Language Lateralization In Patients Research Articles

Noninvasive Prediction of Language Lateralization Through Arcuate Fasciculus Tractography in Patients With Low-Grade Gliomas: Correlation With The Wada Test.

Language lateralization is unique to humans, so clarifying dominant side is helpful for removing gliomas involving language areas. This study investigated the arcuate fasciculus (AF) reconstructed by diffusion tensor imaging–based tractography (DTT) in predicting language lateralization in patients with low-grade gliomas. Wada test was performed to determine the language Dominant Hemisphere (DH) and the Contralateral Hemisphere. DTI data [1.5-T magnetic resonance imaging (MRI)] was used to reconstruct AF by two independent operators using a DTT method. Fiber number, volume, and fractional anisotropy (FA) of bilateral reconstructed AF were measured. Lateralization indexes (LIs), including Number Index (NI), Volume Index (VI), and FA Index (FI), were accordingly calculated by mean values. A total of 21 patients with WHO Grade II gliomas in the left hemisphere were included. Every patient received a successful Wada test and reconstruction of bilateral AF. DTT metrics of reconstructed AF, such as fiber number, volume, and FA, showed significantly asymmetric between hemispheres. All the LI (NI, VI, and FI) values were statistically higher in the DH determined by the Wada test. No discrepancy was found between the prediction using the cutoff values of DTT metrics and the results of WADA test. The Kappa values were 0.829, 0.696, and 0.611, indicating NI and VI as more reliable predictor than FI although FI itself may also be feasible. Compared with the Wada test, we consider that DTT of AF is a non-invasive, simple, relatively accurate, and feasible method in predicting language lateralization in patients with low-grade gliomas.

Evaluation of the crossed cerebro-cerebellar activation to determine language lateralization in patients with brain tumors

The crossed cerebro-cerebellar (CCC) activation facilitates the diagnosis of cortical language lateralization, but needs to be explored with language tasks suitable for patients with different age ranges, educational attainment and eventual presence of language deficits. To determine the effect of demographic variables in the performance of three language tasks in healthy volunteers and to determine the CCC activation of these tasks as a functional magnetic resonance imaging (fMRI) paradigm in brain tumor patients. The behavioral performance (correct responses and reaction time) of three language tasks (verbal fluency, semantic and phonological decision tasks) was first examined in 76 healthy volunteers balanced by age and educational level. Later, these tasks were implemented as fMRI paradigms to explore CCC language activation of 20 patients with potential diagnosis of brain tumors. The performance of the verbal fluency task was affected by age. The CCC language activation was reproducible with the semantic and phonological tasks. The combination of the tasks determined typical and atypical language lateralization in 60% and 40% of our patients, respectively. The verbal fluency task must be implemented with care as a clinical fMRI paradigm. Our results suggest that semantic and phonological tasks can be a good alternative for brain tumor patients with language deficits.

Resting-State Functional Connectivity of the Middle Frontal Gyrus Can Predict Language Lateralization in Patients with Brain Tumors.

A recent study using task-based fMRI demonstrated that the middle frontal gyrus is comparable with Broca's area in its ability to determine language laterality using a measure of verbal fluency. This study investigated whether the middle frontal gyrus can be used as an indicator for language-hemispheric dominance in patients with brain tumors using task-free resting-state fMRI. We hypothesized that no significant difference in language lateralization would occur between the middle frontal gyrus and Broca area and that the middle frontal gyrus can serve as a simple and reliable means of measuring language laterality. Using resting-state fMRI, we compared the middle frontal gyrus with the Broca area in 51 patients with glial neoplasms for voxel activation, the language laterality index, and the effect of tumor grade on the laterality index. The laterality index derived by resting-state fMRI and task-based fMRI was compared in a subset of 40 patients. Voxel activations in the left middle frontal gyrus and left Broca area were positively correlated (r = 0.47, P < .001). Positive correlations were seen between the laterality index of the Broca area and middle frontal gyrus regions (r = 0.56, P < .0005). Twenty-seven of 40 patients (67.5%) showed concordance of the laterality index based on the Broca area using resting-state fMRI and the laterality index based on a language task. Thirty of 40 patients (75%) showed concordance of the laterality index based on the middle frontal gyrus using resting-state fMRI and the laterality index based on a language task. The middle frontal gyrus is comparable with the Broca area in its ability to determine hemispheric dominance for language using resting-state fMRI. Our results suggest the addition of resting-state fMRI of the middle frontal gyrus to the list of noninvasive modalities that could be used in patients with gliomas to evaluate hemispheric dominance of language before tumor resection. In patients who cannot participate in traditional task-based fMRI, resting-state fMRI offers a task-free alternate to presurgically map the eloquent cortex.

