事件相关功能磁共振成像

事件相关设计是功能磁共振成像的一种新的实验范式,与传统的组块设计相比,其主要特点有三：（1）任务刺激和刺激间隔时间的随机化;（2）可基于任务类型和被试反应类型进行选择性处理;（3）提供更加细致的脑的局部信息。     

Real-time functional magnetic resonance imaging.

Magnetic resonance imaging (MRI) has been shown to be useful in the detection of brain activity via the relatively indirect coupling of neural activity to cerebral blood flow and subsequently to magnetic resonance signal intensity. Recent technical advances have made possible the continuous collection of successive images at a rate rapid compared with such signal changes and in the statistical processing of these image time series to produce tomographic maps of brain activity in real time, with updates of 10 frames/s or better. We describe here our preferred method of real-time functional MRI and some of the early results we have obtained with its use.     

High-resolution functional magnetic resonance imaging of the animal brain

To fully understand brain function, one must look beyond the level of a single neuron. By elucidating the spatial properties of the columnar and laminar functional architectures, information regarding the neural processing in the brain can be gained. To map these fine functional structures noninvasively and repeatedly, functional magnetic resonance imaging (fMRI) can be employed. In this article the basic principles of fMRI are introduced, including specific hardware requirements and the equipment necessary for animal magnetic resonance research. Since fMRI measures a change in secondary hemodynamic responses induced by neural activity, it is critical to understand the principles and potential pitfalls of fMRI techniques. Thus, the underlying physics of conventional blood oxygenation, cerebral blood flow, and cerebral blood volume-based fMRI techniques are extensively discussed. Tissue-specific signal change is close to the site of neural activity, while signals from large vessels can be distant from the actual active site. Thus, methods to minimize large vessel contributions and to maximize tissue signals are described. The fundamental limitation of fMRI spatial resolution is the intrinsic hemodynamic response. Based on our high-resolution fMRI studies, the hemodynamic response is regulated at submillimeter functional domains and thus spatial resolution can be achieved to an order of 100 microm. Since hemodynamic responses are sluggish, it is difficult to obtain very high temporal resolution. By using an approach with multiple experiments with different stimulus conditions, temporal resolution can be improved on the order of 100 ms. With current fMRI technologies, submillimeter columnar- and laminar-specific specific functional images can be obtained from animal brains.     

Functional magnetic resonance imaging: imaging techniques and contrast mechanisms.

Functional magnetic resonance imaging (fMRI) is a widely used technique for generating images or maps of human brain activity. The applications of the technique are widespread in cognitive neuroscience and it is hoped they will eventually extend into clinical practice. The activation signal measured with fMRI is predicated on indirectly measuring changes in the concentration of deoxyhaemoglobin which arise from an increase in blood oxygenation in the vicinity of neuronal firing. The exact mechanisms of this blood oxygenation level dependent (BOLD) contrast are highly complex. The signal measured is dependent on both the underlying physiological events and the imaging physics. BOLD contrast, although sensitive, is not a quantifiable measure of neuronal activity. A number of different imaging techniques and parameters can be used for fMRI, the choice of which depends on the particular requirements of each functional imaging experiment. The high-speed MRI technique, echo-planar imaging provides the basis for most fMRI experiments. The problems inherent to this method and the ways in which these may be overcome are particularly important in the move towards performing functional studies on higher field MRI systems. Future developments in techniques and hardware are also likely to enhance the measurement of brain activity using MRI.     

Neural responses to intravenous serotonin revealed by functional magnetic resonance imaging.

