Reliability and Validity of Functional Neuroimaging Techniques for Identifying Language-Critical Areas in Children and Adults

Advances in neuroimaging technologies over the last 15 years have prompted their relatively widespread use in the study of brain mechanisms supporting language function in children and adults. We reviewed reliability and external validity studies of 3 of the most common functional imaging methods, functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and positron emission tomography (PET). Although reliability and validity reports for fMRI are generally quite favorable, significant variability was found across studies with respect to methodology, preventing in some cases either the assessment of the reliability of individual datasets, or cross-study comparisons. Reliability and validity reports of MEG are strong, yet methodological questions regarding optimal modeling techniques remain. PET investigators report good concordance of language maps with data from more invasive brain mapping techniques, but its use of radioactive tracers and poorer spatial and temporal resolution make it the least optimal of the 3 methods for language mapping. Investigations of the cortical networks supporting language function during development and into adulthood should be viewed in the context of the validity and reliability of the methods used, with careful attention to details regarding the methodologies employed in the acquisition and analysis of statistical maps.     

Transcranial magnetic stimulation--a new tool for functional imaging of the brain

Recent progress in the theory and technology of transcranial magnetic stimulation (TMS) is leading to novel approaches in brain mapping. TMS becomes a powerful functional brain mapping tool when other imaging methods are used to record TMS-evoked activity or when peripheral effects are observed as a function of stimulus location. TMS-evoked activity currently can be recorded by EEG, PET, and fMRI. In addition to providing indices of cortical excitability, these methods allow one to study brain connectivity directly, without the need for behavioral activations. When the coordinate systems in the different imaging modalities are combined, anatomical structures seen in MRI and activation sites determined by PET, fMRI, or MEG/EEG can be used for the selection of target areas in the brain. PET and fMRI can be used to map the spatial distribution of TMS-evoked activity. On the other hand, the combination of TMS and high-resolution EEG may often be the method of choice for basic neuroscience and for clinical diagnosis, for example, in the assessment of brain connectivity in patients suffering from neurodegenerative diseases or head injuries.     

Recent advances in investigations into brain function and its clinical application

Recent advances in investigations into brain function and its clinical application are described. The investigations were divided into three method groups consisting of the examinations of; 1) brain electric activity; 2) imaging techniques on activated brain tissue; and 3) collation of the metabolic information on the area of brain focused on. The first group included electroencephalogram(EEG), dipole tracing(DT) and magnetoencephalogram(MEG). The second one, single photon emission computed tomography(SPECT), positron emission tomography(PET) and functional magnetic resonance imaging(fMRI), and the third, magnetic resonance spectrometry(MRS). Here I overview these examinations and report some cases diagnosed with these technologies.     

Brain imaging studies of cocaine abuse: implications for medication development

Contemporary in vivo brain imaging techniques confer the ability to assess brain function and structure noninvasively, and thereby can yield information to help guide the development of new treatments for substance abuse. The advantages and limitations of the major imaging modalities (positron emission tomography [PET], single photon emission computed tomography [SPECT], structural and functional magnetic resonance imaging [MRI, fMRI, respectively]) are discussed with respect to their applicability to research on cocaine abuse. The effects of acute administration of cocaine have been studied using PET and fMRI, with PET manifesting decreases in cerebral glucose metabolism and blood flow, and fMRI revealing regional effects that are correlated temporally with subjective responses. In addition, studies of drug abusers, abstinent from cocaine for various lengths of time, have revealed persistent differences in brain function and structure, especially in the frontal cortex, when compared with parameters in the brains of subjects who do not use illicit drugs of abuse. PET studies also have revealed abnormalities in markers for dopaminergic and opioid systems during withdrawal from cocaine. Moreover, studies of cue-elicited craving for cocaine demonstrate a connection between the response to drug-related stimuli and neural elements of cognition and emotion. The future directions of in vivo brain imaging to identify functional and structural alterations in the brains of cocaine abusers are discussed in relation to the development of medications to treat cocaine dependence.     

