Modular Patterns of Phase Desynchronization Networks During a Simple Visuomotor Task.

By performing sensor-level analysis on magnetoencephalography (MEG) data we identified the dynamic evolution of the functional connectivity networks during a simple visuomotor task. The functional connectivity networks were constructed using the concept of phase-locking value (PLV). We illustrate that the task-related activity is mediated by distinct complex networks related to the PLV desynchronization that configure their architecture dynamically during the task. These networks are prominent at ß and α band, and are characterized by coherent modular organization. Moreover the time for the development of the desynchronization networks at α band predicts the intra-subject variability of reaction time. Thus, the spatio-temporal dynamics and the structural properties of the emerged functional networks share common characteristics with the mechanism of coactivation and resting state networks.

Altered temporal correlations in resting-state connectivity fluctuations in children with reading difficulties detected via MEG.

In this study we investigate systematic patterns of rapidly changing sensor-level interdependencies in resting MEG data obtained from 23 children experiencing reading difficulties (RD) and 27 non-impaired readers (NI). Three-minute MEG time series were band-passed and subjected to blind source separation (BSS) prior to estimating sensor interdependencies using the weighted phase synchronization measure (wPLI). Dynamic sensor-level network properties were then derived for two network metrics (global and local efficiency). The temporal decay of long-range temporal correlations in network metrics (LRTC) was quantified using the scaling exponent (SE) in detrended fluctuation analysis (DFA) plots. Having established the reliability of SE estimates as robust descriptors of network dynamics, we found that RD students displayed significantly reduced (a) overall sensor-level network organization across all frequency bands (global efficiency), and (b) temporal correlations between sensors covering the left temporoparietal region and the remaining sensors in the ß3 band (local efficiency). Importantly, both groups displayed scale-free global network connectivity dynamics. The direct application of DFA to MEG signals failed to reveal significant group differences. Results are discussed in relation to prior evidence for disrupted temporoparietal functional circuits for reading in developmental reading disability.

Language dysfunction after stroke and damage to white matter tracts evaluated using diffusion tensor imaging.

BACKGROUND AND PURPOSE: Knowledge of the anatomic basis of aphasia after stroke has both theoretic and clinical implications by informing models of cortical connectivity and providing data for diagnosis and prognosis. In this study we use diffusion tensor imaging to address the relationship between damage to specific white matter tracts and linguistic deficits after left hemisphere stroke. MATERIALS AND METHODS: Twenty patients aged 38-77 years with a history of stroke in the left hemisphere underwent diffusion tensor imaging, structural MR imaging, and language testing. All of the patients were premorbidly right handed and underwent imaging and language testing at least 1 month after stroke. RESULTS: Lower fractional anisotropy (FA) values in the superior longitudinal and arcuate fasciculi of the left hemisphere, an indication of greater damage to these tracts, were correlated with decreased ability to repeat spoken language. Comprehension deficits after stroke were associated with lower FA values in the arcuate fasciculus of the left hemisphere. The findings for repetition were independent of MR imaging ratings of the degree of damage to cortical areas of the left hemisphere involved in language function. There were no findings for homotopic tracts in the right hemisphere. CONCLUSION: This study provides support for a specific role for damage to the superior longitudinal and arcuate fasciculi in the left hemisphere in patients with deficits in repetition of speech in aphasia after stroke.

Disruption of limbic pathways in a case of profound amnesia.

We report a case of episodic amnesia in which the anatomical basis of injury was investigated by diffusion tensor imaging (DTI). Two months after an adult male suffered severe closed head injury, conventional magnetic resonance imaging (CMRI) revealed only a right superior frontal lesion. However, 14 years later, DTI revealed structural anomalies not visible on CMRI involving limbic white matter tracts, notably the fornix, which could explain the amnesia.

Functional neuroimaging with MEG: normative language profiles.

The reliability of language-specific brain activation profiles was assessed using Magnetoencephalography (MEG) in five experiments involving ninety-seven normal volunteers of both genders ranging in age from seven to eighty-four years. MEG data were analyzed with a fully automated method to eliminate subjective judgments in the process of deriving the activation profiles. Across all experiments, profiles were characterized by significant bilateral activity centered in the superior temporal gyrus, and in activity lateralized to the left middle temporal gyrus. These features were invariant across age, gender, variation in task characteristics, and mode of stimulus presentation. The absolute amount of activation, however, did decline with age in the auditory tasks. Moreover, contrary to the commonly held belief that left hemisphere dominance for language is greater in men than in women, our data revealed an opposite albeit a not consistently significant trend.

