Functional and Structural Alterations in Temporal Lobe Tumor Patients: Evidence of Functional Compensation in the Human Brain

Patients with temporal lobe tumor are frequently accompanied by cognitive impairments. This study aims to combine diffusion tensor imaging(DTI) with resting-state functional magnetic resonance image(fMRI) to explore the underlying cognitive alternation and functional reorganization in patients with temporal lobe tumor.Twenty patients with right temporal lobe tumor and seventeen healthy volunteers were recruited in this study. Independent component analysis(ICA) was utilized to divide the whole brain into six sub functional networks, and DTI combined with graph-based topological analysis was used to calculate the structural properties of whole-brain and sub functional networks. Besides, the rich hubs in both patients and healthy controls(HCs)were identified and a further analysis of their internal functional and structural connectivity was also conducted. The E_(global) in self-referential network(SRN) of patients is higher than HCs, while decreased E_(global) of dorsal attention network(DAN) and default mode network(DMN) were found in patients. For the patients, brain regions with increased nodal efficiency(E_(nodal)) were located in the frontal lobe(corresponding to SRN). Six identical hubs were found in two groups. Compared patients with HCs, significant between-group differences in both functional and structural connectivity were observed between right insula(INS.R) and right lenticular nucleus, putamen(PUT.R). The findings provide evidence that impaired cognition are closely related to functional and structural abnormalities and the compensatory roles of frontal lobe were also identified in patients.The proposed combination of DTI and f MRI promises a widespread utilization in clinical research on the mechanisms of neurological diseases.     

慢性失眠患者大脑蓝斑的异常静息态功能连接

目的:利用功能连接方法观察慢性失眠患者静息态下蓝斑的异常功能连接。方法:采集49例慢性失眠患者以及47例性别年龄和受教育程度相匹配的健康对照组的功能磁共振图像,以蓝斑为感兴趣区域,与全脑其他体素进行功能连接分析,得到两组之间功能连接的差异脑区,再对异常连接脑区的功能连接值与临床量表分数做相关分析。结果:与对照组相比,慢性失眠患者蓝斑与右楔前叶皮质、右后扣带回皮质、左颞中回皮质、左距状沟周围皮质、右眶部额上回皮质之间的功能连接增强（P<0.05, FDR校正）,并且蓝斑与左颞中回皮质之间功能连接值与抑郁自评量表呈正相关（P=0.021）。结论:慢性失眠患者蓝斑与多个脑区（主要是默认模式网络）出现的异常功能连接,可能有助于更好地理解慢性失眠的神经生物学机制,可能为失眠的高度唤醒假说提供新的影像学证据。     

Resting state fMRI in Alzheimer's disease: beyond the default mode network

Using resting state (RS) functional magnetic resonance imaging (fMRI), the connectivity patterns of the default mode (DMN), frontoparietal, executive, and salience networks were explored in 13 Alzheimer's disease (AD) patients, 12 amnestic mild cognitive impairment (aMCI) patients, and 13 healthy controls. Compared with controls and aMCI, AD was associated with opposing connectivity effects in the DMN (decreased) and frontal networks (enhanced). The only RS abnormality found in aMCI patients compared with controls was a precuneus connectivity reduction in the DMN. RS fMRI group differences were only partly related to gray matter atrophy. In AD patients, the mean executive network connectivity was positively associated with frontal-executive and language neuropsychological scores. These results suggest that AD is associated with an alteration of large-scale functional brain networks, which extends well beyond the DMN. In AD, the limited resources of the DMN may be paralleled, in an attempt to maintain cognitive efficiency, by an increased prefrontal connectivity. A medial parietal RS fMRI signal change seems to be present since the early phase of AD.     