Processing of Syntactic Information Monitored by Brain Surface Current Density Mapping Based on MEG

The cortical network subserving language processing is likely to exhibit a high spatial and temporal complexity. Studies using brain imaging methods, like fMRI or PET, succeeded in identifying a number of brain structures that seem to contribute to the processing of syntactic structures, while their dynamic interaction remains unclear due to the low temporal resolution of the methods. On the other hand, ERP studies have revealed a great deal of the temporal dimension of language processing without being able to provide more than very coarse information on the localisation of the underlying generators. MEG has a temporal resolution similar to EEG combined with a better spatial resolution. In this paper, Brain Surface Current Density (BSCD) mapping in a standard brain model was used to identify statistically significant differences between the activity of certain brain regions due to syntactically correct and incorrect auditory language input. The results show that the activity in the first 600 ms after violation onset is mainly concentrated in the temporal cortex and the adjacent frontal and parietal areas of both hemispheres. The statistical analysis reveals significantly different activity mainly in both frontal and temporal cortices. For longer latencies above 250 ms, the differential activity is more prominent in the right hemisphere. These findings confirm other recent results that suggest right hemisphere involvement in auditory language processing. One interpretation might be that right hemisphere regions play an important role in repair and re-analysis processes in order to free the specialised left hemisphere language areas for processing further input.     

痛觉的脑成像研究进展

痛觉是日常生活中最重要的感觉之一,痛觉的机理非常复杂.随着20世纪90年代各种脑成像技术的成熟,现在人们对于大脑的痛觉处理过程有了更好的理解.综述了痛觉脑成像的研究方法,包括电生理技术和脑功能成像技术,重点关注了这些技术在痛觉研究方面的相关成果.指出了解剖学上的痛觉处理机制.并分析了目前痛觉脑功能成像研究存在的缺陷和不足.     

Functional neuroimaging of the olfactory system in humans.

Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have begun to provide unique information regarding the neural underpinnings of olfactory functioning in humans. We review the relative strengths and weaknesses of PET and fMRI techniques for studying olfaction. We then review PET and fMRI studies relating to the olfactory functions of the pyriform cortex, orbitofrontal cortex, amygdala and the entorhinal/hippocampal region. A pixelwise correlational analysis of PET data is also presented in order to clarify the relationship between blood flow in the medial temporal lobes and psychoperceptual variables.     

Comprehensive Functional Mapping Scheme for Non-Invasive Primary Sensorimotor Cortex Mapping

We introduce a novel multimodal scheme for primary sensorimotor hand area (SM1ha) mapping integrating multiple functional indicators from functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). Ten right-handed healthy subjects (19–33 years; 5 females, 5 males) and four patients (24–64 years; 2 females, 2 males) suffering from space-occupying brain lesion close to the central sulcus were studied. Functional indicators of the SM1ha were obtained from block-design fMRI motor protocol, and six MEG protocols: somatosensory evoked fields to electrical median-nerve stimulation, mu-rhythm suppression (~10 and ~20 Hz), corticomuscular coherence, and corticokinematic coherence with and without finger contacts. To assess the spatial spread of the functional indicators, their coordinates were subjected to principal component analysis to produce a centered ellipsoid with axis along principal components. Five to seven functional indicators were obtained for each participant. In all participants, the ellipsoid co-localized with the anatomical SM1ha. In healthy subjects, 50–100 % of functional indicators were located within 10 mm from the center of the ellipsoid. In patients, 17–100 % of functional indicators were located within 10 mm from the center of the ellipsoid. In conclusion, the multimodal scheme proposed led to a functional mapping of SM1ha that co-localized with anatomical SM1ha in all participants. The spread of the SM1ha functional indicators in some patients with brain lesions highlights the potential benefit of the proposed multimodal approach to assess the reliability of the non-invasive SM1ha mapping.     

