A noninvasive, presurgical expressive and receptive language investigation in a 9-year-old epileptic boy using near-infrared spectroscopy

The intracarotid amobarbital test (IAT) is used for presurgical evaluation of language lateralization. However, this procedure has many limitations, especially in children. As an alternative to IAT, in the case described here, near-infrared spectroscopy (NIRS) was used to investigate expressive and receptive language lateralization as part of the presurgical evaluation of a 9-year-old Yiddish-speaking boy with a probable left temporal epileptic focus. This child could not tolerate IAT or functional MRI. He underwent two NIRS recording sessions while performing expressive and receptive language tasks. Results indicated predominantly left-sided expressive language in Broca's area with ipsilateral cortical recruitment of more posterior regions. Receptive language showed a bilateral cerebral pattern, perhaps as an expression of cerebral plasticity or compensation in this young patient. This case report illustrates that NIRS may contribute to presurgical investigation and could become a noninvasive alternative to IAT and functional MRI in determining speech lateralization in children.     

Language lateralization in temporal lobe epilepsy: a comparison between fMRI and the Wada Test

PURPOSE: Recent studies have claimed that language functional magnetic resonance imaging (fMRI) can identify language lateralization in patients with temporal lobe epilepsy (TLE) and that fMRI-based findings are highly concordant with the conventional assessment procedure of speech dominance, the intracarotid amobarbital test (IAT). METHODS: To establish the power of language fMRI to detect language lateralization during presurgical assessment, we compared the findings of a semantic decision paradigm with the results of a standard IAT in 68 patients with chronic intractable right and left temporal lobe epilepsy (rTLE, n=28; lTLE, n=40) who consecutively underwent a presurgical evaluation program. The patient group also included 14 (20.6%) subjects with atypical (bilateral or right hemisphere) speech. Four raters used a visual analysis procedure to determine the laterality of speech-related activation individually for each patient. RESULTS: Overall congruence between fMRI-based laterality and the laterality quotient of the IAT was 89.3% in rTLE and 72.5% in lTLE patients. Concordance was best in rTLE patients with left speech. In lTLE patients, language fMRI identified atypical, right hemisphere speech dominance in every case, but missed left hemisphere speech dominance in 17.2%. Frontal activations had higher concordance with the IAT than did activations in temporoparietal or combined regions of interest (ROIs). Because of methodologic problems, recognition of bilateral speech was difficult. CONCLUSIONS: These data provide evidence that language fMRI as used in the present study has limited correlation with the IAT, especially in patients with lTLE and with mixed speech dominance. Further refinements regarding the paradigms and analysis procedures will be needed to improve the contribution of language fMRI for presurgical assessment.     

fMRI study of language lateralization in children and adults

Language lateralization in the brain is dependent on family history of handedness, personal handedness, pathology, and other factors. The influence of age on language lateralization is not completely understood. Increasing left lateralization of language with age has been observed in children, while the reverse has been noted in healthy young adults. It is not known whether the trend of decreasing language lateralization with age continues in the late decades of life and at what age the inflection in language lateralization trend as a function of age occurs. In this study, we examined the effect of age on language lateralization in 170 healthy right-handed children and adults ages 5-67 using functional MRI (fMRI) and a verb generation task. Our findings indicate that language lateralization to the dominant hemisphere increases between the ages 5 and 20 years, plateaus between 20 and 25 years, and slowly decreases between 25 and 70 years.     

Language brain dominance in patients with refractory temporal lobe epilepsy: a comparative study between functional magnetic resonance imaging and dichotic listening test

PURPOSE: To identify brain dominance for language functions with DLT and correlate these results with those obtained from fMRI in patients suffering from intractable temporal lobe epilepsy. METHOD: This study reports on 13 patients who underwent pre-surgical epileptic evaluation between April and October 2004 at the Epilepsy Surgery Program, Hospital Sao Lucas, PUCRS. In DLT, dominance was assessed through a consonant-vowel task, whereas in fMRI patients performed a verb generation task. RESULTS: Our results identified a correlation between the fMRI lateralization index and the DLT ear predominance index and reply difference index (r=0.6, p=0.02; Pearson Correlation Coefficient), showing positive correlation between results obtained from fMRI and DLT. CONCLUSION: DLT was found to significantly correlate with fMRI. These findings indicate that DLT (a non-invasive procedure) could be a useful tool to evaluate language brain dominance in pre-surgical epileptic patients as it is cheaper to perform than fMRI.     

Comprehensive presurgical functional MRI language evaluation in adult patients with epilepsy

Functional magnetic resonance imaging (fMRI) has the potential to replace the intracarotid amobarbital procedure (IAP) in presurgical evaluation of patients with epilepsy. In this study, we compared fMRI verb generation (VG) and semantic decision/tone decision (SDTD) tasks and the IAP in their ability to localize language functions in patients with epilepsy undergoing presurgical evaluation. We enrolled 50 healthy controls to establish normal language activation patterns for VG and SDTD tasks at 3 or 4 T, and to design language regions of interest (ROIs) that were later applied to 38 patients with epilepsy (28 of 38 also underwent the IAP). We calculated laterality indices (LIs) for each task for each subject based on the ROIs, and we used general linear modeling to analyze the fMRI data. All healthy and epileptic subjects activated language areas with both fMRI tasks. We found significant correlations in language lateralization between the fMRI tasks (r=0.495, P<0.001) and between VG and IAP (r=0.652, P<0.001) and SDTD and IAP (r=0.735, P<0.001). The differences in LIs between SDTD and VG tasks were small and not affected by age, gender, epilepsy status, handedness, or performance. SDTD and VG tasks combined explained approximately 58.4% in the variability of the IAP/language. In the general linear modeling, only the SDTD task significantly contributed to the determination of language lateralization in patients with epilepsy undergoing presurgical evaluation. Results indicate a moderate convergent validity between both fMRI language tasks and between IAP and fMRI tasks. The results of this study indicate that either of these fMRI tasks can be used for language lateralization in patients with epilepsy undergoing presurgical evaluation, but that the SDTD task is likely to provide more information regarding language lateralization than the VG task.     

Frontal activation and connectivity using near-infrared spectroscopy: verbal fluency language study

Near infrared spectroscopy (NIRS) is an optical technique with high temporal resolution and reasonably good spatial resolution, which allows non invasive measurement of the blood oxygenation of tissue. The current work is focused in assessing and correlating brain activation, connectivity and cortical lateralization of the frontal cortex in response to language-based stimuli, using NIRS. Experimental studies were performed on 15 normal right-handed adults, wherein the participants were presented with a verbal fluency task. The hemodynamic responses in the pre- and anterior frontal cortex were assessed in response to a Word generation task in comparison to the baseline random Jaw movement and Rest conditions. The functional connectivity analysis was performed using zero-order correlations and the cortical lateralization was evaluated as well. An increase in oxy- and a decrease in deoxy-hemoglobin were observed during verbal fluency task in the frontal cortex. Unlike in the pre-frontal cortex, the hemodynamic response in the anterior frontal during verbal fluency task was not significantly different from that during random Jaw movement. Bilateral activation and symmetrical connectivity were observed in the pre-frontal cortex, independent of the stimuli presented. A left cortical dominance and asymmetry connectivity was observed in the anterior frontal during the verbal fluency task. The work is focused to target the pediatric epileptic populations in the future, where understanding the brain functionality (activation, connectivity, and dominance) in response to language is essential as a part of the pre-surgical evaluation in a clinical environment.     

Usefulness of language and memory testing during intracarotid amobarbital testing: observations from an fMRI study

BACKGROUND: Several procedures for testing language lateralization and memory function exist during the intracarotid amobarbital test (IAT). The use of functional magnetic resonance imaging (fMRI) gives the opportunity to assess the validity of some of these procedures, or at least to inspect the neuronal correlates. A comprehensive fMRI protocol was tested, aimed at addressing aspects of lateralization of language, as well as testing memory in relation to activation of mesiotemporal regions. Here we report observations with possible consequences for the current IAT procedures. MATERIALS AND METHODS: The protocol consisted of three language tasks (overt naming, semantic decision and silent word generation) and two memory tasks (encoding and retrieving visual scenes). The paradigms used a block-related procedure in nine right-handed normal volunteers. During the procedure dynamic weighted full brain images were acquired which are sensitive to the blood oxygenation activation effect. RESULTS : Encoding showed symmetrical bilateral activation in the mesiotemporal regions, specifically the hippocampus, parahippocampal gyrus and fusiform gyrus. With a retrieval task activation of the mesiotemporal areas was restricted to the posterior hippocampal area. Overt object naming showed results, similar to encoding tasks with bilateral activation of hippocampal areas. Silent word generation showed much stronger ability to lateralize than the other two language-related tasks and especially object naming. CONCLUSION: Activation revealed by fMRI activation shows that IAT procedures, using active semantic language processing or comprehensive procedures with multiple language tasks have the highest guarantee for individual activation lateralization. Simple object naming does not guarantee a lateralized language fMRI activation pattern. Of the different memory procedures during IAT, the procedures (Interview and the Montreal) demanding encoding processing will be related to larger areas of bilateral hippocampal activation than procedures (Seattle) exclusively requiring retrieval. Moreover, tasks using recognition of previously presented language items (naming objects) are equally effective for assessing hippocampal activation compared with presenting separate memory items.     

