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.     

MEG study on neural activities associated with syntactic and semantic violations in spoken Korean sentences

We carried out an magnetoencephalography (MEG) study to record cortical responses elicited in the left hemisphere by ending verb phrases, which had syntactic or semantic anomalies, in Korean sentences of subject-object-verb order. Using the high temporal and spatial resolution of MEG, the study was aimed at identifying neural activities that occur during a latency course associated with the syntactic or semantic process in the spoken sentence. Major responses, distinct from the responses to normal sentences, were observed in two latency periods of about 400 and 600 ms following the onset of the verb phrase. Source localization of the grand average fields indicated separate activities in the inferior frontal region and the vicinity of the auditory cortex for the first 400-ms response to the syntactic anomaly. The region around the auditory cortex was indicated for the response to the semantic anomaly in a similar latency. The second 600-ms response indicated activity around the middle temporal gyrus inferior to the auditory cortex for both syntactic and semantic anomalies. The results are discussed with reference to the ERP components established for Indo-European languages, and the possibility of concurrent processing of syntactic and semantic aspects is suggested.     

Context modulates processing of speech sounds in the right auditory cortex of human subjects

Functionally, the cerebellum is not only involved in motor control but is also thought to influence higher cognitive function including language. Anatomical data would suggest crossed reciprocal connections between the cerebellum and higher order cortical association areas. In the following study, one left- and one right-handed female volunteer underwent functional magnetic resonance imaging in a conventional block design. Regions of activation were detected after performance of a silent verbal fluency task inside the scanner. In the right-handed volunteer we found an activation of the left fronto-parietal cortex and the right cerebellar hemisphere, while in the left-handed volunteer the activation was seen in the right fronto-parieto-temporal cortex and the left cerebellar hemisphere. These initial results demonstrate that cerebellar activation is contralateral to the activation of the frontal cortex even under conditions of different language dominance. They provide evidence for the hypothesis of a lateralized organization of the cerebellum crossed to the cerebral hemispheres in supporting higher cognitive function.     

Laterality of interhemispheric inhibition depends on handedness

There is some evidence that handedness is related to lateralisation of excitability in the motor system. We investigated lateralisation of interhemispheric inhibition (IHI), motor thresholds and short interval intracortical inhibition (SICI) and facilitation (SICF) in relation to handedness in 12 right (RH) and 13 left handed (LH) subjects. Because there is some controversy as to the optimal localisation to produce IHI we also compared IHI induced by conditioning the dorsal premotor cortex (dPM) versus primary motor cortex (M1) in ten RH. IHI was stronger following conditioning the motor dominant as compared to the motor non-dominant hemisphere in RH and LH. Motor thresholds were higher when elicited over the right hemisphere than over the left in both RH and LH, while SICI and SICF showed no differences between hemispheres or dependency from handedness. We hypothesize that IHI is a function of handedness perhaps reflecting predominant usage of the dominant hand, while lateralisation of thresholds and intracortical excitability are determined by other factors.     

Covert word reading induces a late response in the hand motor system of the language dominant hemisphere

Recent work has demonstrated that overt reading influences the excitability of the language-dominant hand motor cortex. However, this effect was related to speech output, whereas results on silent reading have been inconsistent, and have not allowed for systematic investigation of the different stages of word recognition. To investigate a possible modulation of the cortical excitability mediating hand movements through different stages of covert reading, motor evoked potentials (MEP) from hand muscles in right-handed subjects were recorded. We showed a significant increase of the excitability of the hand motor cortex of the dominant hemisphere during late stages of covert word reading, whereas processing of abstract shapes had no effect and covert articulation induced a decrease in hand motor cortex excitability. There was no significant change of MEP amplitudes during earlier stages of covert reading in the dominant hemisphere or in the non-dominant hemisphere. Our results demonstrate a functional connection between cortical networks mediating linguistic processing and hand movements without concurrent activation of the motor cortex through overt articulation at late stages of word reading, which have been shown to involve converging activation of classic left frontal language regions. We speculate that the effect reported here is related to a cortical network mediating gestures which are a part of verbal communication. This supports recent theories on language evolution which postulate that language emerged through manual gestures.     

