Functional Neuroimaging Studies of Cognitive Recovery After Acquired Brain Damage in Adults

The first two decades of cognitive neuroimaging research have provided a constant increase of the knowledge about the neural organization of cognitive processes. Many cognitive functions (e.g.working memory) can now be associated with particular neural structures, and ongoing research promises to clarify this picture further, providing a new mapping between cognitive and neural function. The main goal of this paper is to outline conceptual issues that are particularly important in the context of imaging changes in neural function through recovery process. This review focuses primarily on studies made in stroke and traumatic brain injury patients, but most of the issues raised here are also relevant to studies using other acquired brain damages. Finally, we summarize aset of methodological issues related to functional neuroimaging that are relevant for the study ofneural plasticity and recovery after rehabilitation. Deceased     

神经成像数据的元分析

随着高空间分辨率神经成像技术如fMRI和PET的普及, 神经成像研究报告的数量增长迅猛。文献的积累为研究者提供了大量的数据, 研究者可以通过对文献的分析来验证研究结论以及提出新的假设。由于神经成像研究的主要目的之一在于寻求认知过程与脑区的空间位置对应关系, 基于坐标的元分析方法满足了这种需求, 成为神经成像数据元分析中主导的方法。其中, 激活可能性估计法(Activation Likelihood Estimation, ALE)由于方法上的合理性和使用上的便利, 成为当前使用最广泛的基于坐标的元分析方法。本文首先介绍了ALE方法的基本原理, 并在此基础上讨论了神经成像数据元分析的两种主要思路：寻找多个研究的一致性以及寻找脑区激活的调节变量。此外, 文章还介绍了新近流行的脑连通性元分析模型(MACM), 即使用元分析方法进行功能连通性分析。最后, 文章讨论了当前神经成像数据元分析的发展趋势。     

Functional neuroimaging in neurology and psychiatry

How can functional neuroimaging be applied to clinical neurology and psychiatry? This article reviews selected contributions of functional neuroimaging to the clinical neurosciences. We review selected technical aspects of positron emission tomography, single photon emission tomography, and functional magnetic resonance imaging with a focus on the relative strengths and weaknesses of these techniques. Consumers of functional neuroimaging research are encouraged to consider the limitations of imaging techniques and theoretical pitfalls of cognitive task design when interpreting results of functional imaging studies. Then, we selectively review the contributions of functional neuroimaging to neurology and psychiatry, including the areas of epilepsy, stroke, chronic pain, schizophrenia, depression, and obsessive-compulsive disorder. Future directions of functional neuroimaging research are offered, with the emphasis that the best conclusions are informed by a convergence of research from functional neuroimaging, neurophysiological, and lesion studies.     

Integrating electrophysiology and neuroimaging in the study of human cognition

Noninvasive recordings of electrical and magnetic fields generated by neuronal activity have helped to characterize the temporal sequencing and mechanisms underlying human cognition. Progress is being made toward the goal of localizing the intracranial loci at which many important electromagnetic signals are generated through the use of new analytic techniques and of scalp recordings of electromagnetic activity in neurological patients and through related work in animals. Such methods alone, however, do not yet have the three-dimensional spatial resolution that is necessary in order to identify the intracranial anatomical structures that are involved in the generation of externally recorded activity and, thus, cannot yet inform us with precision about the anatomical substrates of neural events. In comparison, neuroimaging methods, such as positron emission tomography and functional magnetic resonance imaging, can provide higher spatial resolution information about which brain structures are involved in perceptual, motor, and cognitive processes. However, these imaging methods do not yield much information about the time course of brain activity. One promising approach is to combine electromagnetic recordings and functional neuroimaging in order to gain knowledge about the spatiotemporal organization of human cognition. Here we review how electrophysiology and functional neuroimaging can be combined in the study of attention in normal humans.     

What can functional neuroimaging tell the experimental psychologist?

