Interhemispheric differences of spectral power in expressive language: a MEG study with clinical applications.

In the last decade we have seen an exponential growth of functional imaging studies investigating multiple aspects of language processing. These studies have sparked an interest in applying some of the paradigms to various clinically relevant questions, such as the identification of the cortical regions mediating language function in surgical candidates for refractory epilepsy. Here we present data from a group of adult control participants in order to investigate the potential of using frequency specific spectral power changes in MEG activation patterns to establish lateralisation of language function using expressive language tasks. In addition, we report on a paediatric patient whose language function was assessed before and after a left hemisphere amygdalo-hippocampectomy. Our verb generation task produced left hemisphere decreases in beta-band power accompanied by right hemisphere increases in low beta-band power in the majority of the control group, a previously unreported phenomenon. This pattern of spectral power was also found in the patient's post-surgery data, though not her pre-surgery data. Comparison of pre and post-operative results also provided some evidence of reorganisation in language related cortex both inter- and intra-hemispherically following surgery. The differences were not limited to changes in localisation of language specific cortex but also changes in the spectral and temporal profile of frontal brain regions during verb generation. While further investigation is required to establish concordance with invasive measures, our data suggest that the methods described may serve as a reliable lateralisation marker for clinical assessment. Furthermore, our findings highlight the potential utility of MEG for the investigation of cortical language functioning in both healthy development and pathology.     

Language fMRI abnormalities associated with FOXP2 gene mutation

Half the members of the KE family suffer from a speech and language disorder caused by a mutation in the FOXP2 gene. We examined functional brain abnormalities associated with this mutation using two fMRI language experiments, one involving covert (silent) verb generation and the other overt (spoken) verb generation and word repetition. The unaffected family members showed a typical left-dominant distribution of activation involving Broca's area in the generation tasks and a more bilateral distribution in the repetition task, whereas the affected members showed a more posterior and more extensively bilateral pattern of activation in all tasks. Consistent with previously reported bilateral morphological abnormalities, the affected members showed significant underactivation relative to the unaffected members in Broca's area and its right homolog, as well as in other cortical language-related regions and in the putamen. Our findings suggest that the FOXP2 gene is critically involved in the development of the neural systems that mediate speech and language.     

Near-infrared spectroscopic study and the Wada test for presurgical evaluation of expressive and receptive language functions in glioma patients: with a case report of dissociated language functions

Near-infrared spectroscopy (NIRS) has proven to be useful for the evaluation of language lateralization in healthy subjects, infants, and epileptic patients. This study for the first time investigated the expressive and receptive language functions separately, using NIRS in presurgical glioma patients. We also describe a special case with dissociated pattern of language functions. Ten glioma patients were examined. Using NIRS, the hemodynamic changes during a verb generation task or story listening task were measured in the cerebral hemisphere on either side covering the language areas. Following the NIRS study, the Wada test was performed in all the patients. The NIRS study revealed increases of oxyhemoglobin and decreases of deoxyhemoglobin in the language areas elicited by both tasks. In 9 patients, who were all right-handed, the expressive and receptive language functions were lateralized to the left hemisphere. The results of the NIRS study were completely consistent with those of the Wada test. In the remaining 1 patient with a right sided insular glioma, who was right-handed, the NIRS study revealed stronger activation of the right inferior frontal region during the verb generation task, and stronger activation of the left superior temporal region during the story listening task. This dissociated language function was validated by the Wada test and the postoperative neurological course. These results demonstrate that a NIRS study using our technique is extremely valuable for preoperative assessment of the language functions and exemplifies how a preoperative NIRS study can allow detection of unforeseen language lateralization.     

