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.     

Amygdala Perfusion Is Predicted by Its Functional Connectivity with the Ventromedial Prefrontal Cortex and Negative Affect

Background

Previous studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect). It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1) amygdala over-activity and 2) reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states.

Methods

Here we used resting-state arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF) and functional connectivity (correlated fluctuations in the BOLD signal) of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA), and subsyndromal anxiety levels in 38 healthy subjects.

Results

BLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety.

Conclusions

These results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach.     

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.     

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.     

Convergent evidence from multimodal imaging reveals amygdala abnormalities in schizophrenic patients and their first-degree relatives

Background

Shared neuropathological features between schizophrenic patients and their first-degree relatives have potential as indicators of genetic vulnerability to schizophrenia. We sought to explore genetic influences on brain morphology and function in schizophrenic patients and their relatives.

Methods

Using a multimodal imaging strategy, we studied 33 schizophrenic patients, 55 of their unaffected parents, 30 healthy controls for patients, and 29 healthy controls for parents with voxel-based morphometry of structural MRI scans and functional connectivity analysis of resting-state functional MRI data.

Results

Schizophrenic patients showed widespread gray matter reductions in the bilateral frontal cortices, bilateral insulae, bilateral occipital cortices, left amygdala and right thalamus, whereas their parents showed more localized reductions in the left amygdala, left thalamus and right orbitofrontal cortex. Patients and their parents shared gray matter loss in the left amygdala. Further investigation of the resting-state functional connectivity of the amygdala in the patients showed abnormal functional connectivity with the bilateral orbitofrontal cortices, bilateral precunei, bilateral dorsolateral frontal cortices and right insula. Their parents showed slightly less, but similar changes in the pattern in the amygdala connectivity. Co-occurrences of abnormal connectivity of the left amygdala with the left orbitofrontal cortex, right dorsolateral frontal cortex and right precuneus were observed in schizophrenic patients and their parents.

Conclusions

Our findings suggest a potential genetic influence on structural and functional abnormalities of the amygdala in schizophrenia. Such information could help future efforts to identify the endophenotypes that characterize the complex disorder of schizophrenia.     

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.     

Altered Fronto-Striatal and Fronto-Cerebellar Circuits in Heroin-Dependent Individuals: A Resting-State fMRI Study

Background

The formation of compulsive pattern of drug use is related to abnormal regional neural activity and functional reorganization in the heroin addicts’ brain, but the relationship between heroin-use-induced disrupted local neural activity and its functional organization pattern in resting-state is unknown.

Methodology/Principal Findings

With fMRI data acquired during resting state from 17 male heroin dependent individuals (HD) and 15 matched normal controls (NC), we analyzed the changes of amplitude of low frequency fluctuation (ALFF) in brain areas, and its relationship with history of heroin use. Then we investigated the addiction related alteration in functional connectivity of the brain regions with changed ALFF using seed-based correlation analysis. Compared with NC, the ALFF of HD was obviously decreased in the right caudate, right dorsal anterior cingulate cortex (dACC), right superior medial frontal cortex and increased in the bilateral cerebellum, left superior temporal gyrus and left superior occipital gyrus. Of the six regions, only the ALFF value of right caudate had a negative correlation with heroin use. Setting the six regions as “seeds”, we found the functional connectivity between the right caudate and dorsolateral prefrontal cortex (dlPFC) was reduced but that between the right caudate and cerebellum was enhanced. Besides, an abnormal lateral PFC-dACC connection was also observed in HD.

Conclusions

The observations of dysfunction of fronto-striatal and fronto-cerebellar circuit in HD implicate an altered balance between local neuronal assemblies activity and their integrated network organization pattern which may be involved in the process from voluntary to habitual and compulsive drug use.     

Metabolic and Functional Connectivity Changes in Mal de Debarquement Syndrome

Background

Individuals with mal de debarquement syndrome (MdDS) experience a chronic illusion of self-motion triggered by prolonged exposure to passive motion, such as from sea or air travel. The experience is one of rocking dizziness similar to when the individual was originally on the motion trigger such as a boat or airplane. MdDS represents a prolonged version of a normal phenomenon familiar to most individuals but which persists for months or years in others. It represents a natural example of the neuroplasticity of motion adaptation. However, the localization of where that motion adaptation occurs is unknown. Our goal was to localize metabolic and functional connectivity changes associated with persistent MdDS.

Methods

Twenty subjects with MdDS lasting a median duration of 17.5 months were compared to 20 normal controls with ¹⁸F FDG PET and resting state fMRI. Resting state metabolism and functional connectivity were calculated using age, grey matter volume, and mood and anxiety scores as nuisance covariates.

