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.     

Normal aging decreases regional homogeneity of the motor areas in the resting state

Our knowledge about aging modulation of the central motor system remains sparse and contradictory. In the current study, we used functional MRI (fMRI) to study the aging influence on regional homogeneity of the motor-related brain areas in the resting state. We found that regional homogeneity in extensive motor regions, like the cingulate motor area, cerebellum, primary motor cortex, premotor area, supplementary motor area, thalamus, globus pallidus and putamen was significantly decreased in aged subjects. Our study indicates that normal aging process may disrupt the function of motor areas in the resting state, which may contribute to the declined motor ability in aged population.     

Spontaneous BOLD event triggered averages for estimating functional connectivity at resting state

Recent neuroimaging studies have demonstrated that the spontaneous brain activity reflects, to a large extent, the same activation patterns measured in response to cognitive and behavioral tasks. This correspondence between activation and rest has been explored with a large repertoire of computational methods, ranging from analysis of pairwise interactions between areas of the brain to the global brain networks yielded by independent component analysis. In this paper we describe an alternative method based on the averaging of the BOLD signal at a region of interest (target) triggered by spontaneous increments in activity at another brain area (seed). The resting BOLD event triggered averages ("rBeta") can be used to estimate functional connectivity at resting state. Using two simple examples, here we illustrate how the analysis of the average response triggered by spontaneous increases/decreases in the BOLD signal is sufficient to capture the aforementioned correspondence in a variety of circumstances. The computation of the non linear response during rest here described allows for a direct comparison with results obtained during task performance, providing an alternative measure of functional interaction between brain areas.     

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.     

Resting state functional connectivity of five neural networks in bipolar disorder and schizophrenia

Background

Bipolar disorder (BPD) and schizophrenia (SCZ) share clinical characteristics and genetic contributions. Functional dysconnectivity across various brain networks has been reported to contribute to the pathophysiology of both SCZ and BPD. However, research examining resting-state neural network dysfunction across multiple networks to understand the relationship between these two disorders is lacking.

Methods

We conducted a resting-state functional connectivity fMRI study of 35 BPD and 25 SCZ patients, and 33 controls. Using previously defined regions-of-interest, we computed the mean connectivity within and between five neural networks: default mode (DM), fronto-parietal (FP), cingulo-opercular (CO), cerebellar (CER), and salience (SAL). Repeated measures ANOVAs were used to compare groups, adjusting false discovery rate to control for multiple comparisons. The relationship of connectivity with the SANS/SAPS, vocabulary and matrix reasoning was investigated using hierarchical linear regression analyses.

Results

Decreased within-network connectivity was only found for the CO network in BPD. Across groups, connectivity was decreased between CO-CER (p<0.001), to a larger degree in SCZ than in BPD. In SCZ, there was also decreased connectivity in CO-SAL, FP-CO, and FP-CER, while BPD showed decreased CER-SAL connectivity. Disorganization symptoms were predicted by connectivity between CO-CER and CER-SAL.

Discussion

Our findings indicate dysfunction in the connections between networks involved in cognitive and emotional processing in the pathophysiology of BPD and SCZ. Both similarities and differences in connectivity were observed across disorders. Further studies are required to investigate relationships of neural networks to more diverse clinical and cognitive domains underlying psychiatric disorders.     

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.     

Brain resting state is disrupted in chronic back pain patients

Recent brain functional magnetic resonance imaging (fMRI) studies have shown that chronic back pain (CBP) alters brain dynamics beyond the feeling of pain. In particular, the response of the brain default mode network (DMN) during an attention task was found abnormal. In the present work similar alterations are demonstrated for spontaneous resting patterns of fMRI brain activity over a population of CBP patients (n = 12, 29–67 years old, mean = 51.2). Results show abnormal correlations of three out of four highly connected sites of the DMN with bilateral insular cortex and regions in the middle frontal gyrus (p < 0.05), in comparison with a control group of healthy subjects (n = 20, 21–60 years old, mean = 38.4). The alterations were confirmed by the calculation of triggered averages, which demonstrated increased coactivation of the DMN and the former regions. These findings demonstrate that CBP disrupts normal activity in the DMN even during the brain resting state, highlighting the impact of enduring pain over brain structure and function.     

Differential relationships between transcallosal structural and functional connectivity in young and older adults

Numerous studies have identified age differences in brain structure and function that correlate with declines in motor performance. While these investigations have typically focused on activity in isolated regions of the brain, resting state functional connectivity magnetic resonance imaging (MRI) and diffusion tensor imaging allow for more integrative assessments of spatially disparate neural networks. The novel contribution of the current study is to combine both resting state functional connectivity and diffusion tensor imaging to examine motor corticocortical circuits in young and older adults. We find that relatively greater functional connectivity between the primary motor cortices was strongly associated with decreased structural connectivity and poorer motor performance solely in older adults. We suggest that greater functional connectivity in older adults may be reflective of a release from the normally predominantly inhibitory interhemispheric communication associated with the primary motor cortices.     

