Gray matter deficits and resting-state abnormalities in abstinent heroin-dependent individuals

Previous neuroimaging studies have demonstrated both structural and functional damages in heroin-dependent individuals. However, few studies investigated gray matter deficits and abnormal resting-state networks together in heroin-dependent individuals. In the present study, voxel-based morphometry (VBM) was used to identify brain regions with gray matter density reduction. Resting-state fMRI connectivity analysis was employed to assess potential functional abnormalities during resting-state. All clinical significances were investigated by examining their association with duration of heroin use. Compared with healthy subjects, heroin-dependent individuals showed significant reduction in gray matter density in the right dorsolateral prefrontal cortex (DLPFC) and a decrease in resting-state functional connectivity between the right DLPFC and left inferior parietal lobe (IPL). The gray matter density of the right DLPFC and its resting-state functional connectivity with the left IPL both showed significantly negative correlation with duration of heroin use, which were likely to be related to the functional impairments in decision-making and cognitive control exhibited by heroin-dependent individuals. Our findings demonstrated that long heroin dependence impairs the right DLPFC in heroin-dependent individuals, including structural deficits and resting-state functional impairments.     

Altered small-world brain functional networks and duration of heroin use in male abstinent heroin-dependent individuals

Although previous studies reported addiction-related alteration in resting-state brain connectivity, it is unclear whether these resting-state connectivity alterations were associated with chronic heroin use. In the current study, graph theory analysis (GTA) was applied to detect abnormal topological properties in heroin-dependent individuals. Several statistical parameters, such as degree (D), clustering coefficient (C) and shortest absolute path length (L), were included to test whether or not there was significant correlation between these parameters and the duration of heroin use. Our results demonstrated abnormal topological properties in several brain regions among our heroin-dependent subjects. Some of these regions are key areas of drug addiction-related circuits (control, reward, motivation/drive and memory), while others are involved in stress regulation. In addition, the duration of heroin use was positively correlated with the parameter D in the right parahippocampal gyrus, left putamen and bilateral cerebellum, but negatively correlated with the parameter L in the same regions. Our findings suggested that there is abnormal functional organization in heroin-dependent individuals and that the duration of heroin use is a critical factor leading to the altered brain connectivity.     

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。     

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。     

Age effect on the default mode network,inner thoughts,and cognitive abilities

Age-related effects on the default mode network (DMN) connectivity as measured at rest using functional magnetic resonance imaging (fMRI) are now well described. Little is known however about the relationships between these changes and age-related effects on cognition or on the unconstrained thoughts which occur during the resting-state scan, called inner experience. Brain resting-state activity, inner experience, and cognitive ability measurements were obtained in 70 participants aged 19–80 years. The anterior-posterior disruption of DMN activity with age reported in previous studies was recovered here. A significant effect of age was also found on cognitive abilities but not on inner experience. Finally, age-related changes in DMN connectivity were found to correlate with cognitive abilities, and more specifically with autobiographical memory performance. These findings provide new information to fuel the debate on the role of the brain default mode and more specifically on the effect of age-related changes in resting-state activity as measured with fMRI.     

基于独立成分分析的青年吸烟者大脑静息态执行网络功能连接变化研究

采用独立成分分析方法探索40名青年吸烟者和40名年龄与性别相匹配的非吸烟者的静息态功能磁共振数据,并结合“双重回归”方法探索吸烟者执行网络功能连接变化,同时将有变化的脑区与吸烟统计学数据进行Pearson’s双变量相关分析,例如年龄、包年、FTND、烟龄等。通过研究发现,青年吸烟者的大脑右中央执行网络的功能连接性增强,相关分析表明执行网络包含的背外侧前额叶皮质与烟龄呈显著性负相关（r=-0.339, P=0.032）。此项研究结果表明,吸烟对右侧中央执行网络的功能连接有一定的影响,研究结果可能为青年吸烟成瘾者的神经机制的特征提供额外的新见解。     

Polymorphisms of brain-derived neurotrophic factor associated with heroin dependence