Oxidative metabolism and the detection of neuronal activation via imaging

Recent years have witnessed a great growth of interest in non-invasive imaging methods, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), permitting identification of brain structures that mediate specific cognitive and behavioural tasks in humans. Because these techniques use physiological responses such as increased perfusion or metabolism as surrogate indicators of evoked neuronal electrical activity, understanding the role of these processes in sustaining the information processing function of neurons is vital to the proper interpretation of functional neuroimaging data. An ultimate goal of these non-invasive techniques is to approach the sensitivity and spatial resolution of earlier autoradiographic methods, which have repeatedly demonstrated exquisitely detailed delineations of neuronal response patterns using metabolic glucose uptake as a physiological tag. Although glucose is generally metabolized in conjunction with oxygen, technical challenges in imaging tissue oxygen consumption in vivo have limited the use of this complementary process in the detection of neuronal activation. In this article we review concepts linking cerebral blood flow and metabolism to neuronal activation, and compare functional imaging techniques that exploit these relationships. We also describe recently introduced MRI based methods for measurement of oxygen consumption and assess the relative contributions of different metabolic pathways during neuronal activation. Our calculations suggest that the bulk of the energy demand evoked during stimulation of neurons in visual cortex is met through oxidative metabolism of glucose, supporting the use of oxygen uptake as a marker for increased neuronal electrical activity.     

Motor map reliability and aging: a TMS/fMRI study

This study compared the reliability of motor maps over 3 sessions from both neuronavigated transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) data between younger and older adults. Seven younger (ages 19–31) and seven older (ages 64–76) adults participated in three joint TMS/fMRI assessment sessions separated by 7 or 14 days. Sessions involved mapping of the right first dorsal interosseous muscle using single-pulse TMS immediately followed by block-design fMRI scanning involving volitional right-hand index finger to thumb oppositional squeeze. Intersession reliability of map volume, evaluated by intraclass correlation and Jaccard Coefficient between testing sessions, was more consistent for younger adults in both fMRI and TMS. A positive correlation was evidenced between fMRI and TMS map volumes and Jaccard Coefficients indicating spatial consistency across sessions between the two measures. Comparisons of map reliability between age groups showed that younger adults have more stable motor maps in both fMRI and TMS. fMRI and TMS maps show consistency across modalities. Future interpretation of motor maps should attempt to account for potential increased variability of such mapping in older age groups. Despite these age group differences in reliability, fMRI and TMS appear to offer consistent and complementary information about cortical representation of the first dorsal interosseous muscle.     

Integrated MEG/fMRI Model Validated Using Real Auditory Data

The main objective of this paper is to present methods and results for the estimation of parameters of our proposed integrated magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) model. We use real auditory MEG and fMRI datasets from 7 normal subjects to estimate the parameters of the model. The MEG and fMRI data were acquired at different times, but the stimulus profile was the same for both techniques. We use independent component analysis (ICA) to extract activation-related signal from the MEG data. The stimulus-correlated ICA component is used to estimate MEG parameters of the model. The temporal and spatial information of the fMRI datasets are used to estimate fMRI parameters of the model. The estimated parameters have reasonable means and standard deviations for all subjects. Goodness of fit of the real data to our model shows the possibility of using the proposed model to simulate realistic datasets for evaluation of integrated MEG/fMRI analysis methods.     

Questioning the questions that have been asked about the infant brain using near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) is a noninvasive diffuse optical-imaging technique that can measure local metabolic demand in the surface of the cortex due to differential absorption of light by oxygenated and deoxygenated blood. Over the past decade, NIRS has become increasingly used as a complement to other neuroimaging techniques, such as electroencephalography (EEG), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI), particularly in paediatric populations who cannot easily be tested using fMRI and MEG. In this review of empirical findings from human infants, ranging in age from birth to 12 months of age, a number of interpretive concerns are raised about what can be concluded from NIRS data. In addition, inconsistencies across studies are highlighted, and strategies are proposed for enhancing the reliability of NIRS data gathered from infants. Finally, a variety of new and promising advances in NIRS techniques are highlighted.     

