Posterior Language Areas Research Articles

More widespread functionality of posterior language area in patients with brain tumors.

Damage to the posterior language area (PLA), or Wernicke's area causes cortical reorganization in the corresponding regions of the contralateral hemisphere. However, the details of reorganization within the ipsilateral hemisphere are not fully understood. In this context, direct electrical stimulation during awake surgery can provide valuable opportunities to investigate neuromodulation of the human brain in vivo, which is difficult through the non-invasive approaches. Thus, in this study, we aimed to investigate the characteristics of the cortical reorganization of the PLA within the ipsilateral hemisphere. Sixty-two patients with left hemispheric gliomas were divided into groups depending on whether the lesion extended to the PLA. All patients underwent direct cortical stimulation with a picture-naming task. We further performed functional connectivity analyses using resting-state functional magnetic resonance imaging (MRI) in a subset of patients and calculated betweenness centrality, an index of the network importance of brain areas. During direct cortical stimulation, the regions showing positive (impaired) responses in the non-PLA group were localized mainly in the posterior superior temporal gyrus (pSTG), whereas those in the PLA group were widely distributed from the pSTG to the posterior supramarginal gyrus (pSMG). Notably, the percentage of positive responses in the pSMG was significantly higher in the PLA group (47%) than in the non-PLA group (8%). In network analyses of functional connectivity, the pSMG was identified as a hub region with high betweenness centrality in both the groups. These findings suggest that the language area can spread beyond the PLA to the pSMG, a hub region, in patients with lesion progression to the pSTG. The change in the pattern of the language area may be a compensatory mechanism to maintain efficient brain networks.

Probabilistic Presurgical Language fMRI Atlas of Patients with Brain Tumors.

Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors. The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, and May 13, 2022. Three hundred seventeen patients (861 fMRI scans) were used to develop the language functional atlas. An independent presurgical language fMRI data set of 39 patients with brain tumors from a previous study was used to evaluate our atlas. Family-wise error-corrected binary functional activation maps from sentence completion, letter fluency, and category fluency presurgical fMRI were used to create probability overlap maps and pooled probabilistic overlap maps in Montreal Neurological Institute standard space. The Wilcoxon signed-rank test was used to determine a significant difference in the maximum Dice coefficient for our atlas compared with a meta-analysis-based template with respect to expert-delineated primary language area activations. Probabilities of activating the left anterior primary language area and left posterior primary language area in the temporal lobe were 87.9% and 91.5%, respectively, for sentence completion, 88.5% and 74.2%, respectively, for letter fluency, and 83.6% and 67.6%, respectively, for category fluency. Maximum Dice coefficients for templates derived from our language atlas were significantly higher than the meta-analysis-based template in the left anterior primary language area (0.351 and 0.326, respectively, P < .05) and the left posterior primary language area in the temporal lobe (0.274 and 0.244, respectively, P < .005). Brain tumor patient- and paradigm-specific probabilistic language atlases were developed. These atlases had superior spatial agreement with fMRI activations in individual patients compared with the meta-analysis-based template.

Bilateral and asymmetrical localization of language function identified by the superselective infusion of propofol in an epilepsy patient with a mild malformation of cortical development: illustrative case.

Atypical localization of language function can result in unexpected postsurgical deficits after cortical resection, but it is difficult to predict the risk in the presurgical evaluation. The authors experienced a rare case of the bilateral and independent existence of different components of language function identified by segmented evaluation of anatomical anterior and posterior language areas using the superselective infusion of propofol. A 32-year-old right-handed female presented with drug-resistant epilepsy. Comprehensive epilepsy evaluation suggested that the epileptic foci involved the whole left frontal lobe but provided less evidence of structural abnormality. To estimate the extent of functional deterioration likely to be caused by an extended left frontal lobectomy, the authors evaluated segmented cortical function in the ipsi- and contralateral hemispheres by the superselective infusion of propofol into the branches of the intracranial artery. The results revealed bilateral and asymmetrical localization of language function because the patient presented with different components of aphasia in each hemisphere. Based on the authors' assessment of her functional tolerance, an extended left frontal lobectomy was performed and resulted in neurological deficits within the anticipated range. An accurate understanding of the correlations between vascular and functional anatomy and the highly specific evaluation of language function provides more advanced presurgical assessment, allowing more tailored planning of cortical resection.

