MT) region at the delta band and between DMN and the bilateral anterior cingulate cortex (ACC) regions at the theta band. The functional change was associated with the lateralization of TLE. The right TLE showed enhanced DMN connectivity with the right MT while the left TLE demonstrated increased DMN connectivity with the bilateral MT. There was no lateralization effect of TLE upon the DMN connectivity with ACC. These findings suggest that the resting-state functional connectivity within the DMN is reinforced in temporal lobe epilepsy during spike-free periods. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction and prognosis in patients with TLE.     

Investigations into resting-state connectivity using independent component analysis

Inferring resting-state connectivity patterns from functional magnetic resonance imaging (fMRI) data is a challenging task for any analytical technique. In this paper, we review a probabilistic independent component analysis (PICA) approach, optimized for the analysis of fMRI data, and discuss the role which this exploratory technique can take in scientific investigations into the structure of these effects. We apply PICA to fMRI data acquired at rest, in order to characterize the spatio-temporal structure of such data, and demonstrate that this is an effective and robust tool for the identification of low-frequency resting-state patterns from data acquired at various different spatial and temporal resolutions. We show that these networks exhibit high spatial consistency across subjects and closely resemble discrete cortical functional networks such as visual cortical areas or sensory-motor cortex.     

Assessing the influence of different ROI selection strategies on functional connectivity analyses of fMRI data acquired during steady-state conditions

In blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), assessing functional connectivity between and within brain networks from datasets acquired during steady-state conditions has become increasingly common. However, in contrast to connectivity analyses based on task-evoked signal changes, selecting the optimal spatial location of the regions of interest (ROIs) whose timecourses will be extracted and used in subsequent analyses is not straightforward. Moreover, it is also unknown how different choices of the precise anatomical locations within given brain regions influence the estimates of functional connectivity under steady-state conditions. The objective of the present study was to assess the variability in estimates of functional connectivity induced by different anatomical choices of ROI locations for a given brain network. We here targeted the default mode network (DMN) sampled during both resting-state and a continuous verbal 2-back working memory task to compare four different methods to extract ROIs in terms of ROI features (spatial overlap, spatial functional heterogeneity), signal features (signal distribution, mean, variance, correlation) as well as strength of functional connectivity as a function of condition. We show that, while different ROI selection methods produced quantitatively different results, all tested ROI selection methods agreed on the final conclusion that functional connectivity within the DMN decreased during the continuous working memory task compared to rest.     

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.     

Intrinsic connectivity reveals functionally distinct cortico-hippocampal networks in the human brain

Episodic memory depends on interactions between the hippocampus and interconnected neocortical regions. Here, using data-driven analyses of resting-state functional magnetic resonance imaging (fMRI) data, we identified the networks that interact with the hippocampus—the default mode network (DMN) and a “medial temporal network” (MTN) that included regions in the medial temporal lobe (MTL) and precuneus. We observed that the MTN plays a critical role in connecting the visual network to the DMN and hippocampus. The DMN could be further divided into 3 subnetworks: a “posterior medial” (PM) subnetwork comprised of posterior cingulate and lateral parietal cortices; an “anterior temporal” (AT) subnetwork comprised of regions in the temporopolar and dorsomedial prefrontal cortex; and a “medial prefrontal” (MP) subnetwork comprised of regions primarily in the medial prefrontal cortex (mPFC). These networks vary in their functional connectivity (FC) along the hippocampal long axis and represent different kinds of information during memory-guided decision-making. Finally, a Neurosynth meta-analysis of fMRI studies suggests new hypotheses regarding the functions of the MTN and DMN subnetworks, providing a framework to guide future research on the neural architecture of episodic memory.

Episodic memory depends on interactions between the hippocampus and interconnected neocortical regions. This study uses network analyses of intrinsic brain networks at rest to identify and characterize brain networks that interact with the hippocampus and have distinct functions during memory-guided decision making.     

Reduction in inter-hemispheric connectivity in disorders of consciousness

Clinical diagnosis of disorders of consciousness (DOC) caused by brain injury poses great challenges since patients are often behaviorally unresponsive. A promising new approach towards objective DOC diagnosis may be offered by the analysis of ultra-slow (<0.1 Hz) spontaneous brain activity fluctuations measured with functional magnetic resonance imaging (fMRI) during the resting-state. Previous work has shown reduced functional connectivity within the "default network", a subset of regions known to be deactivated during engaging tasks, which correlated with the degree of consciousness impairment. However, it remains unclear whether the breakdown of connectivity is restricted to the "default network", and to what degree changes in functional connectivity can be observed at the single subject level. Here, we analyzed resting-state inter-hemispheric connectivity in three homotopic regions of interest, which could reliably be identified based on distinct anatomical landmarks, and were part of the "Extrinsic" (externally oriented, task positive) network (pre- and postcentral gyrus, and intraparietal sulcus). Resting-state fMRI data were acquired for a group of 11 healthy subjects and 8 DOC patients. At the group level, our results indicate decreased inter-hemispheric functional connectivity in subjects with impaired awareness as compared to subjects with intact awareness. Individual connectivity scores significantly correlated with the degree of consciousness. Furthermore, a single-case statistic indicated a significant deviation from the healthy sample in 5/8 patients. Importantly, of the three patients whose connectivity indices were comparable to the healthy sample, one was diagnosed as locked-in. Taken together, our results further highlight the clinical potential of resting-state connectivity analysis and might guide the way towards a connectivity measure complementing existing DOC diagnosis.