Adult age differences in the functional neuroanatomy of visual attention: a combined fMRI and DTI study

We combined measures from event-related functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and cognitive performance (visual search response time) to test the hypotheses that differences between younger and older adults in top-down (goal-directed) attention would be related to cortical activation, and that white matter integrity as measured by DTI (fractional anisotropy, FA) would be a mediator of this age-related effect. Activation in frontal and parietal cortical regions was overall greater for older adults than for younger adults. The relation between activation and search performance supported the hypothesis of age differences in top-down attention. When the task involved top-down control (increased target predictability), performance was associated with frontoparietal activation for older adults, but with occipital (fusiform) activation for younger adults. White matter integrity (FA) exhibited an age-related decline that was more pronounced for anterior brain regions than for posterior regions, but white matter integrity did not specifically mediate the age-related increase in activation of the frontoparietal attentional network.     

Sympathetically induced spontaneous fluctuations of the photoplethysmographic signal

The photoplethysmographic signal shows very low-frequency (VLF) spontaneous fluctuations that have been shown to be mediated by the sympathetic nervous system. In the current study, the photoplethysmographic signal was simultaneously measured in the two index fingers and the two second toes of 54 healthy male subjects. For each photoplethysmographic pulse, two parameters were derived: the pulse amplitude and its baseline, which are related to the arterial wall compliance and to the arterial blood volume, respectively. The baseline and the amplitude VLF fluctuations showed high right-left correlation both for hands (mean±SD 0.94±0.05 and 0.92±0.07, respectively) and for feet (0.90±0.08 and 0.89±0.07, respectively) that only slightly depended on the subject's age. Lower correlation was found between the hand and the foot (0.73±0.12 and 0.72±0.12 for the baseline and the amplitude, respectively). For each hand and foot the baseline and the amplitude VLF fluctuations were also correlated, with the baseline fluctuations lagging the amplitude fluctuations by 3–20 pulses. The amplitude-baseline correlation and the standard deviation of the amplitude or the baseline divided by its mean significantly decreased with age. The VLF fluctuations of the photoplethysmographic parameters and the correlation coefficients between them provide better understanding of the autonomic nervous regulation of the blood circulation.     

Reduced functional connectivity in early-stage drug-naive Parkinson's disease: a resting-state fMRI study

Although cardinal motor symptoms in Parkinson's disease (PD) are attributed to dysfunction of corticostriatal loops, early clinical nonmotor features are more likely to be associated with other pathologic mechanisms. We enrolled 52 early-stage drug-naive PD patients and 52 age- and sex-matched healthy controls and used resting-state functional connectivity magnetic resonance imaging to evaluate alteration of the functional brain network in PD, focusing in particular on the functional connectivity of the striatum subregions. Relative to healthy controls, the PD patient group showed reduced functional connectivity in mesolimbic-striatal and corticostriatal loops. Although the deceased functional connectivity within cortical sensorimotor areas was only evident in the most affected putamen subregion, reduced functional connectivity with mesolimbic regions was prevalent throughout the striatum. No increased functional connectivity was found in this cohort. By studying a cohort of early-stage drug-naive PD patients, we ruled out the potential confounding effect of prolonged antiparkinson medication use on the functional integration of neural networks. We demonstrate decreased functional integration across neural networks involving striatum, mesolimbic cortex, and sensorimotor regions in these patients and postulate that the prevalent disconnection in mesolimbic-striatal loops is associated with some early clinical nonmotor features in PD. This study offers additional insight into the early functional integration of neural networks in PD.     

State-dependent functional connectivity of rat olfactory system assessed by fMRI

Functional connectivity between the piriform cortex and limbic and neocortical areas was assessed using functional magnetic resonance imaging (fMRI) of urethane anesthetized rats that spontaneously cycled between slow-wave and fast-wave states. Slow-wave and fast-wave states were determined indirectly through monitoring of respiration rate, which was confirmed to co-vary with state as determined by electrophysiological recordings. Previous electrophysiological data have suggested that the piriform cortex shifts between responsiveness to afferent odor input during fast-wave states and enhanced functional connectivity with limbic areas during slow-wave state. The present results demonstrate that fMRI-based resting state functional connectivity between the piriform cortex and both limbic and neocortical areas is enhanced during slow-wave state compared to fast-wave state using respiration as an indirect measure of state in urethane anesthetized rats. This state-dependent shift in functional connectivity may be important for sleep-dependent odor memory consolidation.     