Features of speech disorders in patients with acute ischemic stroke

Introduction. Various speech disorders that lead to impaired communication occur in 3050% of ischemic stroke (IS) survivors. Although most attention is traditionally paid to aphasia, speech disorders also include the following: dysarthria, dysphonia (isolated or in combination with dysarthria and/or dysphagia), fluency disorders, and non-specific speech disorders associated with the severity of condition and a cognitive disorder.&#x0D; Objective: to study the variety of speech disorders and their features in patients with acute IS.&#x0D; Materials and methods. We examined 69 right-handed patients with mild-to-moderate acute IS and NIHSS score of 412. The patients were enrolled in the study on days 17 of the IS.&#x0D; Results. We found aphasia in 27/69 patients (39.1%), dysarthria in 21/69 patients (30.4%), dysphonia (isolated or in combination with dysarthria) in 17/69 patients (24.6%), fluency disorders in 19/69 patients (27.5%; 2 patients with tachylalia and 17 patients with bradylalia). In addition, 30 patients (43.5%) had dysphagia (isolated or in combination with dysarthria). At the initial examination, patients admitted within the 17 days of the acute IS onset presented with global or severe sensory and motor aphasia. At the same time, we discovered a pronounced positive dynamics in speech recovery thanks to speech therapy sessions. A significant remission in a speech disorder component led to the development of cortical aphasia affecting either anterior or posterior language areas at the end of the most acute IS period, while aphasia severity reduced to mild or moderate.&#x0D; Conclusions. A fast reduction in aphasic disorders due to the speech therapy sessions suggests that the focal and connectional diaschisis are the basis for the severe speech disorders.

Language Network Connectivity of Euthymic Bipolar Patients Is Altered at Rest and during a Verbal Fluency Task.

Abnormalities of the Language Network (LN) have been found in different psychiatric conditions (e.g., schizophrenia and bipolar disorder), supporting the hypothesis that language plays a central role in a high-level integration/connectivity of second-level cognitive processes and the underlying cortical regions. This view implies a continuum of shared neural alterations along the psychotic disorder spectrum. In particular, bipolar disorder (BD) patients were recently documented to have an altered LN asymmetry during resting state. The extent to which the LN architecture is altered and stable also during a language task has yet to be investigated. To address this question, we analyzed fMRI data recorded during an open-eyes resting state session and a silent verbal fluency task in 16 euthymic BD patients and 16 matched healthy controls (HC). Functional connectivity in the LN of both groups was computed using spatial independent component analysis, and group comparisons were carried out to assess the network organization during both rest and active linguistic task conditions. The LN of BD patients involved left and right brain areas during both resting state and linguistic task. Compared to the left-lateralized network found in HC, the BD group was characterized by two anterior clusters (in left frontal and right temporo-insular regions) and the disengagement of the posterior language areas, especially during the verbal fluency task. Our findings support the hypothesis that reduced language lateralization may represent a biological marker across different psychotic disorders and that the altered language network connectivity found at rest in bipolar patients is stable and pervasive as it is also impaired during a verbal fluency task.

Preservation of language function by mapping the arcuate fasciculus using intraoperative corticocortical evoked potential under general anesthesia in glioma surgery.

Intraoperative language mapping under general anesthesia is imperative for brain tumor surgery because awake surgery is not always feasible. Monitoring corticocortical evoked potential (CCEP) is known to be a useful method for tracking neuronal connectivity and localizing functional areas. The authors evaluated the clinical benefit of intraoperative CCEP monitoring for language function preservation in patients undergoing glioma surgery. Between January 2019 and June 2021, the authors performed a total of 29 consecutive glioma surgeries using CCEP monitoring under general anesthesia because of a risk of speech impairment; these were analyzed. Language area mapping was implemented by the anterior language area to posterior language area CCEP method for arcuate fasciculus mapping, and tumor resection was performed while avoiding the localized language areas. Language function before and after surgery was evaluated by the Controlled Oral Word Association Test (COWAT). Intraoperative CCEP was successfully monitored in 25 patients (86.2%), and a valid signal was undetectable in the other 4 patients. