Presurgical language fMRI: Technical practices in epilepsy surgical planning.

Little is known about how language functional MRI (fMRI) is executed in clinical practice in spite of its widespread use. Here we comprehensively documented its execution in surgical planning in epilepsy. A questionnaire focusing on cognitive design, image acquisition, analysis and interpretation, and practical considerations was developed. Individuals responsible for collecting, analyzing, and interpreting clinical language fMRI data at 63 epilepsy surgical programs responded. The central finding was of marked heterogeneity in all aspects of fMRI. Most programs use multiple tasks, with a fifth routinely using 2, 3, 4, or 5 tasks with a modal run duration of 5 min. Variants of over 15 protocols are in routine use with forms of noun-verb generation, verbal fluency, and semantic decision-making used most often. Nearly all aspects of data acquisition and analysis vary markedly. Neither of the two best-validated protocols was used by more than 10% of respondents. Preprocessing steps are broadly consistent across sites, language-related blood flow is most often identified using general linear modeling (76% of respondents), and statistical thresholding typically varies by patient (79%). The software SPM is most often used. fMRI programs inconsistently include input from experts with all required skills (imaging, cognitive assessment, MR physics, statistical analysis, and brain-behavior relationships). These data highlight marked gaps between the evidence supporting fMRI and its clinical application. Teams performing language fMRI may benefit from evaluating practice with reference to the best-validated protocols to date and ensuring individuals trained in all aspects of fMRI are involved to optimize patient care.

Presurgical language fMRI: Clinical practices and patient outcomes in epilepsy surgical planning.

The goal of this study was to document current clinical practice and report patient outcomes in presurgical language functional MRI (fMRI) for epilepsy surgery. Epilepsy surgical programs worldwide were surveyed as to the utility, implementation, and efficacy of language fMRI in the clinic; 82 programs responded. Respondents were predominantly US (61%) academic programs (85%), and evaluated adults (44%), adults and children (40%), or children only (16%). Nearly all (96%) reported using language fMRI. Surprisingly, fMRI is used to guide surgical margins (44% of programs) as well as lateralize language (100%). Sites using fMRI for localization most often use a distance margin around activation of 10mm. While considered useful, 56% of programs reported at least one instance of disagreement with other measures. Direct brain stimulation typically confirmed fMRI findings (74%) when guiding margins, but instances of unpredicted decline were reported by 17% of programs and 54% reported unexpected preservation of function. Programs reporting unexpected decline did not clearly differ from those which did not. Clinicians using fMRI to guide surgical margins do not typically map known language-critical areas beyond Broca's and Wernicke's. This initial data shows many clinical teams are confident using fMRI not only for language lateralization but also to guide surgical margins. Reported cases of unexpected language preservation when fMRI activation is resected, and cases of language decline when it is not, emphasize a critical need for further validation. Comprehensive studies comparing commonly-used fMRI paradigms to predict stimulation mapping and post-surgical language decline remain of high importance.

Presurgical language fMRI: Mapping of six critical regions.

Language mapping is a key goal in neurosurgical planning. fMRI mapping typically proceeds with a focus on Broca's and Wernicke's areas, although multiple other language-critical areas are now well-known. We evaluated whether clinicians could use a novel approach, including clinician-driven individualized thresholding, to reliably identify six language regions, including Broca's Area, Wernicke's Area (inferior, superior), Exner's Area, Supplementary Speech Area, Angular Gyrus, and Basal Temporal Language Area. We studied 22 epilepsy and tumor patients who received Wada and fMRI (age 36.4[12.5]; Wada language left/right/mixed in 18/3/1). fMRI tasks (two × three tasks) were analyzed by two clinical neuropsychologists who flexibly thresholded and combined these to identify the six regions. The resulting maps were compared to fixed threshold maps. Clinicians generated maps that overlapped significantly, and were highly consistent, when at least one task came from the same set. Cases diverged when clinicians prioritized different language regions or addressed noise differently. Language laterality closely mirrored Wada data (85% accuracy). Activation consistent with all six language regions was consistently identified. In blind review, three external, independent clinicians rated the individualized fMRI language maps as superior to fixed threshold maps; identified the majority of regions significantly more frequently; and judged language laterality to mirror Wada lateralization more often. These data provide initial validation of a novel, clinician-based approach to localizing language cortex. They also demonstrate clinical fMRI is superior when analyzed by an experienced clinician and that when fMRI data is of low quality judgments of laterality are unreliable and should be withheld. Hum Brain Mapp 38:4239-4255, 2017. © 2017 Wiley Periodicals, Inc.