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.     

基于静息态功能磁共振图像的动态功能连接特征的智商预测

目的近年来越来越多的研究表明大脑不同脑区间的功能连接的动态波动具有生理意义,但关于智商(intelligence quotient,IQ)的相关研究较少。本文基于动态功能连接(dynamic functional connectivity,DFC)提取动态特征对智商进行评估,为智商预测探索新的特征参数和预测模型。方法基于97个儿童静息态功能磁共振图像(resting state functional magnetic resonance image,RS-fMRI),采用滑动窗相关计算方法构建DFC。基于DFC提取相应时域、频域特征,通过弹性网(elastic-net,E-Net)和最小角回归(least angle regression,LAR)算法建立智商回归模型进行个体智商预测,并通过置换检验验证其显著性。结果基于动态功能连接的特定频段(0.075~0.1 Hz)频域特征和波动均值特征,可以实现对智商的基本预测,且频域特征的表现优于时域特征。另外,基于LAR算法构建的预测模型的表现优于E-Net算法。结论个体脑功能连接随时间的动态波动足以预测个体智商,且特定频段的频域特征和LAR算法能够提高预测准确率,这可为个体智商评估研究和动态功能连接的应用提供新的思路。     

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.     

Cortico-striatal-thalamic network functional connectivity in hemiparkinsonism

Cortico-striatal-thalamic network functional connectivity (FC) and its relationship with levodopa (L-dopa) were investigated in 69 patients with hemiparkinsonism (25 drug-naïve [n-PD] and 44 under stable/optimized dopaminergic treatment [t-PD]) and 27 controls. Relative to controls, n-PD patients showed an increased FC between the left and the right basal ganglia, and a decreased connectivity of the affected caudate nucleus and thalamus with the ipsilateral frontal and insular cortices. Compared with both controls and n-PD patients, t-PD patients showed a decreased FC among the striatal and thalamic regions, and an increased FC between the striatum and temporal cortex, and between the thalamus and several sensorimotor, parietal, temporal, and occipital regions. In both n-PD and t-PD, patients with more severe motor disability had an increased striatal and/or thalamic FC with temporal, parietal, occipital, and cerebellar regions. Cortico-striatal-thalamic functional abnormalities occur in patients with hemiparkinsonism, antecede the onset of the motor symptoms on the opposite body side and are modulated by L-dopa. In patients with hemiparkinsonism, L-dopa is likely to facilitate a compensation of functional abnormalities possibly through an increased thalamic FC.     

A preliminary study of functional connectivity in comorbid adolescent depression

Major depressive disorder (MDD) begins frequently in adolescence and is associated with severe outcomes, but the developmental neurobiology of MDD is not well understood. Research in adults has implicated fronto-limbic neural networks in the pathophysiology of MDD, particularly in relation to the subgenual anterior cingulate cortex (ACC). Developmental changes in brain networks during adolescence highlight the need to examine MDD-related circuitry in teens separately from adults. Using resting state functional magnetic resonance imaging (fMRI), this study examined functional connectivity in adolescents with MDD (n = 12) and healthy adolescents (n = 14). Seed-based connectivity analysis revealed that adolescents with MDD have decreased functional connectivity in a subgenual ACC-based neural network that includes the supragenual ACC (BA 32), the right medial frontal cortex (BA 10), the left inferior (BA 47) and superior frontal cortex (BA 22), superior temporal gyrus (BA 22), and the insular cortex (BA 13). These preliminary data suggest that MDD in adolescence is associated with abnormal connectivity within neural circuits that mediate emotion processing. Future research in larger, un-medicated samples will be necessary to confirm this finding. We conclude that hypothesis-driven, seed-based analyses of resting state fMRI data hold promise for advancing our current understanding of abnormal development of neural circuitry in adolescents with MDD.     

Functional connectivity tracks clinical deterioration in Alzheimer's disease

While resting state functional connectivity has been shown to decrease in patients with mild and/or moderate Alzheimer's disease, it is not yet known how functional connectivity changes in patients as the disease progresses. Furthermore, it has been noted that the default mode network is not as homogenous as previously assumed and several fractionations of the network have been proposed. Here, we separately investigated the modulation of 3 default mode subnetworks, as identified with group independent component analysis, by comparing Alzheimer's disease patients to healthy controls and by assessing connectivity changes over time. Our results showed decreased connectivity at baseline in patients versus controls in the posterior default mode network, and increased connectivity in the anterior and ventral default mode networks. At follow-up, functional connectivity decreased across all default mode systems in patients. Our results suggest that earlier in the disease, regions of the posterior default mode network start to disengage whereas regions within the anterior and ventral networks enhance their connectivity. However, as the disease progresses, connectivity within all systems eventually deteriorates.     