Rodent functional and anatomical imaging of pain

Human brain imaging has provided much information about pain processing and pain modulation, but brain imaging in rodents can provide information not attainable in human studies. First, the short lifespan of rats and mice, as well as the ability to have homogenous genetics and environments, allows for longitudinal studies of the effects of chronic pain on the brain. Second, brain imaging in animals allows for the testing of central actions of novel pharmacological and nonpharmacological analgesics before they can be tested in humans. The two most commonly used brain imaging methods in rodents are magnetic resonance imaging (MRI) and positron emission tomography (PET). MRI provides better spatial and temporal resolution than PET, but PET allows for the imaging of neurotransmitters and non-neuronal cells, such as astrocytes, in addition to functional imaging. One problem with rodent brain imaging involves methods for keeping the subject still in the scanner. Both anesthetic agents and restraint techniques have potential confounds. Some PET methods allow for tracer uptake before the animal is anesthetized, but imaging a moving animal also has potential confounds. Despite the challenges associated with the various techniques, the 31 studies using either functional MRI or PET to image pain processing in rodents have yielded surprisingly consistent results, with brain regions commonly activated in human pain imaging studies (somatosensory cortex, cingulate cortex, thalamus) also being activated in the majority of these studies. Pharmacological imaging in rodents shows overlapping activation patterns with pain and opiate analgesics, similar to what is found in humans. Despite the many structural imaging studies in human chronic pain patients, only one study has been performed in rodents, but that study confirmed human findings of decreased cortical thickness associated with chronic pain. Future directions in rodent pain imaging include miniaturized PET for the freely moving animal, as well as new MRI techniques that enable ongoing chronic pain imaging.     

Methods on Skull Stripping of MRI Head Scan Images—a Review

The high resolution magnetic resonance (MR) brain images contain some non-brain tissues such as skin, fat, muscle, neck, and eye balls compared to the functional images namely positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI) which usually contain relatively less non-brain tissues. The presence of these non-brain tissues is considered as a major obstacle for automatic brain image segmentation and analysis techniques. Therefore, quantitative morphometric studies of MR brain images often require a preliminary processing to isolate the brain from extra-cranial or non-brain tissues, commonly referred to as skull stripping. This paper describes the available methods on skull stripping and an exploratory review of recent literature on the existing skull stripping methods.     

A technique to consider mismatches between fMRI and EEG/MEG sources for fMRI-constrained EEG/MEG source imaging: a preliminary simulation study

fMRI-constrained EEG/MEG source imaging can be a powerful tool in studying human brain functions with enhanced spatial and temporal resolutions. Recent studies on the combination of fMRI and EEG/MEG have suggested that fMRI prior information could be readily implemented by simply imposing different weighting factors to cortical sources overlapping with the fMRI activations. It has been also reported, however, that such a hard constraint may cause severe distortions or elimination of meaningful EEG/MEG sources when there are distinct mismatches between the fMRI activations and the EEG/MEG sources. If one wants to obtain the actual EEG/MEG source locations and uses the fMRI prior information as just an auxiliary tool to enhance focality of the distributed EEG/MEG sources, it is reasonable to weaken the strength of fMRI constraint when severe mismatches between fMRI and EEG/MEG sources are observed. The present study suggests an efficient technique to automatically adjust the strength of fMRI constraint according to the mismatch level. The use of the proposed technique rarely affects the results of conventional fMRI-constrained EEG/MEG source imaging if no major mismatch between the two modalities is detected; while the new results become similar to those of typical EEG/MEG source imaging without fMRI constraint if the mismatch level is significant. A preliminary simulation study using realistic EEG signals demonstrated that the proposed technique can be a promising tool to selectively apply fMRI prior information to EEG/MEG source imaging.     

Localization of Broca's area using verb generation tasks in the MEG: Validation against fMRI

Functional MRI (fMRI) is routinely used to non-invasively localize language areas. Magnetoencephalography (MEG) is being explored as an alternative technique. MEG tasks to localize receptive language are well established although there are no standardized tasks to localize expressive language areas. We developed two expressive language tasks for MEG and validated their localizations against fMRI data. Ten right-handed adolescents (μ = 17.5 years) were tested with fMRI and MEG on two tasks: verb generation to pictures and verb generation to words. MEG and fMRI data were normalized and overlaid. The number of overlapping voxels activated in fMRI and MEG were counted for each subject, for each task, at different thresholding levels. For picture verb generation, there was 100% concordance between MEG and fMRI lateralization, and for word verb generation, there was 75% concordance. A count showed 79.6% overlap of voxels activated by both MEG and fMRI for picture verb generation and 50.2% overlap for word verb generation. The percentage overlap decreased with increasingly stringent activation thresholds. Our novel MEG expressive language tasks successfully identified neural regions involved in language production and showed high concordance with fMRI laterality. Percentage overlap of activated voxels was also high when validated against fMRI, but showed task-specific and threshold-related effects. The high concordance and high percentage overlap between fMRI and MEG activations confirm the validity of our new MEG task. Furthermore, the higher concordance from the picture verb generation task suggests that this is a promising task for use in the young clinical population.     