Organization of receptive language-specific cortex before and after left temporal lobectomy.

OBJECTIVE: To examine brain activation associated with receptive language in patients with left temporal lobe epilepsy (TLE) before and after an anterior temporal lobectomy using magnetoencephalography (MEG), and to evaluate which patients were most likely to show a change in the lateralization and localization of the mechanisms supporting receptive language and if such changes were associated with neuropsychological function. METHODS: Twelve patients with left TLE underwent preoperative Wada testing, and pre- and postoperative neuropsychological testing and MEG language mapping. The anatomic location of receptive language-related activity sources observed with MEG was determined by coregistering MEG data with structural MRI scans. Language laterality indices were calculated based on the number of reproducible activity sources in each hemisphere. The proximity of language-specific activity sources to Wernicke's area was also examined. RESULTS: Although the small sample size precluded formal statistical analyses, patients with atypical (bilateral) hemispheric dominance preoperatively were more likely than patients with typical (left-hemisphere) dominance to show evidence of increased right hemisphere participation in language functions after surgery. Patients with left hemispheric dominance preoperatively were more likely to show intrahemispheric changes involving a slight inferior shift of the putative location of Wernicke's area. Patients with bilateral representation tended to perform worse on neuropsychological test measures obtained both pre- and postoperatively. CONCLUSION: Interhemispheric functional reorganization of language-specific areas may occur in patients undergoing left anterior temporal lobectomy. Intrahemispheric reorganization may take place even when the resection does not directly impinge upon Wernicke's area.

Spatio-temporal cortical dynamics of phonemic and semantic fluency.

Hemodynamic brain imaging and lesion studies have suggested differential involvement of expressive language-related cortical regions based on the phonemic versus semantic characteristics of verbal cues. The aims of this study were: 1) to elucidate the relative timing of the activity of inferior frontal and anterior insular versus motor and supplementary motor cortex during a fluency task and 2) to assess potential differences in the location or timing of activity in anterior and posterior language areas based on letter versus category cues. Using magnetic source imaging (MSI), we found significantly earlier onset latencies and a greater number of activity sources in motor and supplementary motor compared with inferior frontal and anterior insular regions. We also observed greater left versus right hemispheric asymmetry of activation for letter compared with category cues. This study provides new insights into cortico-cortical interactions during expressive language tasks.

Reorganization of language-specific cortex in patients with lesions or mesial temporal epilepsy.

OBJECTIVE: To examine brain activation profiles for receptive language function, using magnetoencephalography (MEG), in patients with left hemisphere space-occupying lesions and patients with left temporal lobe epilepsy due to mesial temporal sclerosis (MTS) and to evaluate whether cross- and intrahemispheric plasticity for language varied as a function of lesion type or location. METHODS: Twenty-one patients with MTS and 23 lesional patients underwent preoperative language mapping while performing a word recognition task. The anatomic location of late activity sources was determined by co-registering MEG coordinates onto structural MRI scans. A language laterality index was calculated based on the number of activity sources in each hemisphere. The location of language-specific activity was examined in relation to its proximity or overlap with Wernicke's area. RESULTS: A higher incidence of atypical language lateralization was noted among patients with MTS than lesional patients (43 vs 13%). The majority of MTS patients with early seizure onset (before age 5) showed atypical language lateralization. In contrast, the precise location of receptive language-specific cortex within the dominant hemisphere was found to be atypical (outside of Wernicke's area) in 30% of lesional patients and only 14% of MTS patients. CONCLUSIONS: There is an increased probability of a partial or total displacement of key components of the brain mechanism responsible for receptive language function to the nondominant hemisphere in mesial temporal sclerosis patients. Early onset of seizures is strongly associated with atypical language lateralization. Lesions in the dominant hemisphere tend to result in an intrahemispheric reorganization of linguistic function.

Spatio-temporal brain activation profiles associated with line bisection judgments and double simultaneous visual stimulation.