I argue here that functional neuroimaging data—which I restrict to the haemodynamic techniques of fMRI and PET—can inform psychological theorizing, provided one assumes a “systematic” function-structure mapping in the brain. In this case, imaging data simply comprise another dependent variable, along with behavioural data, that can be used to test competing theories. In particular, I distinguish two types of inference: function-to-structure deduction and structure-to-function induction. With the former inference, a qualitatively different pattern of activity over the brain under two experimental conditions implies at least one different function associated with changes in the independent variable. With the second type of inference, activity of the same brain region(s) under two conditions implies a common function, possibly not predicted a priori. I illustrate these inferences with imaging studies of recognition memory, short-term memory, and repetition priming. I then consider in greater detail what is meant by a “systematic” function-structure mapping and argue that, particularly for structure-to-function induction, this entails a one-to-one mapping between functional and structural units, although the structural unit may be a network of interacting regions and care must be taken over the appropriate level of functional/structural abstraction. Nonetheless, the assumption of a systematic function-structure mapping is a “working hypothesis” that, in common with other scientific fields, cannot be proved on independent grounds and is probably best evaluated by the success of the enterprise as a whole. I also consider statistical issues such as the definition of a qualitative difference and methodological issues such as the relationship between imaging and behavioural data. I finish by reviewing various objections to neuroimaging, including neophrenology, functionalism, and equipotentiality, and by observing some criticisms of current practice in the imaging literature.     

Functional MRI of Language in Aphasia: A Review of the Literature and the Methodological Challenges

Animal analogue studies show that damaged adult brains reorganize to accommodate compromised functions. In the human arena, functional magnetic resonance imaging (fMRI) and other functional neuroimaging techniques have been used to study reorganization of language substrates in aphasia. The resulting controversy regarding whether the right or the left hemisphere supports language recovery and treatment progress must be reframed. A more appropriate question is when left-hemisphere mechanisms and when right-hemisphere mechanisms support recovery of language functions. Small lesions generally lead to good recoveries supported by left-hemisphere mechanisms. However, when too much language eloquent cortex is damaged, right-hemisphere structures may provide the better substrate for recovery of language. Some studies suggest that recovery is particularly supported by homologues of damaged left-hemisphere structures. Evidence also suggests that under some circumstances, activity in both the left and right hemispheres can interfere with recovery of function. Further research will be needed to address these issues. However, daunting methodological problems must be managed to maximize the yield of future fMRI research in aphasia, especially in the area of language production. In this review, we cover six challenges for imaging language functions in aphasia with fMRI, with an emphasis on language production: (1) selection of a baseline task, (2) structure of language production trials, (3) mitigation of motion-related artifacts, (4) the use of stimulus onset versus response onset in fMRI analyses, (5) use of trials with correct responses and errors in analyses, and (6) reliability and stability of fMRI images across sessions. However, this list of methodological challenges is not exhaustive. Once methodology is advanced, knowledge from conceptually driven fMRI studies can be used to develop theoretically driven, mechanism-based treatments that will result in more effective therapy and to identify the best patient candidates for specific treatments. While the promise of fMRI in the study of aphasia is great, there is much work to be done before this technique will be a useful clinical tool.     

Probing emotion in the developing brain: functional neuroimaging in the assessment of the neural substrates of emotion in normal and disordered children and adolescents

Virtually all developmental neuropsychiatric disorders involve some dysfunction or dysregulation of emotion. Moreover, many psychiatric disorders with adult onset have early subclinical manifestations in children. This essay selectively reviews the literature on the neuroimaging of affect and disorders of affect in children. Some critical definitional and conceptual issues are first addressed, including the distinctions between the perception and production of emotion and between emotional states and traits. Developmental changes in morphometric measures of brain structure are then discussed and the implications of such findings for studies of functional brain activity are considered. Data on functional neuroimaging and childhood depression are then reviewed. While the extant data in this area are meager, they are consistent with studies in adults that have observed decreased left-sided anterolateral prefrontal cortex activation in depression. Studies in children on the recognition of emotion and affective intent in faces using functional magnetic resonance imaging are then reviewed. These findings indicate that the amygdala plays an important role in such affective face processing in children, similar to the patterns of activation observed in adults. Moreover, one study has reported abnormalities in amygdala activation during a task requiring the judgment of affective intent from the eye region of the face in subjects with autism. Some of the methodological complexities of developmental research in this area are discussed, and directions for future research are suggested.     