Brain-derived neurotrophic factor (BDNF) promotes synaptic remodeling and modulates the function of other neurotransmitters. It also plays a role in the reward response to many drugs, including heroin. To identify genetic variants associated with heroin dependence, we compared four single nucleotide polymorphisms (SNPs, rs13306221, rs6265, rs56164415, and rs16917204) of the BDNF gene in 487 subjects with heroin dependence and 492 healthy individuals. The analysis revealed the G allele of rs6265 was significantly more common in heroin-dependent subjects than in the healthy controls (P=0.001 after Bonferroni correction). Among heroin-dependent individuals, the onset of dependence was significantly earlier in individuals with GG or GA genotypes compared to AA individuals (P<0.01). Additionally, we found that the G allele of rs13306221 was significantly more frequent in heroin-dependent subjects than in controls (P=0.005 after Bonferroni correction). These findings support a role of BDNF rs6265 and rs13306221 polymorphisms in heroin dependence and may guide future studies to identify other genetic risk factors for heroin dependence.     

Dysfunctional connectivity patterns in chronic heroin users: An fMRI study

Recent functional neuroimaging studies have examined cognitive inhibitory control, decision-making and stress regulation in heroin addiction using a cue-reactivity paradigm. Few studies have considered impairments in heroin users from an integrated perspective for evaluation of their brain functions. We hypothesized that the brain regions that are dysregulated in the chronic heroin users during cue-reactivity studies may also show dysfunctional connectivity in memory, inhibition and motivation-related dysfunctions during a resting state free of cues. The present study used resting functional magnetic resonance imaging (fMRI) to compare the interaction of brain regions between 12 chronic heroin users and 12 controls by employing a novel graph theory analysis (GTA) method. As a data-driven approach, GTA has the advantage of evaluating the strength as well as the temporal and spatial patterns of interactions among the brain regions. Abnormal topological properties were explored in the brain of chronic heroin users, such as the dysfunctional connectivity in the prefrontal cortex, ACC, SMA, ventral striatum, insula, amygdala and hippocampus. Our results suggest that GTA is a useful tool in defining dysregulated neural networks even during rest. This dysfunctional brain connectivity may contribute to decrease self-control, impaired inhibitory function as well deficits in stress regulation in chronic heroin users.     

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.     

原发性失眠患者大脑背外侧前额叶的异常静息态功能连接

目的:利用功能连接方法观察原发性失眠患者静息态下的背外侧前额叶的异常功能连接。方法:采集33 例原 发性失眠患者以及33 例年龄、性别和受教育程度相匹配的健康对照的功能磁共振图像,以背外侧前额叶为感兴趣区 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,再对异常功能连接脑区与临床的量表分 数做相关分析。结果:与对照组相比,发现失眠患者左侧背外侧前额叶与左侧枕下回、右侧枕下回、右侧枕中回、右侧 颞叶、左侧额中回,左侧额下回以及右侧梭状回之间的功能连接增强（P<0.05,体素簇个数≥100,FDR校正）,与左侧前 扣带皮层、右侧海马旁回、右侧脑岛、右侧背外侧额上回、右侧顶上回、右侧中央后回以及右侧中央前回之间的功能连 接减弱（P<0.05,体素簇个数≥100,FDR校正）。并且左侧背外侧前额叶与左侧枕叶下回的功能连接值与睡眠状况自评 量表分数成正相关（P=0.035）。结论:原发性失眠患者背外侧前额叶与大脑多个脑区出现异常的功能连接,可能为理 解原发性失眠患者的神经机制提供一些新的影像学依据。     

Age-related differences of saccade induced cortical activation

Recent functional MRI (fMRI) studies have described the increased task-related brain activation in older subjects during motor, cognitive and perceptual tasks. Age affects the ability to control saccadic eye movements. To investigate the age-related changes of oculomotor control, we studied the representation of saccades in 11 young (median age 29 years) and 11 older (median age 62 years) healthy individuals using fMRI. Brain activation was measured during a visually guided prosaccade trial. Differences in activation between rest and saccades as well as between younger and older subjects were assessed with statistical parametric mapping (SPM). In both age groups, activation of a frontoparietal network was observed. Older subjects showed increased activation compared to younger subjects with overactivation in bilateral parietal eye fields, the right frontal eye field, as well as in the right extrastriate cortex. We conclude that older adults increase activation in an extended oculomotor and visual network to maintain performance during simple prosaccades. This observation also underlines the importance of using appropriate age-matched control groups in fMRI studies after brain lesions.     

