High-resolution functional MRI at 3T in healthy and epilepsy subjects: hippocampal activation with picture encoding task

Functional MRI (fMRI) studies of memory with coarse resolution of 4 x 4 x 5 mm often fail to demonstrate blood oxygenation level-dependent (BOLD) activation in the hippocampal formation. This failure occurs when nonactivating white matter is averaged with the signal from hippocampal gray matter, attenuating the total BOLD signal from a single voxel due to the "partial volume effect." In this study, we evaluated the suitability of high-resolution fMRI at 3T (voxel size 2 x 2 x 3 mm) for improved visualization of hippocampal activation during memory encoding in 21 healthy and 6 epilepsy subjects. We used a picture encoding task (block design) that involved memorization of indoor and outdoor scenes along with an appropriate resting task. Region-of-interest (ROI) analysis was performed; laterality indices (LIs) were calculated based on hippocampal ROIs (hROIs) or on global medial temporal ROIs (mtROIs). In 19 healthy subjects, robust bilateral BOLD signal changes within both ROIs were noted. The mean LI+/-SD for the hROIs is -0.12+/-0.06 and that for the medial temporal ROIs -0.12+/-0.05, with correlation between the LIs (r = 0.59, P = 0.009). Good concordance was noted between the surgical outcome and memory lateralization with the fMRI task employed in this study. The preliminary results are encouraging, and with continuing improvements in MRI scanner technology, we expect fMRI of the hippocampal formation at higher resolution to be possible and preferable. Furthermore, these results suggest that a larger study to test the utility of high-resolution fMRI in epilepsy presurgical evaluation is needed.     

Lateralizing language with magnetic source imaging: Validation based on the Wada test

Purpose:   Magnetoencephalography (MEG)/magnetic source imaging (MSI) is a noninvasive functional neuroimaging procedure used to localize language-specific regions in the brain. The Wada test, or intracarotid amobarbital procedure (IAP), is the gold standard in determining speech/language lateralization for presurgical planning, although it is invasive and associated with morbidity. The purpose of this study is to provide further validation on the use of MSI for presurgical language lateralization by comparing results against the IAP.
Methods:   The sample consisted of 35 patients with epilepsy and/or brain tumor undergoing presurgical evaluation at the Minnesota Epilepsy Group. All patients received both an IAP and MSI to determine hemispheric language dominance. For MSI, a 148-channel MEG system was used to record activation of language-specific cortex by an auditory word-recognition task.
Results:   The MSI and IAP were concordant in determining language in the hemisphere to be treated in 86% of the cases with sensitivity and specificity values of 80% and 100%, respectively.
Conclusions:   The results from this study are consistent with prior research findings comparing functional neuroimaging procedures to the IAP in determining language lateralization in presurgical patients. The current study provides an important replication and support for Papanicolaou et al.'s findings in 2004 using a consecutive clinical sample from a different institution. An unusually high rate of atypical IAP language cases in this sample and differences between the two procedures are believed to explain the noted discrepancies. MSI is a viable noninvasive alternative to the IAP in the presurgical determination of language lateralization.     

Medial temporal fMRI activation reflects memory lateralization and memory performance in patients with epilepsy

Memory difficulties are a frequent cognitive complaint of patients with chronic epilepsy. Previous studies have suggested that the presence of a seizure focus causes reorganization of brain mechanisms underlying memory function. Here we examine whether seizure onset in the left hemisphere and onset in the right hemisphere have different effects on memory lateralization and whether longer duration of epilepsy is associated with increased lateralization of memory functions to the unaffected hemisphere. We hypothesized that hemisphere of onset and duration of epilepsy would influence plasticity of memory mechanisms, similar to the plasticity observed for language mechanisms. Healthy controls (HC, N = 10) and patients with epilepsy (N = 23, 11 with a left- and 12 with a right-hemisphere focus) performed a scene-encoding fMRI task at 4 T. Active voxels (relative to scrambled image viewing) were identified for each participant. Memory laterality indices (LIs) were calculated in three regions of interest (ROIs) designed on the basis of HC group data: a functional ROI, an anatomical-hippocampal ROI, and an anatomical-medial temporal ROI encompassing hippocampus and parahippocampal gyrus. In healthy controls, LIs were suggestive of slight left lateralization of encoding memory for pictures. Patients with right hemisphere epilepsy showed a nonsignificant increase in degree of left lateralization. In contrast, patients with left hemispheric epilepsy showed right-lateralized activation, differing significantly from controls and from patients with right hemispheric epilepsy. Neuropsychological measures of memory (WMS-III Story Recall) across epilepsy patients predicted LIs in the anatomical ROIs: higher scores were associated with more left-lateralized medial temporal fMRI activation. Neither age of onset nor duration of epilepsy was significantly related to LI. These results indicate that focal epilepsy may influence the functional neuroanatomy of memory function.     

