Altered small-world,functional brain networks in patients with lower back pain

In this study, we aimed to investigate the functional network changes that occur in patients with lower back pain(LBP). We also investigated the link between LBP and the small-world properties of functional networks within the brain. Functional MRI(fMRI) was performed on 20 individuals with LBP and 17 age and gender-matched normal controls during the resting state. The severity of the pain in the individuals with LBP ranged from 5 to 8 on a 0–10 scale, with 0 indicating no pain. Network-based statistics were performed to investigate the differences between the brain networks of individuals with LBP and those of normal controls. Several small-world parameters of brain networks were calculated, including the clustering coefficient, characteristic path length, local efficiency, and global efficiency. These criteria reflect the overall network efficiency. The brain networks in the individuals with LBP due to herniation of a lumbar disc demonstrated a significantly longer characteristic path length as well as a lower clustering coefficient, global efficiency, and local efficiency compared to those in control subjects. We found that LBP patients tended to have unstable and inefficient brain networks when compared with healthy controls. In addition, LBP individuals showed significantly decreased functional connectivity in the anterior cingulate cortex, middle cingulate cortex, post cingulate cortex, inferior frontal gyrus, middle temporal gyrus, occipital gyrus, postcentral gyrus, precentral gyrus, supplementary motor area, thalamus, fusiform, caudate, and cerebellum. We believe that these regions may be involved in the pathophysiology of lower back pain.     

早期经验对大鼠脑区一氧化氮合酶活性的影响

目的　探讨NO与早期饲养环境所引起脑效应的关系。方法　将断乳大鼠在丰富环境 (EC)和单调环境 (IC)中饲养 30d。环境暴露后通过NADPH -黄递酶组化方法对海马齿状回 (DEN)和大脑皮层NOS活性进行定量测定以及对大鼠进行Morris水迷宫作业训练。结果　EC大鼠与IC大鼠相比 ,海马齿状回 (DEN)和大脑皮层NOS活性明显下降 ,迷宫测试表明EC大鼠的空间认知显著优于IC大鼠。在环境暴露期间隔日注射一氧化氮合酶 (NOS)抑制物L -NAME(50mg/kg) ,未引起EC或IC大鼠认知行为的明显改变 ,但导致DEN和大脑皮层NOS活性的不同改变。结论　NO可能与早期经验脑效应有关。     

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

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

Effective Connectivity Extracted from Resting-State fMRI Images Using Transfer Entropy

Background and objectiveBased on magnetic resonance imaging (MRI), macroscopic structural and functional connectivity of human brain has been widely explored in the last decade. However, little work has been done on effective connectivity between individual brain parcels. In this preliminary study, we aim to investigate whole-brain effective connectivity networks from resting-state functional MRI (rs-fMRI) images.Material and methodsAfter the functional connectivity networks of 26 healthy subjects (aged from 25 to 35 years old) from Human Connectome Project database were derived from rs-fMRI images with dynamic time warping, proportional thresholding (PT) was performed on the functional connectivity matrices by retaining the PT% strongest functional connections. PT% ranges from 40% to 10% in steps of 5%. Then, effective connections corresponding to the PT% strongest functional connections, both bi-directional and unidirectional, were estimated with Renyi's 2-order transfer entropy (TE) method. Topological metrics of the built functional and effective connectivity networks were further characterized, including clustering coefficient, transitivity, and modularity.ResultsIt is found that the effective connectivity networks exhibit small world attributes, and that the networks contain a subset of highly interactive regions, including right frontal pole (in-degree 6), left middle frontal gyrus (in-degree 8, out-degree 1), right precentral gyrus (out-degree 9), left precentral gyrus (out-degree 7), right posterior division of supramarginal gyrus (in-degree 2, out-degree 3), left angular gyrus (out-degree 6), left inferior division of lateral occipital cortex (out-degree 6), right occipital pole (in-degree 5), right cerebellum 7b parcel (in-degree 15), and right cerebellum 8 parcel (in-degree 7, out-degree 1).ConclusionsThe observations in this study provide information about the casual interactions among brain parcels in resting state, helping reveal how different subregions of large-scale distributed neural networks are coupled together in performing cognitive functions.     

Increased Functional Connectivity between Prefrontal Cortex and Reward System in Pathological Gambling

Pathological gambling (PG) shares clinical characteristics with substance-use disorders and is thus discussed as a behavioral addiction. Recent neuroimaging studies on PG report functional changes in prefrontal structures and the mesolimbic reward system. While an imbalance between these structures has been related to addictive behavior, whether their dysfunction in PG is reflected in the interaction between them remains unclear. We addressed this question using functional connectivity resting-state fMRI in male subjects with PG and controls. Seed-based functional connectivity was computed using two regions-of-interest, based on the results of a previous voxel-based morphometry study, located in the prefrontal cortex and the mesolimbic reward system (right middle frontal gyrus and right ventral striatum). PG patients demonstrated increased connectivity from the right middle frontal gyrus to the right striatum as compared to controls, which was also positively correlated with nonplanning aspect of impulsiveness, smoking and craving scores in the PG group. Moreover, PG patients demonstrated decreased connectivity from the right middle frontal gyrus to other prefrontal areas as compared to controls. The right ventral striatum demonstrated increased connectivity to the right superior and middle frontal gyrus and left cerebellum in PG patients as compared to controls. The increased connectivity to the cerebellum was positively correlated with smoking in the PG group. Our results provide further evidence for alterations in functional connectivity in PG with increased connectivity between prefrontal regions and the reward system, similar to connectivity changes reported in substance use disorder.     