Mouth asymmetry during speech of epileptic patients who have undergone carotid amytal testing

Asymmetry in the opening of the two sides of the mouth during speech has been suggested as an observable correlate of lateralization of cerebral speech motor control. For 24 epileptic patients who suffered speech disturbance only during left hemisphere carotid amytal anesthetization, 22 showed the expected greater opening of the right side of the mouth during a repetition task. However, all four of the patients who suffered speech disturbance following only right hemisphere anesthetization, and 8 of the 11 "bilateral speech" patients, also showed greater opening of the right side of the mouth. The speech dominant patients may, however, have genetic left speech dominance but a pathology-forced shift of some components of language to the right hemisphere. Basic mouth asymmetry, as measured here, may primarily reflect lateralization of a component of the motor/speech/language control system that may not be shifted by pathology in epileptic patients sustaining early brain insult. Relative change in mouth asymmetry as the speech task becomes more demanding may, however, be a more sensitive indicator or cerebral asymmetries for language in pathological cases.     

A comparison of five fMRI protocols for mapping speech comprehension systems

Aims: Many fMRI protocols for localizing speech comprehension have been described, but there has been little quantitative comparison of these methods. We compared five such protocols in terms of areas activated, extent of activation, and lateralization. Methods: fMRI BOLD signals were measured in 26 healthy adults during passive listening and active tasks using words and tones. Contrasts were designed to identify speech perception and semantic processing systems. Activation extent and lateralization were quantified by counting activated voxels in each hemisphere for each participant. Results: Passive listening to words produced bilateral superior temporal activation. After controlling for prelinguistic auditory processing, only a small area in the left superior temporal sulcus responded selectively to speech. Active tasks engaged an extensive, bilateral attention, and executive processing network. Optimal results (consistent activation and strongly lateralized pattern) were obtained by contrasting an active semantic decision task with a tone decision task. There was striking similarity between the network of brain regions activated by the semantic task and the network of brain regions that showed task‐induced deactivation, suggesting that semantic processing occurs during the resting state. Conclusions: fMRI protocols for mapping speech comprehension systems differ dramatically in pattern, extent, and lateralization of activation. Brain regions involved in semantic processing were identified only when an active, nonlinguistic task was used as a baseline, supporting the notion that semantic processing occurs whenever attentional resources are not controlled. Identification of these lexical‐semantic regions is particularly important for predicting language outcome in patients undergoing temporal lobe surgery.     

Determination of language dominance with near-infrared spectroscopy: comparison with the intracarotid amobarbital procedure.

PURPOSE: To determine the efficacy of near-infrared spectroscopy (NIRS) in identifying the hemisphere associated with language by measuring changes in bilateral lateral inferior frontal blood flow during a word generation task in epilepsy surgery patients and healthy volunteers. METHODS: Sixteen patients who underwent the intracarotid amobarbital procedure (IAP) and eight healthy right-handed/right-footed individuals were tested with NIRS during a word generation paradigm. RESULTS: Increases in lateral inferior frontal total hemoglobin concentrations agreed with the IAP in 11 of 16 patients, including 2 of 3 with right hemisphere (atypical) speech dominance (P = 0.13). NIRS revealed increases in lateral inferior frontal total hemoglobin concentrations congruent with language dominance predicted by handedness/footedness in 18 of 24 subjects, including 100% of healthy right-handed subjects (P = 0.02). CONCLUSION: NIRS is a simple, non-invasive, safe modality for measuring cerebral blood flow. Further research and development of testing procedures and instrumentation are needed before routine implementation in pre-surgical testing.     

Clinical functional MRI of the language domain in children with epilepsy

Functional MRI (fMRI) for the assessment of language functions is increasingly used in the diagnostic workup of patients with epilepsy. Termed "clinical fMRI," such an approach is also feasible in children who may display specific patterns of language reorganization. This study was aimed at assessing language reorganization in pediatric epilepsy patients, using fMRI. We studied 26 pediatric epilepsy patients (median age, 13.05 years; range, 5.6-18.7 years) and 23 healthy control children (median age, 9.37 years; range, 6.2-15.4 years), using two child-friendly fMRI tasks and adapted data-processing streams. Overall, 81 functional series could be analyzed. Reorganization seemed to occur primarily in homotopic regions in the contralateral hemisphere, but lateralization in the frontal as well as in the temporal lobes was significantly different between patients and controls. The likelihood to find atypical language organization was significantly higher in patients. Additionally, we found significantly stronger activation in the healthy controls in a primarily passive task, suggesting a systematic confounding influence of antiepileptic medication. The presence of a focal cortical dysplasia was significantly associated with atypical language lateralization. We conclude that important confounds need to be considered and that the pattern of language reorganization may be distinct from the patterns seen in later-onset epilepsy.     