Unilateral intracarotid amobarbital procedure for language lateralization

PURPOSE: The determination of language dominance as part of the presurgical workup of patients with pharmacoresistant epilepsies has experienced fundamental changes. With the introduction of noninvasive functional magnetic resonance imaging (fMRI), the number of patients receiving intracarotid amobarbital procedures (IAPs) for assessment of language dominance has decreased considerably. However, recent studies show that because of methodologic limitations of fMRI, IAP remains an important tool for language lateralization. The current study examines whether unilateral instead of bilateral IAP is an adequate way to apply IAP with reduced invasiveness. METHODS: We retrospectively examine the predictive value of unilateral IAP for the results of bilateral IAP based on a sample of 75 patients with various types of language dominance. Target parameters are the prediction of the language-dominant hemisphere and the identification of patients with atypical language dominance. For language assessment based on unilateral IAP, we introduce the measure hemispheric language capacity (HLC). RESULTS: Unilateral IAP performed on the side of intended surgery quantifies language capacity contralateral to the intended surgery. It detects atypical (bilateral or right) language dominance in the majority of patients. Experience with a separate series of 107 patients requiring presurgical language lateralization shows that in >80%, bilateral IAPs are redundant. CONCLUSIONS: Unilateral IAP is principally sufficient for language lateralization in the presurgical evaluation of patients with pharmacoresistant epilepsies. Necessity of bilateral IAP is restricted to few indications (e.g., callosotomy). In times of noninvasive language lateralization, we propose unilateral IAP as the method of choice for the verification of doubtful (bilateral) fMRI activation patterns.     

Unexpected right hemisphere language representation identified by the intracarotid amobarbital procedure in right-handed epilepsy surgery candidates

The intracarotid amobarbital procedure (IAP) is used for language lateralization in the presurgical evaluation for intractable epilepsy. Some epilepsy surgical centers forgo IAP for right temporal lobectomies in right-handed patients with no personal/family history of left-handedness, implying that right hemisphere language representation does not occur in these patients. To test this hypothesis, a retrospective analysis was performed on 156 consecutive epilepsy surgery candidates who underwent IAP. Of the 156 candidates, 122 were right-handed, and 55 of the 122 demonstrated right hemisphere seizure focus. Right hemisphere language representation was found in 22 of 55 patients, with two demonstrating significant right hemisphere language despite a right hemisphere seizure focus and no family history of left-handedness. Only 1 of 156 patients undergoing IAP experienced permanent neurological complications. Although relatively uncommon, right hemisphere language representation may occur more frequently than complications from cerebral angiography and, therefore, presurgical IAP is recommended for all epilepsy surgery candidates regardless of handedness to minimize the risk of severe language decline.     

Lessons learned from a comparison of language localisation using fMRI and electrocortical mapping: case studies of neocortical epilepsy patients

Electrocortical mapping (ECM) is recognised as an established method for localisation of eloquent cortex in patients undergoing resective surgery for epilepsy management. Functional MRI (fMRI) has been utilised for language and other cortical function localisation. We describe language localisation in two patients using both ECM and fMRI. Co-registration of fMRI and ECM revealed that although two fMRI tasks localised multiple language areas, the verb generation task had an advantage over the semantic decision/tone decision task in that there was a clear overlap between the language areas identified by the verb generation task and ECM. In addition to the language areas detected by ECM, fMRI showed other language-related areas that may be important for post-operative language outcome. Therefore, fMRI may provide additional and complementary information to ECM in presurgical evaluation of patients with epilepsy. The correlation between fMRI and ECM may depend on the language testing methods utilised during the procedures.     

Topiramate and its effect on fMRI of language in patients with right or left temporal lobe epilepsy

Topiramate (TPM) is well recognized for its negative effects on cognition, language performance and lateralization results on the intracarotid amobarbital procedure (IAP). But, the effects of TPM on functional MRI (fMRI) of language and the fMRI signals are less clear. Functional MRI is increasingly used for presurgical evaluation of epilepsy patients in place of IAP for language lateralization. Thus, the goal of this study was to assess the effects of TPM on fMRI signals. In this study, we included 8 patients with right temporal lobe epilepsy (RTLE) and 8 with left temporal lobe epilepsy (LTLE) taking TPM (+TPM). Matched to them for age, handedness and side of seizure onset were 8 patients with RTLE and 8 with LTLE not taking TPM (-TPM). Matched for age and handedness to the patients with TLE were 32 healthy controls. The fMRI paradigm involved semantic decision/tone decision task (in-scanner behavioral data were collected). All epilepsy patients received a standard neuropsychological language battery. One sample t-tests were performed within each group to assess task-specific activations. Functional MRI data random-effects analysis was performed to determine significant group activation differences and to assess the effect of TPM dose on task activation. Direct group comparisons of fMRI, language and demographic data between patients with R/L TLE +TPM vs. -TPM and the analysis of the effects of TPM on blood oxygenation level-dependent (BOLD) signal were performed. Groups were matched for age, handedness and, within the R/L TLE groups, for the age of epilepsy onset/duration and the number of AEDs/TPM dose. The in-scanner language performance of patients was worse when compared to healthy controls - all p<0.044. While all groups showed fMRI activation typical for this task, regression analyses comparing L/R TLE +TPM vs. -TPM showed significant fMRI signal differences between groups (increases in left cingulate gyrus and decreases in left superior temporal gyrus in the patients with LTLE +TPM; increases in the right BA 10 and left visual cortex and decreases in the left BA 47 in +TPM RTLE). Further, TPM dose showed positive relationship with activation in the basal ganglia and negative associations with activation in anterior cingulate and posterior visual cortex. Thus, TPM appears to have a different effect on fMRI language distribution in patients with R/L TLE and a dose-dependent effect on fMRI signals. These findings may, in part, explain the negative effects of TPM on cognition and language performance and support the notion that TPM may affect the results of language fMRI lateralization/localization.     

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.     

Language activation distributions revealed by fMRI in post-operative epilepsy patients: differences between left- and right-sided resections

OBJECTIVE: To reveal differences of cerebral activation related to language functions in post-operative temporal lobe epilepsy (TLE) patients. METHODS: Right (RTL) and left temporal lobe (LTL) resected patients, and healthy controls were studied using functional magnetic resonance imaging (fMRI). Only patients with complete left-hemispheric language dominance according to the intracarotid amytal procedure (IAP) were included. Language-related activations were evoked by performing word generation and text reading language tasks. Activation lateralization and temporo-frontal distribution effects were analysed. RESULTS: For word generation, only LTL patients showed reduced left lateralized activation compared to controls, due to a decrease in activation in the left prefrontal cortex and an increase in the right prefrontal cortex. For reading, the left-hemispheric lateralization in RTL patients increased because of enhanced activity in the left prefrontal cortex, whereas for LTL patients the activation became bilaterally distributed over the temporal lobes. Lateralization results between pre-operative IAP and post-operative fMRI were highly discordant. Significant temporo-frontal distribution changes manifested from the reading but not from the word generation task. CONCLUSION: The cerebral language representation in post-operative LTL epilepsy patients is more bi-hemispherically lateralized than in controls and RTL patients. Post-operative temporo-frontal and interhemispheric redistribution effects, involving contralateral homologous brain areas, are suggested to contribute to the cerebral reorganisation of language function.     

Presurgical language fMRI in patients with drug-resistant epilepsy: effects of task performance

PURPOSE: To determine whether language functional magnetic resonance imaging (fMRI) before epilepsy surgery can be similarly interpreted in patients with greatly different performance levels. METHODS: An fMRI paradigm using a semantic decision task with performance control and a perceptual control task was applied to 226 consecutive patients with drug-resistant localization-related epilepsy during their presurgical evaluations. The volume of activation and lateralization in an inferior frontal and a temporoparietal area was assessed in correlation with individual performance levels. RESULTS: We observed differential effects of task performance on the volume of activation in the inferior frontal and the temporoparietal region of interest, but performance measures did not correlate with the lateralization of activation. CONCLUSIONS: fMRI, as applied here, in patients with a wide range of cognitive abilities, can be interpreted regarding language lateralization in a similar way.     