Integrated MEG and fMRI Model: Synthesis and Analysis

Summary: An integrated model for magnetoencephalography (MEG) and functional Magnetic Resonance Imaging (fMRI) is proposed. In the model, the neural activity is related to the Post Synaptic Potentials (PSPs) which is common link between MEG and fMRI. Each PSP is modeled by the direction and strength of its current flow which are treated as random variables. The overall neural activity in each voxel is used for equivalent current dipole in MEG and as input of extended Balloon model in fMRI. The proposed model shows the possibility of detecting activation by fMRI in a voxel while the voxel is silent for MEG and vice versa. Parameters of the model can illustrate situations like closed field due to non-pyramidal cells, canceling effect of inhibitory PSP on excitatory PSP, and effect of synchronicity. In addition, the model shows that the crosstalk from neural activities of the adjacent voxels in fMRI may result in the detection of activations in these voxels that contain no neural activities. The proposed model is instrumental in evaluating and comparing different analysis methods of MEG and fMRI. It is also useful in characterizing the upcoming combined methods for simultaneous analysis of MEG and fMRI. This work was supported in part by the Research Council of the University of Tehran, Tehran, Iran. The authors would like to thank Dr. John Moran from the Neurology Department, Henry Ford Health System, Detroit, Michigan, USA for his helpful discussions and kind assistance.     

Effects of single-trial averaging on spatial extent of brain activation detected by fMRI are subject and task dependent

Aim

The effects of single-trial averaging on the spatial extent of event-related fMRI activation may vary between subjects and tasks. The purpose of this study was to evaluate this variability using a visual task and a word generation task.

Patients, materials, and methods

Five Chinese right-handed male volunteers participated in the experiment. Experiments were conducted using a 1.5 T clinical MRI scanner with a T2*-weighted single-shot gradient-echo EPI sequence. Each task contained 150 trials that were separated into 5 runs. For each voxel, time courses averaged across different numbers of randomly selected trials, were obtained. They were applied for determining the voxels with significant activations, using a students’ t-test (p<0.001, uncorrected).

Results

Consistent with previous findings, the number of the activated voxels increased monotonically with the number of trials combined. The ascending rate and the maximum number of the activated voxels were different, however, between tasks and among subjects.

Conclusions

The effects of single-trial averaging were found to vary significantly between tasks and subjects. Therefore, we strongly advise to carefully consider such variability when using the spatial extent of activation as a measure in a group or a task comparison.     

人脑对握力刺激响应特征的数值计算分析方法

为研究人脑对握力刺激的响应特征,提出一种新的数值计算分析方法：结合独立成分分析和云模型,对握力刺激脑响应特征进行数值计算。采集10名健康受试者不同握力任务下的功能磁共振（fMRI）数据并进行预处理,应用独立成分分析获取不同握力刺激条件下的脑激活区域位置和大小,然后通过云模型计算脑激活区域内的数据分布特征。结果表明,握力刺激的脑激活区域主要分布在对侧大脑Brodmann 2、3、4、6区和同侧小脑,并且随着握力强度的增加,中央前回、中央后回等激活区域增大(激活簇体素个数分别为4 075、4 218、4 965);在不同握力刺激条件下,激活区域的任务态与非任务态间的期望、熵、超熵（Ex、En、He）均有明显的统计学差异,Ex（P<0001）和En(P<0.005)增大,He(P<0.005)减小;不同握力刺激间三个参数的差异不明显,并且非激活区域内任务状态与非任务状态间的期望、熵、超熵均无统计学差异。该方法可为不同任务下大脑激活区域的数据分布特征研究提供一种新的分析手段。     

空间ICA在fMRI数据上的应用与分析

独立成分分析(ICA)技术试图将多维数据分解成若干个相互统计独立的分量。时间ICA和空间ICA都可以用于分析功能核磁共振成像(fMRI)数据。但由于fMRI数据空间维数远远大于时间维数，为计算方便，在分析fMRI数据时。则更多的使用空间ICA方法。本文在单任务激励实验中，利用ICA方法从fMRI数据中分离出若干个与任务相关的独立分量，其中包括与任务相关的恒定分量(CTR)和与任务相关的暂态分量(TTR)；通过将这些独立分量进行空间映射，得到了与任务相关的脑部激活区域。将此结果与SPM的分析比较，得到了一致的结果。在对结果的分析中，我们进一步指出了ICA方法的特点和局限性。     