Changes of functional connectivity of the motor network in the resting state in Parkinson's disease

We used functional MRI (fMRI) and a network model based on graph theory to measure functional connectivity of brain motor network in the resting state in patients with Parkinson's disease (PD). FMRIs were acquired in 22 PD patients before and after levodopa administration, and in age- and sex-matched normal controls. The total connectivity degree of each region within the motor network was calculated and compared between patients and controls. We found that PD patients at off state had significantly decreased functional connectivity in the supplementary motor area, left dorsal lateral prefrontal cortex and left putamen, and had increased functional connectivity in the left cerebellum, left primary motor cortex, and left parietal cortex compared to normal subjects. Administration of levodopa relatively normalized the pattern of functional connectivity in PD patients. The functional connectivity in most of regions in the motor network correlated with the Unified Parkinson's Disease Rating Scale motor score in the patients. Our findings demonstrate that the pattern of functional connectivity of the motor network in the resting state is disrupted in PD. This change is secondary to dopamine deficiency, and related to the severity of the disease. We postulate that this abnormal functional connectivity of motor network in the baseline state is possibly an important factor contributing to some motor deficits in PD, e.g. akinesia.     

运动想象的大尺度动态功能网络连接

运动想象是一个多维度的高级脑认知活动,被广泛应用于脑-机接口控制和临床康复。然而,运动想象应用背后的神经机制仍然不清楚。为进一步理解运动想象潜在的神经机制,从大尺度水平探索运动想象的动态脑网络连接,征集26名健康被试进行运动想象功能磁共振扫描实验。基于运动想象任务态磁共振数据,首先,利用独立成分分析,获取11个大尺度功能子网络,并提取子网络对应的时间序列;然后,利用滑窗分析法,构建动态网络连接矩阵,并对所有的连接矩阵进行k-means聚类分析,得到状态依赖的动态连接;最后,利用网络统计分析方法,评估左/右手运动想象动态网络连接差异。结果表明,机器学习方法能更有效地获取数据特征,得到基于数据驱动的最优窗长为31个时间点,并且对左/右手运动想象的分类准确率达75.6%;运动想象大尺度网络连接模式是一种状态依赖的动态变化过程,共聚类出4个动态重构连接模式;左/右手运动想象大尺度动态网络连接模式的特异性,主要体现在额顶网络(FPN)和背侧注意网络(DAN)与其他子网络之间的交互上。该研究的发现,为理解运动想象潜在的神经机制提供新的观点。     

Interleukin-1 beta C-511T polymorphism modulates functional connectivity of anterior midcingulate cortex in non-demented elderly Han males

Recent resting fMRI studies have suggested that the functional connectivity of the brain’s large-scale networks is associated with the cognitive decline of aging and is modulated by genetic factors. Our previous study found a significant association between interleukin-1 (IL-1 beta) C-511T polymorphism and working memory performance among elderly people. This study investigates the effects of IL-1 beta C-511T polymorphism on the functional connectivity of the cognitive division of the cingulate cortex [i.e., the anterior midcingulate (aMCC)] in non-demented Han elderly people and tests the hypothesis that T/T carriers are associated with lowered FC. Non-demented elderly males (n = 95) received resting MRI scanning, genotyping, and cognitive evaluation using the cognitive abilities screening instrument (CASI) and the Wechsler digit span task test. The functional connectivity map in each subject was derived based on positive correlations of low-frequency fMRI fluctuations with a seed in the aMCC according to structural definition. Between-group difference was compared by random effect analysis. Compared to the C/C or C/T carriers, the T/T carriers had a significantly worse CASI performance, especially in the abstraction scores. For the functional connectivity analysis, the T/T carriers exhibited significantly lower functional connectivity with several prefrontal areas and the left putamen. The cortico-striatal connection between the aMCC and left putamen was correlated with the CASI abstraction and attention scores. The results were consistent with our hypothesis and supported that the brains’ functional connectivity in elderly people may be modulated by genetic polymorphism associated with local inflammation processes.     