Threshold-independent functional MRI determination of language dominance: A validation study against clinical gold standards

Functional MRI (fMRI) is often used for presurgical language lateralization. In the most common approach, a laterality index (LI) is calculated on the basis of suprathreshold voxels. However, strong dependencies between LI and threshold can diminish the effectiveness of this technique; in this study we investigated an original methodology that is independent of threshold. We compared this threshold-independent method against the common threshold-dependent method in 14 patients with epilepsy who underwent Wada testing. In addition, clinical results from electrocortical language mapping and postoperative language findings were used to assess the validity of the fMRI lateralization method. The threshold-dependent methodology yielded ambiguous or incongruent lateralization outcomes in 4 of 14 patients in the inferior frontal gyrus (IFG) and in 6 of 14 patients in the supramarginal gyrus (SMG). Conversely, the threshold-independent method yielded unambiguous lateralization in all the patients tested, and demonstrated lateralization outcomes incongruent with clinical standards in 2 of 14 patients in IFG and in 1 of 14 patients in SMG. This validation study demonstrates that the threshold-dependent LI calculation is prone to significant within-patient variability that could render results unreliable; the threshold-independent method can generate distinct LIs that are more concordant with gold standard clinical findings.     

Cerebral lesions can impair fMRI-based language lateralization

Purpose:   Several small patient studies and case reports raise concerns that the reliability of functional magnetic resonance imaging (fMRI) may be impaired in the vicinity of cerebral lesions. This could affect the clinical validity of fMRI for presurgical language lateralization. The current study sets out to identify if a systematic effect of lesion type and localization on fMRI exists.
Methods:   We classify lesions typically occurring in epilepsy patients according to (1) their potential to disturb blood oxygenation level dependent (BOLD)–effect generation or detection or to disturb spatial brain normalization, and (2) the proximity of lesions to protocol-specific volumes of interest (VOIs). The effect of lesions is evaluated through the examination of 238 epilepsy patients and a subgroup of 37 patients with suspected unilateral left-language dominance according to the Wada test.
Results:   Patients with fMRI-critical lesions such as cavernomas, gliomas, and mass defects close to VOIs, or with severe atrophy, show lower lateralization indices (LIs) and more often discordant language lateralization with the Wada test than do patients without such lesions.
Discussion:   This study points seriously toward fMRI-language lateralization being sensitive to cerebral lesions. Some lesion types and locations are more critical than others. Our results question the noncritical application of fMRI in patients with cerebral lesions.     

Language laterality determined by MEG mapping with MR-FOCUSS

Magnetoencephalography recordings were made on 27 patients with localization related epilepsy during two different language tasks involving semantic and phonological processing (verb generation and picture naming). These patients underwent the semi-invasive intracarotid amobarbital procedure (IAP), also referred to as the Wada test, to determine the language-dominant hemisphere. Magnetoencephalography (MEG) data were analyzed by MR-FOCUSS, a current density imaging technique. A laterality index (LI) was calculated from this solution to determine which hemisphere had more neural activation during these language tasks. The LIs for three separate latencies, within each language task, were calculated to determine the latency that correlated best with each patient's IAP result. The LI for all language processing was calculated for the interval 150-550 ms, the second LI was calculated for the interval 230-290 ms (Wernicke's activation), and the third LI was calculated for the interval 396-460 ms (Broca's activation). In 23 of 24 epilepsy patients with a successful IAP, the LIs for Broca's activation, during the picture naming task, were in agreement with the results of the IAP (96% agreement). One of three patients who had an undetermined or bilateral IAP had an LI calculated for Broca's activation (396-460 ms) that agreed with intracranial mapping and clinical testing. These results indicate an 89% agreement rate (24 of 27) for magnetoencephalographic LI determination of the hemisphere of language dominance.     