Magnetoencephalography: in search of neural processes for visual motion information

Magnetoencephalography (MEG) has become a standard approach to the investigation of human brain functions. This review starts with a brief review of the human visual system and studies on visual motion detection mechanisms is followed by the presentation of MEG studies that have contributed to the field. Emphasis is placed on the fact that because the neural activities measured in functional magnetic resonance imaging (fMRI) differ substantially from those measured in MEG--fMRI data cannot be used directly to estimate MEG signal sources. The basic ideas behind the methods of signal processing and analyses generally used in MEG studies are described and theoretical considerations of the neural mechanisms determining MEG response latency and amplitude changes are discussed. Here, scalar fields theory is proposed to explain MEG responses to incoherent motions, and the ways in which detection of complex motions such as transparency, rotation and expansion can be explained by this theory are also presented. Relationships between human behavioral reaction time and MEG response latency suggest a new concept underlying the reasons why humans are late in detecting slow motion.     

Evaluation of a pre-surgical functional MRI workflow: From data acquisition to reporting

PurposePresent and assess clinical protocols and associated automated workflow for pre-surgical functional magnetic resonance imaging in brain tumor patients.MethodsProtocols were validated using a single-subject reliability approach based on 10 healthy control subjects. Results from the automated workflow were evaluated in 9 patients with brain tumors, comparing fMRI results to direct electrical stimulation (DES) of the cortex.ResultsUsing a new approach to compute single-subject fMRI reliability in controls, we show that not all tasks are suitable in the clinical context, even if they show meaningful results at the group level. Comparison of the fMRI results from patients to DES showed good correspondence between techniques (odds ratio 36).ConclusionProviding that validated and reliable fMRI protocols are used, fMRI can accurately delineate eloquent areas, thus providing an aid to medical decision regarding brain tumor surgery.     

Recovery of motor and language abilities after stroke: the contribution of functional imaging

In recent years, functional imaging techniques, like functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and transcranial magnetic stimulation (TMS), have shown that the improvement of motor and language function after ischemic stroke is accompanied by extensive reorganizational changes in the human cortex. To better understand these changes and to judge to what extent they could be responsible for clinical improvement, some basic principles of the organization of the motor and language system are discussed.Non-invasive functional imaging can have only a limited contribution in determining which of the possible underlying neural mechanisms, as they are known from animal experiments, play a role in functional recovery. However, they make it possible to define the functional consequences of anatomical lesions in individual patients and to correlate these functional consequences in the motor and language system with the clinical deficit. They can be used to assess the influence on the cortical reorganization of established and newer physiotherapies, logopedics and medical intervention, and they could be a useful tool in determining prognosis.     

Combined DTI–fMRI Analysis for a Quantitative Assessment of Connections Between WM Bundles and Their Peripheral Cortical Fields in Verbal Fluency

Diffusion tensor imaging (DTI) tractography and functional magnetic resonance imaging (fMRI) are powerful techniques to elucidate the anatomical and functional aspects of brain connectivity. However, integrating these approaches to describe the precise link between structure and function within specific brain circuits remains challenging. In this study, a novel DTI–fMRI integration method is proposed, to provide the topographical characterization and the volumetric assessment of the functional and anatomical connections within the language circuit. In a group of 21 healthy elderly subjects (mean age 68.5 ± 5.8 years), the volume of connection between the cortical activity elicited by a verbal fluency task and the cortico-cortical fiber tracts associated with this function are mapped and quantified. An application of the method to a case study in neuro-rehabilitation context is also presented. Integrating structural and functional data within the same framework, this approach provides an overall view of white and gray matter when studying specific brain circuits.