fMRI Validation of fNIRS Measurements During a Naturalistic Task

We present a method to compare brain activity recorded with near-infrared spectroscopy (fNIRS) in a dance video game task to that recorded in a reduced version of the task using fMRI (functional magnetic resonance imaging). Recently, it has been shown that fNIRS can accurately record functional brain activities equivalent to those concurrently recorded with functional magnetic resonance imaging for classic psychophysical tasks and simple finger tapping paradigms. However, an often quoted benefit of fNIRS is that the technique allows for studying neural mechanisms of complex, naturalistic behaviors that are not possible using the constrained environment of fMRI. Our goal was to extend the findings of previous studies that have shown high correlation between concurrently recorded fNIRS and fMRI signals to compare neural recordings obtained in fMRI procedures to those separately obtained in naturalistic fNIRS experiments. Specifically, we developed a modified version of the dance video game Dance Dance Revolution (DDR) to be compatible with both fMRI and fNIRS imaging procedures. In this methodology we explain the modifications to the software and hardware for compatibility with each technique as well as the scanning and calibration procedures used to obtain representative results. The results of the study show a task-related increase in oxyhemoglobin in both modalities and demonstrate that it is possible to replicate the findings of fMRI using fNIRS in a naturalistic task. This technique represents a methodology to compare fMRI imaging paradigms which utilize a reduced-world environment to fNIRS in closer approximation to naturalistic, full-body activities and behaviors. Further development of this technique may apply to neurodegenerative diseases, such as Parkinson’s disease, late states of dementia, or those with magnetic susceptibility which are contraindicated for fMRI scanning.     

功能磁共振和脑电神经成像技术与大脑刺激相结合的研究进展

随着对神经机制问题阐述水平的迅速提高,所应用的神经成像技术、方法及各种工具的复杂程度也在不断提高．一方面是神经成像技术本身的不断发展,另一方面则是大脑直接刺激与神经成像技术同步记录方法的发展．经颅磁刺激-功能磁共振成像同步技术(TMS-fMRI)和经颅磁刺激-脑电技术(TMS-EEG)能为研究大脑网络的功能和有效连通性提供技术手段,该技术在多种认知领域的发展和应用,为神经科学、认知心理学、神经信息学等学科的研究者对人脑的研究开启了多条通道,更加有利于深入地理解人类大脑的工作机制．     

Use of an Eight-arm Radial Water Maze to Assess Working and Reference Memory Following Neonatal Brain Injury

Working and reference memory are commonly assessed using the land based radial arm maze. However, this paradigm requires pretraining, food deprivation, and may introduce scent cue confounds. The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs. Specifically, subjects are required to avoid the arms previously used for escape during each testing day (working memory) as well as avoid the fixed arms, which never contain escape platforms (reference memory). Re-entries into arms that have already been used for escape during a testing session (and thus the escape platform has been removed) and re-entries into reference memory arms are indicative of working memory deficits. Alternatively, first entries into reference memory arms are indicative of reference memory deficits. We used this maze to compare performance of rats with neonatal brain injury and sham controls following induction of hypoxia-ischemia and show significant deficits in both working and reference memory after eleven days of testing. This protocol could be easily modified to examine many other models of learning impairment.     

Cognitive Ergonomics in Virtual Environments: Development of an Intuitive and Appropriate Input Device for Navigating in a Virtual Maze

For patients suffering from mild cognitive impairments, the navigation through a virtual maze should be as intuitive and efficient as possible in order to minimize cognitive and physical strain. This paper discusses the appropriateness of interaction devices for being used for easy navigation tasks. Information gained from human centered evaluation was used to develop an intuitive and ergonomic interaction device. Two experiments examined the usability of tracked interaction devices. Usability problems with the devices are discussed. The findings from the experiments were translated into general design guidance, in addition to specific recommendations. A new device was designed on the basis of these recommendations and its usability was evaluated in a second experiment. The results were used to develop a lightweight interaction device for navigation in the virtual maze.     

