Intracarotid Amobarbital Procedure Research Articles

WADA test for postoperative memory prediction in left TLE. Is it still useful in the 21st century?

BackgroundEpilepsy surgery offers an effective treatment to achieve seizure freedom in refractory temporal lobe epilepsy. Since left temporal lobe surgery can be associated with verbal memory deterioration, control of cognitive decline is a main goal of therapy. This study analyzes the prognostic value of intracarotid amobarbital procedure (Wada test) in addition to specific neuropsychological and clinical variables for postoperative memory changes. MethodBetween 2013 and 2021 thirty-six patients (18 females, 18 males, mean age 41.0 years) from the Epilepsy Center Erlangen (ECE) with left hemispheric temporal lobe epilepsy underwent neuropsychological assessment preoperatively – including the Wada test – and six months postoperatively. In addition, a group of 92 patients (40 females, 52 males, mean age 36.1 years) with left or right hemispheric focus who underwent Wada test and surgery before 2013 was included as a standardization group. In all patients Wada test was carried out preoperatively to determine language dominance and memory capacity. ResultsPostoperative verbal memory scores showed no significant difference from preoperative performance. Preoperative verbal memory performance as well as the hippocampal resection extent is particularly important in predicting postoperative verbal memory change. After left temporal lobe surgery, a significantly higher postoperative functional level was shown for figural memory. Specifically, a good contralateral hemispheric performance level assessed by the Wada test proved to be a compensatory factor for postoperative losses. ConclusionThe Wada test is no longer necessary as a diagnostic tool for a broad group of patients with temporal lobe epilepsy. However, it can be useful for a subgroup of patients with clinical indicators such as nonspecific or incongruent preoperative verbal and figural memory impairments. In this study, Wada test data about the functional level of the contralateral hemisphere specifically allowed estimation of postoperative figural memory changes.

Drug load and memory during intracarotid amobarbital procedure in epilepsy.

Anti-seizure medications (ASMs) have been related to poor cognitive function, but their relationship with intracarotid amobarbital procedure (IAP) results remains unclear. To elucidate whether the number and drug load of ASMs are associated with memory scores of the IAP and the neuropsychological assessment. Fifty-nine adult patients with drug-resistant epilepsy (mean age=36.1, SD=11.6) underwent bilateral IAP (with drawings and words as memory items) and a neuropsychological assessment to assess the risk of post-surgical memory decline. Total ASM drug load was calculated by summing the daily dose/defined daily dose ratio of every ASM of each patient. Pearson's correlations and hierarchical regressions were computed. Total IAP memory score was associated with total ASM drug load (r=-0.30, p=0.02) and seizure frequency (r=-0.25, p=0.05). After controlling clinical variables, total ASM drug load explained 16% of the variance of total IAP memory score. This relationship was especially prominent in patients with left hemisphere focus (r=-0.33, p=0.04). The number of current ASMs was not related to IAP memory score (r=-0.16, p=0.24). The number or drug load of ASMs were not related to neuropsychological assessment results (for all, p>0.07). Our findings suggest that total drug load can be a confounding variable in the IAP memory performance that could explain, at least in part, the reverse asymmetries reported in different studies.

Utilization of MEG Among the US Epilepsy Centers: A Survey-Based Appraisal.

The purported underutilization of magnetoencephalography (MEG) among the USA epilepsy centers has never been studied, and any evidence-based understanding of its magnitude is lacking. Two hundred twenty-five National Association of Epilepsy Centers centers (2016) were invited to participate anonymously in a 13-question web-based survey of clinical practice focused on MEG use. On average, centers (N = 70; 61 of which were level 4) reported <6 epileptologists, >7 dedicated epilepsy monitoring unit beds, 206 phase 1 studies, 15 phase 2 studies, 10 direct resections, and 9 indirect resections; 27% owned MEG. On average, 11.2 MEGs per year were ordered for epilepsy localization and 7.6 for any presurgical mapping modalities. Wada test aka the intracarotid sodium amobarbital procedure (ISAP) (43%) and functional MRI (29%) were preferred over MEG (4%) for language mapping. The number of epileptologists and the number of epilepsy monitoring unit beds correlated positively with the most clinical volumes. The centers who own a MEG had surgical volumes significantly higher than those without. The number and complexity of patients as well as the proximity of a MEG were perceived as significant contributors/obstacles to increased MEG use. Only the centers with larger surgical volumes incorporate MEG regularly in presurgical evaluation of patients with drug-resistant epilepsy. A reversal of the pervasive underutilization of epilepsy surgery can benefit from MEG, but this requires a sustained concerted promotion by the epilepsy and MEG communities.