Language lateralization in epilepsy patients: fMRI validated with the Wada procedure

Purpose:  This work examines the efficacy of functional magnetic resonance imaging (fMRI) for language lateralization using a comprehensive three-task language-mapping approach. Two localization methods and four different metrics for quantifying activation within hemisphere are compared and validated with Wada testing. Sources of discordance between fMRI and Wada lateralization are discussed with respect to specific patient examples.
Methods:  fMRI language mapping was performed in patients with epilepsy (N = 40) using reading sentence comprehension, auditory sentence comprehension, and a verbal fluency task. This was compared with the Wada procedure using both whole-brain and midline exclusion–based analyses. Different laterality scores were examined as a function of statistical threshold to investigate the sensitivity to threshold effects.
Results:  For the lateralized patients categorized by Wada, fMRI laterality indices (LIs) were concordant with the Wada procedure results in 83.87% patients for the reading task, 83.33% patients for the auditory task, 76.92% patients for the verbal fluency task, and in 91.3% patients for the conjunction analysis. The patients categorized as bilateral via the Wada procedure showed some hemispheric dominance in fMRI, and discrepancies between the Wada test findings and the functional laterality scores arose for a range of reasons.
Discussion:  Discordance was dependent upon whether whole-brain or midline exclusion method–based lateralization was calculated, and in the former case the inclusion of the occipital and other midline regions often negatively influenced the lateralization scores. Overall fMRI was in agreement with the Wada test in 91.3% of patients, suggesting its utility for clinical use with the proper consideration given to the confounds discussed in this work.     

Lateralization of language function in epilepsy patients: A high-density scalp-derived event-related potentials (ERP) study

Objectives

Language functional magnetic resonance imaging (fMRI) represents the clinical standard for language lateralization assessment in presurgical epilepsy evaluation, but still many patients experience postoperative language deficits. Event-related potentials (ERPs), especially the negative component around and after 400 ms, are related to language processing and could therefore represent a complementary method of language lateralization assessment.

MEG language lateralization in partial epilepsy using dSPM of auditory event-related fields

ObjectiveMethods employed to determine hemispheric language dominance using magnetoencephalography (MEG) have differed significantly across studies in the choice of language-task, the nature of the physiological response studied, recording hardware, and source modeling methods. Our goal was to determine whether an analysis based on distributed source modeling can replicate the results of prior studies that have used dipole-modeling of event-related fields (ERFs) generated by an auditory word-recognition task to determine language dominance in patients with epilepsy.MethodsWe analyzed data from 45 adult patients with drug-resistant partial epilepsy who performed an auditory word-recognition task during MEG recording and also completed a language fMRI study as part of their evaluation for epilepsy surgery. Source imaging of auditory ERFs was performed using dynamic statistical parametric mapping (dSPM). Language laterality indices (LIs) were calculated for four regions of interest (ROIs) by counting above-threshold activations within a 300–600 ms time window after stimulus onset. Language laterality (LL) classifications based on these LIs were compared to the results from fMRI.ResultsThe most lateralized MEG responses to language stimuli were observed in a parietal region that included the angular and supramarginal gyri (AngSmg). In this region, using a half-maximal threshold, source activations were left dominant in 32 (71%) patients, right dominant in 8 (18%), and symmetric in 5 patients (11%). The best agreement between MEG and fMRI on the ternary classification of regional language dominance into left, right, or symmetric groups was also found at the AngSmg ROI (69%). This was followed by the whole-hemisphere and temporal ROIs (both 62%). The frontal ROI showed the least agreement with fMRI (51%). Gross discordances between MEG and FMRI findings were disproportionately of the type where MEG favored atypical right-hemispheric language in a patient with right-hemispheric seizure origin (p < 0.05 at three of the four ROIs).SignificanceIn a parietal region that includes the angular and supramarginal gyri, language laterality estimates based on dSPM of ERFs during auditory word-recognition shows a degree of MEG-fMRI concordance that is comparable to previously published estimates for MEG-Wada concordance using dipole counting methods and the same task. Our data also suggest that MEG language laterality estimates based on this task may be influenced by the laterality of epileptic networks in some patients. This has not been reported previously and deserves further study.     