Deficits in spatial learning after exposure of mice to a 50 Hz magnetic field

A series of four experiments was performed to determine the effect of exposure to a 50 Hz magnetic field on memory-related behaviour of adult, male C57BL/6J mice. Experimental subjects were exposed to a vertical, sinusoidal magnetic field at 0.75 mT (rms), for 45 min immediately before daily testing sessions on a spatial learning task in an eight-arm radial maze. Control subjects were only exposed to a background time-varying field of less than 50 nT and the ambient static field of about 40 μT. In each experiment, exposure significantly reduced the rate of acquisition of the task but did not affect overall accuracy. This finding is consistent with the results of another study that found that prior exposure to 60 Hz magnetic fields affected spatial learning in rats. Bioelectromagnetics 19:79–84, 1998. © 1998 Wiley-Liss, Inc.     

50 Hz magnetic field effects on the performance of a spatial learning task by mice

Intense magnetic fields have been shown to affect memory-related behaviours of rodents. A series of experiments was performed to investigate further the effects of a 50 Hz magnetic field on the foraging behaviour of adult, male C57BL/6J mice performing a spatial learning task in an eight-arm radial maze. Exposure to vertical, sinusoidal magnetic fields between 7.5 μT and 7.5 mT for 45 min immediately before daily testing sessions caused transient decreases in performance that depended on the applied flux density. Exposure above a threshold of between 7.5 and 75 μT significantly increased the number of errors the animals made and reduced the rate of acquisition of the task without any effect on overall accuracy. However, the imposition of a 45-minute delay between exposure at 0.75 mT and behavioural testing resulted in the elimination of any deficit. Similarly, exposure to fields between 7.5 μT and 0.75 mT for 45 min each day for 4 days after training had no amnesic effects on the retention and subsequent performance of the task. Overall, these results provide additional evidence that 50 Hz magnetic fields may cause subtle changes in the processing of spatial information in mice. Although these effects appear dependent on field strength, even at high flux densities the field-induced deficits tend to be transient and reversible. Bioelectromagnetics 19:486–493, 1998. © 1998 Wiley-Liss, Inc.     

Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders

Induction of phosphorylated extracellular-regulated kinase (pERK) is a reliable molecular readout of learning-dependent neuronal activation. Here, we describe a pERK immunohistochemistry protocol to study the profile of hippocampal neuron activation following exposure to a spatial learning task in a mouse model characterized by cognitive deficits of neurodevelopmental origin. Specifically, we used pERK immunostaining to study neuronal activation following Morris water maze (MWM, a classical hippocampal-dependent learning task) in Engrailed-2 knockout (En2^-/-) mice, a model of autism spectrum disorders (ASD). As compared to wild-type (WT) controls, En2^-/- mice showed significant spatial learning deficits in the MWM. After MWM, significant differences in the number of pERK-positive neurons were detected in specific hippocampal subfields of En2^-/- mice, as compared to WT animals. Thus, our protocol can robustly detect differences in pERK-positive neurons associated to hippocampal-dependent learning impairment in a mouse model of ASD. More generally, our protocol can be applied to investigate the profile of hippocampal neuron activation in both genetic or pharmacological mouse models characterized by cognitive deficits.     

基于时间聚类分析和独立成分分析的癫痫fMRI盲分析方法

提出了一种基于时间聚类分析和独立成分分析的癫痫fMRI数据盲分析方法,并将两种方法有效联合,提取发作间期的癫痫fMRI激活时空信息.该方法首先由时间聚类分析得到与激活相关的时间峰度特征曲线,以此特征作为时间参考信息;再由空间独立成分分析分解fMRI信号得到空间独立成分;最后将每个独立成分所对应的时间曲线与参考曲线做相关分析提取相应脑激活图.提出的方法无需任何关于癫痫fMRI的先验假设信息,有效解决了独立成分的排序问题,实现了对数据的盲分析.仿真试验结果阐明了这一方法的有效性及可靠性,对癫痫数据的试验结果显示空间定位准确性优于统计参数图方法.     