Abnormal Functional Connectivity Density in Post-traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that occurs in individuals who have experienced life-threatening mental traumas. Previous neuroimaging studies have indicated that the pathology of PTSD may be associated with the abnormal functional integration among brain regions. In the current study, we used functional connectivity density (FCD) mapping, a novel voxel-wise data-driven approach based on graph theory, to explore aberrant FC through the resting-state functional magnetic resonance imaging of the PTSD. We calculated both short- and long-range FCD in PTSD patients and healthy controls (HCs). Compared with HCs, PTSD patients showed significantly increased long-range FCD in the left dorsolateral prefrontal cortex (DLPFC), but no abnormal short-range FCD was found in PTSD. Furthermore, seed-based FC analysis of the left DLPFC showed increased connectivity in the left superior parietal lobe and visual cortex of PTSD patients. The results suggested that PTSD patients experienced a disruption of intrinsic long-range functional connections in the fronto-parietal network and visual cortex, which are associated with attention control and visual information processing.     

Neural mechanisms of oxytocin receptor gene mediating anxiety-related temperament

A common variant (rs53576) of the OXTR gene has been implicated in a number of socio-emotional phenotypes, such as anxiety-related behavior. Previous studies have demonstrated that A-allele carriers have higher levels of physiological and dispositional stress reactivity and depressive symptomatology compared to those with the GG genotype, but the mediating neural mechanisms remain poorly understood. We combined voxel-based morphometry and resting-state functional connectivity analyses in a large cohort of healthy young Chinese Han individuals to test the hypothesis that the OXTR gene polymorphism influences an anxiety-related temperamental trait, as assessed by the harm avoidance subscale from the Tridimensional Personality Questionnaire via modulating the gray matter volume and resting-state functional connectivity of the brain, especially the limbic system. We revealed that female subjects with the AA genotype showed increased harm avoidance scores relative to G-carrier females. We also found that, compared to female individuals with the GG/GA genotype, female individuals with the AA genotype exhibited significantly smaller amygdala volumes bilaterally (especially the centromedial subregion), with a trend of allele-load-dependence. Compared to female individuals with the GG/GA genotype, female subjects with the AA genotype demonstrated reduced resting-state functional coupling between the prefrontal cortex and amygdala bilaterally, also with an allele-load-dependent trend. Furthermore, the magnitude of prefrontal-amygdala coupling in the left hemisphere was positively correlated with harm avoidance scores in female subjects. Our findings highlight a possible neural pathway by which a naturally occurring variation of the OXTR gene may affect an anxiety-related temperamental trait in female subjects by modulating prefrontal-amygdala functional connectivity.     

Rapid geodesic mapping of brain functional connectivity: Implementation of a dedicated co-processor in a field-programmable gate array (FPGA) and application to resting state functional MRI

Graph theory-based analyses of brain network topology can be used to model the spatiotemporal correlations in neural activity detected through fMRI, and such approaches have wide-ranging potential, from detection of alterations in preclinical Alzheimer's disease through to command identification in brain–machine interfaces. However, due to prohibitive computational costs, graph-based analyses to date have principally focused on measuring connection density rather than mapping the topological architecture in full by exhaustive shortest-path determination. This paper outlines a solution to this problem through parallel implementation of Dijkstra's algorithm in programmable logic. The processor design is optimized for large, sparse graphs and provided in full as synthesizable VHDL code. An acceleration factor between 15 and 18 is obtained on a representative resting-state fMRI dataset, and maps of Euclidean path length reveal the anticipated heterogeneous cortical involvement in long-range integrative processing. These results enable high-resolution geodesic connectivity mapping for resting-state fMRI in patient populations and real-time geodesic mapping to support identification of imagined actions for fMRI-based brain–machine interfaces.     

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.     

Brain Networks are Independently Modulated by Donepezil,Sleep, and Sleep Deprivation

