The Default Mode Network and the Working Memory Network Are Not Anti-Correlated during All Phases of a Working Memory Task

Introduction

The default mode network and the working memory network are known to be anti-correlated during sustained cognitive processing, in a load-dependent manner. We hypothesized that functional connectivity among nodes of the two networks could be dynamically modulated by task phases across time.

Methods

To address the dynamic links between default mode network and the working memory network, we used a delayed visuo-spatial working memory paradigm, which allowed us to separate three different phases of working memory (encoding, maintenance, and retrieval), and analyzed the functional connectivity during each phase within and between the default mode network and the working memory network networks.

Results

We found that the two networks are anti-correlated only during the maintenance phase of working memory, i.e. when attention is focused on a memorized stimulus in the absence of external input. Conversely, during the encoding and retrieval phases, when the external stimulation is present, the default mode network is positively coupled with the working memory network, suggesting the existence of a dynamically switching of functional connectivity between “task-positive” and “task-negative” brain networks.

Conclusions

Our results demonstrate that the well-established dichotomy of the human brain (anti-correlated networks during rest and balanced activation-deactivation during cognition) has a more nuanced organization than previously thought and engages in different patterns of correlation and anti-correlation during specific sub-phases of a cognitive task. This nuanced organization reinforces the hypothesis of a direct involvement of the default mode network in cognitive functions, as represented by a dynamic rather than static interaction with specific task-positive networks, such as the working memory network.     

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.     

Disturbed Small-World Networks and Neurocognitive Function in Frontal Lobe Low-Grade Glioma Patients

Background

Brain tumor patients often associated with losses of the small-world configuration and neurocognitive functions before operations. However, few studies were performed on the impairments of frontal lobe low-grade gliomas (LGG) after tumor resection using small-world network features.

Methodology/Principal Findings

To detect differences in the whole brain topology among LGG patients before and after operation, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI data was performed. We collected resting-state fMRI data of 12 carefully selected frontal lobe LGG patients before and after operation. We calculated the topological properties of brain functional networks in the 12 LGG, and compared with 12 healthy controls (HCs). We also applied Montreal Cognitive Assessment (MoCA) in a subset of patients (n = 12, including before and after operation groups) and HCs (n = 12). The resulting functional connectivity matrices were constructed for all 12 patients, and binary network analysis was performed. In the range of , the functional networks in preoperative LGG and postoperative one both fitted the definition of small-worldness. We proposed as small-world network interval, and the results showed that the topological properties were found to be disrupted in the two LGG groups, meanwhile the global efficiency increased and the local efficiency decreased. in the two LGG groups both were longer than HCs. in the LGG groups were smaller than HCs. Compared with the Hcs, MoCA in the two LGG groups were lower than HCs with significant difference, and the disturbed networks in the LGG were negatively related to worse MoCA scores.

Conclusions

Disturbed small-worldness preperty in the two LGG groups was found and widely spread in the strength and spatial organization of brain networks, and the alterated small-world network may be responsible for cognitive dysfunction in frontal lobe LGG patients.     

Anomalous Gray Matter Structural Networks in Patients with Hepatitis B Virus-Related Cirrhosis without Overt Hepatic Encephalopathy

Background and Purpose

Increasing evidence suggests that cirrhosis may affect the connectivity among different brain regions in patients before overt hepatic encephalopathy (OHE) occurs. However, there has been no study investigating the structural reorganization of these altered connections at the network level. The primary focus of this study was to investigate the abnormal topological organization of the structural network in patients with hepatitis B virus-related cirrhosis (HBV-RC) without OHE using structural MRI.

Methods

Using graph theoretical analysis, we compared the global and regional topological properties of gray matter structural networks between 28 patients with HBV-RC without OHE and 30 age-, sex- and education-matched healthy controls. The structural correlation networks were constructed for the two groups based on measures of gray matter volume.

Results

The brain network of the HBV-RC group exhibited a significant decrease in the clustering coefficient and reduced small-worldness at the global level across a range of network densities. Regionally, brain areas with altered nodal degree/betweenness centrality were observed predominantly in association cortices (frontal and temporal regions) (p < 0.05, uncorrected), including a significantly decreased nodal degree in the inferior temporal gyrus (p < 0.001, uncorrected). Furthermore, the HBV-RC group exhibited a loss of association hubs and the emergence of an increased number of non-association hubs compared with the healthy controls.