We used magnetic source imaging (MSI) to investigate the spatio-temporal patterns of brain activity associated with line bisection judgments and double simultaneous visual stimulation in 14 healthy adults. Consistent with lesion and hemodynamic neuroimaging studies, we found the greatest number of activity sources in right inferior parietal cortex. These sources were most prominent, on average, between 200 and 300 ms after the onset of single (left, right, or center) target stimuli. A greater number of significant activity sources were found in right inferior parietal, occipital, and prefrontal cortices during bilateral compared with unilateral stimulus presentation. Based on these observations, we suggest that a more parsimonious physiological explanation of visual extinction than the hemispheric rivalry account may be the additional neuronal excitation required in right occipital and parietal cortices for accurate bilateral visual perception.

Does magnetoencephalography add to scalp video-EEG as a diagnostic tool in epilepsy surgery?

OBJECTIVE: The authors evaluated the sensitivity and selectivity of interictal magnetoencephalography (MEG) versus prolonged ictal and interictal scalp video-electroencephalography (V-EEG) in order to identify patient groups that would benefit from preoperative MEG testing. METHODS: The authors evaluated 113 consecutive patients with medically refractory epilepsy who underwent surgery. The epileptogenic region predicted by interictal and ictal V-EEG and MEG was defined in relation to the resected area as perfectly overlapping with the resected area, partially overlapping, or nonoverlapping. RESULTS: The sensitivity of a 30-minute interictal MEG study for detecting clinically significant epileptiform activity was 79.2%. Using MEG, we were able to localize the resected region in a greater proportion of patients (72.3%) than with noninvasive V-EEG (40%). MEG contributed to the localization of the resected region in 58.8% of the patients with a nonlocalizing V-EEG study and 72.8% of the patients for whom V-EEG only partially identified the resected zone. Overall, MEG and V-EEG results were equivalent in 32.3% of the cases, and additional localization information was obtained using MEG in 40% of the patients. CONCLUSION: MEG is most useful for presurgical planning in patients who have either partially or nonlocalizing V-EEG results.

Cortical organization for receptive language functions in Chinese, English, and Spanish: a cross-linguistic MEG study.

Chinese differs from Indo-European languages in both its written and spoken forms. Being a tonal language, tones convey lexically meaningful information. The current study examines patterns of neurophysiological activity in temporal and temporoparietal brain areas as speakers of two Indo-European languages (Spanish and English) and speakers of Mandarin-Chinese were engaged in a spoken-word recognition task that is used clinically for the presurgical determination of hemispheric dominace for receptive language functions. Brain magnetic activation profiles were obtained from 92 healthy adult volunteers: 30 monolingual native speakers of Mandarin-Chinese, 20 Spanish-speaking, and 42 native speakers of American English. Activation scans were acquired in two different whole-head MEG systems using identical testing methods. Results indicate that (a) the degree of hemispheric asymmetry in the duration of neurophysiological activity in temporal and temporoparietal regions was reduced in the Chinese group, (b) the proportion of individuals who showed bilaterally symmetric activation was significantly higher in this group, and (c) group differences in functional hemispheric asymmetry were first noted after the initial sensory processing of the word stimuli. Furthermore, group differences in the degree of hemispheric asymmetry were primarily due to greater degree of activation in the right temporoparietal region in the Chinese group, suggesting increased participation of this region in the spoken word recognition in Mandarin-Chinese.

[Insights into brain function though magnetic source imaging: A review of research and clinical applications]. / Aproximación a la función cerebral a través de la imagen de fuente magnética: aplicaciones clínicas y experimentales.

INTRODUCTION AND DEVELOPMENT: The paper presents a brief outline of the rationale behind the use of non invasive functional imaging and of the features that any imaging technique should display in order to make a substantial contribution to the search of the brain mechanisms responsible for cognitive functions. One such technique, magnetic source imaging (MSI), that meets these specifications, is described in more detail. Advantages of MSI include the capacity to provide direct measures of regional neurophysiological activity, a millisecond range temporal resolution, and the capacity to provide images of brain activity on an individual basis. We then describe applications of MSI to the study of brain mechanisms involved in various language functions such as oral comprehension and reading. Among these applications, the accuracy of MSI protocols in determining hemispheric dominance for language functions and in identifying the precise location and extent language specific cortex (Wernicke s area) has been verified through comparison with standard invasive techniques (Wada procedure and electrocortical stimulation mapping) in over 60 consecutive cases. In another series of studies we combined data from MSI and direct cortical stimulation to determine the role of temporoparietal areas in phonological analysis of spoken language and in phonological decoding of print. Finally, we have used MSI to gain unique insights into the brain mechanisms that support reading in developmental reading disability. CONCLUSION: Results from over 21 children diagnosed with this disorder suggest that impaired reading is associated with aberrant functional connections between temporal and temporoparietal areas of the left hemisphere that are normally engaged in reading.