Correlation of behavior changes and BOLD signal in Alzheimer-like rat model

Memory impairment is usually the early and most promi-nent clinical manifestation of Alzheimer disease (AD), aprogressive neurodegenerative illness characterized bygradual deposition of neuritic plaques and neurofibrillarytangles in the brain of the patie…     

Optogenetic Functional MRI

The investigation of the functional connectivity of precise neural circuits across the entire intact brain can be achieved through optogenetic functional magnetic resonance imaging (ofMRI), which is a novel technique that combines the relatively high spatial resolution of high-field fMRI with the precision of optogenetic stimulation. Fiber optics that enable delivery of specific wavelengths of light deep into the brain in vivo are implanted into regions of interest in order to specifically stimulate targeted cell types that have been genetically induced to express light-sensitive trans-membrane conductance channels, called opsins. fMRI is used to provide a non-invasive method of determining the brain''s global dynamic response to optogenetic stimulation of specific neural circuits through measurement of the blood-oxygen-level-dependent (BOLD) signal, which provides an indirect measurement of neuronal activity. This protocol describes the construction of fiber optic implants, the implantation surgeries, the imaging with photostimulation and the data analysis required to successfully perform ofMRI. In summary, the precise stimulation and whole-brain monitoring ability of ofMRI are crucial factors in making ofMRI a powerful tool for the study of the connectomics of the brain in both healthy and diseased states.     

脑科学和脑功能MR成像

目的：在对大脑认知功能进行脑功能成像研究之中,随着磁共振成像技术的发展,人们现在可以对脑的认知功能,如视觉、运动、语言和记忆等功能中枢进行成像。本文首先介绍了脑科学的发展历程,并从脑功能MR成像的方法出发,分析了其成像机理,探讨了用脑功能MR成像为手段对脑科学—认知科学进行的方法研究,最后对脑功能MR成像应用于脑科学的研究作了展望。     

Effect of Satiation on Brain Activity in Obese and Lean Women

Objective: To investigate the response of the brains of women to the ingestion of a meal. Research Methods and Procedures: We used measures of regional cerebral blood flow (rCBF), a marker of neuronal activity, by positron emission tomography to describe the functional anatomy of satiation, i.e., the response to a liquid meal in the context of extreme hunger (36‐hour fast) in 10 lean (BMI ≤ 25 kg/m²; 32 ± 10 years old, 61 ± 7 kg; mean ± SD) and 12 obese (BMI ≥ 35 kg/m²; 30 ± 7 years old, 110 ± 14 kg) women. Results: In lean and obese women, satiation produced significant increases in rCBF in the vicinity of the prefrontal cortex (p < 0.005). Satiation also produced significant decreases in rCBF in several regions including the thalamus, insular cortex, parahippocampal gyrus, temporal cortex, and cerebellum (in lean and obese women), and hypothalamus, cingulate, nucleus accumbens, and amygdala (in obese women only; all p < 0.005). Compared with lean women, obese women had significantly greater increases in rCBF in the ventral prefrontal cortex and had significantly greater decreases in the paralimbic areas and in areas of the frontal and temporal cortex. Discussion: This study indicates that satiation elicits differential brain responses in obese and lean women. It also lends additional support to the hypothesis that the paralimbic areas participate in a central orexigenic network modulated by the prefrontal cortex through feedback loops.     

Topographical Estimation of Visual Population Receptive Fields by fMRI

Visual cortex is retinotopically organized so that neighboring populations of cells map to neighboring parts of the visual field. Functional magnetic resonance imaging allows us to estimate voxel-based population receptive fields (pRF), i.e., the part of the visual field that activates the cells within each voxel. Prior, direct, pRF estimation methods¹ suffer from certain limitations: 1) the pRF model is chosen a-priori and may not fully capture the actual pRF shape, and 2) pRF centers are prone to mislocalization near the border of the stimulus space. Here a new topographical pRF estimation method² is proposed that largely circumvents these limitations. A linear model is used to predict the Blood Oxygen Level-Dependent (BOLD) signal by convolving the linear response of the pRF to the visual stimulus with the canonical hemodynamic response function. PRF topography is represented as a weight vector whose components represent the strength of the aggregate response of voxel neurons to stimuli presented at different visual field locations. The resulting linear equations can be solved for the pRF weight vector using ridge regression³, yielding the pRF topography. A pRF model that is matched to the estimated topography can then be chosen post-hoc, thereby improving the estimates of pRF parameters such as pRF-center location, pRF orientation, size, etc. Having the pRF topography available also allows the visual verification of pRF parameter estimates allowing the extraction of various pRF properties without having to make a-priori assumptions about the pRF structure. This approach promises to be particularly useful for investigating the pRF organization of patients with disorders of the visual system.     