Restoration of mammillothalamic functional connectivity through thiamine replacement therapy in Wernicke's encephalopathy

Resting-state functional MRI (fMRI) is now providing further understanding of neuropsychiatric illnesses. However, its practical applicability in the clinical realms is still questionable. Here we report three consecutive followed-up resting-state fMRI data in a single case with Wernicke encephalopathy before and after high-dose thiamine replacement therapy ranging over 20 months. We measured the mammillothalamic functional connectivity strength between the first ROI (mammillary body) and a voxel which showed the highest co-activation among voxels within the anterior thalamus (the second ROI) to enhance the specificity of the functional connectivity data. We found that the time-series changes in the mammillothalamic functional connectivity generally paralleled to the changes in delayed verbal and nonverbal recall memory scores in the left and right hemisphere, respectively. Among these, the left-side connectivity and delayed verbal recall score seemed to be related to the overall clinical status change. Modified directed transfer function (dDTF) analysis also identified significant information flows with mammillary-to-thalamic direction except at the acute illness state. Our findings, though preliminary in nature, suggest the practical applicability of resting-state fMRI to trace an effect of thiamine replacement therapy on the memory tract function in Wernicke encephalopathy at single-patient level.     

1H magnetic resonance spectroscopy at 3 T in cryptogenic and mesial temporal lobe epilepsy

The objectives of this work were to compare concentrations of N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln), Glx (=Glu + Gln), myo-inositol (mI), total creatine (Cre) and other metabolites in the temporal lobes of patients with mesial temporal lobe epilepsy (mTLE), cryptogenic TLE (cTLE), who show no abnormalities in high-resolution MRI, and healthy controls using single voxel (1)H MRS at 3 T. Twelve patients with mTLE, nine with cTLE and 22 controls were investigated using a short echo time STEAM protocol. Voxels were positioned bilaterally in the medial and lateral temporal lobes. Spectra were processed with LCModel. Significantly lower mean NAA were detected in mTLE patients (P < 0.001) and a trend towards lower NAA in cTLE patients compared to controls (P = 0.053). Glx was not different between groups. Estimates of Glu showed a different metabolic pattern in mTLE with elevated Glu in lateral compared with medial voxels on the ipsilateral side to seizure onset (P = 0.019). MI concentrations were significantly lower in cTLE (P < 0.001) and in mTLE patients (P = 0.005) compared with healthy controls. MI/Cre was significantly reduced in cTLE patients only (P = 0.004). The results confirm low NAA in mTLE and to a lesser extent in cTLE patients. MI and mI/Cre were identified as potential metabolic indicators of the epileptogenic area in cTLE.     

基于功能连接的屈光参差性弱视视觉网络损伤研究

目的基于功能连接算法分析屈光参差性弱视和正常对照组的功能性磁共振成像(functional magnetic resonance imaging,fMRI)数据,通过对比弱视患者脑部自发活动的视觉网络功能连接异常,揭示其视觉损伤机制。方法在闭眼静息条件下采集21名弱视成年人和21名正常对照组的fMRI数据,进行去噪、校正等预处理后,计算初级视觉网络、高级视觉网络和视觉空间网络3个典型的视觉网络内和网络间的功能连接系数,并采用双样本t检验进行统计分析。结果屈光参差性弱视与正常对照组在初级视觉网络中差异无统计学意义,在高级视觉网络和视觉空间网络中差异具有统计学意义,并且它们网络之间的功能连接差异也无统计学意义。结论基于功能连接的静息态功能磁共振分析是有效的非侵入式脑区功能性连接异常研究方法,能够反映屈光参差性弱视不同视觉网络的自发脑部活动脑区异常表现,对于弱视致病机制模型研究和提出新的治疗方法都有重要启发。     

海洛因成瘾者静息状态下脑功能连接研究

目的:探讨海洛因成瘾者在静息状态下脑功能连接与正常对照的区别。方法:对16例海洛因成瘾者和16例匹配的正常对照进行静息状态下的脑功能扫描。选择杏仁核为种子区,比较两组之间脑功能连接的区别。结果:同正常对照相比,海洛因成瘾者杏仁核与左右扣带回、左右扣带回前部以及右侧Brodmann 24脑区功能连接下降。结论:这种功能连接的下降可能反映出海洛因成瘾者的杏仁核功能处于脱抑制状态,造成海洛因成瘾者犒赏、动机、记忆功能异常,从而参与了海洛因成瘾行为产生和维持。     

