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.     

Altered Functional Connectivity in Patients with Subcortical Vascular Cognitive Impairment—A Resting-State Functional Magnetic Resonance Imaging Study

Recent neuroimaging studies have shown that people with subcortical vascular cognitive impairment (sVCI) have structural and functional abnormalities in the frontal lobe and subcortical brain sites. In this study, we used seed-based resting-state functional connectivity (rsFC) analysis and voxel-mirrored homotopic connectivity (VMHC) techniques to investigate the alteration of rsFC in patients with sVCI. rsFC and structural magnetic resonance images were acquired for 51 patients with subcortical cerebrovascular disease. All patients were subdivided based on cognitive status into 29 with sVCI and 22 controls; patient characteristics were matched. rsFC of the posterior cingulate cortex (PCC) and VMHC were calculated separately, and rsFC of the PCC and VMHC between the two groups were compared. The regions showing abnormal rsFC of the PCC or VMHC in sVCI patients were adopted as regions of interest for correlation analyses. Our results are as follows: The patients with sVCI exhibited increases in rsFC in the left middle temporal lobe, right inferior temporal lobe and left superior frontal gyrus, and significant decreases in rsFC of the left thalamus with the PCC. sVCI patients showed a significant deficit in VMHC between the bilateral lingual gyrus, putamen, and precentral gyrus. Additionally, the z-memory score was significantly positively associated with connectivity between the left thalamus and the PCC (r = 0.41, p = 0.03, uncorrected) in the sVCI group. Our findings suggest that the frontal lobe and subcortical brain sites play an important role in the pathogenesis of sVCI. Furthermore, rsFC between the left thalamus and the PCC might indicate the severity of sVCI.     

Voxel-Based Morphometry in Women with Borderline Personality Disorder with and without Comorbid Posttraumatic Stress Disorder

Patients with Borderline Personality Disorder (BPD) showed reduced volume of amygdala and hippocampus, but similar findings are evident in Posttraumatic Stress Disorder (PTSD). Applying voxel-based morphometry (VBM) in a larger cohort of patients with BPD, we sought to extend earlier findings of volume abnormalities in limbic regions and to evaluate the influence of co-occurring PTSD in BPD patients. We used voxel-based morphometry to study gray matter volume (GMV) in 60 healthy controls (HC) and 60 patients with BPD. Subgroup analyses on 53 patients concerning the role of co-occurring PTSD were conducted. Additionally, regression analyses were calculated to assess the relation between borderline symptom severity as well as dissociative experiences and GMV. Differences in local GMV between patients with BPD and HC were observed in the amygdale and hippocampus as well as in the fusiform and cingulate gyrus. Co-occurring PTSD was accompanied by increased GMV in the superior temporal gyrus and dorsolateral prefrontal cortex. Independent of co-occurring PTSD, severity of BPD symptoms predicted smaller GMV in the amygdala and dorsal ACC. Dissociation was positively related to GMV in the middle temporal gyrus. We could replicate earlier findings of diminished limbic GMV in patients with BPD and additionally show that patients with co-morbid PTSD feature increased GMV in prefrontal regions associated with cognitive control.     

Resting-State fMRI Activity Predicts Unsupervised Learning and Memory in an Immersive Virtual Reality Environment

In the real world, learning often proceeds in an unsupervised manner without explicit instructions or feedback. In this study, we employed an experimental paradigm in which subjects explored an immersive virtual reality environment on each of two days. On day 1, subjects implicitly learned the location of 39 objects in an unsupervised fashion. On day 2, the locations of some of the objects were changed, and object location recall performance was assessed and found to vary across subjects. As prior work had shown that functional magnetic resonance imaging (fMRI) measures of resting-state brain activity can predict various measures of brain performance across individuals, we examined whether resting-state fMRI measures could be used to predict object location recall performance. We found a significant correlation between performance and the variability of the resting-state fMRI signal in the basal ganglia, hippocampus, amygdala, thalamus, insula, and regions in the frontal and temporal lobes, regions important for spatial exploration, learning, memory, and decision making. In addition, performance was significantly correlated with resting-state fMRI connectivity between the left caudate and the right fusiform gyrus, lateral occipital complex, and superior temporal gyrus. Given the basal ganglia''s role in exploration, these findings suggest that tighter integration of the brain systems responsible for exploration and visuospatial processing may be critical for learning in a complex environment.     