P01.087 Reduced language lateralization in patients with a left-hemispheric glioma

P01.087 Reduced language lateralization in patients with a left-hemispheric glioma

Relationships between corpus callosum and language lateralization in patients with schizophrenia and bipolar disorders.

The question of whether there is a continuum or a dichotomy among patients with schizophrenia (SZ) and bipolar disorders (BD) has not been clearly resolved and remains a challenge. Thus, the identification of specific biomarkers of these disorders might be helpful. The present study investigated the volume of the corpus callosum (CC) and functional lateralization for language as potential biomarkers and their relationships in SZ and BD. The study included 20 patients with SZ, 20 patients with BD and 40 healthy controls (HC). A functional lateralization index (FLI) was computed for each participant within the language comprehension network. For each participant, the volume of the total CC and those of three subregions were extracted. These variables and their anatomo-functional relationships were investigated. In comparison to HC, SZ patients presented a decreased leftward lateralization for language, whereas this was not found in BD patients. However, as compared to SZ patients and HC, BD patients showed a reduction in CC volume associated with a lower leftward lateralization for language. Our study revealed that SZ patients displayed a reduction of the leftward functional lateralization for language; however, no reduction of CC volume was observed, whereas BD patients presented a decreased volume of the CC associated with a lower leftward asymmetry for language. The results of our study detected distinct anomalies in both SZ and BD that may be considered as specific biomarkers of these disorders related to neurodevelopmental models.

Corpus Callosum Diffusion and Language Lateralization in Patients with Brain Tumors: A DTI and fMRI Study.

Examining how left-hemisphere brain tumors might impact both the microstructure of the corpus callosum (CC) as measured by fractional anisotropy (FA) values in diffusion tensor imaging (DTI) as well as cortical language lateralization measured with functional MRI (fMRI). fMRI tasks (phonemic fluency and verb generation) were performed in order to detect activation in Broca's and Wernicke's area. Twenty patients with left-hemisphere brain tumors were investigated. fMRI results were divided into left dominant (LD), right dominant (RD), or codominant (CD) for language function. DTI was performed to generate FA maps in the anterior and posterior CC. FA values were correlated with the degree of language dominance. Patients who were LD or RD for language in Broca's area had lower FA in the anterior CC than those who were CD for language (median for CD = .72, LD = .66, RD = .65, P < .09). Lateralized versus CD group level analysis also showed that CD patients had higher FA in the anterior CC than patients who displayed strong lateralization in either hemisphere (median for CD = .72, lateralized = .65, P < .05). Our preliminary observations indicate that the greater FA in CD patients may reflect a more directional microstructure for the CC in this region, suggesting a greater need for interhemispheric transfer of information. Because brain tumors can cause compensatory codominance, our findings may suggest a mechanism by which interhemispheric transfer is facilitated during plasticity in the presence of a tumor.

Concordance Rate Between the Wada Test and fMRI for Language Lateralization in Patients with Medically Intractable Epilepsy. (P6.293)

Concordance Rate Between the Wada Test and fMRI for Language Lateralization in Patients with Medically Intractable Epilepsy. (P6.293)

Atypical language organization in temporal lobe epilepsy revealed by a passive semantic paradigm.

BackgroundMesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adults and can be successfully cured by surgery. One of the main complications of this surgery however is a decline in language abilities. The magnitude of this decline is related to the degree of language lateralization to the left hemisphere. Most fMRI paradigms used to determine language dominance in epileptic populations have used active language tasks. Sometimes, these paradigms are too complex and may result in patient underperformance. Only a few studies have used purely passive tasks, such as listening to standard speech.MethodsIn the present study we characterized language lateralization in patients with MTLE using a rapid and passive semantic language task. We used functional magnetic resonance imaging (fMRI) to study 23 patients [12 with Left (LMTLE), 11 with Right mesial temporal lobe epilepsy (RMTLE)] and 19 healthy right-handed controls using a 6 minute long semantic task in which subjects passively listened to groups of sentences (SEN) and pseudo sentences (PSEN). A lateralization index (LI) was computed using a priori regions of interest of the temporal lobe.ResultsThe LI for the significant contrasts produced activations for all participants in both temporal lobes. 81.8% of RMTLE patients and 79% of healthy individuals had a bilateral language representation for this particular task. However, 50% of LMTLE patients presented an atypical right hemispheric dominance in the LI. More importantly, the degree of right lateralization in LMTLE patients was correlated with the age of epilepsy onset.ConclusionsThe simple, rapid, non-collaboration dependent, passive task described in this study, produces a robust activation in the temporal lobe in both patients and controls and is capable of illustrating a pattern of atypical language organization for LMTLE patients. Furthermore, we observed that the atypical right-lateralization patterns in LMTLE patients was associated to earlier age at epilepsy onset. These results are in line with the idea that early onset of epileptic activity is associated to larger neuroplastic changes.

