Combining spatial and temporal information to explore resting-state networks changes in abstinent heroin-dependent individuals

Majority of previous heroin fMRI studies focused on abnormal brain function in heroin-dependent individuals. However, few fMRI studies focused on the resting-state abnormalities in heroin-dependent individuals and assessed the relationship between the resting-state functional connectivity changes and duration of heroin use. In the present study, discrete cosine transform (DCT) was employed to explore spatial distribution of low frequency BOLD oscillations in heroin-dependent individuals and healthy subjects during resting-state; meanwhile resting-state functional connectivity analysis was used to investigate the temporal signatures of overlapping brain regions obtained in DCT analysis among these two groups. Main finding of the present study is that the default mode network (DMN) and rostral anterior cingulate cortex (rACC) network of heroin-dependent individuals were changed compared with healthy subjects. More importantly, these changes negatively correlated with duration of heroin use. These resting-state functional abnormalites in heroin-dependent individuals provided evidence for abnormal functional organization in heroin-dependent individuals, such as functional impairments in decision-making and inhibitory control.     

Age-related alterations in default mode network: impact on working memory performance

The default mode network (DMN) is a set of functionally connected brain regions which shows deactivation (task-induced deactivation, TID) during a cognitive task. Evidence shows an age-related decline in task-load-related modulation of the activity within the DMN during cognitive tasks. However, the effect of age on the functional coupling within the DMN and their relation to cognitive performance has hitherto been unexplored. Using functional magnetic resonance imaging, we investigated functional connectivity within the DMN in older and younger subjects during a working memory task with increasing task load. Older adults showed decreased connectivity and ability to suppress low frequency oscillations of the DMN. Additionally, the strength of the functional coupling of posterior cingulate (pCC) with medial prefrontal cortex (PFC) correlated positively with performance and was lower in older adults. pCC was also negatively coupled with task-related regions, namely the dorsolateral PFC and cingulate regions. Our results show that in addition to changes in canonical task-related brain regions, normal aging is also associated with alterations in the activity and connectivity of brain regions within the DMN. These changes may be a reflection of a deficit in cognitive control associated with advancing age that results in deficient resource allocation to the task at hand.     

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.     

基于动态功能连接分析的青少年吸烟者大脑静息态默认模式网络

采集30名青少年吸烟者和相匹配的30名非吸烟者的静息态功能性磁共振成像数据。通过独立成分分析、滑动窗相关法和k-均值聚类分析探讨青少年吸烟者的默认模式网络的动态功能连接变化。同时,使用斯皮尔曼相关分析评估动态功能连接指标（时间分数、平均停留时间和转换次数）与吸烟统计学数据（烟龄、包年和FTND）的关系。结果显示,相比于非吸烟组,青少年吸烟者大脑的默认模式网络的功能连接性降低,进一步的相关性分析表明动态功能连接指标中的平均停留时间与烟龄呈显著性正相关。此项研究从动态功能网络连接的角度分析吸烟对青少年吸烟者默认模式网络的影响,可以为进一步探索青少年吸烟成瘾机制提供新的视角。     

Brain activity at rest: a multiscale hierarchical functional organization

Spontaneous brain activity was mapped with functional MRI (fMRI) in a sample of 180 subjects while in a conscious resting-state condition. With the use of independent component analysis (ICA) of each individual fMRI signal and classification of the ICA-defined components across subjects, a set of 23 resting-state networks (RNs) was identified. Functional connectivity between each pair of RNs was assessed using temporal correlation analyses in the 0.01- to 0.1-Hz frequency band, and the corresponding set of correlation coefficients was used to obtain a hierarchical clustering of the 23 RNs. At the highest hierarchical level, we found two anticorrelated systems in charge of intrinsic and extrinsic processing, respectively. At a lower level, the intrinsic system appears to be partitioned in three modules that subserve generation of spontaneous thoughts (M1a; default mode), inner maintenance and manipulation of information (M1b), and cognitive control and switching activity (M1c), respectively. The extrinsic system was found to be made of two distinct modules: one including primary somatosensory and auditory areas and the dorsal attentional network (M2a) and the other encompassing the visual areas (M2b). Functional connectivity analyses revealed that M1b played a central role in the functioning of the intrinsic system, whereas M1c seems to mediate exchange of information between the intrinsic and extrinsic systems.     

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.     

Increased default mode network connectivity associated with meditation

Areas associated with the default mode network (DMN) are substantially similar to those associated with meditation practice. However, no studies on DMN connectivity during resting states have been conducted on meditation practitioners. It was hypothesized that meditators would show heightened functional connectivity in areas of cortical midline activity. Thirty-five meditation practitioners and 33 healthy controls without meditation experience were included in this study. All subjects received 4.68-min resting state functional scanning runs. The posterior cingulate cortex and medial prefrontal cortex were chosen as seed regions for the DMN map. Meditation practitioners demonstrated greater functional connectivity within the DMN in the medial prefrontal cortex area (xyz=339-21) than did controls. These results suggest that the long-term practice of meditation may be associated with functional changes in regions related to internalized attention even when meditation is not being practiced.     

