Organization of language networks in children: Functional magnetic resonance imaging studies

Functional magnetic resonance imaging (fMRI) is a relatively new neuroimaging procedure that has been used to study a wide variety of cognitive phenomena in adults, including attention, language, and memory. More recently, this technique has been successfully applied to pediatric populations as well. In particular, many investigators have employed fMRI as a tool to study language development in normal children. This paper reviews the current imaging research on the identification of cortex subserving components of language processing in young children. The literature suggests that fMRI can successfully identify regions of language cortex in children in much the same capacity as it can with adults, and that generally, adults and children show fundamental similarities in the patterns of activation. However, special considerations with pediatric imaging, paradigm design, and image analysis are also discussed.     

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.     

Functional MRI in children with epilepsy

Advances in brain mapping with functional magnetic resonance imaging (fMRI) have opened an important window into understanding how language is organized in the developing brain. Children with epilepsy, particularly those anticipating surgical intervention, may benefit from preoperative language localization with fMRI, thus minimizing the risk of incurring new deficits. Clinical applications of fMRI, however, await more information on how different linguistic skills are represented in the developing brain and how epileptic lesions impact on this organization at different stages of cognitive development. This article presents some of the current methods for brain mapping in children as well as early results using fMRI for language mapping in pediatric epilepsy. Copyright Copyright 1999 S. Karger AG, Basel     

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.     

Near-infrared spectroscopy as an alternative to the Wada test for language mapping in children, adults and special populations.

The intracarotid amobarbital test (IAT) is the most widely used procedure for pre-surgical evaluation of language lateralization in epileptic patients. However, apart from being invasive, this technique is not applicable in young children or patients who present mental retardation and/or language deficits. Functional magnetic resonance imaging (fMRI) is increasingly employed as a non-invasive alternative. Again, this method is more difficult to use with young children, especially hyperactive ones, since they have to remain motionless during data acquisition. The aim of this study was to determine whether near-infrared spectroscopy (NIRS) can be used as an alternative technique to investigate language lateralization in children and special populations. Unlike Wada test, NIRS is non-invasive, and it is more tolerant to movement artefacts than fMRI. In the present study, NIRS data were acquired in four epileptic children, a 12-year-old boy with pervasive developmental disorder and a 3-year-old, healthy child, as well as three healthy and two epileptic adults, while they performed a verbal fluency task and a control task. When applicable, the results were compared to the subjects' fMRI and/or IAT findings. Clear laterality of speech was obtained in all participants, including the two non-epileptic children, and NIRS results matched fMRI and IAT findings. These results, if replicable in larger samples, are encouraging and suggest that NIRS has the potential to become a viable, non-invasive alternative to IAT and fMRI in the determination of speech lateralization in children and clinical populations that cannot be submitted to more invasive techniques.     

fMRI shows atypical language lateralization in pediatric epilepsy patients

PURPOSE: The goal of this study was to compare language lateralization between pediatric epilepsy patients and healthy children. METHODS: Two groups of subjects were evaluated with functional magnetic resonance imaging (fMRI) by using a silent verb-generation task. The first group included 18 pediatric epilepsy patients, whereas the control group consisted of 18 age/gender/handedness-matched healthy subjects. RESULTS: A significant difference in hemispheric lateralization index (LI) was found between children with epilepsy (mean LI =-0.038) and the age/gender/handedness-matched healthy control subjects (mean LI=0.257; t=6.490, p<0.0001). A dramatic difference also was observed in the percentage of children with epilepsy (77.78%) who had atypical LI (right-hemispheric or bilateral, LI<0.1) when compared with the age/gender/handedness-matched group (11.11%; chi(2)=16.02, p<0.001). A linear regression analysis showed a trend toward increasing language lateralization with age in healthy controls (R(2)=0.152; p=0.108). This association was not observed in pediatric epilepsy subjects (R(2)=0.004, p=0.80). A significant association between language LI and epilepsy duration also was found (R(2)=0.234, p<0.05). CONCLUSIONS: This study shows that epilepsy during childhood is associated with neuroplasticity and reorganization of language function.     

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.     

Comparing the Intracarotid Amobarbital Test and Functional MRI for the Presurgical Evaluation of Language in Epilepsy

Surgery is the treatment of choice for drug-resistant temporal lobe epilepsy (TLE). However, such surgery frequently causes deficits in language function, especially if performed on the dominant hemisphere. In recent years, the intracarotid amobarbital test (IAT) has been gradually replaced by functional magnetic resonance imaging (fMRI) in the preoperative identification of language areas to estimate the risk of postoperative language decline. In this paper, we review the neural substrates for language processing, how language impairment can result both from TLE itself and from surgical attempts to treat it. Subsequently, we discuss the strengths and limitations of, and current indications for fMRI and IAT during the preoperative workup, both by discussion of the studies that have evaluated them individually and through meta-analysis of data from 31 studies deemed eligible for analysis. Electrocortical stimulation mapping (ESM) is also discussed, as is the usefulness of the novel technique of resting-state fMRI. Finally, surgical techniques designed to avoid or reduce language decline in patients at risk are explored.     