Optimizing Magnetoencephalographic Imaging Estimation of Language Lateralization for Simpler Language Tasks.

Magnetoencephalographic imaging (MEGI) offers a non-invasive alternative for defining preoperative language lateralization in neurosurgery patients. MEGI indeed can be used for accurate estimation of language lateralization with a complex language task – auditory verb generation. However, since language function may vary considerably in patients with focal lesions, it is important to optimize MEGI for estimation of language function with other simpler language tasks. The goal of this study was to optimize MEGI laterality analyses for two such simpler language tasks that can have compliance from those with impaired language function: a non-word repetition (NWR) task and a picture naming (PN) task. Language lateralization results for these two tasks were compared to the verb-generation (VG) task. MEGI reconstruction parameters (regions and time windows) for NWR and PN were first defined in a presurgical training cohort by benchmarking these against laterality indices for VG. Optimized time windows and regions of interest (ROIs) for NWR and PN were determined by examining oscillations in the beta band (12–30 Hz) a marker of neural activity known to be concordant with the VG laterality index (LI). For NWR, additional ROIs include areas MTG/ITG and for both NWR and PN, the postcentral gyrus was included in analyses. Optimal time windows for NWR were defined as 650–850 ms (stimulus-locked) and −350 to −150 ms (response-locked) and for PN −450 to −250 ms (response-locked). To verify the optimal parameters defined in our training cohort for NWR and PN, we examined an independent validation cohort (n = 30 for NWR, n = 28 for PN) and found high concordance between VG laterality and PN laterality (82%) and between VG laterality and NWR laterality (87%). Finally, in a test cohort (n = 8) that underwent both the intracarotid amobarbital procedure (IAP) test and MEG for VG, NWR, and PN, we identified excellent concordance (100%) with IAP for VG + NWR + PN composite LI, high concordance for PN alone (87.5%), and moderate concordance for NWR alone (66.7%). These findings provide task options for non-invasive language mapping with MEGI that can be calibrated for language abilities of individual patients. Results also demonstrate that more accurate estimates can be obtained by combining laterality estimates obtained from multiple tasks. MEGI

Presurgical Language fMRI in Children, Adolescents and Young Adults : AValidation Study.

To validate four established, child-friendly functional magnetic resonance imaging (fMRI) language tasks (word chain task [WCT], vowel identification task [VIT], synonym task [SYT] and beep story task [BST]) in apredominantly pediatric cohort. Intracarotid amobarbital procedures (IAP) (n = 17) and unchanged language after hemispherotomy (n = 6) were used as gold standards. The fMRI activations of nine regions of interest (ROI) in the frontal, temporal and parietal lobes as well as in the cerebellum were visually assessed in 23fMRI examinations (in total 117 fMRI task sessions) of 23patients (age range 10.0-23.0 years) with drug-refractory epilepsies. The ROIs were considered valid when they showed activation in more than 25% of all sessions for the respective task and never showed false lateralization (in comparison to gold standards). Thus, 13valid, task-specific ROIs were identified: 5 ROIs for the WCT (frontal operculum, inferior frontal gyrus, middle frontal gyrus, intraparietal sulcus, cerebellum), 3 ROIs for the VIT (frontal operculum, inferior frontal gyrus, middle frontal gyrus), 3 ROIs for the SYT (frontal operculum, inferior frontal gyrus, temporal language area) and 2 ROIs for the BST (inferior frontal gyrus, middle frontal gyrus). Clinical fMRI using the battery of four tasks is avalid tool for lateralizing language in children, adolescents and young adults. Each task proved to be specifically useful, which confirms that applying different tasks increases the probability of diagnosing language dominance in presurgical candidates.