Effectiveness of four different clinical fMRI paradigms for preoperative regional determination of language lateralization in patients with brain tumors

Blood oxygen level-dependent functional magnetic resonance imaging (fMRI) has demonstrated its capability to provide comparable results to gold standard intracarotid sodium amobarbital (Wada) testing for preoperative determination of language hemispheric dominance. However, thus far, no consensus has been established regarding which fMRI paradigms are the most effective for the determination of hemispheric language lateralization in specific categories of patients and specific regions of interest (ROIs). Forty-one brain tumor patients who performed four different language tasks-rhyming (R), silent word generation (SWG) sentence completion, and sentence listening comprehension (LC)-for presurgical language mapping by fMRI were included in this study. A statistical threshold-independent lateralization index (LI) was calculated and compared among the paradigms in four different ROIs for language activation: functional Broca's (BA) and Wernicke's areas (WA) as well as larger anatomically defined expressive (EA) and receptive (RA) areas. The two expressive paradigms evaluated in this study are very good lateralizing tasks in expressive language areas; specifically, a significantly higher mean LI value was noted for SWG (0.36 ± 0.25) compared to LC (0.16 ± 0.24, p = 0.009) and for R (0.40 ± 0.22) compared to LC (0.16 ± 0.24, p = 0.001) in BA. SWG LI (0.28 ± 0.19) was higher than LC LI (0.12 ± 0.16, p = 0.01) also in EA. No significant differences in LI were found among these paradigms in WA or RA. SWG and R are sufficient for the determination of lateralization in expressive language areas, whereas new semantic or receptive paradigms need to be designed for an improved assessment of lateralization in receptive language areas.

Clinical Standardized fMRI Reveals Altered Language Lateralization in Patients with Brain Tumor

Brain tumors affecting language-relevant areas may influence language lateralization. The purpose of this study was to systematically investigate language lateralization in brain tumor patients using clinical language fMRI, comparing the results with a group of healthy volunteers. Fifty-seven strictly right-handed patients with left-hemispheric-space intracranial masses (mainly neoplastic) affecting either the Broca area (n = 19) or Wernicke area (n = 38) were prospectively enrolled in this study. Fourteen healthy volunteers served as a control group. Standardized clinical language fMRI, using visually triggered sentence- and word-generation paradigms, was performed on a 1.5T MR scanner. Semiautomated analyses of all functional data were conducted on an individual basis using BrainVoyager. A regional lateralization index was calculated for Broca and Wernicke areas separately versus their corresponding right-hemisphere homologs. In masses affecting the Broca area, a significant decrease in the lateralization index was found when performing word generation (P = .0017), whereas when applying sentence generation, the decrease did not reach statistical significance (P = .851). Masses affecting the Wernicke area induced a significant decrease of the lateralization index when performing sentence generation (P = .0007), whereas when applying word generation, the decrease was not statistically significant (P = .310). Clinical language fMRI was feasible for patients with brain tumors and provided relevant presurgical information by localizing essential language areas and determining language dominance. A significant effect of the brain masses on language lateralization was observed, with a shift toward the contralesional, nondominant hemisphere. This may reflect compensatory mechanisms of the brain to maintain communicative abilities.

Verbal declarative memory and language lateralization in patients with major depression: A functional transcranial Doppler sonography (fTCD) study

Verbal declarative memory and language lateralization in patients with major depression: A functional transcranial Doppler sonography (fTCD) study

Reduced language lateralization in first-episode schizophrenia: An fMRI index of functional asymmetry

