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.

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.

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.

Continuum of impulsiveness caused by auditory masking.

OBJECTIVE: Impulsivity is a hallmark of attention deficit/hyperactivity disorder (ADHD). Various auditory masking procedures can quantify the impulsivity caused by distracting background sounds. This study compares the impulsiveness and distraction caused by informational masking (unpredictable tones) with previously published data on central masking (contralateral noise) in children with and without ADHD. METHODS: Twenty-six normal and 14 children diagnosed as having ADHD (combined type), all between the ages of 7 and 13, indicated whether they heard a 512-ms, 500-Hz pure tone in a single-interval task under conditions of informational masking and in quiet. The masker consisted of 10 randomly selected frequencies between 1,000 and 2,500 Hz presented simultaneously at an overall level of 60 dB SPL. A maximum-likelihood method estimated thresholds and false alarm rates. RESULTS: There were no differences due to ADHD in thresholds or false alarm rates either with informational masking or in quiet. With informational masking, normal children had high false alarm rates, similar to those from children with ADHD under central masking. With informational masking, all children tended to say a stimulus was present when it was not. CONCLUSIONS: All children behave impulsively under some conditions. Pediatric patients with attention disorders can thus be reassured that impulsiveness with unpredictable background sounds is normal, to some extent. Response biases of children with ADHD may only diverge from normal in situations where distracting external stimuli have an intermediate level of predictability. A previous study showed that with central masking, children with ADHD are more impulsive than normal. There appears to be a limit to the uncertainty in auditory masking that can be tolerated by children. Children with ADHD become impulsive at lower levels of uncertainty than normal. Increasing the predictability of distracting background sounds may thus improve the performance of children with ADHD. Informational masking may, for normal listeners, mimic something of what it is like to have an attention deficit. ADHD can be profitably studied with auditory tasks.

[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.

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.

Perception of voice and tone onset time continua in children with dyslexia with and without attention deficit/hyperactivity disorder.

Tasks assessing perception of a phonemic contrast based on voice onset time (VOT) and a nonspeech analog of a VOT contrast using tone onset time (TOT) were administered to children (ages 7.5 to 15.9 years) identified as having reading disability (RD; n = 21), attention deficit/hyperactivity disorder (ADHD; n = 22), comorbid RD and ADHD (n = 26), or no impairment (NI; n = 26). Children with RD, whether they had been identified as having ADHD or not, exhibited reduced perceptual skills on both tasks as indicated by shallower slopes on category labeling functions and reduced accuracy even at the endpoints of the series where cues are most salient. Correlations between performance on the VOT task and measures of single word decoding and phonemic awareness were significant only in the groups without ADHD. These findings suggest that (a) children with RD have difficulty in processing speech and nonspeech stimuli containing similar auditory temporal cues, (b) phoneme perception is related to phonemic awareness and decoding skills, and (c) the potential presence of ADHD needs to be taken into account in studies of perception in children with RD.

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.

Lateralization of activity associated with language function using magnetoencephalography: a reliability study.

This study was conducted to investigate the reliability of magnetoencephalography in lateralizing and localizing brain activity associated with receptive language function. Sixteen right-handed adults with no history of neurologic disorder engaged in a continuous recognition memory task for visually presented words in two separate sessions. The magnetic flux normal to the scalp surface was measured with a whole-head neuromagnetometer during task performance. Using the total number of acceptable activity sources as an index, overall activation was greater in the left compared with the right hemisphere for all 16 subjects in both sessions. Sources of activity were consistently found in the temporoparietal areas of the left hemisphere in all subjects. Moreover, clusters of activity sources in this region either overlapped spatially or were found in close proximity across sessions. Medial and basal temporal lobe activity was also observed in most subjects during at least one session, and tended to be lateralized to left hemisphere. These results suggest that magnetoencephalography is a promising tool for determination of cerebral dominance for language and localization of temporal lobe language areas.

Brain mechanisms for reading: the role of the superior temporal gyrus in word and pseudoword naming.