Cortical gray–white matter blurring and declarative memory impairment in MRI-negative temporal lobe epilepsy

Magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE) may be a distinct syndrome from TLE with mesial temporal sclerosis (TLE-MTS). Imaging and neuropsychological features of TLE-MTS are well-known; yet, these features are only beginning to be described in MRI-negative TLE. This study examined whether a quantitative measure of cortical gray and white matter blurring (GWB) was elevated in the temporal lobes ipsilateral to the seizure onset zone of individuals with MRI-negative TLE relative to TLE-MTS and healthy controls (HCs) and whether GWB elevations were associated with neuropsychological comorbidity. Gray–white matter blurring from 34 cortical regions and hippocampal volumes were quantified and compared across 28 people with MRI-negative TLE, 15 people with TLE-MTS, and 51 HCs. Declarative memory was assessed with standard neuropsychological tests and the intracarotid amobarbital procedure (IAP). In the group with MRI-negative TLE (left and right onsets combined), hippocampal volumes were within normal range but GWB was elevated, relative to HCs, across several mesial and lateral temporal lobe regions ipsilateral to the seizure onset zone. Gray–white matter blurring did not differ between the groups with TLE-MTS and HC or between the groups with TLE-MTS and MRI-negative TLE. The group with MRI-negative TLE could not be distinguished from the group with TLE-MTS on any of the standard neuropsychological tests; however, ipsilateral hippocampal volumes and IAP memory scores were lower in the group with TLE-MTS than in the group with MRI-negative TLE. The group with left MRI-negative TLE had lower general cognitive abilities and verbal fluency relative to the HC group, which adds to the characterization of neuropsychological comorbidities in left MRI-negative TLE. In addition, ipsilateral IAP memory performance was reduced relative to contralateral memory performance in MRI-negative TLE, indicating some degree of ipsilateral memory dysfunction. There was no relationship between hippocampal volume and IAP memory scores in MRI-negative TLE; however, decreased ipsilateral IAP memory scores were correlated with elevated GWB in the ipsilateral superior temporal sulcus of people with left MRI-negative TLE. In sum, GWB elevations in the ipsilateral temporal lobe of people with MRI-negative TLE suggest that GWB may serve as a marker for reduced structural integrity in regions in or near the seizure onset zone. Although mesial temporal abnormalities might be the major driver of memory dysfunction in TLE-MTS, a loss of structural integrity in lateral temporal lobe regions may contribute to IAP memory dysfunction in MRI-negative TLE.

A simple magnetoencephalographic auditory paradigm may aid in confirming left-hemispheric language dominance in epilepsy patients.

ObjectiveThe intracarotid amobarbital procedure (IAP) is the current “gold standard” in the preoperative assessment of language lateralization in epilepsy surgery candidates. It is, however, invasive and has several limitations. Here we tested a simple noninvasive language lateralization test performed with magnetoencephalography (MEG).MethodsWe recorded auditory MEG responses to pairs of vowels and pure tones in 16 epilepsy surgery candidates who had undergone IAP. For each individual, we selected the pair of planar gradiometer sensors with the strongest N100m response to vowels in each hemisphere and—from the vector sum of signals of this gradiometer pair—calculated the vowel/tone amplitude ratio in the left (L) and right (R) hemisphere and, subsequently, the laterality index: LI = (L–R)/(L+R). In addition to the analysis using a single sensor pair, an alternative analysis was performed using averaged responses over 18 temporal sensor pairs in both hemispheres.ResultsThe laterality index did not correlate significantly with the lateralization data obtained from the IAP. However, an MEG pattern of stronger responses to vowels than tones in the left hemisphere and stronger responses to tones than vowels in the right hemisphere was associated with left-hemispheric language dominance in the IAP in all the six patients who showed this pattern. This results in a specificity of 100% and a sensitivity of 67% of this MEG pattern in predicting left-hemispheric language dominance (p = 0.01, Fisher's exact test). In the analysis using averaged responses over temporal channels, one additional patient who was left-dominant in IAP showed this particular MEG pattern, increasing the sensitivity to 78% (p = 0.003).SignificanceThis simple MEG paradigm shows promise in feasibly and noninvasively confirming left-hemispheric language dominance in epilepsy surgery candidates. It may aid in reducing the need for the IAP, if the results are confirmed in larger patient samples.

Assessment of grammar optimizes language tasks for the intracarotid amobarbital procedure

PurposeA previous study showed that assessment of language laterality could be improved by adding grammar tests to the recovery phase of the intracarotid amobarbital procedure (IAP) (Połczyńska et al. 2014). The aim of this study was to further investigate the extent to which grammar tests lateralize language function during the recovery phase of the IAP in a larger patient sample. MethodsForty patients with drug-resistant epilepsy (14 females, thirty-two right-handed, mean age 38.5years, SD=10.6) participated in this study. On EEG, 24 patients had seizures originating in the left hemisphere (LH), 13 in the right hemisphere (RH), and 4 demonstrated mixed seizure origin. Thirty participants (75%) had bilateral injections, and ten (25%) had unilateral injections (five RH and five LH). Based on results from the encoding phase, we segregated our study participants to a LH language dominant and a mixed dominance group. In the recovery phase of the IAP, the participants were administered a new grammar test (the CYCLE-N) and a standard language test. We analyzed the laterality index measure and effect sizes in the two tests. Key findingsIn the LH-dominant group, the CYCLE-N generated more profound language deficits in the recovery phase than the standard after injection to either hemisphere (p<0.001). At the same time, the laterality index for the grammar tasks was still higher than for the standard tests. Critically, the CYCLE-N administered in the recovery phase was nearly as effective as the standard tests given during the encoding phase. SignificanceThe results may be significant for individuals with epilepsy undergoing IAP. The grammar tests may be a highly efficient measure for lateralizing language function in the recovery phase.

Author response: Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

Objective: To assess the diagnostic accuracy and prognostic value of functional MRI (fMRI) in determining lateralization and predicting postsurgical language and memory outcomes. Methods: An 11-member panel evaluated and rated available evidence according to the 2004 American Academy of Neurology process. At least 2 panelists reviewed the full text of 172 articles and selected 37 for data extraction. Case reports, reports with Results and recommendations: The use of fMRI may be considered an option for lateralizing language functions in place of intracarotid amobarbital procedure (IAP) in patients with medial temporal lobe epilepsy (MTLE; Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C). For patients with temporal neocortical epilepsy or temporal tumors, the evidence is insufficient (Level U). fMRI may be considered to predict postsurgical language deficits after anterior temporal lobe resection (Level C). The use of fMRI may be considered for lateralizing memory functions in place of IAP in patients with MTLE (Level C) but is of unclear utility in other epilepsy types (Level U). fMRI of verbal memory or language encoding should be considered for predicting verbal memory outcome (Level B). fMRI using nonverbal memory encoding may be considered for predicting visuospatial memory outcomes (Level C). Presurgical fMRI could be an adequate alternative to IAP memory testing for predicting verbal memory outcome (Level C). Clinicians should carefully advise patients of the risks and benefits of fMRI vs IAP during discussions concerning choice of specific modality in each case.

Practice guideline summary: Use of fMRI in the presurgical evaluation of patients with epilepsy

To assess the diagnostic accuracy and prognostic value of functional MRI (fMRI) in determining lateralization and predicting postsurgical language and memory outcomes. An 11-member panel evaluated and rated available evidence according to the 2004 American Academy of Neurology process. At least 2 panelists reviewed the full text of 172 articles and selected 37 for data extraction. Case reports, reports with <15 cases, meta-analyses, and editorials were excluded. The use of fMRI may be considered an option for lateralizing language functions in place of intracarotid amobarbital procedure (IAP) in patients with medial temporal lobe epilepsy (MTLE; Level C), temporal epilepsy in general (Level C), or extratemporal epilepsy (Level C). For patients with temporal neocortical epilepsy or temporal tumors, the evidence is insufficient (Level U). fMRI may be considered to predict postsurgical language deficits after anterior temporal lobe resection (Level C). The use of fMRI may be considered for lateralizing memory functions in place of IAP in patients with MTLE (Level C) but is of unclear utility in other epilepsy types (Level U). fMRI of verbal memory or language encoding should be considered for predicting verbal memory outcome (Level B). fMRI using nonverbal memory encoding may be considered for predicting visuospatial memory outcomes (Level C). Presurgical fMRI could be an adequate alternative to IAP memory testing for predicting verbal memory outcome (Level C). Clinicians should carefully advise patients of the risks and benefits of fMRI vs IAP during discussions concerning choice of specific modality in each case.

Resting-State Functional MR Imaging for Determining Language Laterality in Intractable Epilepsy.