We examined the sequence of neural responses to the hypotension, bradycardia, and apnea evoked by intravenous administration of 5-hydroxytryptamine (serotonin). Functional magnetic resonance imaging signal changes were assessed in nine isoflurane-anesthetized cats during baseline and after a bolus intravenous low dose (10 microg/kg) or high dose (20-30 microg/kg) of 5-hydroxytryptamine. In all cats, high-dose challenges elicited rapid-onset, transient signal declines in the intermediate portion of the solitary tract nucleus, caudal midline and caudal and rostral ventrolateral medulla, and fastigial nucleus of the cerebellum. Slightly delayed phasic declines appeared in the dentate and interpositus nuclei and dorsolateral pons. Late-developing responses also emerged in the solitary tract nucleus, parapyramidal region, periaqueductal gray, spinal trigeminal nucleus, inferior olivary nucleus, cerebellar vermis, and fastigial nucleus. Amygdala and hypothalamic sites showed delayed and prolonged signal increases. Intravenous serotonin infusion recruits cerebellar, amygdala, and hypothalamic sites in addition to classic brain stem cardiopulmonary areas and exhibits site-specific temporal patterns.     

Functional imaging of memory processes in humans: positron emission tomography and functional magnetic resonance imaging

Human memory is not a unitary function; it consists of multiple memory systems, with different characteristics and specialisations that are implemented in the brain. The cognitive neuroscience of human memory tries to comprehend how we encode, store, and retrieve memory items within and across those systems. The emergence of functional neuroimaging techniques offered the unprecedented opportunity to directly observe the brain regions engaged in memory functions. Brain imaging techniques can roughly be divided into those measuring the electric or magnetic fields generated by neuronal activity (EEG, magnetencephalography [MEG]) and those measuring the haemodynamic or metabolic sequelae of neuronal activity (positron emission tomography [PET], functional magnetic resonance imaging [fMRI]). Out of these techniques, the following two will be discussed in detail: fMRI and PET. Although functional neuroimaging is able to acquire images of the brain engaged in consolidating or retrieving memories, these processes are not clearly visible in the data. Statistical techniques are needed to reduce the complexity of the data and to extract the processes of interest. This article outlines the experimental and analytical procedures of neuroimaging studies with PET and fMRI. We will use a PET-study on episodic memory in human volunteers to illustrate design, analysis, and interpretation of functional imaging studies on memory.     

REST: a toolkit for resting-state functional magnetic resonance imaging data processing

Resting-state fMRI (RS-fMRI) has been drawing more and more attention in recent years. However, a publicly available, systematically integrated and easy-to-use tool for RS-fMRI data processing is still lacking. We developed a toolkit for the analysis of RS-fMRI data, namely the RESting-state fMRI data analysis Toolkit (REST). REST was developed in MATLAB with graphical user interface (GUI). After data preprocessing with SPM or AFNI, a few analytic methods can be performed in REST, including functional connectivity analysis based on linear correlation, regional homogeneity, amplitude of low frequency fluctuation (ALFF), and fractional ALFF. A few additional functions were implemented in REST, including a DICOM sorter, linear trend removal, bandpass filtering, time course extraction, regression of covariates, image calculator, statistical analysis, and slice viewer (for result visualization, multiple comparison correction, etc.). REST is an open-source package and is freely available at http://www.restfmri.net.     

Developing functional magnetic resonance imaging techniques for alert macaque monkeys

Functional magnetic resonance imaging (fMRI) has developed rapidly into a major non-invasive tool for studying the human brain. However, due to a variety of technical difficulties, it has yet to be widely adopted for use in alert, trained non-human primates. Our laboratory has been developing techniques for such fMRI studies. As background, we first consider basic principles of fMRI imaging, experimental design, and post-processing. We discuss appropriate MRI system hardware and components for conducting fMRI studies in alert macaques, and the animal preparation and behavior necessary for optimal experiments. Finally, we consider alternative fMRI techniques using exogenous contrast agents, arterial spin labeling, and more direct measures of neural activation.     

Human ocular dominance columns as revealed by high-field functional magnetic resonance imaging.

We mapped ocular dominance columns (ODCs) in normal human subjects using high-field (4 T) functional magnetic resonance imaging (fMRI) with a segmented echo planar imaging technique and an in-plane resolution of 0.47 x 0.47 mm(2). The differential responses to left or right eye stimulation could be reliably resolved in anatomically well-defined sections of V1. The orientation and width ( approximately 1 mm) of mapped ODC stripes conformed to those previously revealed in postmortem brains stained with cytochrome oxidase. In addition, we showed that mapped ODC patterns could be largely reproduced in different experiments conducted within the same experimental session or over different sessions. Our results demonstrate that high-field fMRI can be used for studying the functions of human brains at columnar spatial resolution.     