正常脑老化中静息态功能磁共振成像功能连接的研究进展

【摘要】静息态功能磁共振成像（fMRI）作为一种不需要任务刺激就能呈现功能脑影像的技术手段,在临床上被广泛应 用。基于静息态fMRI的静息态功能连接（RSFC）,作为一种重要的计算机辅助分析法,能够度量不同脑区的脑功能连接 强度,对脑老化相关的神经科学领域的研究具有重要意义。本文介绍了功能连接的基本概念,总结了近年来脑老化相关 的人脑功能连接的研究成果,最后提出了该研究领域存在的问题及未来的研究方向。     

The organization of the human cerebellum estimated by intrinsic functional connectivity

The cerebral cortex communicates with the cerebellum via polysynaptic circuits. Separate regions of the cerebellum are connected to distinct cerebral areas, forming a complex topography. In this study we explored the organization of cerebrocerebellar circuits in the human using resting-state functional connectivity MRI (fcMRI). Data from 1,000 subjects were registered using nonlinear deformation of the cerebellum in combination with surface-based alignment of the cerebral cortex. The foot, hand, and tongue representations were localized in subjects performing movements. fcMRI maps derived from seed regions placed in different parts of the motor body representation yielded the expected inverted map of somatomotor topography in the anterior lobe and the upright map in the posterior lobe. Next, we mapped the complete topography of the cerebellum by estimating the principal cerebral target for each point in the cerebellum in a discovery sample of 500 subjects and replicated the topography in 500 independent subjects. The majority of the human cerebellum maps to association areas. Quantitative analysis of 17 distinct cerebral networks revealed that the extent of the cerebellum dedicated to each network is proportional to the network's extent in the cerebrum with a few exceptions, including primary visual cortex, which is not represented in the cerebellum. Like somatomotor representations, cerebellar regions linked to association cortex have separate anterior and posterior representations that are oriented as mirror images of one another. The orderly topography of the representations suggests that the cerebellum possesses at least two large, homotopic maps of the full cerebrum and possibly a smaller third map.     

脑梗死运动性失语患者语言任务fMRI功能连接初步研究

目的 对脑梗死运动性失语患者进行词语联想任务下的功能连接研究,探讨语言任务相关脑区在运动性失语后的功能连接变化形式及神经机制.方法 采用1.5 T磁共振扫描仪对10例脑梗死后运动性失语患者[均为男性,年龄43～77岁,平均(56.7±8.6岁)]及10名正常志愿者[均为男性,年龄46～74岁,平均(56.2±9.0)岁]行词语联想任务下的功能磁共振成像(fMRI)数据采集,应用SPM2,AFNI、Matlab软件进行预处理和统计分析,并根据正常人激活结果选择左侧额下回后部激活区作为功能连接的种子点,[中心区蒙特利尔神经研究所(MNI)坐标为“-51、9、21”],与全脑其他所有体素的时间序列做相关分析.采用单样本t检验和两样本t检验进行组内和组间分析,统计阈值设定为voxel＞ 30,P＜0.001(未校正).结果 对照组与种子点正相关的脑区主要包括左侧额下回、额中回、岛叶,左侧楔前叶、顶下小叶,左侧颞中回,左侧基底节,左侧丘脑,右侧额下回、额中回、岛叶,右侧颞下回、颞上回,双侧辅助运动区(SMA),右侧顶下小叶.患者组与种子点正相关的脑区主要包括左侧额下回后部、左岛叶,左侧中央后回,左侧顶下小叶.对照组与种子点的相关性大于患者组的脑区包括右侧颞中回、颞上回,右侧额下回,SMA.患者组与种子点的相关性大于对照组的脑区为左侧外侧裂周围区,包括左侧岛叶、左侧额下回.结论 .左侧额下回后部与右侧半球失去功能连接是运动性失语发生的一种神经机制.左侧外侧裂周围区对失语早期语言功能的维持有重要作用.     