Nouns and verbs in the brain: Grammatical class and task specific effects as revealed by fMRI

The wide variety of techniques and tasks used to study the neural correlates of noun and verb processing has resulted in a body of inconsistent evidence. We performed a functional magnetic resonance imaging (fMRI) experiment to detect grammatical class effects that generalize across tasks. A total of 12 participants undertook a grammatical-class switching task (GCST), in which they were presented with a noun (or a verb) and were asked to retrieve the corresponding verb (or noun), and a classical picture naming task (PNT) widely used in the previous aphasiological and imaging literature. The GCST was explicitly designed to ensure control over confounding variables, such as stimulus complexity or imageability. Conjunction analyses of the haemodynamic responses measured in the two tasks indicated a shared verb-related activation of a dorsal premotor and posterior parietal network, pointing to a strong relationship between verb representation and action-oriented (visuo-)spatial knowledge. On the other hand, no brain area was consistently associated with nouns in both tasks. Moreover, there were task-dependent differences between noun and verb retrieval both at behavioural and at physiological level; the grammatical class that elicited the longest reaction times in both tasks (i.e., verbs in the PNT and nouns in the GCST) triggered a greater activation of the left inferior frontal gyrus. Therefore, we suggest that this area reflects a general increase in task demand rather than verb processing per se.     

Spatio-temporal Dynamics of Referential and Inferential Naming: Different Brain and Cognitive Operations to Lexical Selection

Picture naming tasks are largely used to elicit the production of specific words and sentences in psycholinguistic and neuroimaging research. However, the generation of lexical concepts from a visual input is clearly not the exclusive way speech production is triggered. In inferential speech encoding, the concept is not provided from a visual input, but is elaborated though semantic and/or episodic associations. It is therefore likely that the cognitive operations leading to lexical selection and word encoding are different in inferential and referential expressive language. In particular, in picture naming lexical selection might ensue from a simple association between a perceptual visual representation and a word with minimal semantic processes, whereas richer semantic associations are involved in lexical retrieval in inferential situations. Here we address this hypothesis by analyzing ERP correlates during word production in a referential and an inferential task. The participants produced the same words elicited from pictures or from short written definitions. The two tasks displayed similar electrophysiological patterns only in the time-period preceding the verbal response. In the stimulus-locked ERPs waveform amplitudes and periods of stable global electrophysiological patterns differed across tasks after the P100 component and until 400–500 ms, suggesting the involvement of different, task-specific neural networks. Based on the analysis of the time-windows affected by specific semantic and lexical variables in each task, we conclude that lexical selection is underpinned by a different set of conceptual and brain processes, with semantic processes clearly preceding word retrieval in naming from definition whereas the semantic information is enriched in parallel with word retrieval in picture naming.     

Exploring cerebral asymmetries for the verb generation task

This study investigated potential right hemisphere involvement in the verb generation task. Six divided visual field experiments explored cerebral asymmetries for word retrieval in the verb generation task as well as in rhyme generation and immediate and delayed word pronunciation. The typical right visual field/left hemisphere (RVF/LH) advantage was observed for pronunciation and rhyme generation. For verb generation, the RVF/LH advantage was obtained only when stimulus items had a single prepotent response and not when there were multiple response alternatives. A semantic priming experiment suggested that activation for less common, related verbs was maintained for a longer time course within the right than within the left hemisphere. The authors suggest that the right hemisphere may play a role in continued activation of semantically related response alternatives in word generation and discuss methodological implications of their findings.     

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.     