Assessment of grammar optimizes language tasks for the intracarotid amobarbital procedure.

PURPOSE: A 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) (Polczynska 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. METHODS: Forty 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 FINDINGS: In 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. SIGNIFICANCE: The 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.

Role of the Wada test and functional magnetic resonance imaging in preoperative mapping of language and memory: two atypical cases.

The Wada test is an invasive procedure used to determine cerebral memory and language dominance as well as risk of cognitive deficits following neurosurgery. However, the potential risks of Wada testing have led some to consider foregoing Wada testing in candidates for resective epilepsy surgery with right hemispheric seizure onset. We present two atypical cases in which the Wada test showed unexpected memory and language lateralization. These cases underscore the importance of functional magnetic resonance in which imaging and Wada examination in right-handed individuals even when the lesion would not suggest atypical language representation.

Grey Matter Reshaping of Language-Related Regions Depends on Tumor Lateralization.

A brain tumor in the left hemisphere can decrease language laterality as assessed through fMRI. However, it remains unclear whether or not this decreased language laterality is associated with a structural reshaping of the grey matter, particularly within the language network. Here, we examine if the disruption of the language hubs exclusively affects the macrostructural properties of the contralateral homologues or whether it affects both hemispheres. This study uses voxel-based morphometry applied to high-resolution MR T1-weighted MPRAGE images from 31 adult patients' left hemisphere, which is dominant for language. Eighteen patients had brain tumors in the left hemisphere, and thirteen had tumors in the right hemisphere. A cohort of 71 healthy individuals matched with respect to age and sex was used as a baseline. We defined 10 ROIs per hemisphere involved in language function. Two separate repeated-measure ANOVAs were conducted with the volume per region as the dependent variable. For the patients, tumor lateralization (right versus left) served as a between-subject factor. The current study demonstrated that the presence of a brain tumor generates global volumetric changes affecting the left language regions and their contralateral homologues. These changes are mediated by the lateralization of the lesion. Our findings suggest that functional mechanisms are supported by the rearrangement of the grey matter.

Grey matter reshaping of language-related regions depends on tumor lateralization.

A brain tumor in the left hemisphere can decrease language laterality as assessed with fMRI. However, it remains unclear whether or not this decreased language laterality is associated with a structural reshaping of the grey matter, particularly within the language network. Here, we examine if the disruption of language hubs exclusively affects macrostructural properties of contralateral homologues (as suggested by previous research), or whether it affects both hemispheres. This study uses voxel-based morphometry applied to high-resolution MR T1-weighted MPRAGE images from 31 adult patients left-dominant for language. Eighteen patients had brain tumors in the left hemisphere, and 13 had tumors in the right hemisphere. A cohort of 71 healthy individuals matched on age and sex was used as a baseline. We defined 10 ROIs per hemisphere known to subserve language function. Two separate repeated-measures ANOVAs were conducted with the volume per region as the dependent variables. For the patients, tumor lateralization (right versus left) served as a between-subject factor. The current study demonstrated that the presence of a brain tumor generates a global volumetric change affecting left language regions and their contralateral homologues. These changes are mediated by the lateralization of the lesion. Our findings suggest that compensatory functional mechanisms are supported by the rearrangement of the grey matter, although future longitudinal research should determine the temporal course of such changes.

Bilingualism and Structural Network Organization in Temporal Lobe Epilepsy: Resilience in Neurologic Disease.