Conclusion

The results of this large-scale gray matter structural network study suggest reduced topological organization efficiency in patients with HBV-RC without OHE. Our findings provide new insight concerning the mechanisms of neurobiological reorganization in the HBV-RC brain from a network perspective.     

Functional Connectivity Changes in Resting-State EEG as Potential Biomarker for Amyotrophic Lateral Sclerosis

Background

Amyotrophic Lateral Sclerosis (ALS) is heterogeneous and overlaps with frontotemporal dementia. Spectral EEG can predict damage in structural and functional networks in frontotemporal dementia but has never been applied to ALS.

Methods

18 incident ALS patients with normal cognition and 17 age matched controls underwent 128 channel EEG and neuropsychology assessment. The EEG data was analyzed using FieldTrip software in MATLAB to calculate simple connectivity measures and scalp network measures. sLORETA was used in nodal analysis for source localization and same methods were applied as above to calculate nodal network measures. Graph theory measures were used to assess network integrity.

Results

Cross spectral density in alpha band was higher in patients. In ALS patients, increased degree values of the network nodes was noted in the central and frontal regions in the theta band across seven of the different connectivity maps (p<0.0005). Among patients, clustering coefficient in alpha and gamma bands was increased in all regions of the scalp and connectivity were significantly increased (p=0.02). Nodal network showed increased assortativity in alpha band in the patients group. The Clustering Coefficient in Partial Directed Connectivity (PDC) showed significantly higher values for patients in alpha, beta, gamma, theta and delta frequencies (p=0.05).

Discussion

There is increased connectivity in the fronto-central regions of the scalp and areas corresponding to Salience and Default Mode network in ALS, suggesting a pathologic disruption of neuronal networking in early disease states. Spectral EEG has potential utility as a biomarker in ALS.     

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.     

Altered Structural and Functional Connectivity in Late Preterm Preadolescence: An Anatomic Seed-Based Study of Resting State Networks Related to the Posteromedial and Lateral Parietal Cortex

Objective

Late preterm birth confers increased risk of developmental delay, academic difficulties and social deficits. The late third trimester may represent a critical period of development of neural networks including the default mode network (DMN), which is essential to normal cognition. Our objective is to identify functional and structural connectivity differences in the posteromedial cortex related to late preterm birth.

Methods

Thirty-eight preadolescents (ages 9–13; 19 born in the late preterm period (≥32 weeks gestational age) and 19 at term) without access to advanced neonatal care were recruited from a low socioeconomic status community in Brazil. Participants underwent neurocognitive testing, 3-dimensional T1-weighted imaging, diffusion-weighted imaging and resting state functional MRI (RS-fMRI). Seed-based probabilistic diffusion tractography and RS-fMRI analyses were performed using unilateral seeds within the posterior DMN (posterior cingulate cortex, precuneus) and lateral parietal DMN (superior marginal and angular gyri).

Results

Late preterm children demonstrated increased functional connectivity within the posterior default mode networks and increased anti-correlation with the central-executive network when seeded from the posteromedial cortex (PMC). Key differences were demonstrated between PMC components with increased anti-correlation with the salience network seen only with posterior cingulate cortex seeding but not with precuneus seeding. Probabilistic tractography showed increased streamlines within the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus within late preterm children while decreased intrahemispheric streamlines were also observed. No significant differences in neurocognitive testing were demonstrated between groups.

Conclusion

Late preterm preadolescence is associated with altered functional connectivity from the PMC and lateral parietal cortex to known distributed functional cortical networks despite no significant executive neurocognitive differences. Selective increased structural connectivity was observed in the setting of decreased posterior interhemispheric connections. Future work is needed to determine if these findings represent a compensatory adaptation employing alternate neural circuitry or could reflect subtle pathology resulting in emotional processing deficits not seen with neurocognitive testing.     

Morphologic and Functional Connectivity Alterations of Corticostriatal and Default Mode Network in Treatment-Na?ve Patients with Obsessive-Compulsive Disorder

Background

Previous studies have demonstrated that structural deficits and functional connectivity imbalances might underlie the pathophysiology of obsessive-compulsive disorder (OCD). The purpose of the present study was to investigate gray matter deficits and abnormal resting-state networks in patients with OCD and further investigate the association between the anatomic and functional alterations and clinical symptoms.

Methods

Participants were 33 treatment-naïve OCD patients and 33 matched healthy controls. Voxel-based morphometry was used to investigate the regions with gray matter abnormalities and resting-state functional connectivity analysis was further conducted between each gray matter abnormal region and the remaining voxels in the brain.