基于ICA的颞叶癫痫背侧注意网络的研究

很多fMRI研究表明部分癫痫患者缺省模式网络存在中断现象,而对于颞叶癫痫背侧注意网络的研究几乎没有涉及。本研究尝试运用独立成分分析(independent component analysis,ICA)分离出16例单侧颞叶癫痫(temporal lobe epilepsy,TLE)患者和20例正常对照的背侧注意网络,并采用拟合度值(goodness-of-fit scores)分析对感兴趣成分进行挑选,将其结果进行组内分析和组间分析。结果表明:背侧注意网络分布于双侧顶内沟、额中回、额眼区、右侧小脑后叶等区域;颞叶癫痫患者的背侧注意网络相比正常人,大部分区域功能连接度下降,以双侧顶内沟、额中回、右侧小脑后叶区域显著,这可能是由于颞叶癫痫患者的大脑功能内源性组织发生破坏。拟合度值下降表明背侧注意网络激活区域为单侧TLE患者提供了一个灵敏的生物信号特征。     

Dissociable attentional and inhibitory networks of dorsal and ventral areas of the right inferior frontal cortex: a combined task-specific and coordinate-based meta-analytic fMRI study

The right inferior frontal cortex (rIFC) is frequently activated during executive control tasks. Whereas the function of the dorsal portion of rIFC, more precisely the inferior frontal junction (rIFJ), is convergingly assigned to the attention system, the functional key role of the ventral portion, i.e., the inferior frontal gyrus (rIFG), is hitherto controversially debated. Here, we used a two-step methodical approach to clarify the differential function of rIFJ and rIFG. First, we used event-related functional magnetic resonance imaging (fMRI) during a modified stop signal task with an attentional capture condition (acSST) to delineate attentional from inhibitory motor processes (step 1). Then, we applied coordinate-based meta-analytic connectivity modeling (MACM) to assess functional connectivity profiles of rIFJ and rIFG across various paradigm classes (step 2). As hypothesized, rIFJ activity was associated with the detection of salient stimuli, and was functionally connected to areas of the ventral and dorsal attention network. RIFG was activated during successful response inhibition even when controlling for attentional capture and revealed the highest functional connectivity with core motor areas. Thereby, rIFJ and rIFG delineated largely independent brain networks for attention and motor control. MACM results attributed a more specific attentional function to rIFJ, suggesting an integrative role between stimulus-driven ventral and goal-directed dorsal attention processes. In contrast, rIFG was disclosed as a region of the motor control but not attention system, being essential for response inhibition. The current study provides decisive evidence regarding a more precise functional characterization of rIFC subregions in attention and inhibition.     

Functional topography of the thalamocortical system in human

Various studies have indicated that the thalamus is involved in controlling both cortico-cortical information flow and cortical communication with the rest of the brain. Detailed anatomy and functional connectivity patterns of the thalamocortical system are essential to understanding the cortical organization and pathophysiology of a wide range of thalamus-related neurological and neuropsychiatric diseases. The current study used resting-state fMRI to investigate the topography of the human thalamocortical system from a functional perspective. The thalamus-related cortical networks were identified by performing independent component analysis on voxel-based thalamic functional connectivity maps across a large group of subjects. The resulting functional brain networks were very similar to well-established resting-state network maps. Using these brain network components in a spatial regression model with each thalamic voxel’s functional connectivity map, we localized the thalamic subdivisions related to each brain network. For instance, the medial dorsal nucleus was shown to be associated with the default mode, the bilateral executive, the medial visual networks; and the pulvinar nucleus was involved in both the dorsal attention and the visual networks. These results revealed that a single nucleus may have functional connections with multiple cortical regions or even multiple functional networks, and may be potentially related to the function of mediation or modulation of multiple cortical networks. This observed organization of thalamocortical system provided a reference for studying the functions of thalamic sub-regions. The importance of intrinsic connectivity-based mapping of the thalamocortical relationship is discussed, as well as the applicability of the approach for future studies.     