Magnetoencephalography and magnetic source imaging: technology overview and applications in psychiatric neuroimaging

Magnetoencephalography (MEG) is an electrophysiologic brain imaging technology that has been applied to the study of mental illness, particularly schizophrenia. Like electroencephalography, it provides excellent temporal resolution, and in combination with magnetic resonance imaging, can also provide good spatial resolution. Studies of the auditory system in schizophrenia using MEG have demonstrated an abnormality in functional cerebral asymmetry, in which persons with schizophrenia typically show reduced, or reversed, cerebral asymmetry compared with normal subjects. This abnormality is sex-specific; it is more pronounced in males with schizophrenia. These findings have not been demonstrated using other neuroimaging strategies. Thus, MEG appears to offer a unique and valuable contribution to psychiatric neuroimaging. Current research and clinical applications of MEG are limited, however, by the high cost of instrumentation. The cost of MEG systems should improve as more applications are developed, in schizophrenia as well as other neuropsychiatric conditions, and hospitals begin to invest in the technology.     

脑成像技术及其在决策研究中的应用

先进的无创神经影像技术(如EEG和fMRI)允许研究者直接观察被试在完成多种知觉、运动和认知任务时的大脑活动。将脑功能成像与严密的实验设计和数据分析方法结合起来, 我们可以考察大脑不同脑区的功能以及它们之间的交互作用。随着脑功能成像技术在研究人类决策行为中的日益成功运用, 一个被称为神经经济学的新兴领域正在逐渐形成和发展起来。本文中首先对脑成像技术进行一个总体介绍, 重点在于探讨近年来在多体素分析和多模态数据整合的最新进展。接下来, 我们以风险决策、跨时间选择以及社会决策领域的几个研究为例, 阐述神经影像技术如何能加深和拓展我们对人类决策的认识。最后, 我们讨论了神经经济学中研究中面临的一些挑战以及未来的研究方向。     

Imaging the medial temporal lobe: exploring new dimensions

Cognitive scientists have used developments in functional imaging to explore the role of the medial temporal lobe (MTL) in memory formation. Lesion studies have suggested that separate MTL subregions make distinct contributions to memory. Functional imaging of these distinct contributions, however, remains a challenge, because the proximity of the MTL substructures tests the spatial resolution limits of current techniques. Recent findings using electrophysiological measures of neural activity highlight the importance of using information from other imaging modalities. Integrating the different modalities of neuroimaging with lesion studies, and, further, combining modalities within experiments, will provide new insights into the function of MTL subregions.     

Ethical,and practical issues in applying functional imaging to the clinical management of Alzheimer's disease

This review outlines ethical, legal, and practical issues related to conducting functional imaging research with Alzheimer's disease (AD) patients. Imaging techniques, with an emphasis on functional MRI and positron emission tomography, are compared and contrasted with respect to the manner in which they can be applied to issues of clinical relevance to AD. Methodological difficulties are raised to assist with critical evaluation of current imaging results. Various potential clinical applications of functional imaging are briefly reviewed and discussed with respect to associated ethical conflicts.     

Single-trial EEG-fMRI reveals the dynamics of cognitive function

Two major non-invasive techniques in cognitive neuroscience, electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), have complementary advantages with regard to their spatial and temporal resolution. Recent hardware and software developments have made it feasible to acquire EEG and fMRI data simultaneously. We emphasize the potential of simultaneous EEG and fMRI recordings to pursue new strategies in cognitive neuroimaging. Specifically, we propose that, by exploiting the combined spatiotemporal resolution of the methods, the integration of EEG and fMRI recordings on a single-trial level enables the rich temporal dynamics of information processing to be characterized within spatially well-defined neural networks.     