BACKGROUND AND OBJECTIVES: There is growing evidence that bilingualism can induce neuroplasticity and modulate neural efficiency, resulting in greater resistance to neurologic disease. However, whether bilingualism is beneficial to neural health in the presence of epilepsy is unknown. We tested whether bilingual individuals with temporal lobe epilepsy (TLE) have improved whole-brain structural white matter network organization. METHODS: Healthy controls and individuals with TLE recruited from 2 specialized epilepsy centers completed diffusion-weighted MRI and neuropsychological testing as part of an observational cohort study. Whole-brain connectomes were generated via diffusion tractography and analyzed using graph theory. Global analyses compared network integration (path length) and specialization (transitivity) in TLE vs controls and in a 2 (left vs right TLE) × 2 (bilingual vs monolingual) model. Local analyses compared mean local efficiency of predefined frontal-executive and language (i.e., perisylvian) subnetworks. Exploratory correlations examined associations between network organization and neuropsychological performance. RESULTS: A total of 29 bilingual and 88 monolingual individuals with TLE matched on several demographic and clinical variables and 81 age-matched healthy controls were included. Globally, a significant interaction between language status and side of seizure onset revealed higher network organization in bilinguals compared with monolinguals but only in left TLE (LTLE). Locally, bilinguals with LTLE showed higher efficiency in frontal-executive but not in perisylvian networks compared with LTLE monolinguals. Improved whole-brain network organization was associated with better executive function performance in bilingual but not monolingual LTLE. DISCUSSION: Higher white matter network organization in bilingual individuals with LTLE suggests a neuromodulatory effect of bilingualism on whole-brain connectivity in epilepsy, providing evidence for neural reserve. This may reflect attenuation of or compensation for epilepsy-related dysfunction of the left hemisphere, potentially driven by increased efficiency of frontal-executive networks that mediate dual-language control. This highlights a potential role of bilingualism as a protective factor in epilepsy, motivating further research across neurologic disorders to define mechanisms and develop interventions.

Can bilingualism increase neuroplasticity of language networks in epilepsy?

Individuals with left temporal lobe epilepsy (TLE) have a higher rate of atypical (i.e., bilateral or right hemisphere) language lateralization compared to healthy controls. In addition, bilinguals have been observed to have a less left-lateralized pattern of language representation. We examined the combined influence of bilingual language experience and side of seizure focus on language lateralization profiles in TLE to determine whether bilingualism promotes re-organization of language networks. Seventy-two monolingual speakers of English (21 left TLE; LTLE, 22 right TLE; RTLE, 29 age-matched healthy controls; HC) and 24 English-dominant bilinguals (6 LTLE, 7 RTLE, 11 HC) completed a lexical-semantic functional MRI task and standardized measures of language in English. Language lateralization was determined using laterality indices based on activations in left vs right homologous perisylvian regions-of-interest (ROIs). In a fronto-temporal ROI, LTLE showed the expected pattern of weaker left language lateralization relative to HC, and monolinguals showed a trend of weaker left language lateralization relative to bilinguals. Importantly, these effects were qualified by a significant group by language status interaction, revealing that bilinguals with LTLE had greater rightward language lateralization relative to monolingual LTLE, with a large effect size particularly in the lateral temporal region. Rightward language lateralization was associated with better language scores in bilingual LTLE. These preliminary findings suggest a combined effect of bilingual language experience and a left hemisphere neurologic insult, which may together increase the likelihood of language re-organization to the right hemisphere. Our data underscore the need to consider bilingualism as an important factor contributing to language laterality in patients with TLE. Bilingualism may be neuroprotective pre-surgically and may mitigate post-surgical language decline following left anterior temporal lobectomy, which will be important to test in larger samples.

The Aftercare Survey: Assessment and intervention practices after brain tumor surgery in Europe.