Results

Compared with healthy controls, patients with OCD showed significantly increased gray matter volume in the left caudate, left thalamus, and posterior cingulate cortex, as well as decreased gray matter volume in the bilateral medial orbitofrontal cortex, left anterior cingulate cortex, and left inferior frontal gyrus. By using the above morphologic deficits areas as seed regions, functional connectivity analysis found abnormal functional integration in the cortical-striatum-thalamic-cortical (CSTC) circuits and default mode network. Subsequent correlation analyses revealed that morphologic deficits in the left thalamus and increased functional connectivity within the CSTC circuits positively correlated with the total Y-BOCS score.

Conclusion

This study provides evidence that morphologic and functional alterations are seen in CSTC circuits and default mode network in treatment-naïve OCD patients. The association between symptom severity and the CSTC circuits suggests that anatomic and functional alterations in CSTC circuits are especially important in the pathophysiology of OCD.     

Gender-related differences in the dysfunctional resting networks of migraine suffers

Background

Migraine shows gender-specific incidence and has a higher prevalence in females. However, little is known about gender-related differences in dysfunctional brain organization, which may account for gender-specific vulnerability and characteristics of migraine. In this study, we considered gender-related differences in the topological property of resting functional networks.

Methodology/Principal Findings

Data was obtained from 38 migraine patients (18 males and 20 females) and 38 healthy subjects (18 males and 20 females). We used the graph theory analysis, which becomes a powerful tool in investigating complex brain networks on a whole brain scale and could describe functional interactions between brain regions. Using this approach, we compared the brain functional networks between these two groups, and several network properties were investigated, such as small-worldness, network resilience, nodal centrality, and interregional connections. In our findings, these network characters were all disrupted in patients suffering from chronic migraine. More importantly, these functional damages in the migraine-affected brain had a skewed balance between males and females. In female patients, brain functional networks showed worse resilience, more regions exhibited decreased nodal centrality, and more functional connections revealed abnormalities than in male patients.

Conclusions

These results indicated that migraine may have an additional influence on females and lead to more dysfunctional organization in their resting functional networks.     

Intrinsic Brain Network Abnormalities in Migraines without Aura Revealed in Resting-State fMRI

Background

Previous studies have defined low-frequency, spatially consistent intrinsic connectivity networks (ICN) in resting functional magnetic resonance imaging (fMRI) data which reflect functional interactions among distinct brain areas. We sought to explore whether and how repeated migraine attacks influence intrinsic brain connectivity, as well as how activity in these networks correlates with clinical indicators of migraine.

Methods/Principal Findings

Resting-state fMRI data in twenty-three patients with migraines without aura (MwoA) and 23 age- and gender-matched healthy controls (HC) were analyzed using independent component analysis (ICA), in combination with a “dual-regression” technique to identify the group differences of three important pain-related networks [default mode network (DMN), bilateral central executive network (CEN), salience network (SN)] between the MwoA patients and HC. Compared with the HC, MwoA patients showed aberrant intrinsic connectivity within the bilateral CEN and SN, and greater connectivity between both the DMN and right CEN (rCEN) and the insula cortex - a critical region involving in pain processing. Furthermore, greater connectivity between both the DMN and rCEN and the insula correlated with duration of migraine.

Conclusions

Our findings may provide new insights into the characterization of migraine as a condition affecting brain activity in intrinsic connectivity networks. Moreover, the abnormalities may be the consequence of a persistent central neural system dysfunction, reflecting cumulative brain insults due to frequent ongoing migraine attacks.     

Default Mode Network Connectivity as a Function of Familial and Environmental Risk for Psychotic Disorder

Background

Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder.

Methods

Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology.

Results

There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity.

Discussion

Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network “connectivity at rest” intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.     

Evidence for Anomalous Network Connectivity during Working Memory Encoding in Schizophrenia: An ICA Based Analysis

Background

Numerous neuroimaging studies report abnormal regional brain activity during working memory performance in schizophrenia, but few have examined brain network integration as determined by “functional connectivity” analyses.

Methodology/Principal Findings

We used independent component analysis (ICA) to identify and characterize dysfunctional spatiotemporal networks in schizophrenia engaged during the different stages (encoding and recognition) of a Sternberg working memory fMRI paradigm. 37 chronic schizophrenia and 54 healthy age/gender-matched participants performed a modified Sternberg Item Recognition fMRI task. Time series images preprocessed with SPM2 were analyzed using ICA. Schizophrenia patients showed relatively less engagement of several distinct “normal” encoding-related working memory networks compared to controls. These encoding networks comprised 1) left posterior parietal-left dorsal/ventrolateral prefrontal cortex, cingulate, basal ganglia, 2) right posterior parietal, right dorsolateral prefrontal cortex and 3) default mode network. In addition, the left fronto-parietal network demonstrated a load-dependent functional response during encoding. Network engagement that differed between groups during recognition comprised the posterior cingulate, cuneus and hippocampus/parahippocampus. As expected, working memory task accuracy differed between groups (p<0.0001) and was associated with degree of network engagement. Functional connectivity within all three encoding-associated functional networks correlated significantly with task accuracy, which further underscores the relevance of abnormal network integration to well-described schizophrenia working memory impairment. No network was significantly associated with task accuracy during the recognition phase.

Conclusions/Significance

This study extends the results of numerous previous schizophrenia studies that identified isolated dysfunctional brain regions by providing evidence of disrupted schizophrenia functional connectivity using ICA within widely-distributed neural networks engaged for working memory cognition.     

Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI

Background

Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging.

Methods

A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity.

Results

Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores.

Conclusion

Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as potential biomarkers for assessment of neuronal damage and the prediction of clinical outcomes in acute SCI.     

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

Background

Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials.

Objective

To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD.

Design

A 24-week randomised, controlled, double-blind, parallel-group, multi-country study.

Participants

179 drug-naïve mild AD patients who participated in the Souvenir II study.

Intervention

Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks.

Outcome

In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance.

Results

The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance.

Conclusions

The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions.

Trial registration

Dutch Trial Register NTR1975.     

Roux-en-Y Gastric Bypass Alters Brain Activity in Regions that Underlie Reward and Taste Perception

Background

Roux-en-Y gastric bypass (RYGB) surgery is a very effective bariatric procedure to achieve significant and sustained weight loss, yet little is known about the procedure’s impact on the brain. This study examined the effects of RYGB on the brain’s response to the anticipation of highly palatable versus regular food.

Methods

High fat diet-induced obese rats underwent RYGB or sham operation and were then tested for conditioned place preference (CPP) for the bacon-paired chamber, relative to the chow-paired chamber. After CPP, animals were placed in either chamber without the food stimulus, and brain-glucose metabolism (BGluM) was measured using positron emission tomography (μPET).

Results

Bacon CPP was only observed in RYGB rats that had stable weight loss following surgery. BGluM assessment revealed that RYGB selectively activated regions of the right and midline cerebellum (Lob 8) involved in subjective processes related to reward or expectation. Also, bacon anticipation led to significant activation in the medial parabrachial nuclei (important in gustatory processing) and dorsomedial tegmental area (key to reward, motivation, cognition and addiction) in RYGB rats; and activation in the retrosplenial cortex (default mode network), and the primary visual cortex in control rats.

Conclusions

RYGB alters brain activity in areas involved in reward expectation and sensory (taste) processing when anticipating a palatable fatty food. Thus, RYGB may lead to changes in brain activity in regions that process reward and taste-related behaviors. Specific cerebellar regions with altered metabolism following RYGB may help identify novel therapeutic targets for treatment of obesity.     

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.     

Alterations in Low-Level Perceptual Networks Related to Clinical Severity in PTSD after an Earthquake: A Resting-State fMRI Study

Background

Several task-based functional MRI (fMRI) studies have highlighted abnormal activation in specific regions involving the low-level perceptual (auditory, visual, and somato-motor) network in posttraumatic stress disorder (PTSD) patients. However, little is known about whether the functional connectivity of the low-level perceptual and higher-order cognitive (attention, central-execution, and default-mode) networks change in medication-naïve PTSD patients during the resting state.

Methods

We investigated the resting state networks (RSNs) using independent component analysis (ICA) in 18 chronic Wenchuan earthquake-related PTSD patients versus 20 healthy survivors (HSs).

Results

Compared to the HSs, PTSD patients displayed both increased and decreased functional connectivity within the salience network (SN), central executive network (CEN), default mode network (DMN), somato-motor network (SMN), auditory network (AN), and visual network (VN). Furthermore, strengthened connectivity involving the inferior temporal gyrus (ITG) and supplementary motor area (SMA) was negatively correlated with clinical severity in PTSD patients.

Limitations

Given the absence of a healthy control group that never experienced the earthquake, our results cannot be used to compare alterations between the PTSD patients, physically healthy trauma survivors, and healthy controls. In addition, the breathing and heart rates were not monitored in our small sample size of subjects. In future studies, specific task paradigms should be used to reveal perceptual impairments.