脑功能成像的新方法——功能性近红外光谱技术（fNIRS）

功能性近红外光谱技术（functional near-infrared spectroscopy, fNIRS）利用血液的主要成分对600-900nm近红外光良好的散射性,从而获得大脑活动时氧合血红蛋白和脱氧血红蛋白的变化情况。目前该技术开始运用于自然情境下的高级认知、发展心理学、异常心理学等多个领域的研究。该技术具有造价较低、便携性好,无噪音、无创性和对实验过程中被试动作不会过份敏感等优点,但也存在空间分辨率不高和校正算法有待进一步完善等方面的不足。未来fNIRS的研究可以与fMRI等其他成像技术进行结合,开展婴幼儿和特殊人群的认知神经科学研究以及自然情境下大脑认知的神经机制研究。     

Neurobiology of Cocaine-Induced Organic Brain Impairment: Contributions from Functional Neuroimaging

The present review is directed at imparting the current knowledge regarding functional neuroimaging as a tool for enhancing the understanding of cerebrophysiologic and neurobehavioral consequences of stimulant abuse. Stimulants like cocaine are capable of inducing clinically significant neurocognitive impairment through direct action on the brain, and indirectly through other organs that influence cerebral physiology. Neurochemical dysregulation including profound effects on the serotonergic and dopaminergic systems have substantial physiological and neurobehavioral consequences. Brain hemorrhages, transient ischemic attacks, strokes, and seizures frequently follow cocaine use. The residual cerebropathologic consequences of cocaine are seen only in significant or pronounced brain events when structural neuroimaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) are employed. However, recent research with newer functional neuroimaging techniques such as single photon emission, positron emission tomography, and quantitative electroencephalography have revealed high rates of significant alteration in brain function among cocaine users, with negative structural imaging studies. These findings are often associated with impairment on neuropsychological evaluation, also in the absence of positive findings on CT and MRI. Both cerebral metabolic and hypoperfusion anomalies are seen, especially in anterior and temporal brain regions. Observed changes can persist for months, and for some patients, may represent a permanent change in brain functioning.     

Advances in magnetic resonance imaging methods for the evaluation of bipolar disorder

This article reviews the current state of magnetic resonance imaging techniques as applied to bipolar disorder. Addressed are conventional methods of structural neuroimaging and recently developed techniques. This latter group comprises volumetric analysis, voxel-based morphometry, the assessment of T2 white matter hyperintensities, shape analysis, cortical surface-based analysis, and diffusion tensor imaging. Structural analysis methods used in magnetic resonance imaging develop exponentially, and now present opportunities to identify disease-specific neuroanatomic alterations. Greater acuity and complementarity in measuring these alterations has led to the generation of further hypotheses regarding the pathophysiology of bipolar disorder. Included in the summary of findings is consideration of a resulting neuroanatomic model. Integrative issues and future directions in this relatively young field, including multi-modal approaches enabling us to produce more comprehensive results, are discussed.     

Imaging or imagining? A neuroethics challenge informed by genetics

From a twenty-first century partnership between bioethics and neuroscience, the modern field of neuroethics is emerging, and technologies enabling functional neuroimaging with unprecedented sensitivity have brought new ethical, social and legal issues to the forefront. Some issues, akin to those surrounding modern genetics, raise critical questions regarding prediction of disease, privacy and identity. However, with new and still-evolving insights into our neurobiology and previously unquantifiable features of profoundly personal behaviors such as social attitude, value and moral agency, the difficulty of carefully and properly interpreting the relationship between brain findings and our own self-concept is unprecedented. Therefore, while the ethics of genetics provides a legitimate starting point--even a backbone--for tackling ethical issues in neuroimaging, they do not suffice. Drawing on recent neuroimaging findings and their plausible real-world applications, we argue that interpretation of neuroimaging data is a key epistemological and ethical challenge. This challenge is two-fold. First, at the scientific level, the sheer complexity of neuroscience research poses challenges for integration of knowledge and meaningful interpretation of data. Second, at the social and cultural level, we find that interpretations of imaging studies are bound by cultural and anthropological frameworks. In particular, the introduction of concepts of self and personhood in neuroimaging illustrates the interaction of interpretation levels and is a major reason why ethical reflection on genetics will only partially help settle neuroethical issues. Indeed, ethical interpretation of such findings will necessitate not only traditional bioethical input but also a wider perspective on the construction of scientific knowledge.     