Increased fMRI signal with age in familial Alzheimer's disease mutation carriers

Although many Alzheimer's disease (AD) patients have a family history of the disease, it is rarely inherited in a predictable way. Functional magnetic resonance imaging (fMRI) studies of nondemented adults carrying familial AD mutations provide an opportunity to prospectively identify brain differences associated with early AD-related changes. We compared fMRI activity of 18 nondemented autosomal dominant AD mutation carriers with fMRI activity in eight of their noncarrier relatives as they performed a novelty encoding task in which they viewed novel and repeated images. Because age of disease onset is relatively consistent within families, we also correlated fMRI activity with subjects' distance from the median age of diagnosis for their family. Mutation carriers did not show significantly different voxelwise fMRI activity from noncarriers as a group. However, as they approached their family age of disease diagnosis, only mutation carriers showed increased fMRI activity in the fusiform and middle temporal gyri. This suggests that during novelty encoding, increased fMRI activity in the temporal lobe may relate to incipient AD processes.     

The organization of the human cerebral cortex estimated by intrinsic functional connectivity

Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.     

Functional brain connectivity and cognition: effects of adult age and task demands

Previous neuroimaging research has documented that patterns of intrinsic (resting state) functional connectivity (FC) among brain regions covary with individual measures of cognitive performance. Here, we examined the relation between intrinsic FC and a reaction time (RT) measure of performance, as a function of age group and task demands. We obtained filtered, event-related functional magnetic resonance imaging data, and RT measures of visual search performance, from 21 younger adults (19–29 years old) and 21 healthy, older adults (60–87 years old). Age-related decline occurred in the connectivity strength in multiple brain regions, consistent with previous findings. Among 8 pairs of regions, across somatomotor, orbitofrontal, and subcortical networks, increasing FC was associated with faster responding (lower RT). Relative to younger adults, older adults exhibited a lower strength of this RT-connectivity relation and greater disruption of this relation by a salient but irrelevant display item (color singleton distractor). Age-related differences in the covariation of intrinsic FC and cognitive performance vary as a function of task demands.     

基于功能连接的大脑年龄预测的影响因素

目的 探索基于静息态功能连接进行大脑生理年龄预测的可行性及相关影响因素.方法 选取来自阿尔茨海默病神经影像学计划(Alzheimer disease neuroimaging initiative,ADNI)数据库的41例满足条件的健康受试者.首先对静息态功能磁共振成像(resting-state functional MRI,rs-fMRI)数据进行预处理并提取功能连接特征,利用基于Bootstrap的特征筛选方法进行特征降维;然后使用支持向量回归建立正常人大脑年龄的预测模型,最后用留一法进行交叉验证,并比较不同大脑模板、全脑信号回归及性别因素对年龄预测的影响.结果 基于AAL-90、AAL-1024、Shen-268、Fan-246脑图谱得到的预测值与真实年龄之间的相关系数r分别为0.23、0.29、0.17、0.38.使用全局信号回归,基于Fan-246脑图谱得到年龄预测模型的相关系数r显著提升为0.66.利用性别分组建模,基于Fan-246脑图谱预测模型的相关系数r提升为0.46.结论 根据静息态功能磁共振的功能连接特征可以较好地估计健康大脑的生理年龄,且大脑模板、全局信号回归对年龄估计模型的性能有较大影响.本研究可加深对大脑老化过程的认识,对阿尔兹海默病的早期诊断和预防有着重要的指导价值.     

Time‐dependent effects of isoflurane and dexmedetomidine on functional connectivity,spectral characteristics,and spatial distribution of spontaneous BOLD fluctuations

Anesthesia is often necessary to perform fMRI experiments in the rodent model; however, commonly used anesthetic protocols may manifest changing brain conditions over the duration of the study. This possibility was explored in the current work. Eleven rats were anesthetized with 2% isoflurane anesthesia; four rats were anesthetized for a short period (30 min, simulating induction and fMRI setup) and seven rats were anesthetized for a long period (3 h, simulating surgical preparation). Following the initial anesthetic period, isoflurane was discontinued, and a dexmedetomidine bolus (0.025 mg/kg) and continuous subcutaneous infusion (0.05 mg/kg/h) were administered. Blood‐oxygen‐level dependent resting state imaging was performed every 30 min from 0.75 h post dexmedetomidine bolus until 5.75 h post‐bolus. Evaluation of power spectra obtained from time courses in the primary somatosensory cortex revealed, in general, a monotonic increase in low‐frequency power (0.05–0.3 Hz) in both groups over the duration of resting state imaging. Greater low‐band spectral power (0.05–0.15 Hz) is present in the short isoflurane group for the first 2.75 h, but the spectra become highly uniform at 3.25 h. The emergence of a ~0.18 Hz peak, beginning at the 3.75 h time point, exists in both groups and evolves similarly, increasing in strength as the duration of dexmedetomidine sedation (and time since isoflurane cessation) extends. In the long isoflurane group only, bilateral functional connectivity strengthens with anesthetic duration, and correlation is linearly linked to low‐band spectral power. Convergence of connectivity and spectral metrics between the short and long isoflurane groups occurs at ~3.25 h, suggesting the effects of isoflurane have subsided. Researchers using dexmedetomidine following isoflurane for functional studies should be aware of the duration specific effects of the pre‐scan isoflurane durations as well as the continuing influences of long‐term imaging under dexmedetomidine. Copyright © 2014 John Wiley & Sons, Ltd.     