Dyslexia-specific brain activation profile becomes normal following successful remedial training.

OBJECTIVES: To examine changes in the spatiotemporal brain activation profiles associated with successful completion of an intensive intervention program in individual dyslexic children. METHODS: The authors obtained magnetic source imaging scans during a pseudoword reading task from eight children (7 to 17 years old) before and after 80 hours of intensive remedial instruction. All children were initially diagnosed with dyslexia, marked by severe difficulties in word recognition and phonologic processing. Eight children who never experienced reading problems were also tested on two occasions separated by a 2-month interval. RESULTS: Before intervention, all children with dyslexia showed distinctly aberrant activation profiles featuring little or no activation of the posterior portion of the superior temporal gyrus (STGp), an area normally involved in phonologic processing, and increased activation of the corresponding right hemisphere area. After intervention that produced significant improvement in reading skills, activity in the left STGp increased by several orders of magnitude in every participant. No systematic changes were obtained in the activation profiles of the children without dyslexia as a function of time. CONCLUSIONS: These findings suggest that the deficit in functional brain organization underlying dyslexia can be reversed after sufficiently intense intervention lasting as little as 2 months, and are consistent with current proposals that reading difficulties in many children represent a variation of normal development that can be altered by intensive intervention.

Levels of word processing and incidental memory: dissociable mechanisms in the temporal lobe.

Word recall is facilitated when deep (e.g. semantic) processing is applied during encoding. This fact raises the question of the existence of specific brain mechanisms supporting different levels of information processing that can modulate incidental memory performance. In this study we obtained spatiotemporal brain activation profiles, using magnetic source imaging, from 10 adult volunteers as they performed a shallow (phonological) processing task and a deep (semantic) processing task. When phonological analysis of the word stimuli into their constituent phonemes was required, activation was largely restricted to the posterior portion of the left superior temporal gyrus (area 22). Conversely, when access to lexical/semantic representations was required, activation was found predominantly in the left middle temporal gyrus and medial temporal cortex. The differential engagement of each mechanism during word encoding was associated with dramatic changes in subsequent incidental memory performance.

Mapping of expressive language cortex using magnetic source imaging.

The accurate localization of primary language cortex is one of the goals in the evaluation of brain surgery candidates. In this paper we describe the localization of expressive language cortex using magnetic source imaging (MSI) in a patient with refractory epilepsy caused by a tumor affecting the left inferior frontal gyrus. The magnetoencephalographic recordings during an expressive language task were co-registered with a magnetic resonance imaging (MRI) scan obtained after subdural grid placement and provided a cluster of sources of brain activation in the vicinity of the lesion. This map of expressive language provided by MSI was verified with electrocortical stimulation before the operation. No speech problems were reported in our patient after the resection of the lesion, suggesting that MSI is an accurate non-invasive method for the pre-surgical mapping of expressive language in cases where there is clear functional risk during tumor resection.

Age-related changes in regional brain activation during phonological decoding and printed word recognition.

Using magnetic source imaging, age-related changes in spatiotemporal brain activation profiles associated with printed word recognition and phonological decoding (pseudoword reading) were examined in 27 adults and 22 children without reading problems. Adults showed a distinct spatiotemporal profile during reading of both types of print consisting of bilateral activation of occipital cortices, followed by strongly left-predominant activation of basal temporal regions, and, finally, left hemisphere temporoparietal (including the angular gyrus) and inferior frontal activation. Children lacked the clear temporal distinction in the engagement of basal and temporoparietal areas and displayed significantly weaker activation of the left inferior frontal gyrus. In addition, the consistent hemispheric asymmetries in the degree of activation of basal temporal regions that were present in the adult readers were not apparent in the children. In contrast, the strong left hemisphere preponderance in the degree of activation of temporoparietal areas was present in children as well as adults, regardless of the type of print they were asked to read. The data suggest that the degree of specialization of cortical regions for reading, as well as the pattern of regional interactions that supports this specialization, may change with age.

Mapping of receptive language cortex in bilingual volunteers by using magnetic source imaging.