Fiber tracking using magnetic resonance diffusion tensor imaging and its applications to human brain development

Diffusion tensor imaging is unique in its ability to noninvasively visualize white matter fiber tracts in the human brain in vivo. Diffusion is the incoherent motion of water molecules on a microscopic scale. This motion is itself dependent on the micro-structural environment that restricts the movement of the water molecules. In white matter fibers there is a pronounced directional dependence on diffusion. With white matter fiber tracking or tractography, projections among brain regions can be detected in the three-dimensional diffusion tensor dataset according to the directionality of the fibers. Examples of developmental changes in diffusion, tracking of major fiber tracts, and examples of how diffusion tensor tractography and functional magnetic resonance imaging can be combined are provided. These techniques are complimentary and allow both the identification of the eloquent areas of the brain involved in specific functional tasks, and the connections between them. The noninvasive nature of magnetic resonance imaging will allow these techniques to be used in both longitudinal developmental and diagnostic studies. An overview of the technique and preliminary applications are presented, along with its current limitations.     

Imaging or Imagining? A Neuroethics Challenge Informed by Genetics

From a twenty-first century partnership between bioethics and neuroscience, the modern field of neuroethics is emerging, and technologies enabling functional neuroimaging with unprecedented sensitivity have brought new ethical, social and legal issues to the forefront. Some issues, akin to those surrounding modern genetics, raise critical questions regarding prediction of disease, privacy and identity. However, with new and still-evolving insights into our neurobiology and previously unquantifiable features of profoundly personal behaviors such as social attitude, value and moral agency, the difficulty of carefully and properly interpreting the relationship between brain findings and our own self-concept is unprecedented. Therefore, while the ethics of genetics provides a legitimate starting point—even a backbone—for tackling ethical issues in neuroimaging, they do not suffice. Drawing on recent neuroimaging findings and their plausible real-world applications, we argue that interpretation of neuroimaging data is a key epistemological and ethical challenge. This challenge is two-fold. First, at the scientific level, the sheer complexity of neuroscience research poses challenges for integration of knowledge and meaningful interpretation of data. Second, at the social and cultural level, we find that interpretations of imaging studies are bound by cultural and anthropological frameworks. In particular, the introduction of concepts of self and personhood in neuroimaging illustrates the interaction of interpretation levels and is a major reason why ethical reflection on genetics will only partially help settle neuroethical issues. Indeed, ethical interpretation of such findings will necessitate not only traditional bioethical input but also a wider perspective on the construction of scientific knowledge.     

The contribution of functional near-infrared spectroscopy (fNIRS) to the presurgical assessment of language function in children

Before performing neurosurgery, an exhaustive presurgical assessment is required, usually including an investigation of language cerebral lateralization. Among the available procedures, the intracarotid amobarbital test (IAT) was formerly the most widely used. However, this procedure has many limitations: it is invasive and potentially traumatic, especially for children. To overcome these limitations, neuroimaging techniques such as functional magnetic resonance imaging (fMRI) have been used. Again, these methods are difficult to use with children, who must remain motionless during data acquisition. Functional near-infrared spectroscopy (fNIRS) is a noninvasive functional imaging technique that is easily applied to pediatric and cognitively limited patients. It has been used recently in epileptic children for presurgical assessment of expressive and receptive language brain lateralization. The aim of this review is to present the contribution of fNIRS to the presurgical assessment of language function in children with neurological diseases.     

Magnetic stimulation studies of visual cognition

The panoply of non-invasive techniques for brain imaging is responsible for much of the current excitement in cognitive neuroscience; sensory, perceptual and cognitive behaviour can now be correlated with cerebral blood flow as assessed by functional imaging, the electrical fields generated by populations of neurons or changes in magnetic fields created by electrical activity. Correlations between localized brain activity and behaviour, however, do not of themselves establish that any brain area is necessary for a particular task; necessity is the domain of the lesion technique. Transcranial magnetic stimulation (TMS) is a technique that can be used non-invasively to produce reversible functional disruption and has already been used to investigate visual detection, discrimination, attention and plasticity. The power of TMS as a `lesion' technique lies in the opportunity to combine reversible disruption with high degrees of spatial and temporal resolution. In this review we trace some of the major developments in the use of TMS as a technique for the investigation of visual cognition.