Dynamical intrinsic functional architecture of the brain during absence seizures

Epilepsy is characterized by recurrent and temporary brain dysfunction due to discharges of interconnected groups of neurons. The brain of epilepsy patients has a dynamic bifurcation that switches between epileptic and normal states. The dysfunctional state involves large-scale brain networks. It is very important to understand the network mechanisms of seizure initiation, maintenance, and termination in epilepsy. Absence epilepsy provides a unique model for neuroimaging investigation on dynamic evolutions of brain networks over seizure repertoire. By using a dynamic functional connectivity and graph theoretical analyses to study absence seizures (AS), we aimed to obtain transition of network properties that account for seizure onset and offset. We measured resting-state functional magnetic resonance imaging and simultaneous electroencephalography (EEG) from children with AS. We used simultaneous EEG to define the preictal, ictal and postictal intervals of seizures. We measured dynamic connectivity maps of the thalamus network and the default mode network (DMN), as well as functional connectome topologies, during the three different seizure intervals. The analysis of dynamic changes of anti-correlation between the thalamus and the DMN is consistent with an inhibitory effect of seizures on the default mode of brain function, which gradually fades out after seizure onset. Also, we observed complex transitions of functional network topology, implicating adaptive reconfiguration of functional brain networks. In conclusion, our work revealed novel insights into modifications in large-scale functional connectome during AS, which may contribute to a better understanding the network mechanisms of state bifurcations in epileptogenesis.     

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.     

Caffeine alters resting‐state functional connectivity measured by blood oxygenation level‐dependent MRI

This study aimed to investigate the pharmacological effect of caffeine on functional connectivity measured by resting‐state blood oxygenation level‐dependent (BOLD) MRI in the motor cortex, visual cortex and default mode network (DMN). The protocols and procedures of the study were reviewed and approved by the Institutional Review Board of our institution. On a 3‐T clinical MR system, 20 healthy volunteers underwent imaging before and after oral ingestion of a 200‐mg over‐the‐counter caffeine pill (data from three individuals were excluded from further analysis because of excessive motion). The demographics of the remaining participants were as follows: female/male, 8/9; age, 21–35 years; non‐habitual caffeine consumers over the past 6 months. Functional connectivity was calculated using the general linear model, assessed in terms of connected area (voxels) and statistical significance (Student t‐values), and correlated with changes in regional cerebral blood flow as measured by arterial spin labeling MRI. Per‐subject data analysis showed that caffeine decreased functional connectivity in the motor/visual cortices, but its effects on DMN varied among subjects. Correlation analysis of the changes in functional connectivity and regional blood flow suggested that the effect of caffeine on BOLD functional connectivity was predominantly neural (motor/visual cortices) and partly vascular (DMN). Group analysis showed that, after caffeine ingestion, DMN involved more attentional networks, and more extrastriate areas were integrated into the functional connectivity of the visual cortex, which may be associated with the known pharmacological effect of caffeine in elevating alertness. Caffeine consumption should thus be considered in the experimental design and data interpretation of functional connectivity studies using resting‐state BOLD MRI. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

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。     

Resting state connectivity of the medial prefrontal cortex covaries with individual differences in high‐frequency heart rate variability

Resting high‐frequency heart rate variability (HF‐HRV) relates to cardiac vagal control and predicts individual differences in health and longevity, but its functional neural correlates are not well defined. The medial prefrontal cortex (mPFC) encompasses visceral control regions that are components of intrinsic networks of the brain, particularly the default mode network (DMN) and the salience network (SN). Might individual differences in resting HF‐HRV covary with resting state neural activity in the DMN and SN, particularly within the mPFC? This question was addressed using fMRI data from an eyes‐open, 5‐min rest period during which echoplanar brain imaging yielded BOLD time series. Independent component analysis yielded functional connectivity estimates defining the DMN and SN. HF‐HRV was measured in a rest period outside of the scanner. Midlife (52% female) adults were assessed in two studies (Study 1, N = 107; Study 2, N = 112). Neither overall DMN nor SN connectivity strength was related to HF‐HRV. However, HF‐HRV related to connectivity of one region within mPFC shared by the DMN and SN, namely, the perigenual anterior cingulate cortex, an area with connectivity to other regions involved in autonomic control. In sum, HF‐HRV does not seem directly related to global resting state activity of intrinsic brain networks, but rather to more localized connectivity. A mPFC region was of particular interest as connectivity related to HF‐HRV was shared by the DMN and SN. These findings may indicate a functional basis for the coordination of autonomic cardiac control with engagement and disengagement from the environment.     