fMRI responses in medial frontal cortex that depend on the temporal frequency of visual input

Functional networks in the human brain have been investigated using electrophysiological methods (EEG/MEG, LFP, and MUA) and steady-state paradigms that apply periodic luminance or contrast modulation to drive cortical networks. We have used this approach with fMRI to characterize a cortical network driven by a checkerboard reversing at a fixed frequency. We found that the fMRI signals in voxels located in occipital cortex were increased by checkerboard reversal at frequencies ranging from 3 to 14 Hz. In contrast, the response of a cluster of voxels centered on basal medial frontal cortex depended strongly on the reversal frequency, consistently exhibiting a peak in the response for specific reversal frequencies between 3 and 5 Hz in each subject. The fMRI signals at the frontal voxels were positively correlated indicating a homogeneous cluster. Some of the occipital voxels were positively correlated to the frontal voxels apparently forming a large-scale functional network. Other occipital voxels were negatively correlated to the frontal voxels, suggesting a functionally distinct network. The results provide preliminary fMRI evidence that during visual stimulation, input frequency can be varied to engage different functional networks.     

Single domain amnestic MCI: A multiple cognitive domains fMRI investigation

Amnestic mild cognitive impairment (a-MCI) is associated with the highest annual incidence of conversion to Alzheimer's disease (AD) (10-15%). a-MCI patients may have only a memory deficit (single domain: sd-a-MCI) or additional dysfunctions affecting other cognitive domains (multiple domain: md-a-MCI). Using functional magnetic resonance imaging (fMRI), we investigated brain activation in 16 sd-a-MCI patients and 14 controls during four different tasks assessing language, memory, attention and empathy functions. We found greater activation in sd-a-MCI compared with controls in the left inferior temporal gyrus (language), the right superior temporal gyrus (memory) and the right dorsal precentral gyrus (attention). Moreover, patients’ activation correlated significantly with neuropsychological scores obtained at tests exploring the corresponding function. These findings indicate that fMRI is sensitive to detect early changes occurring in AD pathology and that individuals with sd-a-MCI show increased activation in multiple task-related brain regions. We suggest that these functional changes relate to the development of early compensatory mechanisms that reduce cognitive deficits associated with the progressive accumulation of brain damage.     

Functional connectivity in fronto-subcortical circuitry during the resting state in obsessive-compulsive disorder

Obsessions and compulsions mediated by cognitive inflexibility might be associated with abnormal resting state functional connectivity in the default mode network (DMN) that represents intrinsically generated neuronal activity. It was hypothesized that decreased functional connectivity in the DMN would occur in components of fronto-subcortical circuits in patients with obsessive-compulsive disorder (OCD). Twenty-two unmedicated OCD patients and 22 age- and sex-matched healthy controls received resting state functional scanning runs. The posterior cingulate cortex (PCC) region was chosen as the seed region for the connectivity analysis. Correlations between temporal connectivity with the seed region and scores on clinical measures and obsessive-compulsive symptom dimensions were also assessed. OCD patients demonstrated less functional connectivity within the DMN in the anterior cingulate cortex, middle frontal gyrus, and putamen compared to controls. The functional connectivity to the PCC seed region in OCD patients was in the direction opposite to that in the prefrontal areas with regard to scores on cleaning and obsessions/checking dimensions of OCD. These data provide evidence for fronto-subcortical dysfunction in OCD. Results from this study also support the notion that OCD is a heterogeneous disorder mediated by distinct circuits.     