Neurophysiological Age Differences During Task-Performance in a Stereoscopic Virtual Environment

In today’s society, there is an increasing number of workplaces in virtual environments (VE). But, there are only a few reports dealing with occupational health issues or age effects. The question arises how VR generally interferes with cognitive processes. This interference might have relevant implications for workability and work-efficiency in virtual environments. Event-related potentials are known to reflect different stages of stimulus reception, evaluation, and response. We have established an electroencephalographic (EEG) monitoring, focussing on event-related potentials (N100; mismatch negativity, i.e., MMN) to obtain access to attention dependent and pre-attentive processing of sensory stimuli applied in VE. The MMN is known to be correlated with the ability of subjects to react to an unexpected event. The aim of the present study was to investigate cognitive responses to distracting auditory stimuli in two different age groups in a virtual environment (VE) and in a real environment (“real reality”), and to compare characteristic neurophysiological response patterns. Data show that stimulus detection as given by the N100 amplitude and latency does not differ in both age groups and task conditions. In contrast, the pre-attentive processing as given by the MMN is altered in the VR such as the non-VR condition in an age-related manner. A relevant finding of the present study was that the age related differences seen in the non-VR condition were not strengthened in VR.     

慢性疼痛患者静息态脑功能磁共振的默认网络研究

运用静息态功能磁共振成像技术(resting-state fMRI)研究慢性疼痛患者脑默认网络结构.通过选择双侧膝骨性关节炎(knee osteoarthritis,KOA)患者20例和正常志愿者20名,以后扣带回(posterior cingulated cortex,PCC)为种子点,分别进行fMRI扫描,分析配对两组受试者的脑功能连接情况.结果显示相对正常受试者,KOA患者存在异常脑功能连接,主要表现为PCC呈负激活,边缘叶、脑岛呈正激活.     

The functional anatomy of cerebral reorganisation after focal brain injury

Stroke is a major cause of disability in all age groups. Although the value of specific rehabilitative therapies is now acknowledged, the mechanisms of impairment and recovery are not well understood. There is growing interest in the role that central nervous system reorganisation might play in the recovery process, and in particular whether this reorganisation can be manipulated to provide clinical benefits for patients. The careful use of non-invasive techniques such as functional magnetic resonance imaging and transcranial magnetic stimulation allows the study of the working human brain, and studies in humans suggest that functionally relevant adaptive changes occur in cerebral networks following stroke. An understanding of how these changes influence the recovery process will facilitate the development of novel therapeutic techniques that are based on neurobiological principles and will allow the delivery of specific therapies to appropriately targeted patients suffering from stroke.     

Bayesian spatiotemporal modeling on complex-valued fMRI signals via kernel convolutions

We propose a model-based approach that combines Bayesian variable selection tools, a novel spatial kernel convolution structure, and autoregressive processes for detecting a subject's brain activation at the voxel level in complex-valued functional magnetic resonance imaging (CV-fMRI) data. A computationally efficient Markov chain Monte Carlo algorithm for posterior inference is developed by taking advantage of the dimension reduction of the kernel-based structure. The proposed spatiotemporal model leads to more accurate posterior probability activation maps and less false positives than alternative spatial approaches based on Gaussian process models, and other complex-valued models that do not incorporate spatial and/or temporal structure. This is illustrated in the analysis of simulated data and human task-related CV-fMRI data. In addition, we show that complex-valued approaches dominate magnitude-only approaches and that the kernel structure in our proposed model considerably improves sensitivity rates when detecting activation at the voxel level.