Language dominance in partial epilepsy patients identified with an fMRI reading task

BACKGROUND: fMRI language tasks readily identify frontal language areas; temporal activation has been less consistent. No studies have compared clinical visual judgment to quantitative region of interest (ROI) analysis. OBJECTIVE: To identify temporal language areas in patients with partial epilepsy using a reading paradigm with clinical and ROI interpretation. METHODS: Thirty patients with temporal lobe epilepsy, aged 8 to 56 years, had 1.5-T fMRI. Patients silently named an object described by a sentence compared to a visual control. Data were analyzed with ROI analysis from t-maps. Regional asymmetry indices (AI) were calculated ([L-R]/[L+R]) and language dominance defined as >0.20. t-Maps were visually rated by three readers at three t thresholds. Twenty-one patients had intracarotid amobarbital test (IAT). RESULTS: The fMRI reading task provided evidence of language lateralization in 27 of 30 patients with ROI analysis. Twenty-five were left dominant, two right, one bilateral, and two were nondiagnostic; IAT and fMRI agreed in most patients, three had partial agreement, none overtly disagreed. Interrater agreement ranged between 0.77 to 0.82 (Cramer V; p < 0.0001); agreement between visual and ROI reading with IAT was 0.71 to 0.77 (Cramer V; p < 0.0001). Viewing data at lower thresholds added interpretation to 12 patients on visual analysis and 8 with ROI analysis. CONCLUSIONS: An fMRI reading paradigm can identify language dominance in frontal and temporal areas. Clinical visual interpretation is comparable to quantitative ROI analysis.     

Language lateralization in unmedicated patients during an acute episode of schizophrenia: a functional MRI study

In a previous fMRI study of high-functioning outpatients with remitted schizophrenia, we found that healthy subjects and schizophrenia patients showed similar patterns of activation during a verbal fluency task. However, the activation in controls was primarily in Broca's area on the left, while it was more bilateral for schizophrenia patients, implicating a reduced language lateralization in schizophrenia patients. The same fMRI procedure was used in this subsequent study to investigate unmedicated patients during an acute episode of schizophrenia. Schizophrenia patients showed reduced language lateralization in the frontal cortex, because of a more bilateral activation of Broca's area compared with a primarily left hemisphere activation in healthy controls. Furthermore decreased lateralization was correlated to the severity of hallucinations. Although patients with schizophrenia showed a significantly reduced performance on the verbal fluency task when compared with healthy subjects, we were not able to find evidence of decreased language-related activity in the left hemisphere. These results suggest that decreased language lateralization is also evident in unmedicated patients experiencing an acute episode of schizophrenia.     

Functional MRI and Wada determination of language lateralization: a case of crossed dominance

The Wada test has historically been the conventional procedure for determining language lateralization before neurosurgery. However, functional magnetic resonance imaging (fMRI) offers a less invasive alternative to the Wada procedure. Research indicates that the two techniques used together may provide comparable, and sometimes complementary, information that results in improved prediction of postsurgical language ability. We present a case in which use of fMRI in conjunction with Wada testing provided complementary information about language lateralization before neurosurgical resection of a mesial temporal subependymoma for seizure control in a patient with schizencephaly.     

Functional MRI and the Wada test provide complementary information for predicting post-operative seizure control

Prediction of post-surgical seizure relief and potential cognitive deficits secondary to anterior temporal lobectomy (ATL) are important to pre-surgical planning. Although the intracarotid amobarbital test (IAT) is predictive of post-ATL seizure outcome, development of non-invasive and more precise means for determining post-ATL seizure relief are needed. We previously reported on a technique utilizing functional MRI (fMRI) to evaluate the relative functional adequacy of mesial temporal lobe structures in preparation for ATL. In the present study, we report follow-up outcome data on eight temporal lobe epilepsy (TLE) patients 1-year post-ATL who were evaluated pre-surgically using IAT and fMRI. Functional memory lateralization using fMRI predicted post-ATL seizure outcome as effectively as the IAT. In general, asymmetry of functional mTL activation favouring the non-epileptic hemisphere was associated with seizure-free status at 1-year follow-up. Moreover, when combined, fMRI and IAT provided complementary data that resulted in improved prediction of post-operative seizure control compared with either procedure alone.     