By our bootstraps: Comparing methods for measuring auditory 40 Hz steady‐state neural activity

Although the 40 Hz auditory steady‐state response (ASSR) is of clinical interest, the construct validity of EEG and MEG measures of 40 Hz ASSR cortical microcircuits is unclear. This study evaluated several MEG and EEG metrics by leveraging findings of (a) an association between the 40 Hz ASSR and age in the left but not right hemisphere, and (b) right‐ > left‐hemisphere differences in the strength of the 40 Hz ASSR. The contention is that, if an analysis method does not demonstrate a left 40 Hz ASSR and age relationship or hemisphere differences, then the obtained measures likely have low validity. Fifty‐three adults were presented 500 Hz stimuli modulated at 40 Hz while MEG and EEG were collected. ASSR activity was examined as a function of phase similarity (intertrial coherence) and percent change from baseline (total power). A variety of head models (spherical and realistic) and a variety of dipole source modeling strategies (dipole source localization and dipoles fixed to Heschl's gyri) were compared. Several sensor analysis strategies were also tested. EEG sensor measures failed to detect left 40 Hz ASSR and age associations or hemisphere differences. A comparison of MEG and EEG head‐source models showed similarity in the 40 Hz ASSR measures and in estimating age and left 40 Hz ASSR associations, indicating good construct validity across models. Given a goal of measuring the 40 Hz ASSR cortical microcircuits, a source‐modeling approach was shown to be superior in measuring this construct versus methods that rely on EEG sensor measures.     

Focal stroke in the barrel cortex of rats enhances ipsilateral response to vibrissal input

Brain injury triggers spontaneous plasticity, often resulting in considerable restoration of function. To investigate mechanisms of this compensatory plasticity we followed changes in the brain's pattern of activation evoked by stimulation of vibrissae, after a focal cortical stroke which destroyed the cortical representation of vibrissae, the barrel cortex. The pattern of brain activation was visualized with [14C]-2-doexyglucose (2DG) autoradiography in rats 7 days after photothrombotic stroke. During isotope incorporation, vibrissae contralateral to stroke were stimulated. In control rats this stimulation activates the barrel cortex and the second somatosensory cortex in the contralateral hemisphere. Seven days after stroke in the barrel cortex, significant increases in activation were found in ipsilateral, uninjured hemisphere in the barrel cortex and anterior vibrissae representation, and also in regions not specifically connected to vibrissae stimulation, such as motor and auditory cortex. Shortly after cortical stroke, the intact hemisphere shows higher metabolic activation in several cortical regions, possibly due to abnormal interactions with the injured hemisphere.     

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.     

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.     

Neuropathologic basis of in vivo cortical atrophy in the aphasic variant of Alzheimer's disease

The neuropathologic basis of in vivo cortical atrophy in clinical dementia syndromes remains poorly understood. This includes primary progressive aphasia (PPA), a language‐based dementia syndrome characterized by asymmetric cortical atrophy. The neurofibrillary tangles (NFTs) and amyloid‐ß plaques (APs) of Alzheimer's disease (AD) can cause PPA, but a quantitative investigation of the relationships between NFTs, APs and in vivo cortical atrophy in PPA‐AD is lacking. The present study measured cortical atrophy from corresponding bilateral regions in five PPA‐AD participants with in vivo magnetic resonance imaging scans 7–30 months before death and acquired stereologic estimates of NFTs and dense‐core APs visualized with the Thioflavin‐S stain. Linear mixed models accounting for repeated measures and stratified by hemisphere and region (language vs. non‐language) were used to determine the relationships between cortical atrophy and AD neuropathology and their regional selectivity. Consistent with the aphasic profile of PPA, left language regions displayed more cortical atrophy (P = 0.01) and NFT densities (P = 0.02) compared to right language homologues. Left language regions also showed more cortical atrophy (P < 0.01) and NFT densities (P = 0.02) than left non‐language regions. A subset of data was analyzed to determine the predilection of AD neuropathology for neocortical regions compared to entorhinal cortex in the left hemisphere, which showed that the three most atrophied language regions had greater NFT (P = 0.04) and AP densities (P < 0.01) than the entorhinal cortex. These results provide quantitative evidence that NFT accumulation in PPA selectively targets the language network and may not follow the Braak staging of neurofibrillary degeneration characteristic of amnestic AD. Only NFT densities, not AP densities, were positively associated with cortical atrophy within left language regions (P < 0.01) and right language homologues (P < 0.01). Given previous findings from amnestic AD, the current study of PPA‐AD provides converging evidence that NFTs are the principal determinants of atrophy and clinical phenotypes associated with AD.     