Associations between insomnia symptoms and functional connectivity in the UK Biobank cohort (n = 29,423)

An increasing number of studies harness resting-state fMRI functional connectivity analysis to investigate the neurobiological mechanisms of insomnia. The results to date are inconsistent and the detection of minor and widely distributed alterations in functional connectivity requires large sample sizes. The present study investigated associations between insomnia symptoms and resting-state functional connectivity at the whole-brain level in the largest sample to date. This cross-sectional analysis used resting-state imaging data from the UK Biobank, a large scale, population-based biomedical database. The analysis included 29,423 participants (age: 63.1 ± 7.5 years, 54.3% female), comprising 9210 with frequent insomnia symptoms and 20,213 controls without. Linear models were adjusted for relevant clinical, imaging, and socio-demographic variables. The Akaike information criterion was used for model selection. Multiple comparisons were corrected using the false discovery rate with a significance level of q < 0.05. Frequent insomnia symptoms were associated with increased connectivity within the default mode network and frontoparietal network, increased negative connectivity between the default mode network and the frontoparietal network, and decreased connectivity between the salience network and a node of the default mode network. Furthermore, frequent insomnia symptoms were associated with altered functional connectivity between nodes comprising sensory areas and the cerebellum. These functional alterations of brain networks may underlie dysfunctional affective and cognitive processing in insomnia and contribute to subjectively and objectively impaired sleep. However, it must be noted that the item that was used to assess frequent insomnia symptoms in this study did not assess all the characteristics of clinically diagnosed insomnia.     

基于独立成分分析的遗尿症儿童脑功能网络研究

目的:用独立成分分析（ICA）的方法对原发性单症状夜间遗尿症（PMNE）儿童的脑功能网络成分间连接进行研究。方法:采集35例PMNE儿童和25例健康儿童脑功能磁共振图像,通过ICA获得每个被试的脑功能网络成分,然后计算每个被试脑功能网络成分间的功能连接强度,比较PMNE儿童与健康对照组的强度差异。结果:与对照组对比,PMNE患者的右侧执行控制网络与默认模式网络、左侧执行控制网络均存在功能连接异常（FDR, P<0.05）。结论:PMNE儿童存在脑功能网络成分间的连接异常,这可能为理解PMNE儿童的病理机制提供一些新的影像学依据。     

Resting state functional connectivity alterations in primary lateral sclerosis

Resting state functional connectivity of the sensorimotor and extramotor brain networks was studied in 24 patients with primary lateral sclerosis (PLS) relative to 26 healthy controls. The relationships of RS functional connectivity with patient clinical and cognitive status and white matter tract damage (i.e., corticospinal tracts, corpus callosum, and superior longitudinal fasciculus) were investigated. Compared with controls, PLS patients showed an increased functional connectivity within the sensorimotor, frontal, and left frontoparietal networks spanning the pre- and postcentral, medial and dorsal frontal, insular, and superior temporal regions. Patients with more severe physical disability and a more rapid rate of disease progression had increased sensorimotor connectivity values. The increased functional connectivity within the frontal network was associated with executive dysfunction. In addition, higher functional connectivity correlated with greater structural damage to network-specific white matter tracts. This study shows clinically meaningful increased resting state functional connectivity in PLS.     

基于fMRI数据的静息脑功能连接

目的:应用功能磁共振成像数据,对静息状态下大脑视觉系统功能连接模式[1]进行考证,并对不同状态下人脑视觉功能连接网络的变化[2,3]情况进行了研究。方法:基于脑区局部同一性[4],测量出一给定体素的时间序列与全脑其他体素时间序列的相似性。我们分别采集了视觉任务和静止两种状态下的功能磁共振成像数据,先是用K-均值的聚类方法[5,6]对视觉任务状态下的功能磁共振成像数据进行分析,做出分类图。然后通过分类图找到感兴趣种子区,平均种子区中各个体素的时间响应曲线,利用这个时间序列曲线与全脑体素作互相关分析[7],得出视觉任务下的全脑功能连接图,再把同样的感兴趣种子区域定位到静息状态下的脑区中用种子相关分析方法,作出静息状态下全脑视觉系统功能连接的网络模式及分布规律。结果:分别得到了视觉任务状态下和静息状态下以相同种子区为中心的功能连接网络图。结论:无论是在静息状态还是在任务状态下,大脑视觉系统各脑区之间的确存在密切的功能连接,而且状态不同所得到的视觉功能连接网络也不相同。