Patients with schizophrenia exhibit a decrease or loss of normal anatomical brain asymmetry that also extends to functional levels. We applied functional magnetic resonance imaging (fMRI) to investigate language lateralization in patients with schizophrenia during their first episode of illness, thus excluding effects of chronic illness and treatment. Brain regions activated during language tasks of verb generation and passive music listening were explored in 12 first-episode patients with schizophrenia and 17 healthy controls. Regions of interest corresponded to Broca's area in the inferior frontal gyrus (IFG) and Wernicke's area in the superior temporal sulcus (STS). Patients with schizophrenia had significantly smaller lateralization indices in language-related regions than controls. A similar effect was observed in their IFG and STS regions. There was no difference between the groups in the auditory cortex for the music task. Patients with schizophrenia demonstrated greater activation than the controls in temporal regions: the difference was larger in patients with more severe positive symptom subscores. In conclusion, patients with schizophrenia demonstrated loss of normal functional brain asymmetry, as reflected in diminished lateralization of language-related activation in frontal and temporal regions. This phenomenon was already present during their first episode of psychosis, possibly reflecting developmental brain abnormalities of the illness.

Language Lateralization in Patients with Temporal Lobe Epilepsy : A Comparison between Volumetric Analysis and the Wada Test

Determining language lateralization is important for the presurgical evaluation of patients with medically intractable epilepsy. The Wada test has been the gold standard for lateralization of language dominance before epilepsy surgery. However, it is an invasive test with risk, and have some limitations. We compared the volumetric analysis with Wada test, and studied the clinical potential of volumetric analysis to assess language laterality in large surgical candidates with temporal lobe epilepsy (TLE). To examine the efficacy of volumetric analysis to determine language lateralization during presurgical evaluation, we compared the volumetric analysis of the bilateral planum temporale with the results of Wada test in 59 patients with chronic intractable TLE (rTLE, n=32; lTLE, n=27) who underwent epilepsy surgery. We measured the gray matter volumes of planum temporale (PT) of each patients using the VoxelPlus2 program (Mevisys, Daejeon, Korea). Overall congruence of the volumetric analysis with the Wada test was 97.75% in rTLE patients and 81.5% in lTLE patients. There were more significant leftward asymmetry of the PT in rTLE patients than lTLE patients. In lTLE patients, relatively high proportion (37%) of the patients showed bilateral or right hemispheric language dominance. These results provide evidence that the volumetric analysis of the PT could be used as an alternatives in language lateralization. Also, the results of the Wada test suggested that there was considerable plasticity of language representation in the brains of patients with intractable TLE and it was associated with an earlier age of brain injury.

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.

Neuropsychology: Traditional and New Methods of Investigation

The neuropsychological assessment is an integral part of the clinical investigation of patients suffering from epilepsy. The aim of the evaluation is to determine disease-related and treatment-related effects on cognition and behavior in order to orient therapeutic interventions, by taking into account the compensatory mechanisms that are available to the patient. Examples of the tests best illustrating the classical neuropsychological protocol are presented. Neuropsychology also plays an important role in the assessment of language lateralization in patients slated for epilepsy surgery. Traditionally, this has been achieved by means of the rather invasive Wada procedure. However, with the advent of new neuroimaging techniques, this procedure is gradually being replaced by minimally invasive or noninvasive methods, such as functional magnetic resonance imaging, positron emission tomography, and optical imaging. In the present paper, we discuss some of the newer techniques that are available to the neuropsychologist for the study of the impact of epilepsy on cerebral functioning.

Language Lateralization in Temporal Lobe Epilepsy: A Comparison between fMRI and the Wada Test

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). 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. 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. 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.

Left hippocampal pathology is associated with atypical language lateralization in patients with focal epilepsy

It is well recognized that the incidence of atypical language lateralization is increased in patients with focal epilepsy. The hypothesis that shifts in language dominance are particularly likely when epileptic lesions are located in close vicinity to the so-called language-eloquent areas rather than in more remote brain regions such as the hippocampus has been challenged by recent studies. This study was undertaken to assess the effect of lesions in different parts of the left hemisphere, lesions present during language acquisition, on language lateralization. We investigated 84 adult patients with drug-resistant focal epilepsy with structural lesions and 45 healthy control subjects with an established functional MRI language paradigm. Out of the 84 patients 43 had left hippocampal sclerosis, 13 a left frontal lobe lesion and 28 a left temporal-lateral lesion. All these lesions were likely to have been present during the first years of life during language acquisition. To assess the lateralization of cerebral language representation globally as well as regionally, we calculated lateralization indices derived from activations in four regions of interest (i.e. global, inferior frontal, temporo-parietal and remaining prefrontal). Patients with left hippocampal sclerosis showed less left lateralized language representations than all other groups of subjects (P < 0.005). This effect was independent of the factor of region, indicating that language lateralization was generally affected by a left hippocampal sclerosis. Patients with left frontal lobe or temporal-lateral lesions displayed the same left lateralization of language-related activations as the control subjects. Thus, the hippocampus seems to play an important role in the establishment of language dominance. Possible underlying mechanisms are discussed.