Use of functional MRI in epilepsy]

For the purpose of examining pathophysiological mechanisms of a memory function in epileptic patients or an utility of fMRI for a presurgical assessment in neurosurgical treatment of epilepsy, activated areas in fMRI during verbal or visual memory task were investigated in patient group of temporal lobe epilepsy and normal subject group. Patient group of temporal lobe epilepsy consisted of 7 cases, of which 3 and 3 cases had left and right temporal foci, respectively, except 1 case having undetermined laterality of temporal foci. Normal subjects were 16 cases. All the epileptic and normal subjects were right-handed except for 1 lefty normal subject. Verbal memory tasks were composed of covert and overt recall tasks of 10 words given auditorily, while visual ones were recall tasks of 6 figures given visually. Eventually, in normal subjects, the left side-dominant medial frontal lobes including the superior frontal and anterior cingulate gyri were mainly activated in fMRI during the covert recall tasks of verbal memory, while the left side-dominant inferior frontal and precentral gyri as the motor language areas were chiefly activated in addition to the medial frontal lobe during the overt recall tasks. Further, the bilateral occipital lobes were activated in fMRI during the recall tasks of visual memory. Also in patient groups of temporal lobe epilepsy, the activated areas in fMRI during these tasks were the same as in normal subject group, regardless of the laterality of epileptic temporal foci. These results suggest that fMRI is useful for the determination of the lateralization of the cerebral hemisphere contributing to verbal memory function and therefore for the presurgical assessment of memory function in neurosurgical treatment of epilepsy.     

Language lateralization in temporal lobe epilepsy using functional MRI and probabilistic tractography

Purpose: Language functional magnetic resonance imaging (fMRI) is used to noninvasively assess hemispheric language specialization as part of the presurgical work-up in temporal lobe epilepsy (TLE). White matter asymmetries on diffusion tensor imaging (DTI) may be related to language specialization as shown in controls and TLE. To refine our understanding of the effect of epilepsy on the structure–function relationships, we focused on the arcuate fasciculus (ArcF) and the inferior occipitofrontal fasciculus (IOF) and tested the relationship between DTI- and fMRI-based lateralization indices in TLE.
Methods: fMRI with three language tasks and DTI were obtained in 20 patients (12 right and 8 left TLE). The ArcF, a major language-related tract, and the IOF were segmented bilaterally using probabilistic tractography to obtain fractional anisotropy (FA) lateralization indices. These were correlated with fMRI-based lateralization indices computed in the inferior frontal gyrus (Pearson's correlation coefficient).
Results: fMRI indices were left-lateralized in 16 patients and bilateral or right-lateralized in four. In the ArcF, FA was higher on the left than on the right side, reaching significance in right but not in left TLE. We found a positive correlation between ArcF anisotropy and fMRI-based lateralization indices in right TLE (p < 0.009), but not in left TLE patients. No correlation was observed for the IOF.
Conclusions: Right TLE patients with more left-lateralized functional activations also showed a leftward-lateralized arcuate fasciculus. The decoupling between the functional and structural indices of the ArcF underlines the complexity of the language network in left TLE patients.     

Language dominance determined by whole brain functional MRI in patients with brain lesions

BACKGROUND: Functional MRI (fMRI) is of potential value in determining hemisphere dominance for language in epileptic patients. OBJECTIVE: To develop and validate an fMRI-based method of determining language dominance for patients with a wide range of potentially operable brain lesions in addition to epilepsy. METHODS: Initially, a within-subjects design was used with 19 healthy volunteers (11 strongly right-handed, 8 left-handed) to determine the relative lateralizing usefulness of three different language tasks in fMRI. An automated, hemispheric analysis of laterality was used to analyze whole brain fMRI data sets. To evaluate the clinical usefulness of this method, we compared fMRI-determined laterality with laterality determined by Wada testing or electrocortical stimulation mapping, or both, in 23 consecutive patients undergoing presurgical evaluation of language dominance. RESULTS: Only the verb generation task was reliably lateralizing. fMRI, using the verb generation task and an automated hemispheric analysis method, was concordant with invasive measures in 22 of 23 patients (12 Wada, 11 cortical stimulation). For the single patient who was discordant, in whom a tumor involved one-third of the left hemisphere, fMRI became concordant when the tumor and its reflection in the right hemisphere were excluded from laterality analysis. No significant negative correlation was obtained between lesion size and strength of laterality for the patients with lesions involving the dominant hemisphere. CONCLUSION: This fMRI method shows potential for evaluating language dominance in patients with a variety of brain lesions.     

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.