Altered Resting-State Amygdala Functional Connectivity after 36 Hours of Total Sleep Deprivation

Objectives

Recent neuroimaging studies have identified a potentially critical role of the amygdala in disrupted emotion neurocircuitry in individuals after total sleep deprivation (TSD). However, connectivity between the amygdala and cerebral cortex due to TSD remains to be elucidated. In this study, we used resting-state functional MRI (fMRI) to investigate the functional connectivity changes of the basolateral amygdala (BLA) and centromedial amygdala (CMA) in the brain after 36 h of TSD.

Materials and Methods

Fourteen healthy adult men aged 25.9±2.3 years (range, 18–28 years) were enrolled in a within-subject crossover study. Using the BLA and CMA as separate seed regions, we examined resting-state functional connectivity with fMRI during rested wakefulness (RW) and after 36 h of TSD.

Results

TSD resulted in a significant decrease in the functional connectivity between the BLA and several executive control regions (left dorsolateral prefrontal cortex [DLPFC], right dorsal anterior cingulate cortex [ACC], right inferior frontal gyrus [IFG]). Increased functional connectivity was found between the BLA and areas including the left posterior cingulate cortex/precuneus (PCC/PrCu) and right parahippocampal gyrus. With regard to CMA, increased functional connectivity was observed with the rostral anterior cingulate cortex (rACC) and right precentral gyrus.

Conclusion

These findings demonstrate that disturbance in amygdala related circuits may contribute to TSD psychophysiology and suggest that functional connectivity studies of the amygdala during the resting state may be used to discern aberrant patterns of coupling within these circuits after TSD.     

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.     

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.     

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.     

Aberrant Resting-State Corticostriatal Functional Connectivity in Cirrhotic Patients with Hyperintense Globus Pallidus on T1-Weighted MR Imaging

Neurobiological and neuroimaging studies have emphasized the structural and functional alterations in the striatum of cirrhotic patients, but alterations in the functional connections between the striatum and other brain regions have not yet been explored. Of note, manganese accumulation in the nervous system, frequently reflected by hyperintensity at the bilateral globus pallidus (GP) on T1-weighted imaging, has been considered a factor affecting the striatal and cortical functions in hepatic decompensation. We employed resting-state functional magnetic resonance imaging to analyze the temporal correlation between the striatum and the remaining brain regions using seed-based correlation analyses. The two-sample t-test was conducted to detect the differences in corticostriatal connectivity between 44 cirrhotic patients with hyperintensity at the bilateral GP and 20 healthy controls. Decreased connectivity of the caudate was detected in the anterior/middle cingulate gyrus, and increased connectivity of the caudate was found in the left motor cortex. A reduction in functional connectivity was found between the putamen and several regions, including the anterior cingulate gyrus, right insular lobe, inferior frontal gyrus, left parahippocampal gyrus, and anterior lobe of the right cerebellum; increased connectivity was detected between the putamen and right middle temporal gyrus. There were significant correlations between the corticostriatal connectivity and neuropsychological performances in the patient group, but not between the striatal connectivity and GP signal intensity. These alterations in the corticostriatal functional connectivity suggested the abnormalities in the intrinsic brain functional organiztion among the cirrhotic patients with manganese deposition, and may be associated with development of metabolic encephalopathy. The manganese deposition in nervous system, however, can not be an independent factor predicting the resting-state brain dysfunction in real time.     

基于内在功能连接推定抑郁症脑网络效率的改变

本文研究了在保留最大化内在功能连接条件下抑郁症患者脑网络效率的改变,并探索了改变的拓扑效率和抑郁症病理学之间的关系.为此,我们收集了20例抑郁症患者和20例在年龄、性别和教育水平相匹配的健康被试的静息态功能磁共振图像数据.图论分析显示,与健康对照组比较,抑郁症患者的节点效率减少在左海马旁回、右杏仁核,左颞横回和左颞极(颞中回)减少.减少的节点效率表明,在抑郁症患者脑网络中这些区域传送信息到其他区域的能力减弱.此外,发现局部效率降低在左内侧额上回、左眶部额上回、右回直肌、左杏仁核、右顶上回、左丘脑和左颞极(颞中回).并且发现左内侧额上回、左杏仁核、左丘脑与PHQ-9得分呈负相关.降低的局部效率表明抑郁症患者脑网络中这些区域的局部网络信息传送能力受到抑制.这些结果进一步确认在抑郁症患者中涉及情感信息处理的前额-丘脑-边缘区域被破坏.我们的发现为抑郁症病人的辅助诊断提供了新的潜在生物学标记物.     