OBJECT: There are conflicting claims in the functional imaging literature concerning whether different languages are represented by distinct brain mechanisms in individuals who are proficient in more than one language. This interesting theoretical issue has practical implications when functional imaging methods are used for presurgical language mapping. To address this issue the authors compared the location and extent of receptive language cortex specific to English and Spanish in neurologically intact bilingual volunteers by using magnetic source imaging. METHODS: Areas of the cortex that were specialized for receptive language functions were identified separately for each language in 11 healthy adults who were bilingual in English and Spanish. The authors performed exactly the same procedures used routinely for presurgical receptive language mapping. In each bilingual individual, the receptive language-specific map always encompassed the posterior portion of the superior temporal gyrus. In every case, however, substantial differences in the receptive language maps were also observed for the two languages, regardless of whether each participant's first language was English or Spanish. CONCLUSIONS: Although the reasons for such differences and their ultimate significance in identifying the cerebral mechanisms of language are subject to continuing investigation, their presence is noteworthy and has practical implications for the surgical management of patients with lesions in the temporal and parietal regions of the dominant hemisphere.

Brain plasticity for sensory and linguistic functions: a functional imaging study using magnetoencephalography with children and young adults.

In this report, the newest of the functional imaging methods, magnetoencephalography, is described, and its use in addressing the issue of brain reorganization for basic sensory and linguistic functions is documented in a series of 10 children and young adults. These patients presented with a wide variety of conditions, ranging from tumors and focal epilepsy to reading disability. In all cases, clear evidence of reorganization of the brain mechanisms of either somatosensory or linguistic functions or both was obtained, demonstrating the utility of magnetoencephalography in studying, completely noninvasively, the issue of plasticity in the developing brain.

Language dominance in children as determined by magnetic source imaging and the intracarotid amobarbital procedure: a comparison.

This study evaluated the validity of data derived from magnetic source imaging regarding hemispheric dominance for language in children and adolescents with intractable seizure disorder by comparison with results of the intracarotid amobarbital procedure. Functional imaging of the receptive language cortex using a whole-head neuromagnetometer was performed in 19 consecutive epilepsy patients, ages 8 to 18 years, who also underwent the intracarotid amobarbital procedure. During magnetic source imaging recordings, patients engaged in a continuous recognition memory task for words in visual and auditory modalities. This task has previously been shown to be valid for the purpose of lateralization and localization of language cortex in adult epilepsy patients who undergo the intracarotid amobarbital procedure and intraoperative language mapping allowing confirmation of magnetic source imaging findings. Results indicated that language laterality indices formed for the intracarotid amobarbital procedure and magnetic source imaging procedures were highly correlated (R = .87). In addition, clinical judgments regarding cerebral dominance for language made by independent raters using the two methods were in excellent agreement. We conclude that magnetic source imaging is a promising method for determination of cerebral dominance for language in children and adults.

Pallidotomy: a comparison of responders and nonresponders.

OBJECTIVE: We reviewed a prospective series of 32 unilateral, large-volume, microelectrode-guided posteroventral pallidotomies to determine the differences between responsive and nonresponsive patients. METHODS: Our patients underwent extensive pre- and postoperative evaluations. One year postoperatively, we correlated the outcomes of 25 patients with their histories, physical findings, neuropsychological assessments, and lesion characteristics to further understand the indications, limitations, and pitfalls of unilateral pallidotomy. Our group judged responsiveness by comparing the preoperative total Unified Parkinson's Disease Rating Scale off-state scores with those obtained 1 year postoperatively. A score indicating greater than 20% improvement at 1-year follow-up was rated a good outcome; improvement of greater than 40% was rated an excellent outcome. RESULTS: Although most patients sustained long-term benefits, some demonstrated little or no improvement. Patient and lesion factors influenced outcome. Younger age (<60 yr), tremor, unilateral predominance, L-dopa responsiveness, motor fluctuations with dyskinesia, and good lesion placement predicted a good response to unilateral pallidotomy. Advanced age (>70 yr), absence of tremor, increased duration of disease, reduced responsiveness to L-dopa, frontal behavioral changes, prominent apraxic phenomena, and improper lesion placement predicted a poor response. CONCLUSION: Unilateral, large-volume pallidotomy with precise lesion control provides long-lasting benefits for carefully selected patients.