What Box: A task for assessing language lateralization in young children

The assessment of active language lateralization in infants and toddlers is challenging. It requires an imaging tool that is unintimidating, quick to setup, and robust to movement, in addition to an engaging and cognitively simple language processing task. Functional Transcranial Doppler Ultrasound (fTCD) offers a suitable technique and here we report on a suitable method to elicit active language production in young children. The 34-second “What Box” trial presents an animated face “searching” for an object. The face “finds” a box that opens to reveal a to-be-labelled object. In a sample of 95 children (1 to 5 years of age), 81% completed the task—32% with ≥10 trials. The task was validated (ρ?=?0.4) against the gold standard Word Generation task in a group of older adults (n?=?65, 60–85 years of age), though was less likely to categorize lateralization as left or right, indicative of greater measurement variability. Existing methods for active language production have been used with 2-year-old children while passive listening has been conducted with sleeping 6-month-olds. This is the first active method to be successfully employed with infants through to pre-schoolers, forming a useful tool for populations in which complex instructions are problematic.     

FMRI lateralization of expressive language in children with cerebral lesions

PURPOSE: Lateralization of language function is crucial to the planning of surgery in children with frontal or temporal lobe lesions. We examined the utility of functional magnetic resonance imaging (fMRI) as a determinant of lateralization of expressive language in children with cerebral lesions. METHODS: fMRI language lateralization was attempted in 35 children (29 with epilepsy) aged 8-18 years with frontal or temporal lobe lesions (28 left hemisphere, five right hemisphere, two bilateral). Axial and coronal fMRI scans through the frontal and temporal lobes were acquired at 1.5 Tesla by using a block-design, covert word-generation paradigm. Activation maps were lateralized by blinded visual inspection and quantitative asymmetry indices (hemispheric and inferior frontal regions of interest, at p<0.001 uncorrected and p<0.05 Bonferroni corrected). RESULTS: Thirty children showed significant activation in the inferior frontal gyrus. Lateralization by visual inspection was left in 21, right in six, and bilateral in three, and concordant with hemispheric and inferior frontal quantitative lateralization in 93% of cases. Developmental tumors and dysplasias involving the inferior left frontal lobe had activation overlying or abutting the lesion in five of six cases. fMRI language lateralization was corroborated in six children by frontal cortex stimulation or intracarotid amytal testing and indirectly supported by aphasiology in a further six cases. In two children, fMRI language lateralization was bilateral, and corroborative methods of language lateralization were left. Neither lesion lateralization, patient handedness, nor developmental versus acquired nature of the lesion was associated with language lateralization. Involvement of the left inferior or middle frontal gyri increased the likelihood of atypical language lateralization. CONCLUSIONS: fMRI lateralizes language in children with cerebral lesions, although caution is needed in interpretation of individual results.     

Functional magnetic resonance imaging in the determination of dominant language cerebral area

Functional magnetic resonance imaging (fMRI) is a technique for detecting minimal changes in brain perfusion and oxygenation secondary to neuronal activation. Its application in the pre-surgical evaluation of epileptic patients with temporal mesial sclerosis is currently being under investigation in several centers. This study aims to describe an activation paradigm for the evaluation of language and memory functions, as an alternative to the worldwide used Wada test, which is an invasive procedure. In order to propose a paradigm adapted to the Portuguese language, we report our experience in determining the dominant cerebral area for language through fMRI with a verbal fluency task. The results of the fMRI from 19 patients studied in Curitiba in a period of approximately two years were studied. Sixteen of them presented with left hemispheric cerebral language dominance. In five patients, results from fMRI and Wada test could be compared and agreed in localization. Our results reinforce the view that fMRI may become an essential tool for medical practice, perhaps for the determination of eloquent areas in the evaluation of candidates for epilepsy surgery.     

Functional MRI and Wada studies in patients with interhemispheric dissociation of language functions

Rare patients with chronic epilepsy show interhemispheric dissociation of language functions on intracarotid amobarbital (Wada) testing. We encountered four patients with interhemispheric dissociation in 490 consecutive Wada language tests. In all cases, performance on overt speech production tasks was supported by the hemisphere contralateral to the seizure focus, whereas performance on comprehension tasks was served by the hemisphere with the seizure focus. These data suggest that speech production capacity is more likely to shift hemispheres than is language comprehension. Wada and fMRI language lateralization scores were discordant in three of the four patients. However, the two methods aligned more closely when Wada measures loading on comprehension were used to calculate lateralization scores. Thus, interhemispheric dissociation of language functions could explain some cases of discordance on Wada/fMRI language comparisons, particularly when the fMRI measure used is not sensitive to speech production processes.