Background: People with gliomas need specialized neurosurgical, neuro-oncological, psycho-oncological, and neuropsychological care. The role of language and cognitive recovery and rehabilitation in patients' well-being and resumption of work is crucial, but there are no clear guidelines for the ideal timing and character of assessments and interventions. The goal of the present work was to describe representative (neuro)psychological practices implemented after brain surgery in Europe. Methods: An online survey was addressed to professionals working with individuals after brain surgery. We inquired about the assessments and interventions and the involvement of caregivers. Additionally, we asked about recommendations for an ideal assessment and intervention plan. Results: Thirty-eight European centers completed the survey. Thirty of them offered at least one postsurgical (neuro)psychological assessment, mainly for language and cognition, especially during the early recovery stage and at long term. Twenty-eight of the participating centers offered postsurgical therapies. Patients who stand the highest chances of being included in evaluation and therapy postsurgically are those who underwent awake brain surgery, harbored a low-grade glioma, or showed poor recovery. Nearly half of the respondents offer support programs to caregivers, and all teams recommend them. Treatments differed between those offered to individuals with low-grade glioma vs those with high-grade glioma. The figure of caregiver is not yet fully recognized in the recovery phase. Conclusion: We stress the need for more complete rehabilitation plans, including the emotional and health-related aspects of recovery. In respondents' opinions, assessment and rehabilitation plans should also be individually tailored and goal-directed (eg, professional reinsertion).

Organizing Variables Affecting fMRI Estimates of Language Dominance in Patients with Brain Tumors.

Numerous variables can affect the assessment of language dominance using presurgical functional magnetic resonance (fMRI) in patients with brain tumors. This work organizes the variables into confounding and modulating factors. Confounding factors give the appearance of changed language dominance. Most confounding factors are fMRI-specific and they can substantially disrupt the evaluation of language dominance. Confounding factors can be divided into two categories: tumor-related and fMRI analysis. The tumor-related confounds further subdivide into tumor characteristics (e.g., tumor grade) and tumor-induced conditions (aphasia). The fMRI analysis confounds represent technical aspects of fMRI methods (e.g., a fixed versus an individual threshold). Modulating factors can modify language dominance without confounding it. They are not fMRI-specific, and they can impact language dominance both in healthy individuals and neurosurgical patients. The effect of most modulating factors on fMRI language dominance is smaller than that of confounding factors. Modulating factors include demographics (e.g., age) and linguistic variables (e.g., early bilingualism). Three cases of brain tumors in the left hemisphere are presented to illustrate how modulating confounding and modulating factors can impact fMRI estimates of language dominance. Distinguishing between confounding and modulating factors can help interpret the results of presurgical language mapping with fMRI.

General principles governing the amount of neuroanatomical overlap between languages in bilinguals.

The literature has identified many important factors affecting the extent to which languages in bilinguals rely on the same neural populations in the specific brain region. The factors include the age of acquisition of the second language (L2), proficiency level of the first language (L1) and L2, and the amount of language exposure, among others. What is lacking is a set of global principles that explain how the many factors relate to the degree to which languages overlap neuroanatomically in bilinguals. We are offering a set of such principles that together account for the numerous sources of data that have been examined individually but not collectively: (1) the principle of acquisition similarity between L1 and L2, (2) the principle of linguistic similarity between L1 and L2, and (3) the principle of cognitive control and effort. Referencing the broad characteristics of language organization in bilinguals, as presented by the principles, can provide a roadmap for future clinical and basic science research.

Prior Neurosurgery Decreases fMRI Estimates of Language Laterality in Patients with Gliomas within Anterior Language Sites.

The impact of previous surgery on the assessment of language dominance with preoperative fMRI remains inconclusive in patients with recurrent brain tumors. Samples in this retrospective study included 17 patients with prior brain surgery and 21 patients without prior surgery (38 patients total; mean age 43.2, SD = 11.9; 18 females; seven left-handed). All the patients were left language dominant, as determined clinically. The two samples were matched on 10 known confounds, including, for example, tumor laterality and location (all tumors affected Brodmann areas 44/45/47). We calculated fMRI language dominance with laterality indices using a whole-brain and region of interest approach (ROI; Broca's and Wernicke's area). Patients with prior surgery had decreased fMRI language dominance (p = 0.03) with more activity in the right hemisphere (p = 0.03) than patients without surgery. Patients with prior brain surgery did not display less language activity in the left hemisphere than patients without surgery. These results were replicated using an ROI approach in the affected Broca's area. Further, we observed no differences between our samples in the unaffected Wernicke's area. In sum, prior brain surgery affecting Broca's area could be a confounding factor that needs to be considered when evaluating fMRI language dominance.

Tumor location and reduction in functional MRI estimates of language laterality.