Purpose To measure the accuracy of resting-state functional magnetic resonance (MR) imaging in determining hemispheric language dominance in patients with medically intractable focal epilepsies against the results of an intracarotid amobarbital procedure (IAP). Materials and Methods This study was approved by the institutional review board, and all subjects gave signed informed consent. Data in 23 patients with medically intractable focal epilepsy were retrospectively analyzed. All 23 patients were candidates for epilepsy surgery and underwent both IAP and resting-state functional MR imaging as part of presurgical evaluation. Language dominance was determined from functional MR imaging data by calculating a laterality index (LI) after using independent component analysis. The accuracy of this method was assessed against that of IAP by using a variety of thresholds. Sensitivity and specificity were calculated by using leave-one-out cross validation. Spatial maps of language components were qualitatively compared among each hemispheric language dominance group. Results Measurement of hemispheric language dominance with resting-state functional MR imaging was highly concordant with IAP results, with up to 96% (22 of 23) accuracy, 96% (22 of 23) sensitivity, and 96% (22 of 23) specificity. Composite language component maps in patients with typical language laterality consistently included classic language areas such as the inferior frontal gyrus, the posterior superior temporal gyrus, and the inferior parietal lobule, while those of patients with atypical language laterality also included non-classical language areas such as the superior and middle frontal gyri, the insula, and the occipital cortex. Conclusion Resting-state functional MR imaging can be used to measure language laterality in patients with medically intractable focal epilepsy. (©) RSNA, 2016 Online supplemental material is available for this article.

Neuropsychology's Role in Pediatric Epilepsy Surgery

Neuropsychology plays an essential role in pediatric epilepsy surgery. Evaluations provide information to inform presurgical decision-making by addressing localization and lateralization of deficits and by informing risk of postsurgical decline. The pediatric neuropsychologist also assists with multiple additional procedures, including the Wada or Intracarotid amobarbital procedure, functional magnetic resonance imaging, and brain mapping (on the ward and in the operating room), to measure localization and lateralization of eloquent cortex as well as adequacy of brain tissue to be resected and risk of resection of specific cortex. Neuropsychology provides postsurgical outcome information not only for individual patients, but as “quality control” for epilepsy surgery. Multiple factors complicate individual patient data interpretation, and these factors are essential to understand and consider. Developmental considerations are paramount. Although methodological differences between studies can also make surgical outcome studies challenging to interpret, neuropsychological data suggest that pediatric surgery can improve developmental outcomes and trajectories, particularly if resection is done early and without lengthy presurgical seizure duration, although longer seizure duration and polypharmacy, more widespread disease, and larger areas of resection, particularly of critical eloquent cortex, can be costly to the individual patient. Additional and more refined research is needed.

Contributions of Magnetoencephalography to Characterizing Brain Function in Pediatric Epilepsy: Evidences of Validity and Added Value

Magnetoencephalography (MEG) and magnetic source imaging are considered among the few available noninvasive modalities that can address, in pediatric populations, clinically relevant questions at the individual level. The contribution of MEG to the localization of the irritative zone (based on interictal epileptiform discharges), and the characterization of function-specific cortex (i.e., functional mapping), has proven to be as accurate as those derived from invasive “gold standard” procedures like the intracarotid amobarbital procedure and cortical stimulation mapping. Here, we will review some of the evidences supporting the added value of MEG in the study of pediatric epilepsy with special interest in the seminal studies where the clinical validity of MEG has been established after comparing MEG-derived estimates with those derived from the well-established invasive “gold standard” procedures. In the first section, we revisit a study where MEG is applied to characterize distinct patterns of propagation of interictal epileptiform discharges in relation with the clinical evolution of children with typical and atypical variants of benign rolandic epilepsy. This study serves to illustrate the additional value of MEG's high spatiotemporal resolution. Intralobar, interlobar, and interhemispheric patterns of propagation were demonstrated using MEG and associated to the clinical features exhibited by children with rolandic epilepsy. The second section of this article reviews part of the experience accumulated, in more than 800 clinical cases, by the MEG Laboratory at the University of Texas-Houston. In different studies, MEG-derived estimates for language and sensorimotor functions were compared with those derived from the gold standard invasive procedures (i.e., intracarotid amobarbital procedure and direct cortical stimulation) and tested against surgical outcome measurements. In these studies, authors benefit from some of the strengths of MEG as a valid, and noninvasive, tool to characterize brain function in pediatric population, demonstrating the utility of MEG in studying the issue of epilepsy in the developing brain.

Quantitative EEG is an objective, sensitive, and reliable indicator of transient anesthetic effects during Wada tests.