Resting-state connectivity has been widely studied in the healthy and pathological brain. Less well-characterized are the brain networks altered during pharmacological interventions and their possible interaction with vigilance. In the hopes of finding new biomarkers which can be used to identify cortical activity and cognitive processes linked to the effects of drugs to treat neurodegenerative diseases such as Alzheimer’s disease, the analysis of networks altered by medication would be particularly interesting. Eleven healthy subjects were recruited in the context of the European Innovative Medicines Initiative ‘PharmaCog’. Each underwent five sessions of simultaneous EEG-fMRI in order to investigate the effects of donepezil and memantine before and after sleep deprivation (SD). The SD approach has been previously proposed as a model for cognitive impairment in healthy subjects. By applying network based statistics (NBS), we observed altered brain networks significantly linked to donepezil intake and sleep deprivation. Taking into account the sleep stages extracted from the EEG data we revealed that a network linked to sleep is interacting with sleep deprivation but not with medication intake. We successfully extracted the functional resting-state networks modified by donepezil intake, sleep and SD. We observed donepezil induced whole brain connectivity alterations forming a network separated from the changes induced by sleep and SD, a result which shows the utility of this approach to check for the validity of pharmacological resting-state analysis of the tested medications without the need of taking into account the subject specific vigilance.     

Detecting Functional Connectivity in fMRI Using PCA and Regression Analysis

A fMRI connectivity analysis approach combining principal component analysis (PCA) and regression analysis is proposed to detect functional connectivity between the brain regions. By first using PCA to identify clusters within the vectors of fMRI time series, more energy and information features in the signal can be maintained than using averaged values from brain regions of interest. Then, regression analysis can be applied to the extracted principal components in order to further investigate functional connectivity. Finally, t-test is applied and the patterns with t-values lager than a threshold are considered as functional connectivity mappings. The validity and reliability of the presented method were demonstrated with both simulated data and human fMRI data obtained during behavioral task and resting state. Compared to the conventional functional connectivity methods such as average signal based correlation analysis, independent component analysis (ICA) and PCA, the proposed method achieves competitive performance with greater accuracy and true positive rate (TPR). Furthermore, the ‘default mode’ and motor network results of resting-state fMRI data indicate that using PCA may improve upon application of existing regression analysis methods in study of human brain functional connectivity.     

Study on Functional Connectivity Density in Patients with Frontal Lobe Tumor at Resting-State

At present, the neuropathological mechanisms and the plastic changes of brain cognitive function in patents with front lobe tumor remain unclear, most studies just focused on global measures of brain functional connectivity without considering the time correlation in the different regions of the brain. This study aims to investigate brain cognitive alterations and functional plasticity in patients with front lobe tumor at resting-state by conducting functional connectivity density(FCD) mapping and granger causality analysis(GCA). Firstly, FCD mapping was used to extract abnormal functional connectivity(FC) of patients with frontal lobe tumor, and analyzed altered brain FC in both short-and long-range FCD. Then, the voxel-wise GCA method was used to analyze the causal relationship between altered FC regions and other regions in order to detect the time correlation between regions of interest(ROI) and reveal the direction of information flow between brain ROIs. It was found that patients had increased short-range FCD in motor and space attention function areas, had increased short-and long-range FCDs both in Temporal and Insula, and the causal coefficients were changed obviously in Temporal and Frontal. The results show that there is a functional plasticity in space attention function areas. Temporal and Insula are affected by tumor in frontal lobe, and functional reorganization appears inside Temporal.     

Decoupling of the Occipitotemporal Cortex and the Brain’s Default-Mode Network in Dyslexia and a Role for the Cingulate Cortex in Good Readers: A Brain Imaging Study of Brazilian Children

The goal of the present study was to investigate intrinsic and reading-related brain function associated with dyslexia and typical readers in monolingual Brazilian children. Two fMRI studies were carried out: a resting-state and a word-reading study. The results show (a) underconnectivity between the occipitotemporal region (visual word form area) and the brain’s default-mode network in dyslexic readers and (b) more activation of the anterior cingulate cortex for typical readers relative to dyslexic readers. The findings provide evidence for brain connectivity and function differences in an underrepresented population in fMRI studies of dyslexia; the results suggest atypical intrinsic function, and differences in directed attention processes in dyslexia.     

首发未服药抑郁症静息态默认网络研究

目的:分析首发未治疗抑郁症患者静息态默认网络功能改变。方法:采用独立成分分析方法,对25例首发抑郁症患者与25名正常被试进行静息态功能磁共振数据处理,并依据空间最匹配原则对缺省模式网络的独立成分进行挑选,分析患者默认网络的改变。结果:与正常对照比较,抑郁症患者的默认网络呈现前部升高后部降低的模式:即背部额内侧回、腹部额内侧回和腹部前扣带回功能连接升高,楔前叶和后扣带回、角回功能连接减低。结论:静息态下抑郁症默认网络存在广泛的异常。