OBJECTIVE: Brain tumors located close to the language cortex may distort functional MRI (fMRI)-based estimates of language dominance. The nature of this distortion, and whether this is an artifact of numerous confounders, remains unknown. The authors hypothesized tumor bias based on laterality estimates independent of confounders and that the effects are the greatest for tumors proximal to Broca's area. METHODS: To answer this question, the authors reviewed more than 1113 patients who underwent preoperative fMRI to match samples on 11 known confounders (tumor location, size, type, and grade; seizure history; prior neurosurgery; aphasia presence and severity; and patient age, sex, and handedness). The samples included 30 patients with left hemisphere tumors (15 anterior and 15 posterior) and 30 with right hemisphere tumors (15 anterior and 15 posterior), thus totaling 60 patients (25 women; 18 left-handed and 4 ambidextrous; mean age 47 [SD 14.1] years). Importantly, the authors matched not only patients with left and right hemisphere tumors but also those with anterior and posterior tumors. Standard fMRI laterality indices (LIs) were calculated using whole-brain and region of interest (ROI) approaches (Broca's and Wernicke's areas). RESULTS: Tumors close to Broca's area in the left hemisphere decreased LIs independently of known confounders. At the whole-brain level, this appeared to reflect a decrease in LI values in patients with left anterior tumors compared with patients with right anterior tumors. ROI analysis replicated these findings. Broca's area LIs were significantly lower (p = 0.02) in patients with left anterior tumors (mean LI 0.28) when compared with patients with right anterior tumors (mean LI 0.70). Changes in Wernicke's area-based LIs did not differ as a function of the tumor hemisphere. Therefore, in patients with left anterior tumors, it is essential to assess language laterality using left posterior ROIs. In all remaining tumor groups (left posterior tumors and right hemisphere tumors), language laterality derived from the anterior language ROI was the most robust measure of language dominance. CONCLUSIONS: Patients with tumors close to Broca's area showed more bilateral fMRI language maps independent of known confounders. The authors caution against the assumption that this reduced language laterality suggests no or little risk to language function following tumor resection in the left inferior frontal gyrus. Their results address how to interpret fMRI data for neurosurgical purposes, along with theoretical questions of contralesional functional compensation and disinhibition.

Factors Modifying the Amount of Neuroanatomical Overlap between Languages in Bilinguals-A Systematic Review of Neurosurgical Language Mapping Studies.

Neurosurgery on individuals with lesions around language areas becomes even more complicated when the patient is bilingual. It is thus important to understand the principles that predict the likelihood of convergent versus separate neuroanatomical organization of the first (L1) and the second language (L2) in these individuals. We reviewed all English-language publications on neurosurgical language mapping in bilinguals before January 2020 in three databases (e.g., PubMed). Our search yielded 28 studies with 207 participants. The reviewed data suggest several principles of language organization in bilingual neurosurgical patients: (1) separate cortical areas uniquely dedicated to each language in both anterior and posterior language sites are the rule rather than occasional findings, (2) In cases where there was a convergent neuroanatomical representation for L1 and L2, two factors explained the overlap: an early age of L2 acquisition and a small linguistic distance between L1 and L2 and (3) When L1 and L2 diverged neuroanatomically, more L1-specific sites were identified for early age of L2 acquisition, high L2 proficiency and a larger linguistic distance. This work provides initial evidence-based principles predicting the likelihood of converging versus separate neural representations of L1 and L2 in neurosurgical patients.

Lateralizing language function with pre-operative functional magnetic resonance imaging in early proficient bilingual patients.

Research on bilinguals with brain lesions is complicated by high patient variability, making it difficult to find well-matched controls. We benefitted from a database of over 700 patients and conducted an analysis of pre-operative functional magnetic resonance imaging data to assess language dominance in 25 early, highly proficient Spanish-English bilinguals, and 25 carefully matched monolingual controls. Our results showed that early bilingualism is associated with greater bilateral hemispheric involvement, and monolingualism is associated with stronger left hemisphere lateralization (p=0.009). The bilinguals showed more pronounced right hemisphere activation (p=0.008). Although language dominance values were concordant in the bilingual group, there were a few (12%) atypical cases with different lateralization patterns in L1 and L2. Finally, we found distinct areas of activity in first and second language within the language network, in addition to regions of convergence. These data underscore the need to map all languages proficiently spoken by surgical candidates.