The intracarotid amobarbital or Wada procedure is a component of the presurgical evaluation for refractory epilepsy, during which monitoring the onset and offset of transient anesthetic effects is critical. In this study, the authors characterized changes of 8 quantitative measures during 26 Wada tests, which included alpha, beta, theta, and delta powers, alpha/delta power ratio, beta/delta power ratio, median amplitude-integrated EEG, and 90% spectral edge frequency (SEF90), and correlated them with contralateral hemiplegia. The authors found that on the side of injection, delta and theta powers, alpha/delta power ratio, beta/delta power ratio, and SEF90 peaked within 1 minute after injection of 70 to 150 mg amobarbital or 4 to 7 mg methohexital. When contralateral arm strength returned to 3/5, delta power and amplitude-integrated EEG decayed on average 24% and 19%, respectively, for amobarbital, similar to that of methohexital (27% and 18%). Because delta power resolution most closely mirrored that of the hemiplegia and amplitude-integrated EEG had the highest signal/noise ratio, these quantitative values appear to be the best measures for decay of anesthetic effects. Increase in alpha power persisted longest, and therefore may be the best measure of late residual anesthetic effects.

Application of envelope trend to analyze early EEG changes in the frontal regions during intracarotid amobarbital procedure in children

BackgroundIntracarotid amobarbital procedure (IAP) is acknowledged as the gold standard test for language lateralization. EEG is performed routinely during IAP to monitor the anesthetization of a brain hemisphere. Here, we studied the correlation between the early EEG changes using envelope trend and the clinical outcome of IAP. MethodFifty consecutive patients underwent IAP at Texas Children's Hospital (2004–2009). Intracarotid amobarbital procedure was considered “complete” or “incomplete” based on the outcome if the procedure was completed or aborted due to behavior changes. Envelope trend was used to calculate the median EEG amplitude changes within the first 60s of IAP. Statistical analysis was performed to determine the role of EEG changes and clinical features on the procedure outcome. ResultsOnly 30 IAP-EEG files were available for review. Amobarbital was administered at the dose of 60–150mg (mean: 110±20). The intracarotid amobarbital procedure was recorded as complete in 23 patients and incomplete in 7 patients. EEG changes occurred within the first few seconds following amobarbital injection. Following amobarbital injection, focal slowing was present in the ipsilateral frontal region or both ipsilateral and contralateral frontal regions. Elapsed time to the first EEG change or duration and change in median EEG amplitude in the ipsilateral frontal regions were indifferent between the complete and incomplete groups (p>0.05). However, the median amplitude changes between the ipsilateral and contralateral frontal regions within each group were found significant only in the complete group (p<0.05), suggesting ipsilateral without contralateral frontal slowing. Other than age at the time of IAP (p=0.03), none of the other clinical features correlated with the clinical outcome of IAP (p>0.05). ConclusionEarly EEG changes during IAP using envelope trend may predict successful completion of the IAP test. Younger children are at risk of behavioral changes during IAP.

Atypical cortical language organization in epilepsy patients: evidence for divergent hemispheric dominance for receptive and expressive language function.

The central goal of presurgical language mapping is to identify brain regions that subserve cortical language function to minimize postsurgical language deficits. Presurgical language mapping in patients with epilepsy presents a key challenge because of the atypical pattern of hemispheric language dominance found in this population, with higher incidences of bilateral and right-biased language dominance than typical. In this prospective study, we combine magnetoencephalography with a panel of tasks designed to separately assess receptive and expressive function to provide a sensitive measure of language function in 15 candidates for resective surgery. We report the following: 4 of 15 patients (27%) showed left hemisphere dominance across all tasks, 4 of 15 patients (27%) showed right hemisphere dominance across all tasks, and 7 of 15 (46%) showed discordant language dominance, with right-dominant receptive and left-dominant expressive language. All patients with discordant language dominance showed this right-receptive and left-expressive pattern. Results provide further evidence supporting the importance of using a panel of tasks to assess separable aspects of language function. The clinical relevance of the findings is discussed, especially about current clinical operative measures for assessing language dominance, which use single hemisphere procedure (intracarotid amobarbital procedure and awake intraoperative stimulation) for determining language laterality.