Sex-specific gray matter volume differences in females with developmental dyslexia

Developmental dyslexia, characterized by unexpected reading difficulty, is associated with anomalous brain anatomy and function. Previous structural neuroimaging studies have converged in reports of less gray matter volume (GMV) in dyslexics within left hemisphere regions known to subserve language. Due to the higher prevalence of dyslexia in males, these studies are heavily weighted towards males, raising the question whether studies of dyslexia in females only and using the same techniques, would generate the same findings. In a replication study of men, we obtained the same findings of less GMV in dyslexics in left middle/inferior temporal gyri and right postcentral/supramarginal gyri as reported in the literature. However, comparisons in women with and without dyslexia did not yield left hemisphere differences, and instead, we found less GMV in right precuneus and paracentral lobule/medial frontal gyrus. In boys, we found less GMV in left inferior parietal cortex (supramarginal/angular gyri), again consistent with previous work, while in girls differences were within right central sulcus, spanning adjacent gyri, and left primary visual cortex. Our investigation into anatomical variants in dyslexia replicates existing studies in males, but at the same time shows that dyslexia in females is not characterized by involvement of left hemisphere language regions but rather early sensory and motor cortices (i.e., motor and premotor cortex, primary visual cortex). Our findings suggest that models on the brain basis of dyslexia, primarily developed through the study of males, may not be appropriate for females and suggest a need for more sex-specific investigations into dyslexia.     

Lateralization in motor facilitation during action observation: a TMS study

Action observation facilitates corticospinal excitability. This is presumably due to a premotor neural system that is active when we perform actions and when we observe actions performed by others. It has been speculated that this neural system is a precursor of neural systems subserving language. If this theory is true, we may expect hemispheric differences in the motor facilitation produced by action observation, with the language-dominant left hemisphere showing stronger facilitation than the right hemisphere. Furthermore, it has been suggested that body parts are recognized via cortical regions controlling sensory and motor processing associated with that body part. If this is true, then corticospinal facilitation during action observation should be modulated by the laterality of the observed body part. The present study addressed these two issues using TMS for each motor cortex separately as participants observed actions being performed by a left hand, a right hand, or a control stimulus on the computer screen. We found no overall difference between the right and left hemisphere for motor-evoked potential (MEP) size during action observation. However, when TMS was applied to the left motor cortex, MEPs were larger while observing right hand actions. Likewise, when TMS was applied to the right motor cortex, MEPs were larger while observing left hand actions. Our data do not suggest left hemisphere superiority in the facilitating effects of action observation on the motor system. However, they do support the notion of a sensory-motor loop according to which sensory stimulus properties (for example, the image of a left hand or a right hand) directly affect motor cortex activity, even when no motor output is required. The pattern of this effect is congruent with the pattern of motor representation in each hemisphere.     

Evidence for interhemispheric processing of inputs from the hands in human S2 and PV