Results

MdDS subjects showed increased metabolism in the left entorhinal cortex and amygdala (z>3.3). Areas of relative hypometabolism included the left superior medial gyrus, left middle frontal gyrus, right amygdala, right insula, and clusters in the left superior, middle, and inferior temporal gyri. MdDS subjects showed increased connectivity between the entorhinal cortex/amygdala cluster and posterior visual and vestibular processing areas including middle temporal gyrus, motion sensitive area MT/V5, superior parietal lobule, and primary visual cortex, while showing decreased connectivity to multiple prefrontal areas.

Conclusion

These data show an association between resting state metabolic activity and functional connectivity between the entorhinal cortex and amygdala in a human disorder of abnormal motion perception. We propose a model for how these biological substrates can allow a limited period of motion exposure to lead to chronic perceptions of self-motion.     

Abnormal brain default-mode network functional connectivity in drug addicts

Background

The default mode network (DMN) is a set of brain regions that exhibit synchronized low frequency oscillations at resting-state, and is believed to be relevant to attention and self-monitoring. As the anterior cingulate cortex and hippocampus are impaired in drug addiction and meanwhile are parts of the DMN, the present study examined addiction-related alteration of functional connectivity of the DMN.

Methodology

Resting-state functional magnetic resonance imaging data of chronic heroin users (14 males, age: 30.1±5.3 years, range from 22 to 39 years) and non-addicted controls (13 males, age: 29.8±7.2 years, range from 20 to 39 years) were investigated with independent component analysis to address their functional connectivity of the DMN.

Principal Findings

Compared with controls, heroin users showed increased functional connectivity in right hippocampus and decreased functional connectivity in right dorsal anterior cingulate cortex and left caudate in the DMN.

Conclusions

These findings suggest drug addicts'' abnormal functional organization of the DMN, and are discussed as addiction-related abnormally increased memory processing but diminished cognitive control related to attention and self-monitoring, which may underlie the hypersensitivity toward drug related cues but weakened strength of cognitive control in the state of addiction.     

Altered Resting State in Diabetic Neuropathic Pain

Background

The spontaneous component of neuropathic pain (NP) has not been explored sufficiently with neuroimaging techniques, given the difficulty to coax out the brain components that sustain background ongoing pain. Here, we address for the first time the correlates of this component in an fMRI study of a group of eight patients suffering from diabetic neuropathic pain and eight healthy control subjects. Specifically, we studied the functional connectivity that is associated with spontaneous neuropathic pain with spatial independent component analysis (sICA).

Principal Findings

Functional connectivity analyses revealed a cortical network consisting of two anti-correlated patterns: one includes the left fusiform gyrus, the left lingual gyrus, the left inferior temporal gyrus, the right inferior occipital gyrus, the dorsal anterior cingulate cortex bilaterally, the pre and postcentral gyrus bilaterally, in which its activity is correlated negatively with pain and positively with the controls; the other includes the left precuneus, dorsolateral prefrontal, frontopolar cortex (both bilaterally), right superior frontal gyrus, left inferior frontal gyrus, thalami, both insulae, inferior parietal lobuli, right mammillary body, and a small area in the left brainstem, in which its activity is correlated positively with pain and negatively with the controls. Furthermore, a power spectra analyses revealed group differences in the frequency bands wherein the sICA signal was decomposed: patients'' spectra are shifted towards higher frequencies.

Conclusion

In conclusion, we have characterized here for the first time a functional network of brain areas that mark the spontaneous component of NP. Pain is the result of aberrant default mode functional connectivity.     

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.     

Alterations in Functional and Structural Connectivity in Pediatric-Onset Multiple Sclerosis

Background

Reduced white matter (WM) integrity is a fundamental aspect of pediatric multiple sclerosis (MS), though relations to resting-state functional MRI (fMRI) connectivity remain unknown. The objective of this study was to relate diffusion-tensor imaging (DTI) measures of WM microstructural integrity to resting-state network (RSN) functional connectivity in pediatric-onset MS to test the hypothesis that abnormalities in RSN reflects changes in structural integrity.

Methods

This study enrolled 19 patients with pediatric-onset MS (mean age = 19, range 13–24 years, 14 female, mean disease duration = 65 months, mean age of disease onset = 13 years) and 16 age- and sex-matched healthy controls (HC). All subjects underwent 3.0T anatomical and functional MRI which included DTI and resting-state acquisitions. DTI processing was performed using Tract-Based Spatial Statistics (TBSS). RSNs were identified using Independent Components Analysis, and a dual regression technique was used to detect between-group differences in the functional connectivity of RSNs. Correlations were investigated between DTI measures and RSN connectivity.