Intracarotid Etomidate is a Safe Alternative to Sodium Amobarbital for the Wada Test

The Wada procedure (the intracarotid amobarbital procedure) has been used widely to evaluate the hemispheric dominance of language and memory before temporal lobe surgery in patients with medically refractory seizures. Because of repeated shortage of sodium amobarbital, attempts have been made to find a suitable alternative to sodium amobarbital. The aim of our study was to review our experience with the use of etomidate as an alternative to sodium amobarbital for Wada testing in patients with medically refractory seizures. After the ethics approval, we retrospectively reviewed the charts of 29 consecutive patients who underwent Wada test with etomidate. Data from a total of 50 hemispheric injections were reviewed and analyzed. This included the electroencephalographic and motor effects of etomidate injection and their time course (onset and recovery), Wada test results (language laterality and memory performance), and all adverse events during the procedure. Intracarotid administration of etomidate produced a predictable electroencephalographic and motor effects in all patients. The desirable effect was seen with a single bolus dose of 2 mg followed by an infusion. Shivering was the most common side effect, seen in all the patients. Successful testing was possible in nearly all patients without any major side effects. The "pass rate" of valid tests was in good accord with our previous experience with the use of sodium amobarbital. From our experience, etomidate is a safe alternative to sodium amobarbital for the Wada test for determining the hemispheric dominance for speech and in predicting the memory outcome.

GEBIN 2013 Sponsors

The intracarotid sodium amobarbital procedure (IAP) is currently regarded as the best method for the determination of hemispheric specialization for speech, and it is universally relied on as a prognostic test for patients with medically refractory epilepsy who are candidates for neurosurgical intervention. Since its initial development, the IAP also has been adapted for assesssing lateralized mesiotemporal contributions to memory functioning in this patient population, and it is now in wide use for both basic and applied research in behavioral neuroscience on language, memory, visuospatial functions, emotion, attention, and consciousness. Despite the IAP's wide range of applications, little has been said about its history and development. This essay recounts and discusses this history.

Language Lateralization Represented by Spatiotemporal Mapping of Magnetoencephalography

Determination of hemispheric language dominance is critical for planning epilepsy surgery. We assess the usefulness of spatiotemporal source analysis of magnetoencephalography for determining language laterality. Thirty-five patients with epilepsy were studied. The patients performed a semantic word-processing task during MEG recording. Epochs containing language-related neuromagnetic activity were averaged after preprocessing. The averaged data between 250 and 550 ms after stimulus were analyzed by using dynamic statistical parametric mapping. ROIs were obtained in the opercular and triangular parts of the inferior frontal gyrus, superior temporal gyrus, and supramarginal gyrus in both hemispheres. We calculated laterality indices according to 1) dSPM-amplitude method, based on the amplitude of activation in the ROIs, and 2) dSPM-counting method, based on the number of unit dipoles with activation over a threshold in the ROIs. The threshold was determined as half of the maximum value in all ROIs for each patient. A LI ≥0.10 or ≤-0.10 was considered left- or right-hemisphere dominance, respectively; a LI between -0.10 and 0.10 was considered bilateral. All patients underwent an intracarotid amobarbital procedure as part of presurgical evaluation. The dSPM-counting method demonstrated laterality consistent with the IAP in 32 of 35 patients (91.4%), the remaining 3 (8.6%) demonstrated bilateral language representation, whereas the dSPM-amplitude method showed 18 (51.4%) concordant and 17 (48.6%) bilateral. No laterality opposite to the IAP was found. Spatiotemporal mapping of language lateralization with the dSPM-counting method may reduce the necessity for an IAP in as many as 90% of patients.

Dynamics of hemispheric dominance for language assessed by magnetoencephalographic imaging

The goal of the current study was to examine the dynamics of language lateralization using magnetoencephalographic (MEG) imaging, to determine the sensitivity and specificity of MEG imaging, and to determine whether MEG imaging can become a viable alternative to the intracarotid amobarbital procedure (IAP), the current gold standard for preoperative language lateralization in neurosurgical candidates. MEG was recorded during an auditory verb generation task and imaging analysis of oscillatory activity was initially performed in 21 subjects with epilepsy, brain tumor, or arteriovenous malformation who had undergone IAP and MEG. Time windows and brain regions of interest that best discriminated between IAP-determined left or right dominance for language were identified. Parameters derived in the retrospective analysis were applied to a prospective cohort of 14 patients and healthy controls. Power decreases in the beta frequency band were consistently observed following auditory stimulation in inferior frontal, superior temporal, and parietal cortices; similar power decreases were also seen in inferior frontal cortex prior to and during overt verb generation. Language lateralization was clearly observed to be a dynamic process that is bilateral for several hundred milliseconds during periods of auditory perception and overt speech production. Correlation with the IAP was seen in 13 of 14 (93%) prospective patients, with the test demonstrating a sensitivity of 100% and specificity of 92%. Our results demonstrate excellent correlation between MEG imaging findings and the IAP for language lateralization, and provide new insights into the spatiotemporal dynamics of cortical speech processing.