Resting state functional connectivity in patients with chronic hallucinations

Auditory verbal hallucinations (AVH) are not only among the most common but also one of the most distressing symptoms of schizophrenia. Despite elaborate research, the underlying brain mechanisms are as yet elusive. Functional MRI studies have associated the experience of AVH with activation of bilateral language-related areas, in particular the right inferior frontal gyrus (rIFG) and the left superior temporal gyrus (lSTG). While these findings helped to understand the neural underpinnings of hearing voices, they provide little information about possible brain mechanisms that predispose a person to experience AVH, i.e. the traits to hallucinate. In this study, we compared resting state connectivity between 49 psychotic patients with chronic AVH and 49 matched controls using the rIFG and the lSTG as seed regions, to identify functional brain systems underlying the predisposition to hallucinate. The right parahippocampal gyrus showed increased connectivity with the rIFG in patients as compared to controls. Reduced connectivity with the rIFG in patients was found for the right dorsolateral prefrontal cortex. Reduced connectivity with the lSTG in patients was identified in the left frontal operculum as well as the parietal opercular area. Connectivity between the lSTG and the left hippocampus was also reduced in patients and showed a negative correlation with the severity of hallucinations. Concluding, we found aberrant connectivity between the seed regions and medial temporal lobe structures which have a prominent role in memory retrieval. Moreover, we found decreased connectivity between language-related areas, indicating aberrant integration in this system potentially including corollary discharge mechanisms.     

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.     

The Relation between Resting State Connectivity and Creativity in Adolescents before and after Training

An important component of creativity is divergent thinking, which involves the ability to generate novel and useful problem solutions. In this study, we tested the relation between resting-state functional connectivity of brain areas activated during a divergent thinking task (i.e., supramarginal gyrus, middle temporal gyrus, medial frontal gyrus) and the effect of practice in 32 adolescents aged 15–16. Over a period of two weeks, an experimental group (n = 16) conducted an 8-session Alternative Uses Task (AUT) training and an active control group (n = 16) conducted an 8-session rule switching training. Resting-state functional connectivity was measured before (pre-test) and after (post-test) training. Across groups at pre-test, stronger connectivity between the middle temporal gyrus and bilateral postcentral gyrus was associated with better divergent thinking performance. The AUT-training, however, did not significantly change functional connectivity. Post hoc analyses showed that change in divergent thinking performance over time was predicted by connectivity between left supramarginal gyrus and right occipital cortex. These results provide evidence for a relation between divergent thinking and resting-state functional connectivity in a task-positive network, taking an important step towards understanding creative cognition and functional brain connectivity.     

Altered effective connectivity network of the amygdala in social anxiety disorder: a resting-state FMRI study

The amygdala is often found to be abnormally recruited in social anxiety disorder (SAD) patients. The question whether amygdala activation is primarily abnormal and affects other brain systems or whether it responds "normally" to an abnormal pattern of information conveyed by other brain structures remained unanswered. To address this question, we investigated a network of effective connectivity associated with the amygdala using Granger causality analysis on resting-state functional MRI data of 22 SAD patients and 21 healthy controls (HC). Implications of abnormal effective connectivity and clinical severity were investigated using the Liebowitz Social Anxiety Scale (LSAS). Decreased influence from inferior temporal gyrus (ITG) to amygdala was found in SAD, while bidirectional influences between amygdala and visual cortices were increased compared to HCs. Clinical relevance of decreased effective connectivity from ITG to amygdala was suggested by a negative correlation of LSAS avoidance scores and the value of Granger causality. Our study is the first to reveal a network of abnormal effective connectivity of core structures in SAD. This is in support of a disregulation in predescribed modules involved in affect control. The amygdala is placed in a central position of dysfunction characterized both by decreased regulatory influence of orbitofrontal cortex and increased crosstalk with visual cortex. The model which is proposed based on our results lends neurobiological support towards cognitive models considering disinhibition and an attentional bias towards negative stimuli as a core feature of the disorder.     