基于功能连接算法的斜视性弱视儿童静息态功能磁共振成像的研究

目的探索斜视性弱视儿童脑功能区及其功能连接的改变,揭示斜视性弱视的发生与脑功能改变的相关性。方法在静息态下采集22位斜视性弱视儿童和10名健康儿童脑功能磁共振图像,利用DPARSF软件计算全脑与ROI功能区的连接系数,并应用t检验对实验组和健康对照组进行组内和组间功能连接系数分析。结果发现斜视性弱视儿童部分脑功能连接低于正常对照组的相应脑区连接,这些功能区主要分布于枕叶、颞叶、小脑后叶、顶叶、额叶、扣带回等脑区。结论基于静息态的f MRI的脑功能连接算法可以反映斜视性弱视儿童视皮层的变化和多脑区神经活动的变化。     

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。     

Blood oxygenation level dependent contrast resting state networks are relevant to functional activity in the neocortical sensorimotor system

The relevance of correlations between blood oxygenation level dependent (BOLD) signal changes across the brain acquired at rest (resting state networks, or RSN) to functional networks was tested using two quantitative criteria: (1) the localisation of major RSN correlation clusters and the task-related maxima defined in BOLD fMRI signal changes from the same subjects; and (2) the relative hemispheric lateralisation (LI) of BOLD fMRI signal changes in sensorimotor cortex. RSN were defined on the basis of signal changes correlated with that of a “seed” voxel in the primary sensorimotor cortex. We found a generally close spatial correspondence between clusters of correlated BOLD signal change in RSN and activation maxima associated with hand movement. Conventional BOLD fMRI during active hand movement showed the expected wide variation in relative hemispheric lateralisation of LI for sensorimotor cortex across the subjects. There was a good correlation between LIs for the active hand movement task and the RSN (r=0.74, p<0.001). The RSN thus define anatomically relevant regions of motor cortex and change with functionally relevant variations in hemispheric lateralisation of sensorimotor cortical interactions with hand movement.     