Resting-State Functional Connectivity Within Medial Prefrontal Cortex Mediates Age Differences in Risk Taking

To investigate the association between age-related changes in risk taking and resting-state functional activity, we recorded resting-state scans from both young (n = 26) and older adults (n = 27). In addition, all participants completed two decision-making tasks: the Cambridge Gambling Task and the Balloon Analogue Risk Task. We found that older adults showed decreased functional connectivity within the medial prefrontal cortex, particularly between the ventromedial prefrontal cortex and the dorsal medial prefrontal cortex. Moreover, these changes in resting-state functional connectivity were associated with the individuals’ risk-taking behavior, and mediated the influence of age on risk taking.     

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.     

Parkinson's disease involves autophagy and abnormal distribution of cathepsin L

Intrinsic brain activity in a resting state incorporates components of the task negative network called default mode network (DMN) and task-positive networks called attentional networks. In the present study, the reciprocal neuronal networks in the elder group were compared with the young group to investigate the differences of the intrinsic brain activity using a method of temporal correlation analysis based on seed regions of posterior cingulate cortex (PCC) and ventromedial prefrontal cortex (vmPFC). We found significant decreased positive correlations and negative correlations with the seeds of PCC and vmPFC in the old group. The decreased coactivations in the DMN network components and their negative networks in the old group may reflect age-related alterations in various brain functions such as attention, motor control and inhibition modulation in cognitive processing. These alterations in the resting state anti-correlative networks could provide neuronal substrates for the aging brain.     

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.     

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 functional connectivity differentiates anxious apprehension and anxious arousal

Brain regions in the default mode network (DMN) display greater functional connectivity at rest or during self‐referential processing than during goal‐directed tasks. The present study assessed resting‐state connectivity as a function of anxious apprehension and anxious arousal, independent of depressive symptoms, in order to understand how these dimensions disrupt cognition. Whole‐brain, seed‐based analyses indicated differences between anxious apprehension and anxious arousal in DMN functional connectivity. Lower connectivity associated with higher anxious apprehension suggests decreased adaptive, inner‐focused thought processes, whereas higher connectivity at higher levels of anxious arousal may reflect elevated monitoring of physiological responses to threat. These findings further the conceptualization of anxious apprehension and anxious arousal as distinct psychological dimensions with distinct neural instantiations.     

The older adult brain is less modular,more integrated,and less efficient at rest: A systematic review of large-scale resting-state functional brain networks in aging

The literature on large-scale resting-state functional brain networks across the adult lifespan was systematically reviewed. Studies published between 1986 and July 2021 were retrieved from PubMed. After reviewing 2938 records, 144 studies were included. Results on 11 network measures were summarized and assessed for certainty of the evidence using a modified GRADE method. The evidence provides high certainty that older adults display reduced within-network and increased between-network functional connectivity. Older adults also show lower segregation, modularity, efficiency and hub function, and decreased lateralization and a posterior to anterior shift at rest. Higher-order functional networks reliably showed age differences, whereas primary sensory and motor networks showed more variable results. The inflection point for network changes is often the third or fourth decade of life. Age effects were found with moderate certainty for within- and between-network altered patterns and speed of dynamic connectivity. Research on within-subject bold variability and connectivity using glucose uptake provides low certainty of age differences but warrants further study. Taken together, these age-related changes may contribute to the cognitive decline often seen in older adults.     

Resting-state fMRI changes in Alzheimer's disease and mild cognitive impairment

Regional functional connectivity (FC) of 39 patients with Alzheimer's disease (AD), 23 patients with mild cognitive impairment (MCI), and 43 healthy elderly controls was studied using resting-state functional magnetic resonance imaging (rs-fMRI). After a mean follow-up of 2.8 ± 1.9 years, 7 MCI patients converted to AD, while 14 patients remained cognitively stable. Resting-state functional magnetic resonance imaging scans were analyzed using independent component analysis (ICA), followed by a "dual-regression" technique to create and compare subject-specific maps of each independent spatiotemporal component, correcting for age, sex, and gray matter atrophy. AD patients displayed lower FC within the default-mode network (DMN) in the precuneus and posterior cingulate cortex compared with controls, independent of cortical atrophy. Regional FC values of MCI patients were numerically in between AD patients and controls, but only the difference between AD and stable MCI patients was statistically significant. Correlation with cognitive dysfunction demonstrated the clinical relevance of FC changes within the DMN. In conclusion, clinically relevant decreased FC within the DMN was observed in AD.