Long-Term Effects of Temporal Lobe Epilepsy on Local Neural Networks: A Graph Theoretical Analysis of Corticography Recordings

Purpose

Pharmaco-resistant temporal lobe epilepsy (TLE) is often treated with surgical intervention at some point. As epilepsy surgery is considered a last resort by most physicians, a long history of epileptic seizures prior to surgery is not uncommon. Little is known about the effects of ongoing TLE on neural functioning. A better understanding of these effects might influence the moment of surgical intervention. Functional connectivity (interaction between spatially distributed brain areas) and network structure (integration and segregation of information processing) are thought to be essential for optimal brain functioning. We report on the impact of TLE duration on temporal lobe functional connectivity and network characteristics.

Methods

Functional connectivity of the temporal lobe at the time of surgery was assessed by means of interictal electrocorticography (ECoG) recordings of 27 TLE patients by using the phase lag index (PLI). Graphs (abstract network representations) were reconstructed from the PLI matrix and characterized by the clustering coefficient C (local clustering), the path length L (overall network interconnectedness), and the “small world index” S (network configuration).

Results

Functional connectivity (average PLI), clustering coefficients, and the small world index were negatively correlated with TLE duration in the broad frequency band (0.5–48 Hz).

Discussion

Temporal lobe functional connectivity is lower in patients with longer TLE history, and longer TLE duration is correlated with more random network configuration. Our findings suggest that the neural networks of TLE patients become more pathological over time, possibly due to temporal lobe changes associated with long-standing lesional epilepsy.     

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.     

Functional disconnection and compensation in mild cognitive impairment: evidence from DLPFC connectivity using resting-state fMRI

The known regional abnormality of the dorsolateral prefrontal cortex (DLPFC) and its role in various neural circuits in mild cognitive impairment (MCI) has given prominence to its importance in studies on the disconnection associated with MCI. The purpose of the current study was to examine the DLPFC functional connectivity patterns during rest in MCI patients and the impact of regional grey matter (GM) atrophy on the functional results. Structural and functional MRI data were collected from 14 MCI patients and 14 age, gender-matched healthy controls. We found that both the bilateral DLPFC showed reduced functional connectivity with the inferior parietal lobule (IPL), superior/medial frontal gyrus and sub-cortical regions (e.g., thalamus, putamen) in MCI patients when compared with healthy controls. Moreover, the DLPFC connectivity with the IPL and thalamus significantly correlated with the cognitive performance of patients as measured by mini-mental state examination (MMSE), clock drawing test (CDT), and California verbal learning test (CVLT) scores. When taking GM atrophy as covariates, these results were approximately consistent with those without correction, although there may be a decrease in the statistical power. These results suggest that the DLPFC disconnections may be the substrates of cognitive impairments in MCI patients. In addition, we also found enhanced functional connectivity between the left DLPFC and the right prefrontal cortex in MCI patients. This is consistent with previous findings of MCI-related increased activation during cognitive tasks, and may represent a compensatory mechanism in MCI patients. Together, the present study demonstrated the coexistence of functional disconnection and compensation in MCI patients using DLPFC functional connectivity analysis, and thus might provide insights into biological mechanism of the disease.     

Task-switching Cost and Intrinsic Functional Connectivity in the Human Brain: Toward Understanding Individual Differences in Cognitive Flexibility

The human ability to flexibly alternate between tasks (i.e., task-switching) represents a critical component of cognitive control. Many functional magnetic resonance imaging (fMRI) studies have explored the neural basis of the task-switching. However, no study to date has examined how individual differences in intrinsic functional architecture of the human brain are related to that of the task-switching. In the present study, we took 11 task-switching relevant areas from a meta-analysis study as the regions of interests (ROIs) and estimated their intrinsic functional connectivity (iFC) with the whole brain. This procedure was repeated for 32 healthy adults based upon their fMRI scans during resting-state (rfMRI) to investigate the correlations between switching cost and the iFC strength across these participants. This analysis found that switch cost was negatively correlated with a set of iFC involved ROIs including left inferior frontal junction, bilateral superior posterior parietal cortex, left precuneus, bilateral inferior parietal lobule, right middle frontal gyrus and bilateral middle occipital gyrus. These connectivity profiles represent an intrinsic functional architecture of task-switching where the left inferior frontal junction plays a hub role in this brain-behavior association. These findings are highly reproducible in another validation independent sample and provide a novel perspective for understanding the neural basis of individual differences in task-switching behaviors reflected in the intrinsic architecture of the human brain.     

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.