The neural basis of the blood-oxygen-level-dependent functional magnetic resonance imaging signal

Magnetic resonance imaging (MRI) has rapidly become an important tool in clinical medicine and biological research. Its functional variant (functional magnetic resonance imaging; fMRI) is currently the most widely used method for brain mapping and studying the neural basis of human cognition. While the method is widespread, there is insufficient knowledge of the physiological basis of the fMRI signal to interpret the data confidently with respect to neural activity. This paper reviews the basic principles of MRI and fMRI, and subsequently discusses in some detail the relationship between the blood-oxygen-level-dependent (BOLD) fMRI signal and the neural activity elicited during sensory stimulation. To examine this relationship, we conducted the first simultaneous intracortical recordings of neural signals and BOLD responses. Depending on the temporal characteristics of the stimulus, a moderate to strong correlation was found between the neural activity measured with microelectrodes and the BOLD signal averaged over a small area around the microelectrode tips. However, the BOLD signal had significantly higher variability than the neural activity, indicating that human fMRI combined with traditional statistical methods underestimates the reliability of the neuronal activity. To understand the relative contribution of several types of neuronal signals to the haemodynamic response, we compared local field potentials (LFPs), single- and multi-unit activity (MUA) with high spatio-temporal fMRI responses recorded simultaneously in monkey visual cortex. At recording sites characterized by transient responses, only the LFP signal was significantly correlated with the haemodynamic response. Furthermore, the LFPs had the largest magnitude signal and linear systems analysis showed that the LFPs were better than the MUAs at predicting the fMRI responses. These findings, together with an analysis of the neural signals, indicate that the BOLD signal primarily measures the input and processing of neuronal information within a region and not the output signal transmitted to other brain regions.     

Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging

The majority of functional neuroscience studies have focused on the brain's response to a task or stimulus. However, the brain is very active even in the absence of explicit input or output. In this Article we review recent studies examining spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal of functional magnetic resonance imaging as a potentially important and revealing manifestation of spontaneous neuronal activity. Although several challenges remain, these studies have provided insight into the intrinsic functional architecture of the brain, variability in behaviour and potential physiological correlates of neurological and psychiatric disease.     

The multisensory attentional consequences of tool use: a functional magnetic resonance imaging study

Background

Tool use in humans requires that multisensory information is integrated across different locations, from objects seen to be distant from the hand, but felt indirectly at the hand via the tool. We tested the hypothesis that using a simple tool to perceive vibrotactile stimuli results in the enhanced processing of visual stimuli presented at the distal, functional part of the tool. Such a finding would be consistent with a shift of spatial attention to the location where the tool is used.

Methodology/Principal Findings

We tested this hypothesis by scanning healthy human participants'' brains using functional magnetic resonance imaging, while they used a simple tool to discriminate between target vibrations, accompanied by congruent or incongruent visual distractors, on the same or opposite side to the tool. The attentional hypothesis was supported: BOLD response in occipital cortex, particularly in the right hemisphere lingual gyrus, varied significantly as a function of tool position, increasing contralaterally, and decreasing ipsilaterally to the tool. Furthermore, these modulations occurred despite the fact that participants were repeatedly instructed to ignore the visual stimuli, to respond only to the vibrotactile stimuli, and to maintain visual fixation centrally. In addition, the magnitude of multisensory (visual-vibrotactile) interactions in participants'' behavioural responses significantly predicted the BOLD response in occipital cortical areas that were also modulated as a function of both visual stimulus position and tool position.

Conclusions/Significance

These results show that using a simple tool to locate and to perceive vibrotactile stimuli is accompanied by a shift of spatial attention to the location where the functional part of the tool is used, resulting in enhanced processing of visual stimuli at that location, and decreased processing at other locations. This was most clearly observed in the right hemisphere lingual gyrus. Such modulations of visual processing may reflect the functional importance of visuospatial information during human tool use.