The purpose of this study was to test the neurological validity of a dual-route model of reading by asking patients, who were undergoing electrocortical stimulation mapping, to read words with irregular print-to-sound correspondences and pseudowords. Brain activation profiles were also obtained from these patients during an auditory and a visual word recognition task using whole-head magnetic source imaging. We demonstrated that reading is subserved by at least two brain mechanisms that are anatomically dissociable. One mechanism subserves assembled phonology and depends on the activity of the posterior part of the left superior temporal gyrus (STGp), whereas the second is responsible for addressed phonology and does not necessarily involve this region. The contribution of STGp to reading appears to be based on its specialization for phonological analysis operations, involved in the processing of both spoken and written language.

Cerebral mechanisms involved in word reading in dyslexic children: a magnetic source imaging approach.

The purpose of the present investigation was to describe spatiotemporal brain activation profiles during word reading using magnetic source imaging (MSI). Ten right-handed dyslexic children with severe phonological decoding problems and eight age-matched non-impaired readers were tested in two recognition tasks, one involving spoken and the other printed words. Dyslexic children's activation profiles during the printed word recognition task consistently featured activation of the left basal temporal cortices followed by activation of the right temporoparietal areas (including the angular gyrus). Non-impaired readers showed predominant activation of left basal followed by left temporoparietal activation. In addition, we were able to rule out the hypothesis that hypoactivation of left temporoparietal areas in dyslexics was due to a more general cerebral dysfunction in these areas. Rather, it seems likely that reading difficulties in developmental dyslexia are associated with an aberrant pattern of functional connectivity between brain areas normally involved in reading, namely ventral visual association cortex and temporoparietal areas in the left hemisphere. The interindividual consistency of activation profiles characteristic of children with dyslexia underlines the potential utility of this technique for examining neurophysiological changes in response to specific educational intervention approaches.

Brain activation profiles in dyslexic children during non-word reading: a magnetic source imaging study.

The purpose of the study was to identify spatiotemporal brain activation profiles associated with phonological decoding in dyslexic children using magnetic source imaging. For this purpose maps of regional cerebral activation were obtained from eleven children diagnosed with dyslexia and ten children without reading problems during engagement in a pseudoword rhyme-matching task. All dyslexic children showed aberrant activation maps consisting of reduced activity in temporoparietal areas in the left hemisphere (including the posterior part of the superior temporal, angular and supramarginal gyri) and increased activity in the right homotopic region. In contrast, the two groups of children did not differ in the degree of activity in basal temporal areas that typically precedes temporoparietal activation. This is the first study to demonstrate the existence of distinct activation profiles associated with phonological decoding in individual dyslexic children.

Insights into brain function and neural plasticity using magnetic source imaging.

This review outlines the rationale for the use of magnetoencephalography (MEG) or magnetic source imaging (MSI), a noninvasive functional imaging technique, and the features that any imaging method should display to make a substantial contribution to cognitive neuroscience. After a brief discussion of the basic experimental approach used in the authors' studies, the use of early sensory components of brain magnetic responses is reviewed to address issues of the functional organization of the primary sensory cortices, followed by a comment on the clinical use of these components. Second, normative studies focusing on the late components of magnetic responses for establishing the validity and reliability of MSI maps of the language-specific cortex in normal subjects are reviewed. Third, the authors' investigations of fine spatiotemporal features of brain activation maps, specific to receptive language and to reading, are reviewed. Fourth, experience with presurgical mapping of the language-specific cortex in neurosurgery candidates and in patients undergoing the "Wada" procedure is summarized followed by a comment on the perfect agreement of the MSI maps with those derived by more direct invasive brain mapping procedures. Fifth. MSI-derived evidence of often dramatic, functional reorganization of brain areas subserving both simple sensory and linguistic functions is summarized along with comments on the use of MSI as a means for investigating brain plasticity. Finally, in the sixth section of this review, the authors relate their experience with the use of MSI in deriving brain activation profiles during silent reading of real words and pseudowords that are specific to dyslexic children. The review concludes with a discussion on the further use of MSI in assessing, among other issues, the effectiveness of intervention strategies designed to improve reading fluency in dyslexic children.