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。     

Effects of aging on functional connectivity of the amygdala during negative evaluation: a network analysis of fMRI data

Previous evidence has suggested both preserved emotional function in aging and age-related differences in emotional processing, but the neural networks underlying such processing alterations in the context of preserved affective function are not clear. Using event-related fMRI, we scanned young and older adults while they made valence ratings for emotional pictures. Behavioral results showed a similar pattern of emotional evaluation, but older adults experienced negatively valenced pictures as being less negative. Consistent with behavioral findings, we identified common activity in the right amygdala, but age-related differences in the functional connectivity of this region with the rest of the brain. Compared to young adults, older adults had greater functional connectivity between the right amygdala and ventral anterior cingulate cortex, possibly reflecting increased emotional regulation. Conversely, older adults showed decreased functional connectivity with posterior brain regions, likely reflecting decreased perceptual processing. Thus, age-related differences in evaluating negatively valenced stimuli might reflect decreased perceptual processing of these stimuli, as well as the engagement of control processes that inhibit the response to negative emotion.     

Effects of olanzapine on cerebellar functional connectivity in schizophrenia measured by fMRI during a simple motor task

BACKGROUND: According to current theories, schizophrenia results from altered connectivity in brain circuits for fundamental cognitive operations. Consequently, the poorly understood mechanisms of neuroleptic treatment may be explainable by altered functional interactions within such networks. The 'cognitive dysmetria' model hypothesizes that one key structure in these circuits is the cerebellum. To investigate the effects of olanzapine on cerebellar functional connectivity (CFC), a seed-voxel correlation analysis (SVCA) was used in a functional magnetic resonance imaging (fMRI) study of a simple finger-tapping task. METHODS: fMRI scans were obtained from six schizophrenic patients under both drug-free and olanzapine-treated conditions and from a matched control group of six healthy subjects at corresponding time points. SVCAs were performed for anatomically and functionally standardized seed voxels in the anterior cerebellum. SVCA results were then processed by three different randomization analyses. RESULTS: The analyses revealed that olanzapine caused widespread changes of CFC, including prominent changes in prefrontal cortex and mediodorsal thalamus. Significant changes in motor structures were found after subtractions within both groups and may thus indicate repetition effects rather than drug effects. Olanzapine 'normalized' the patients' CFC patterns for the right, but not for the left cerebellum. CONCLUSION: Even for a simple motor task, olanzapine affects functional interactions between the cerebellum and many non-motor brain regions, including elements of the 'cognitive dysmetria' circuit. Altogether, our findings suggest that olanzapine has a stronger differential effect on neural activity in prefrontal cortex and thalamus than in motor structures.     

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.     

Changes in resting connectivity with age: a simultaneous electroencephalogram and functional magnetic resonance imaging investigation

Resting fluctuations in the blood oxygenation level-dependent signal have attracted considerable interest for their sensitivity to pathological brain processes. However, these analyses are susceptible to confound by nonneural physiological factors such as vasculature, breathing, and head movement which is a concern when investigating elderly or pathological groups. Here, we used simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) (EEG/fMRI) to constrain the analysis of resting state networks (RSNs) and identify aging differences. Four of 26 RSNs showed fMRI and EEG/fMRI group differences; anterior default-mode network, left frontal-parietal network, bilateral middle frontal, and postcentral gyri. Seven RSNs showed only EEG/fMRI differences suggesting the combination of these 2 methods might be more sensitive to age-related neural changes than fMRI alone. Five RSNs showed only fMRI differences and might reflect nonneural group differences. Activity within some EEG/fMRI RSNs was better explained by neuropsychological measures (Mini Mental State Examination and Stroop) than age. These results support previous studies suggesting that age-related changes in specific RSNs are neural in origin, and show that changes in some RSNs relate better to elderly cognition than age.