Conclusions

These findings suggest that PTSD patients have widespread deficits in both the low-level perceptual and higher-order cognitive networks. Decreased connectivity within the low-level perceptual networks was related to clinical symptoms, which may be associated with traumatic reminders causing attentional bias to negative emotion in response to threatening stimuli and resulting in emotional dysregulation.     

Aberrant Default Mode Functional Connectivity in Early Onset Schizophrenia

Background

The default mode network (DMN) has been linked to a number of mental disorders including schizophrenia. However, the abnormal connectivity of DMN in early onset schizophrenia (EOS) has been rarely reported.

Methods

Independent component analysis (ICA) was used to investigate functional connectivity (FC) of the DMN in 32 first-episode adolescents with EOS and 32 age and gender-matched healthy controls.

Results

Compared to healthy controls, patients with EOS showed increased FC between the medial frontal gyrus and other areas of the DMN. Partial correlation analyses showed that the FC of medial frontal gyrus significantly correlated with PANSS-positive symptoms (partial correlation coefficient  = 0.538, Bonferoni corrected P = 0.018).

Limitations

Although the sample size of participants was comparable with most fMRI studies to date, it was still relatively small. Pediatric brains were registered to the MNI adult brain template. However, possible age-specific differences in spatial normalization that arise from registering pediatric brains to the MNI adult brain template may have little effect on fMRI results.

Conclusion

This study provides evidence for functional abnormalities of DMN in first-episode EOS. These abnormalities could be a source of abnormal introspectively-oriented mental actives.     

Resting-state brain organization revealed by functional covariance networks

Background

Brain network studies using techniques of intrinsic connectivity network based on fMRI time series (TS-ICN) and structural covariance network (SCN) have mapped out functional and structural organization of human brain at respective time scales. However, there lacks a meso-time-scale network to bridge the ICN and SCN and get insights of brain functional organization.

Methodology and Principal Findings

We proposed a functional covariance network (FCN) method by measuring the covariance of amplitude of low-frequency fluctuations (ALFF) in BOLD signals across subjects, and compared the patterns of ALFF-FCNs with the TS-ICNs and SCNs by mapping the brain networks of default network, task-positive network and sensory networks. We demonstrated large overlap among FCNs, ICNs and SCNs and modular nature in FCNs and ICNs by using conjunctional analysis. Most interestingly, FCN analysis showed a network dichotomy consisting of anti-correlated high-level cognitive system and low-level perceptive system, which is a novel finding different from the ICN dichotomy consisting of the default-mode network and the task-positive network.

Conclusion

The current study proposed an ALFF-FCN approach to measure the interregional correlation of brain activity responding to short periods of state, and revealed novel organization patterns of resting-state brain activity from an intermediate time scale.     

Structural and Functional Brain Alterations in End Stage Renal Disease Patients on Routine Hemodialysis: A Voxel-Based Morphometry and Resting State Functional Connectivity Study

Background and Purpose

Cognitive impairment is a well-described phenomenon in end-stage renal disease (ESRD) patients. However, its pathogenesis remains poorly understood. The primary focus of this study was to examine structural and functional brain deficits in ESRD patients.

Materials and Methods

Thirty ESRD patients on hemodialysis (without clinical neurological disease) and 30 age- and gender-matched control individuals (without renal or neurological problems) were recruited in a prospective, single-center study. High-resolution structural magnetic resonance imaging (MRI) and resting state functional MRI were performed on both groups to detect the subtle cerebral deficits in ESRD patients. Voxel-based morphometry was used to characterize gray matter deficits in ESRD patients. The impact of abnormal morphometry on the cerebral functional integrity was investigated by evaluating the alterations in resting state functional connectivity when brain regions with gray matter volume reduction were used as seed areas.

Results

A significant decrease in gray matter volume was observed in ESRD patients in the bilateral medial orbito-prefrontal cortices, bilateral dorsal lateral prefrontal cortices, and the left middle temporal cortex. When brain regions with gray matter volume reduction were used as seed areas, the integration was found to be significantly decreased in ESRD patients in the fronto-cerebellum circuits and within prefrontal circuits. In addition, significantly enhanced functional connectivity was found between the prefrontal cortex and the left temporal cortex and within the prefrontal circuits.

Conclusions

Our study revealed that both the structural and functional cerebral cortices were impaired in ESRD patients on routine hemodialysis.