Correlation between language organization and diffusion tensor abnormalities in refractory partial epilepsy.

Atypical language organization is more frequently found in patients with refractory partial epilepsy than in healthy controls; however, the reasons for this are not well known. Here we assess the relation between language laterality index (LI) and white-matter tract changes. Nine patients with refractory partial epilepsy were assessed with a 3-T GE scanner. Functional magnetic resonance imaging (fMRI) of language and diffusion tensor imaging (DTI) were acquired. For the fMRI, a noun-verb generation task was performed, all images were motion corrected, and activated pixels in classic language areas were counted. The DTI images were acquired in six standard directions with an initial non-diffusion-weighted scan. The "average anisotropy" was determined in a region of interest in the frontal lobe, temporal lobe, and parietal lobe white matter. An asymmetry index (AI) was calculated for language and DTI. Atypical language lateralization was diagnosed if the lateralization index (LI)-language was smaller than 0.4. Two of the nine patients had atypical language localization (LI-language, -0.6, and 0.3); both had left temporal DTI asymmetry (LI-DTI, -0.3 and -0.2). The remaining seven patients had typical language localization, and no marked DTI abnormalities. Asymmetry in temporal lobe DTI correlated with LI-language (r= 0.8; p = 0.006). Atypical language lateralization in patients with partial epilepsy may be associated with white-matter tract abnormalities.

Language lateralization in patients with temporal lobe epilepsy: a comparison of functional transcranial Doppler sonography and the Wada test

This study prospectively investigates whether noninvasive functional transcranial Doppler sonography (fTCD) is a useful tool to determine hemispheric language lateralization in the presurgical evaluation of patients with medically intractable temporal lobe epilepsy (TLE). fTCD results were compared with the Wada test as the gold standard. Wada test and fTCD were performed in 13 patients suffering from TLE. fTCD continuously measured blood flow velocities in both middle cerebral arteries, while the patient was performing a cued word generation task. During the Wada test, spontaneous speech, comprehension, reading, naming, and repetition were investigated. A laterality index (LI) was obtained by both procedures. Due to a lack of an acoustic temporal bone window, fTCD could not be performed in two patients (15%). In 9 of the remaining 11 patients hemispheric language dominance was found on the left side, in 1 patient on the right side, and 1 patient showed bihemispheric language representation. In all patients fTCD and the Wada test were in good agreement regarding hemispheric language lateralization, and the LI of both techniques were highly correlated ( r = 0.776, P = 0.005). fTCD gives predictions of hemispheric language dominance consistent with the Wada test results even in children, patients with low IQ, and nonnative speakers. It is an alternative to the Wada test in determining language lateralization in patients with temporal lobe epilepsy.

Quantitative fMRI assessment of the differences in lateralization of language-related brain activation in patients with temporal lobe epilepsy

Defining language lateralization is important to minimize morbidity in patients treated surgically for temporal lobe epilepsy (TLE). Functional magnetic resonance imaging (fMRI) offers a promising, noninvasive, alternative strategy to the Wada test. Here we have used fMRI to study healthy controls and patients with TLE in order to (i) define language-related activation patterns and their reproducibility; (ii) compare lateralization determined by fMRI with those from of the Wada test; and (iii) contrast different methods of assessing fMRI lateralization. Twelve healthy right-handed controls and 19 right-handed preoperative patients with TLE (12 left- and seven right-TLE) were studied at 3T using fMRI and a verbal fluency paradigm. A Wada test also was performed on each of the patients. Greater activation was found in several areas in the right hemisphere for the left-TLE group relative to controls or right-TLE patients. Relative hemispheric activations calculated based on either the extent or the mean signal change gave consistent results showing a more bihemispheric language representation in the left-TLE patients. There was good agreement between the Wada and fMRI results, although the latter were more sensitive to involvement of the nondominant right hemisphere. The reproducibility of the fMRI values was lowest for the more bihemispherically represented left-TLE patients. Overall, our results further demonstrate that noninvasive fMRI measures of language-related lateralization may provide a practical and reliable alternative to invasive testing for presurgical language lateralization in patients with TLE. The high proportion (33%) of left-TLE patients showing bilateral or right hemispheric language-related lateralization suggests that there is considerable plasticity of language representation in the brains of patients with intractable TLE.