原发全面强直阵挛癫痫患者皮层-纹状体-丘脑-小脑网络的静息态功能MRI的对照研究

目的 探讨应用静息态功能MRI网络技术描绘原发全面强直阵挛癫痫 (IGE-GTCS)患者皮层-纹状体-丘脑-小脑网络的模式。方法 前瞻性纳入2009年7月—2016年10月IGE-GTCS患者60例为IGE-GTCS组,同时纳入与IGE-GTCS组患者年龄、性别相匹配的健康志愿者60名为正常对照组。两组受试者于3 T超导MR仪下行静息态功能MRI数据收集,采用北京师范大学脑影像处理分析软件DPARSF 4.4完成预处理。采用皮层分区模板,将整个大脑分成额叶皮层、运动皮层、感觉皮层、顶枕皮层、颞叶皮层5个感兴趣区域(ROI),自动解剖标记模板定义丘脑、纹状体(包括尾状核、壳核、苍白球)和小脑的皮层下结构,构建皮层-皮层下核团-小脑网络。分别计算5个皮层区域与皮层下核团体素间的功能连接系数,获得系数图;并将得到的相关系数通过Fisher Z 转换,符合正态分布的功能连接系数图用于后续统计分析。使用SPM 12软件的两样本t检验,对IGE-GTCS组与正常对照组间皮层-皮层下核团-小脑功能连接的异常进行比较,应用高斯随机场理论(GRF)进行多重比较校正,体素校正水平取P＜0.01,团块校正水平取P＜0.05,双尾校正;并将IGE-GTCS患者功能连接改变的区域与临床病程进行Pearson相关分析。结果 因头动过大, IGE-GTCS组排除5例,最终纳入55例,男35例、女20例,年龄(25.11±6.0)岁,病程(11.3±6.6)年;正常对照组共60名,其中男37名、女23名,年龄(26.38±6.5)岁。两组受试者年龄、性别差异均无统计学意义(t=1.086、χ²=0.048, P值均＞0.05)。相比于正常对照组,IGE-GTCS组功能连接结果差异均有统计学意义(GRF校正,体素水平P值均＜0.01、团块水平P值均＜0.05):(1)额叶皮层,与双侧小脑脚2区(左右半球体素分别为115、182, t值分别为-5.57、-3.82)、右侧苍白球(体素=28, t=-7.42)连接降低,与双侧丘脑(左右半球体素分别为121、134, t值分别为10.48、9.16)、尾状核(左右半球体素分别为206、199, t值分别为13.40、11.59)、壳核(左右半球体素分别为178、219, t值分别为7.29、8.79)及小脑4、5区(左右半球体素分别为55、45, t值分别为2.63、2.74)连接增加。(2)运动皮层,与左侧小脑脚1区(体素=98, t=-3.10)、双侧苍白球(左右半球体素分别为26、31, t值分别为-7.05、-6.86)连接降低,与丘脑(左右半球体素分别为137、145, t值分别为11.06、9.77)、尾状核(左右半球体素分别为202、197, t值分别为12.88、11.79)、壳核(左右半球体素分别为104、120, t值分别为7.54、10.71)、小脑4、5区(左右半球体素分别为64、43, t值分别为4.62、5.13)及小脑脚2区(左右半球体素分别为85、85, t值分别为4.23、4.23)连接增加。(3)感觉皮层,与左侧小脑脚1区(体素=103, t=-3.87)连接降低,小脑4、5区(左右半球体素分别为72、63, t值分别为4.58、5.96)、双侧小脑脚2区(左右半球体素分别为173、173, t值分别为4.22、4.22)、丘脑(左右半球体素分别为143、151, t值分别为10.41、7.91)、尾状核(左右半球体素分别为198、195, t值分别为10.30、8.82)、壳核(左右半球体素分别为105、110, t值分别为6.38、8.06)、苍白球(左右半球体素分别为8、9, t分别为4.95、4.31)连接增加。(4)顶枕皮层,与右侧苍白球(体素=23, t=-7.45)连接降低,与小脑4、5区(左右半球体素分别为32、28, t值分别为3.56、3.89)、左侧小脑脚2区(体素=15, t=4.56)、丘脑(左右半球体素分别为107、118, t值分别为10.57、10.62)、尾状核(左右半球体素分别为201、197, t值分别为7.52、8.43)及壳核(左右半球体素分别为112、164, t值分别为6.53、7.21)连接增加。(5)颞叶皮层,与右侧小脑4、5区(体素=29, t=6.35)、双侧小脑脚2区(左右半球体素分别为58、128, t值分别为4.66、2.77)、丘脑(左右半球体素分别为128、136, t值分别为10.32、10.48)、尾状核(左右半球体素分别为207、203, t值分别为10.88、10.31)及壳核(左右半球体素分别为134、157, t值分别为7.39、6.75)连接均增加。额叶皮层-左侧小脑8区、运动皮层-左侧小脑8区、感觉皮层-小脑蚓部6区、顶枕皮层-左侧小脑8区、颞叶皮层-右侧小脑脚2区功能连接与病程相关系数分别为-0.385、-0.455、-0.362、-0.332、-0.544,差异均有统计学意义(P值均＜0.01)。结论 IGE-GTCS存在广泛的皮层-纹状体-丘脑-小脑网络功能连接的异常,表现为特异核团的功能连接的增高与降低,部分功能连接的改变与病程呈负相关。     

Compensatory mechanisms in the aging motor system

Motor functions decline with age due to a number of factors. There is interest in whether these changes are reflected in the organisation of the cerebral motor system in older subjects and whether such changes might be in some way compensatory. Most studies in humans have used functional brain imaging techniques to compare motor system activation in younger and older subjects. Interpretation of these results is made more difficult by potential neurovascular changes in older subjects. However, in general, there appears to be greater motor task-related brain activity in a wider network of brain regions in older compared to younger subjects. The evidence that these changes are compensatory in nature is less clear. Incorporation of behavioural and anatomical data will be required in order to fully interpret the functional imaging results.     

Aging increases the susceptibility to motor memory interference and reduces off-line gains in motor skill learning

Declines in the ability to learn motor skills in older adults are commonly attributed to deficits in the encoding of sensorimotor information during motor practice. We investigated whether aging also impairs motor memory consolidation by assessing the susceptibility to memory interference and off-line gains in motor skill learning after practice in children, young, and older adults. Subjects performed a ballistic task (A) followed by an accuracy-tracking task (B) designed to disrupt the consolidation of A. Retention tests of A were performed immediately and 24 hours after B. Older adults showed greater susceptibility to memory interference and no off-line gains in motor skill learning. Performing B produced memory interference and reduced off-line gains only in the older group. However, older adults also showed deficits in memory consolidation independent of the interfering effects of B. Age-related declines in motor skill learning are not produced exclusively by deficits in the encoding of sensorimotor information during practice. Aging also increases the susceptibility to memory interference and reduces off-line gains in motor skill learning after practice.