Results

Lower fractional anisotropy (FA) was observed in the pediatric-onset MS group compared to HC group within the entire WM skeleton, and particularly the corpus callosum, posterior thalamic radiation, corona radiata and sagittal stratum (all p < .01, corrected). Relative to HCs, MS patients showed higher functional connectivity involving the anterior cingulate cortex and right precuneus of the default-mode network, as well as involving the anterior cingulate cortex and left middle frontal gyrus of the frontoparietal network (all p < .005 uncorrected, k≥30 voxels). Higher functional connectivity of the right precuneus within the default-mode network was associated with lower FA of the entire WM skeleton (r = -.525, p = .02), genu of the corpus callosum (r = -.553, p = .014), and left (r = -.467, p = .044) and right (r = -.615, p = .005) sagittal stratum.

Conclusions

Loss of WM microstructural integrity is associated with increased resting-state functional connectivity in pediatric MS, which may reflect a diffuse and potentially compensatory activation early in MS.     

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.     

Differential neural responses to food images in women with bulimia versus anorexia nervosa

Background

Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known.

Methods

We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI).

Results

In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area.

Conclusions

Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.     

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.     

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

Background

Previous studies have demonstrated that patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) differed at neural level. However, it remains unclear if these two subtypes of depression differ in the interhemispheric coordination. This study was undertaken for two purposes: (1) to explore the differences in interhemispheric coordination between these two subtypes by using the voxel-mirrored homotopic connectivity (VMHC) method; and (2) to determine if the difference of interhemispheric coordination can be used as a biomarker(s) to differentiate TRD from both TSD and healthy subjects (HS).

Methods

Twenty-three patients with TRD, 22 with TSD, and 19 HS participated in the study. Data of these participants were analyzed with the VMHC and seed-based functional connectivity (FC) approaches.

Results

Compared to the TSD group, the TRD group showed significantly lower VMHC values in the calcarine cortex, fusiform gyrus, hippocampus, superior temporal gyrus, middle cingulum, and precentral gyrus. Lower VMHC values were also observed in the TRD group in the calcarine cortex relative to the HS group. However, the TSD group had no significant change in VMHC value in any brain region compared to the HS group. Receiver operating characteristic curves (ROC) analysis revealed that the VMHC values in the calcarine cortex had discriminatory function distinguishing patients with TRD from patients with TSD as well as those participants in the HS group.

Conclusions

Lower VMHC values of patients with TRD relative to those with TSD and those in the HS group in the calcarine cortex appeared to be a unique feature for patients with TRD and it may be used as an imaging biomarker to separate patients with TRD from those with TSD or HS.     

Identify Changes of Brain Regional Homogeneity in Bipolar Disorder and Unipolar Depression Using Resting-State fMRI

Background

To identify changes in brain activation patterns in bipolar disorder (BD) and unipolar depression (UD) patients.

Methodology/Principal Findings

Resting-state fMRI scans of 16 healthy controls, 17 BD and 16 UD patients were obtained. T-test of normalized regional homogeneity (ReHo) was performed in a voxel-by-voxel manner. A combined threshold of á = 0.05, minimum cluster volume of V = 10503 mm³ (389 voxels) were used to determine ReHo differences between groups. In UD group, fMRI revealed ReHo increases in the left middle occipital lobe, right inferior parietal lobule, right precuneus and left convolution; and ReHo decreases in the left parahippocampalgyrus, right precentralgyrus, left postcentralgyrus, left precentralgyrus and left cingulated. In BD group, ReHo increases in the right insular cortex, left middle frontal gyrus, left precuneus, left occipital lobe, left parietal, left superior frontal gyrus and left thalamus; and ReHo decreases in the right anterior lobe of cerebellum, pons, right precentralgyrus, left postcentralgyrus, left inferior frontal gyrus, and right cingulate. There were some overlaps in ReHo profiles between UD and BD groups, but a marked difference was seen in the thalamus of BD.

Conclusions/Significance

The resting-state fMRI and ReHo mapping are a promising tool to assist the detection of functional deficits and distinguish clinical and pathophysiological signs of BD and UD.     

Spontaneous Brain Activity in the Default Mode Network Is Sensitive to Different Resting-State Conditions with Limited Cognitive Load

Background

Recent functional MRI (fMRI) studies have demonstrated that there is an intrinsically organized default mode network (DMN) in the resting brain, primarily made up of the posterior cingulate cortex (PCC) and the medial prefrontal cortex (MPFC). Several previous studies have found that the DMN is minimally disturbed during different resting-state conditions with limited cognitive demand. However, this conclusion was drawn from the visual inspection of the functional connectivity patterns within the DMN and no statistical comparison was performed.