Atypical language representation in children with intractable temporal lobe epilepsy

This study evaluated language organization in children with intractable epilepsy caused by temporal lobe focal cortical dysplasia (FCD) alone or dual pathology (temporal lobe FCD and hippocampal sclerosis, HS). We analyzed clinical, neurological, fMRI, neuropsychological, and histopathologic data in 46 pediatric patients with temporal lobe lesions who underwent excisional epilepsy surgery. The frequency of atypical language representation was similar in both groups, but children with dual pathology were more likely to be left-handed. Atypical receptive language cortex correlated with lower intellectual capacity, verbal abstract conceptualization, receptive language abilities, verbal working memory, and a history of status epilepticus but did not correlate with higher seizure frequency or early seizure onset. Histopathologic substrate had only a minor influence on neuropsychological status. Greater verbal comprehension deficits were noted in children with atypical receptive language representation, a risk factor for cognitive morbidity.     

Functional anatomy of cognitive development: fMRI of verbal fluency in children and adults

OBJECTIVE: To identify age-dependent activation patterns of verbal fluency with functional MRI (fMRI). BACKGROUND: Few fMRI language studies have been performed in children, and none provide comparison data to adult studies. Normative data are important for interpretation of similar studies in patients with epilepsy. METHODS: A total of 10 normal children (5 boys, 5 girls; mean age, 10.7 years; range, 8.1 to 13.1 years) and 10 normal adults (5 men, 5 women; mean age, 28.7 years; range, 19.3 to 48 years) were studied on a 1.5-T Signa MRI scanner using BOLD echo planar imaging of the frontal lobes with a verbal fluency paradigm, covert word generation to letters. Studies were analyzed with a cross-correlation algorithm (r = 0.7). A region-of-interest analysis was used to determine the extent, magnitude, and laterality of brain activation. RESULTS: Children and adults activated similar regions, predominantly in left inferior frontal cortex (Broca's area) and left middle frontal gyrus (dorsolateral prefrontal cortex). Children had, on average, 60% greater extent of activation than adults, with a trend for greater magnitude of activation. Children also had significantly more right hemisphere and inferior frontal gyrus activation than adults. CONCLUSIONS: In a test of verbal fluency, children tended to activate cortex more widely than adults, but activation patterns for fluency appear to be established by middle childhood. Thus, functional MRI using verbal fluency paradigms may be applied to pediatric patient populations for determining language dominance in anterior brain regions. The greater activation found in children, including the right inferior frontal gyrus, may reflect developmental plasticity for the ongoing organization of neural networks, which underlie language capacity.     

Presurgical language mapping in children with epilepsy: clinical usefulness of functional magnetic resonance imaging for the planning of cortical stimulation

Purpose: Presurgical language mapping in dominant hemisphere epilepsy to evaluate the risk of postoperative deficit is particularly difficult in children. Extraoperative invasive cortical stimulation can show some areas critical to language, but not all of them, due to scarce sampling, poor cooperation, cortical immaturity, or network reorganization, whereas functional magnetic resonance imaging (fMRI) displays entire networks involved in, but not necessarily critical to, language. In a homogeneous series of children with epilepsy, we compared the contributions of language fMRI and depth electrode stimulations to optimize language mapping. Methods: Eight children (7.5–15.5 years) with left frontal or temporal epilepsy underwent language fMRI and language stimulation with depth electrodes as part of their comprehensive presurgical workup. fMRI data collected during sentence generation were analyzed using statistical parametric mapping (SPM2) (false discovery rate [FDR] p < 0.05). Bipolar stimulations were performed during language production tasks. By coregistering fMRI and postimplantation computed tomography (CT) images, we were able to directly compare the cortical areas identified by both investigations. Key Findings: fMRI during sentence generation robustly showed activation in the whole perisylvian regions with little reorganization (left hemisphere dominant in 7). Of the 184 electrode contacts tested for language, only 8 were positive (language disruption) in three of the seven patients with periictal language impairment and left language dominance. All of the positive contacts colocalized with an fMRI activated cluster, that is, fMRI did not miss any region critical to language (sensitivity = 100%). However, 54 of the 176 negative contacts were within activated clusters (low specificity). Significance: In children with epilepsy, the sensitivity of fMRI during sentence generation allows for the detection of all critical regions displayed by cortical stimulation within the large perisylvian language network, but with a low specificity. It is, therefore, useful to optimize the placement of intracranial electrodes when language mapping is necessary. Systematic planning of the electrode placement according to language fMRI maps should increase the yield of extraoperative cortical stimulation, which appears rather low in children when compared to adults.     