In the present investigation, we identified cortical areas involved in the integration of bimanual inputs in human somatosensory cortex. Using functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG), we compared the responses to unilateral versus bilateral stimulation in anterior parietal cortex and areas in the Sylvian fissure of the contralateral hemisphere. The extent of fMRI activation on the upper bank of the Sylvian fissure, in the second somatosensory (S2) and the parietal ventral (PV) areas, was significantly larger for bilateral stimulation than for unilateral stimulation. Using MEG, we were able to describe the latency of response in S1 and S2/PV to unilateral and bilateral stimulation. The MEG response had three components under both stimulus conditions. An early peak in S1 at 40 ms, a middle peak in S2/PV at 80-160 ms, and three late peaks in S2/PV at 250-420 ms. There was an increase in magnetic field strength in S2/PV to bilateral stimulation at 300-400 ms post stimulus. The fMRI results indicate that, as in monkeys, S2/PV receives inputs from both the contralateral and ipsilateral hand. The MEG data suggest that information is processed serially from S1 to S2. The very late response in S2/PV indicates that extensive intrahemispheric processing occurs before information is transferred to the opposite hemisphere. The neural substrate for the increased activation and field strength at long latencies during bilateral stimulation can be accounted for in three ways. Under bilateral stimulus conditions, more neurons may be active, neuronal firing rate may increase, and/or neural activity may be more synchronous.     

Methohexital-Induced Changes in Spectral Power of Neuromagnetic Signals: Beta Augmentation is Smaller Over the Hemisphere Containing the Epileptogenic Focus

Previous research has suggested that methohexital, a short-term barbiturate, alters activity in the primary epileptogenic area. It can be assumed that drug-induced activation of the epileptogenic focus provides a rapid and safe method to obtain a sufficient amount of information relevant for the lateralization and localisation of the primary epileptogenic area. This study shows that methohexital changes spectral power in the beta band derived from magnetoencephalographic (MEG) signals over the hemisphere ipsilateral to the primary epileptogenic area. This effect was demonstrated for 10/13 of the investigated patients suffering from unilateral temporal lobe epilepsy (TLE). The side and location of the primary epileptogenic area of these patients (5 left TLE, 8 right TLE) was determined invasively during presurgical evaluation. During a 1-2 minute interval after intravenous bolus injection of 100 mg methohexital a clear lateralization effect in the beta band was observed, which differed marginally between fronto-central, fronto-temporal and temporo-parietal brain regions. In addition, bilateral spectral power changes were obtained in the theta, alpha and gamma bands that differed between brain regions. Analyses of simultaneously recorded scalp electroencephalographic (EEG) data revealed effects consistent with those of the MEG analysis. The reduced enhancement of beta band spectral power of MEG recordings provides a potential application for the non-invasive lateralization of the primary epileptogenic area.     

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.     

Disruption of structural covariance networks for language in autism is modulated by verbal ability

The presence of widespread speech and language deficits is a core feature of autism spectrum disorders (ASD). These impairments have often been attributed to altered connections between brain regions. Recent developments in anatomical correlation-based approaches to map structural covariance offer an effective way of studying such connections in vivo. In this study, we employed such a structural covariance network (SCN)-based approach to investigate the integrity of anatomical networks in fronto-temporal brain regions of twenty children with ASD compared to an age and gender-matched control group of twenty-two children. Our findings reflected large-scale disruption of inter and intrahemispheric covariance in left frontal SCNs in the ASD group compared to controls, but no differences in right fronto-temporal SCNs. Interhemispheric covariance in left-seeded networks was further found to be modulated by verbal ability of the participants irrespective of autism diagnosis, suggesting that language function might be related to the strength of interhemispheric structural covariance between frontal regions. Additionally, regional cortical thickening was observed in right frontal and left posterior regions, which was predicted by decreasing symptom severity and increasing verbal ability in ASD. These findings unify reports of regional differences in cortical morphology in ASD. They also suggest that reduced left hemisphere asymmetry and increased frontal growth may not only reflect neurodevelopmental aberrations but also compensatory mechanisms.     