Methodology/Principal Findings

Four resting-state fMRI sessions were acquired: 1) eyes-closed (EC) (used to generate the DMN mask); 2) EC; 3) eyes-open with no fixation (EO); and 4) eyes-open with a fixation (EO-F). The 2–4 sessions were counterbalanced across participants (n = 20, 10 males). We examined the statistical differences in both functional connectivity and regional amplitude of low frequency fluctuation (ALFF) within the DMN among the 2–4 resting-state conditions (i.e., EC, EO, and EO-F). Although the connectivity patterns of the DMN were visually similar across these three different conditions, we observed significantly higher functional connectivity and ALFF in both the EO and the EO-F conditions as compared to the EC condition. In addition, the first and second resting EC conditions showed significant differences within the DMN, suggesting an order effect on the DMN activity.

Conclusions/Significance

Our findings of the higher DMN connectivity and regional spontaneous activities in the resting state with the eyes open suggest that the participants might have more non-specific or non-goal-directed visual information gathering and evaluation, and mind wandering or daydreaming during the resting state with the eyes open as compared to that with the eyes closed, thus providing insights into the understanding of unconstrained mental activity within the DMN. Our results also suggest that it should be cautious when choosing the type of a resting condition and designating the order of the resting condition in multiple scanning sessions in experimental design.     

Analysis of Whole-Brain Resting-State fMRI Data Using Hierarchical Clustering Approach

Background

Previous studies using hierarchical clustering approach to analyze resting-state fMRI data were limited to a few slices or regions-of-interest (ROIs) after substantial data reduction.

Purpose

To develop a framework that can perform voxel-wise hierarchical clustering of whole-brain resting-state fMRI data from a group of subjects.

Materials and Methods

Resting-state fMRI measurements were conducted for 86 adult subjects using a single-shot echo-planar imaging (EPI) technique. After pre-processing and co-registration to a standard template, pair-wise cross-correlation coefficients (CC) were calculated for all voxels inside the brain and translated into absolute Pearson''s distances after imposing a threshold CC≥0.3. The group averages of the Pearson''s distances were then used to perform hierarchical clustering with the developed framework, which entails gray matter masking and an iterative scheme to analyze the dendrogram.

Results

With the hierarchical clustering framework, we identified most of the functional connectivity networks reported previously in the literature, such as the motor, sensory, visual, memory, and the default-mode functional networks (DMN). Furthermore, the DMN and visual system were split into their corresponding hierarchical sub-networks.

Conclusion

It is feasible to use the proposed hierarchical clustering scheme for voxel-wise analysis of whole-brain resting-state fMRI data. The hierarchical clustering result not only confirmed generally the finding in functional connectivity networks identified previously using other data processing techniques, such as ICA, but also revealed directly the hierarchical structure within the functional connectivity networks.     

Disrupted Functional Connectivity of the Anterior Cingulate Cortex in Cirrhotic Patients without Overt Hepatic Encephalopathy: A Resting State fMRI Study

Background

To evaluate the changes of functional connectivity of the anterior cingulate cortex (ACC) in patients with cirrhosis without overt hepatic encephalopathy (HE) using resting state functional MRI.

Methodology/Principal Findings

Participants included 67 cirrhotic patients (27 minimal hepatic encephalopathy (MHE) and 40 cirrhotic patients without MHE (non-HE)), and 40 age- and gender- matched healthy controls. rsfMRI were performed on 3 Telsa scanners. The pregenual ACC resting-state networks (RSNs) were characterized by using a standard seed-based whole-brain correlation method and compared between cirrhotic patients and healthy controls. Pearson correlation analysis was performed between the ACC RSNs and venous blood ammonia levels, neuropsychological tests (number connection test type A [NCT-A] and digit symbol test [DST]) scores in cirrhotic patients. All thresholds were set at P<0.05, with false discovery rate corrected. Compared with controls, non-HE and MHE patients showed significantly decreased functional connectivity in the bilateral ACC, bilateral middle frontal cortex (MFC), bilateral middle cingulate cortex (MCC), bilateral superior temporal gyri (STG)/middle temporal gyri (MTG), bilateral thalami, bilateral putamen and bilateral insula, and increased functional connectivity of bilateral precuneus and left temporo-occipital lobe and bilateral lingual gyri. Compared with non-HE patients, MHE showed the decreased functional connectivity of right MCC, bilateral STG/MTG and right putamen. This indicates decreased ACC functional connectivity predominated with the increasing severity of HE. NCT-A scores negatively correlated with ACC functional connectivity in the bilateral MCC, right temporal lobe, and DST scores positively correlated with functional connectivity in the bilateral ACC and the right putamen. No correlation was found between venous blood ammonia levels and functional connectivity in ACC in cirrhotic patients.

Conclusions/Significance

Disrupted functional connectivity in ACC was found in cirrhotic patients which further deteriorated with the increasing severity of HE and correlated cognitive dysfunction in cirrhotic patients.