Functional magnetic resonance imaging in the treatment of epilepsy

Although structural magnetic resonance imaging (MRI) is now in routine use in the evaluation and management of epilepsy, functional MRI (fMRI) has recently begun to provide a noninvasive and widely available modality for assessing regional brain function. fMRI studies of language and memory are able to show discrete areas of activation in cerebral cortex, are useful in lateralizing language and memory during presurgical evaluation, and are providing further insight into the processes underlying cerebral plasticity in the brains of epilepsy patients. The use of fMRI for localization of ictal phenomena may also contribute to the localization of seizure foci and to a better understanding of the pathophysiology of electrographic spikes. The combination of fMRI with electroencephalogram and other advanced structural imaging techniques may not only improve seizure localization, but may also contribute valuable information towards a better understanding of the pathophysiology of epilepsy and its consequences on brain development.     

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 MRI applications in epilepsy surgery

Functional magnetic resonance imaging (fMRI) is a non-invasive neuroimaging technique that has grown rapidly in popularity over the past decade. It is already prevalent in psychology, cognitive and basic neuroscience research and is being used increasingly as a tool for clinical decision-making in epilepsy. It has been used to determine language location and laterality in patients, sometimes eliminating the need for invasive tests. fMRI can been used pre-surgically to guide resection margins, preserving eloquent cortex. Other fMRI paradigms assessing memory, visual and somatosensory systems have limited clinical applications currently, but show great promise. Simultaneous recording of electroencephalogram (EEG) and fMRI has also provided insights into the networks underlying seizure generation and is increasingly being used in epilepsy centres. In this review, we present some of the current clinical applications for fMRI in the pre-surgical assessment of epilepsy patients, and examine a number of new techniques that may soon become clinically relevant.     

Anatomical and functional distribution of functional MRI language mapping

ObjectiveThe aim of the present study was to compare localization of the language cortex using electrical cortical stimulation (ECS) and functional magnetic resonance imaging (fMRI) to establish the relevance of fMRI language mapping.MethodsLanguage mapping with fMRI and functional ECS mapping were retrospectively compared in ten patients with refractory epilepsy who underwent fMRI language mapping and functional ECS mapping between June 2012 and April 2019. A shiritori task, a popular Japanese word chain game, was used for fMRI language mapping.ResultsBOLD signal activation was observed in the left inferior frontal gyrus (including the pars opecularis and the pars triangularis), and superior temporal gyrus, which is a language-related area, as well as in the left superior and middle frontal gyri, the intraparietal sulcus, and fusiform gyrus. These results were compared with ECS to elucidate the functional role of the activated areas during fMRI language tasks. These activated areas included language areas, negative motor areas, supplementary motor areas (SMAs), and non-functional areas.ConclusionThe activated areas of fMRI language mapping include language-related areas, the negative motor area, and SMAs. These findings suggest the involvement of language and higher order motor networks in verbal expression.     

Functional MRI reveals an interhemispheric dissociation of frontal and temporal language regions in a patient with focal epilepsy

We report the case of a patient with frontal lobe epilepsy in whom the Wada test failed to lateralize representation of language (fluent speech was observed after amobarbital injection on both the right and left side). Functional magnetic resonance imaging (fMRI) during a lexical processing task revealed an atypical organization of language represented by an interhemispheric dissociation of language regions with a right frontal dominance and a left temporal dominance. Consistent with the fMRI results, the patient's ability to name pictures was not reliably impaired by electrocortical stimulation (ECS) of left frontal cortex. The findings from Wada, fMRI, and ECS were confirmed by a lack of language impairment after left frontal lobectomy for seizures. This case illustrates that fMRI can precisely map cortical language networks in epileptic patients and that fMRI may be used to help interpret laterality results provided by the Wada procedure.     

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.     

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.     

Utility of Functional MRI in Pediatric Neurology

Functional MRI (fMRI), a tool increasingly used to study cognitive function, is also an important tool for understanding not only normal development in healthy children, but also abnormal development, as seen in children with epilepsy, attention-deficit/hyperactivity disorder, and autism. Since its inception almost 15 years ago, fMRI has seen an explosion in its use and applications in the adult literature. However, only recently has it found a home in pediatric neurology. New adaptations in study design and technologic advances, especially the study of resting state functional connectivity as well as the use of passive task design in sedated children, have increased the utility of functional imaging in pediatrics to help us gain understanding into the developing brain at work. This article reviews the background of fMRI in pediatrics and highlights the most recent literature and clinical applications.     

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.