Changes in Thalamic Connectivity in the Early and Late Stages of Amnestic Mild Cognitive Impairment: A Resting-State Functional Magnetic Resonance Study from ADNI

We used resting-state functional magnetic resonance imaging (fMRI) to investigate changes in the thalamus functional connectivity in early and late stages of amnestic mild cognitive impairment. Data of 25 late stages of amnestic mild cognitive impairment (LMCI) patients, 30 early stages of amnestic mild cognitive impairment (EMCI) patients and 30 well-matched healthy controls (HC) were analyzed from the Alzheimer’s disease Neuroimaging Initiative (ADNI). We focused on the correlation between low frequency fMRI signal fluctuations in the thalamus and those in all other brain regions. Compared to healthy controls, we found functional connectivity between the left/right thalamus and a set of brain areas was decreased in LMCI and/or EMCI including right fusiform gyrus (FG), left and right superior temporal gyrus, left medial frontal gyrus extending into supplementary motor area, right insula, left middle temporal gyrus (MTG) extending into middle occipital gyrus (MOG). We also observed increased functional connectivity between the left/right thalamus and several regions in LMCI and/or EMCI including left FG, right MOG, left and right precuneus, right MTG and left inferior temporal gyrus. In the direct comparison between the LMCI and EMCI groups, we obtained several brain regions showed thalamus-seeded functional connectivity differences such as the precentral gyrus, hippocampus, FG and MTG. Briefly, these brain regions mentioned above were mainly located in the thalamo-related networks including thalamo-hippocampus, thalamo-temporal, thalamo-visual, and thalamo-default mode network. The decreased functional connectivity of the thalamus might suggest reduced functional integrity of thalamo-related networks and increased functional connectivity indicated that aMCI patients could use additional brain resources to compensate for the loss of cognitive function. Our study provided a new sight to understand the two important states of aMCI and revealed resting-state fMRI is an appropriate method for exploring pathophysiological changes in aMCI.     

Temporal Dynamics of Stress-Induced Alternations of Intrinsic Amygdala Connectivity and Neuroendocrine Levels

Stress-induced changes in functional brain connectivity have been linked to the etiology of stress-related disorders. Resting state functional connectivity (rsFC) is especially informative in characterizing the temporal trajectory of glucocorticoids during stress adaptation. Using the imaging Maastricht Acute Stress Test (iMAST), we induced acute stress in 39 healthy volunteers and monitored the neuroendocrine stress levels during three runs of resting state functional magnetic resonance imaging (rs-fMRI): before (run 1), immediately following (run 2), and 30min after acute stress (run 3). The iMAST resulted in strong increases in cortisol levels. Whole-brain analysis revealed that acute stress (run 2 - 1) was characterized by changes in connectivity of the amygdala with the ventrolateral prefrontal cortex (vlPFC), ventral posterior cingulate cortex (PCC), cuneus, parahippocampal gyrus, and culmen. Additionally, cortisol responders were characterized by enhanced amygdala - medial prefrontal cortex (mPFC) connectivity. Stress recovery (run 3 - 2) was characterized by altered amygdala connectivity with the dorsolateral prefrontal cortex (dlPFC), ventral and dorsal anterior cingulate cortex (ACC), anterior hippocampal complex, cuneus, and presupplementary motor area (preSMA). Opposite to non-responders, cortisol responders were characterized by enhanced amygdala connectivity with the anterior hippocampal complex and parahippocampal gyrus, and reduced connectivity with left dlPFC, dACC, and culmen during early recovery. Acute stress responding and recovery are thus associated with changes in the functional connectivity of the amygdala network. Our findings show that these changes may be regulated via stress-induced neuroendocrine levels. Defining stress-induced neuronal network changes is pertinent to developing treatments that target abnormal neuronal activity.     

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.     

Hyperthermia-Induced Disruption of Functional Connectivity in the Human Brain Network

Background

Passive hyperthermia is a potential risk factor to human cognitive performance and work behavior in many extreme work environments. Previous studies have demonstrated significant effects of passive hyperthermia on human cognitive performance and work behavior. However, there is a lack of a clear understanding of the exact affected brain regions and inter-regional connectivities.