Spatial Correspondence Between Functional MRI (fMRI) Activations and Cortical Current Density Maps of Event-Related Potentials (ERP): A Study with Four Tasks

We investigated the spatial correspondence between functional MRI (fMRI) activations and cortical current density maps of event-related potentials (ERPs) reconstructed without fMRI priors. The presence of a significant spatial correspondence is a prerequisite for direct integration of the two modalities, enabling to combine the high spatial resolution of fMRI with the high temporal resolution of ERPs. Four separate tasks were employed: visual stimulation with a pattern-reversal chequerboard, recognition of images of nameable objects, recognition of written words, and auditory stimulation with a piano note. ERPs were acquired with 19 recording channels, and source localisation was performed using a realistic head model, a standard cortical mesh and the multiple sparse priors method. Spatial correspondence was evaluated at group level over 10 subjects, by means of a voxel-by-voxel test and a test on the distribution of local maxima. Although not complete, it was significant for the visual stimulation task, image and word recognition tasks (P < 0.001 for both types of test), but not for the auditory stimulation task. These findings indicate that partial but significant spatial correspondence between the two modalities can be found even with a small number of channels, for three of the four tasks employed. Absence of correspondence for the auditory stimulation task was caused by the unfavourable situation of the activated cortex being perpendicular to the overlying scalp, whose consequences were exacerbated by the small number of channels. The present study corroborates existing literature in this field, and may be of particular relevance to those interested in combining fMRI with ERPs acquired with the standard 10-20 system.     

fMRI responses in medial frontal cortex that depend on the temporal frequency of visual input

Functional networks in the human brain have been investigated using electrophysiological methods (EEG/MEG, LFP, and MUA) and steady-state paradigms that apply periodic luminance or contrast modulation to drive cortical networks. We have used this approach with fMRI to characterize a cortical network driven by a checkerboard reversing at a fixed frequency. We found that the fMRI signals in voxels located in occipital cortex were increased by checkerboard reversal at frequencies ranging from 3 to 14 Hz. In contrast, the response of a cluster of voxels centered on basal medial frontal cortex depended strongly on the reversal frequency, consistently exhibiting a peak in the response for specific reversal frequencies between 3 and 5 Hz in each subject. The fMRI signals at the frontal voxels were positively correlated indicating a homogeneous cluster. Some of the occipital voxels were positively correlated to the frontal voxels apparently forming a large-scale functional network. Other occipital voxels were negatively correlated to the frontal voxels, suggesting a functionally distinct network. The results provide preliminary fMRI evidence that during visual stimulation, input frequency can be varied to engage different functional networks.     

Neurophysiology of Hungarian subject–verb dependencies with varying intervening complexity

Non-adjacent dependencies are thought to be more costly to process than sentences wherein dependents immediately follow or precede what they depend on. In English locality effects have been revealed, while in languages with rich case marking (German and Hindi) sentence final structures show anti-locality-effects. The motivation of the current study is to test whether locality effects can be directly applied to a typologically different language than those investigated so far. Hungarian is a “topic prominent” language; it permits a variation of possible word sequencing for semantic reasons, including SVO word order. Hungarian also has a rich morphological system (e.g., rich case system) and postpositions to indicate grammatical functions. In the present ERP study, Hungarian subject–verb dependencies were compared by manipulating the mismatch of number agreement between the sentence's initial noun phrase and the sentence's final intransitive verb as well as the complexity of the intervening sentence material, interrupting the dependencies. Possible lexical class and frequency or cloze-probability effects for the first two words of the intervening sentence material were revealed when used separate baseline for each word, while at the third word of the intervening material as well as at the main verb ERPs were not modulated by complexity but at the verb ERPs were enhanced by grammaticality. Ungrammatical sentences enlarged the amplitude of both LAN and P600 components at the main verb. These results are in line with studies suggesting that the retrieval of the first element of a dependency is not influenced by distance from the second element, as the first element is directly accessible when needed for integration (e.g., McElree, 2000).     

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.     

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.     

A definition of drowsiness: One purpose for sleep?