Integration of cortical areas during performance of a catching ball task

The study aimed to elucidate electrophysiological and cortical mechanisms involved in anticipatory actions when healthy subjects had to catch balls in free drop; specifically through quantitative electroencephalography (qEEG) alpha absolute power changes. Our hypothesis is that during the preparation of motor action (i.e., 2 s before ball’s drop) occurred integration among left medial frontal, left primary somatomotor and left posterior parietal cortices, showing a differentiated activity involving expectation, planning and preparedness. This hypothesis supports a lateralization of motor function. Although we contend that in right-handers the left hemisphere takes on a dominant role for the regulation of motor behavior. The sample was composed of 23 healthy subjects (13 male and 10 female), right handed, with ages varying between 25 and 40 years old (32.5 ± 7.5), absence of mental and physical illness, right handed, and do not make use of any psychoactive or psychotropic substance at the time of the study. The experiment consisted of a task of catching balls in free drop. The three-way ANOVA analysis demonstrated an interaction between moment and position in left medial frontal cortex (F3 electrode), somatomotor cortex (C3 electrode) and posterior parietal cortex (P3 electrode; p < 0.001). Summarizing, through experimental task employed, it was possible to observe integration among frontal, central and parietal regions. This integration appears to be more predominant in expectation, planning and motor preparation. In this way, it established an absolute predominance of this mechanism under the left hemisphere.     

Blood oxygenation level dependent contrast resting state networks are relevant to functional activity in the neocortical sensorimotor system

The relevance of correlations between blood oxygenation level dependent (BOLD) signal changes across the brain acquired at rest (resting state networks, or RSN) to functional networks was tested using two quantitative criteria: (1) the localisation of major RSN correlation clusters and the task-related maxima defined in BOLD fMRI signal changes from the same subjects; and (2) the relative hemispheric lateralisation (LI) of BOLD fMRI signal changes in sensorimotor cortex. RSN were defined on the basis of signal changes correlated with that of a “seed” voxel in the primary sensorimotor cortex. We found a generally close spatial correspondence between clusters of correlated BOLD signal change in RSN and activation maxima associated with hand movement. Conventional BOLD fMRI during active hand movement showed the expected wide variation in relative hemispheric lateralisation of LI for sensorimotor cortex across the subjects. There was a good correlation between LIs for the active hand movement task and the RSN (r=0.74, p<0.001). The RSN thus define anatomically relevant regions of motor cortex and change with functionally relevant variations in hemispheric lateralisation of sensorimotor cortical interactions with hand movement.     

Magnetic Field Tomography Analysis of Continuous Speech

In this article we investigate MEG correlates of syntactic violations in continuous speech. An early left anterior negativity (ELAN) has been reported in previous EEG studies and has been related to syntactic processing. We used Magnetic Field Tomography (MFT) to extract a 3D estimate of the current density distribution J, from MEG data recorded while subjects listened to continuous speech. Separate estimates were obtained from the activity associated with the first word of the sentence, and the last words of the sentence which signified syntactic violation, semantic violation or correct sentences. In each case independent 3D MFT estimates of activity were obtained 2 ms apart. After converting the solutions into a PET-like format we perform a statistical analysis on a voxel-by-voxel basis. Visual inspection of the power of J at the time of the ELAN component and the statistical maps overlaid on the individual anatomical MRI suggests generators in the vicinity of the auditory cortex and in left frontal regions. Directional activation curves are computed to show the variation of activity as a function of time, from well circumscribed areas. The activation curve for the auditory cortex has a characteristic pattern consisting of three peaks, seen in the average time-locked to the onset of the first word, and the critical word of the syntactic violation. The left auditory cortex shows a delay of about 30 ms in the syntactic violation condition compared to the first word condition. No such delay is seen in the right auditory cortex.     

Functional Hemispheric Asymmetry Assessment in a Visual Language Task Using MEG

We used magnetoencephalography (MEG) to assess the degree of hemispheric activation in eleven normal, right-handed subjects with no history of neurological disorder or learning disability during performance of a word- and a face-recognition tasks. Neuromagnetic activity was recorded using a whole-head system, and the sources of the recorded magnetic fields were modeled as single equivalent current dipoles. Early (<200 msec) cerebral activation, defined by the number of dipoles identified by the data-fitting algorithm, was localized in the occipital cortex during both tasks, as expected. During the language task, the extent of the later (>200 msec) cerebral activation was approximately double in the left hemisphere in almost all subjects, involving temporal and temporoparietal areas. In contrast, during the face-recognition task, the corresponding activation was mostly symmetrical across the two occipital lobes, also involving the posterior-inferior aspect of the right temporal lobe. Our results suggest that the MEG is a suitable method of assessing noninvasively hemispheric specialization for language.