Methodology and Principal Findings

We simulated 1 hour environmental heat exposure to thirty-six participants under two environmental temperature conditions (25°C and 50°C), and collected resting-state functional brain activity. The functional connectivities with a preselected region of interest (ROI) in the posterior cingulate cortex and precuneus (PCC/PCu), furthermore, inter-regional connectivities throughout the entire brain using a prior Anatomical Automatic Labeling (AAL) atlas were calculated. We identified decreased correlations of a set of regions with the PCC/PCu, including the medial orbitofrontal cortex (mOFC) and bilateral medial temporal cortex, as well as increased correlations with the partial orbitofrontal cortex particularly in the bilateral orbital superior frontal gyrus. Compared with the normal control (NC) group, the hyperthermia (HT) group showed 65 disturbed functional connectivities with 50 of them being decreased and 15 of them being increased. While the decreased correlations mainly involved with the mOFC, temporal lobe and occipital lobe, increased correlations were mainly located within the limbic system. In consideration of physiological system changes, we explored the correlations of the number of significantly altered inter-regional connectivities with differential rectal temperatures and weight loss, but failed to obtain significant correlations. More importantly, during the attention network test (ANT) we found that the number of significantly altered functional connectivities was positively correlated with an increase in executive control reaction time.

Conclusions/Significance

We first identified the hyperthermia-induced altered functional connectivity patterns. The changes in the functional connectivity network might be a possible explanation for the cognitive performance and work behavior alteration.     

Prefrontal Control of the Amygdala during Real-Time fMRI Neurofeedback Training of Emotion Regulation

We observed in a previous study (PLoS ONE 6:e24522) that the self-regulation of amygdala activity via real-time fMRI neurofeedback (rtfMRI-nf) with positive emotion induction was associated, in healthy participants, with an enhancement in the functional connectivity between the left amygdala (LA) and six regions of the prefrontal cortex. These regions included the left rostral anterior cingulate cortex (rACC), bilateral dorsomedial prefrontal cortex (DMPFC), bilateral superior frontal gyrus (SFG), and right medial frontopolar cortex (MFPC). Together with the LA, these six prefrontal regions thus formed the functional neuroanatomical network engaged during the rtfMRI-nf procedure. Here we perform a structural vector autoregression (SVAR) analysis of the effective connectivity for this network. The SVAR analysis demonstrates that the left rACC plays an important role during the rtfMRI-nf training, modulating the LA and the other network regions. According to the analysis, the rtfMRI-nf training leads to a significant enhancement in the time-lagged effect of the left rACC on the LA, potentially consistent with the ipsilateral distribution of the monosynaptic projections between these regions. The training is also accompanied by significant increases in the instantaneous (contemporaneous) effects of the left rACC on four other regions – the bilateral DMPFC, the right MFPC, and the left SFG. The instantaneous effects of the LA on the bilateral DMPFC are also significantly enhanced. Our results are consistent with a broad literature supporting the role of the rACC in emotion processing and regulation. Our exploratory analysis provides, for the first time, insights into the causal relationships within the network of regions engaged during the rtfMRI-nf procedure targeting the amygdala. It suggests that the rACC may constitute a promising target for rtfMRI-nf training along with the amygdala in patients with affective disorders, particularly posttraumatic stress disorder (PTSD).     

Functional Connectivity of the Caudal Anterior Cingulate Cortex Is Decreased in Autism

The anterior cingulate cortex (ACC) is frequently reported to have functionally distinct sub-regions that play key roles in different intrinsic networks. However, the contribution of the ACC, which is connected to several cortical areas and the limbic system, to autism is not clearly understood, although it may be involved in dysfunctions across several distinct but related functional domains. By comparing resting-state fMRI data from persons with autism and healthy controls, we sought to identify the abnormalities in the functional connectivity (FC) of ACC sub-regions in autism. The analyses found autism-related reductions in FC between the left caudal ACC and the right rolandic operculum, insula, postcentral gyrus, superior temporal gyrus, and the middle temporal gyrus. The FC (z-scores) between the left caudal ACC and the right insula was negatively correlated with the Stereotyped Behaviors and Restricted Interests scores of the autism group. These findings suggest that the caudal ACC is recruited selectively in the pathomechanism of autism.