While significant research has been done into the physiological mechanisms that underlie sleep and the sleep/wake cycle, the available data regarding the nature of drowsiness is far more limited. An objective measurement of drowsiness would have clinical utility, and a precise definition of the drowsy state could offer insights into the nature and purpose of sleep. Studies utilizing fMRI have demonstrated increased area of central nervous system involvement with tasks of increasing complexity. Preliminary data from studies of magnetoencephalography (MEG) with a receptive language task have demonstrated a progressive increase in global coherence of activity between MEG sensors with increasing drowsiness. The relationship between global coherence and the level of drowsiness suggests that the former may serve as an objective measurement of the latter. If true, the relationship suggests the hypothesis that drowsiness may be defined as a progressive loss of cortical network processing efficiency, requiring the recruitment of greater amounts of cortical tissue to perform the same task.     

Early 'visual' cortex activation correlates with superior verbal memory performance in the blind

The visual cortex may be more modifiable than previously considered. Using functional magnetic resonance imaging (fMRI) in ten congenitally blind human participants, we found robust occipital activation during a verbal-memory task (in the absence of any sensory input), as well as during verb generation and Braille reading. We also found evidence for reorganization and specialization of the occipital cortex, along the anterior-posterior axis. Whereas anterior regions showed preference for Braille, posterior regions (including V1) showed preference for verbal-memory and verb generation (which both require memory of verbal material). No such occipital activation was found in sighted subjects. This difference between the groups was mirrored by superior performance of the blind in various verbal-memory tasks. Moreover, the magnitude of V1 activation during the verbal-memory condition was highly correlated with the blind individual's abilities in a variety of verbal-memory tests, suggesting that the additional occipital activation may have a functional role.     

Differentiating cortical areas related to pain perception from stimulus identification: temporal analysis of fMRI activity.

In a recent functional magnetic resonance imaging study (fMRI), we reported the cortical areas activated in a thermal painful task and compared the extent of overlap between this cortical network and those activated during a vibrotactile task and a motor task. In the present study we examine the temporal properties of the cortical activations for all three tasks and use linear systems identification techniques to functionally differentiate the cortical regions identified in the painful thermal task. Cortical activity was examined in the contralateral middle third of the brain of 10 right-handed subjects, using echo-planar imaging and a surface coil. In another eight subjects the temporal properties of the thermal task were examined psychophysically. The fMRI impulse response function was estimated from the cortical activations in the vibrotactile and motor tasks and shown to correspond to earlier reports. Given the fMRI impulse response function and the time courses for the thermal stimulus and the associated pain ratings, predictor functions were generated. The correlation between these predictor functions and cortical activations in the painful thermal task indicated a gradual transition of information processing anteroposteriorly in the parietal cortex. Within this region, activity in the anterior areas more closely reflected thermal stimulus parameters, whereas activity more posteriorly was better related to the temporal properties of pain perception. Insular cortex at the level of the anterior commissure was the region best related to the thermal stimulus, and Brodmann's area 5/7 was the region best related to the pain perception. The functional implications of these observations are discussed.     

Implicit Memory Development in School-Aged Children With Attention Deficit Hyperactivity Disorder (ADHD): Conceptual Priming Deficit?

Previous research has shown that children with attention deficit hyperactivity disorder (ADHD) often demonstrate performance deficits on effortful, strategic memory tasks, whereas relatively rote tasks of memory reveal no such deficit. Thus far, research in this domain has focused primarily on explicit memory. This study examined performance on multiple measures of implicit and explicit memory in children aged 7 to 14 years with and without ADHD. Memory for words and pictures was assessed at 15-min and 24-hr intervals. ADHD and non-ADHD groups performed similarly on tests of explicit memory (category-cued recall and recognition) and on perceptual aspects of implicit memory (word stem completion and picture fragment identification) as a function of age, retention interval, and stimulus format (i.e., picture or word). However, there was no evidence of priming on a conceptual implicit memory test (category exemplar generation) for boys with ADHD. This type of conceptual task, which is likely mediated by frontal systems, may indicate a unique memory deficit associated with ADHD.