Improving language mapping in clinical fMRI through assessment of grammar.

INTRODUCTION: Brain surgery in the language dominant hemisphere remains challenging due to unintended post-surgical language deficits, despite using pre-surgical functional magnetic resonance (fMRI) and intraoperative cortical stimulation. Moreover, patients are often recommended not to undergo surgery if the accompanying risk to language appears to be too high. While standard fMRI language mapping protocols may have relatively good predictive value at the group level, they remain sub-optimal on an individual level. The standard tests used typically assess lexico-semantic aspects of language, and they do not accurately reflect the complexity of language either in comprehension or production at the sentence level. Among patients who had left hemisphere language dominance we assessed which tests are best at activating language areas in the brain. METHOD: We compared grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking) with standard tests (object naming, auditory and visual responsive naming), using pre-operative fMRI. Twenty-five surgical candidates (13 females) participated in this study. Sixteen patients presented with a brain tumor, and nine with epilepsy. All participants underwent two pre-operative fMRI protocols: one including CYCLE-N grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking); and a second one with standard fMRI tests (object naming, auditory and visual responsive naming). fMRI activations during performance in both protocols were compared at the group level, as well as in individual candidates. RESULTS: The grammar tests generated more volume of activation in the left hemisphere (left/right angular gyrus, right anterior/posterior superior temporal gyrus) and identified additional language regions not shown by the standard tests (e.g., left anterior/posterior supramarginal gyrus). The standard tests produced more activation in left BA 47. Ten participants had more robust activations in the left hemisphere in the grammar tests and two in the standard tests. The grammar tests also elicited substantial activations in the right hemisphere and thus turned out to be superior at identifying both right and left hemisphere contribution to language processing. CONCLUSION: The grammar tests may be an important addition to the standard pre-operative fMRI testing.

Language system organization in a quadrilingual with a brain tumor: Implications for understanding of the language network.

In pre-neurosurgery language mapping it is critical to identify language-specific regions in multilingual speakers. We conducted pre-operative functional magnetic resonance imaging, and intraoperative language mapping in the unique case of a highly proficient quadrilingual with a left frontal brain tumor who acquired her second language at age 5, and her third and fourth languages at 15. We found a predominantly different organization in each language with only a few areas shared by all 4 languages. Contrary to existing evidence, impairment across languages was not related to age of acquisition, amount of exposure, or language similarity. This case suggests that the functional structure of the language system may be highly idiosyncratic in multilingual individuals and supports detailed study in this group to inform neurocognitive models of language.

Grammar tests increase the ability to lateralize language function in the Wada test.

INTRODUCTION: Grammar is a core component of the language system, yet it is rarely assessed during the Wada (intracarotid amobarbital) test. It is hypothesized that adding grammar tests to the recovery phase of the Wada test will increase our ability to lateralize language function. METHOD: Sixteen individuals (nine females, fifteen right-handed, mean age 38.4 years, SD=10.7) with medically refractory temporal lobe epilepsy participated in the study. On EEG ten patients had seizures originating in the left hemisphere (LH), five in the right hemisphere (RH), and one was insufficiently lateralized. We included only patients who were LH-dominant on the standard test in the encoding phase of the Wada test. In the recovery phase of Wada testing the participants underwent evaluation with a standard language and a new test of grammar, the CYCLE-N. Ten patients underwent bilateral injections, six unilateral (one RH, five LH). RESULTS: As expected, injection in the LH decreased language performance to a greater extent than injection to the RH on both tests. However, the CYCLE-N produced more profound language deficits in the injected LH compared to the RH (p=0.01), whereas the standard tests did not cause such pronounced differences (p=0.2). CONCLUSION: The results suggest that the standard tests did not significantly differentiate the effects of the injections and the CYCLE-N, for the most part, did. Our results are of particular relevance to patients who are too obtunded to speak in the encoding phase. In sum, the CYCLE-N may be helpful in assessing hemispheric dominance for language.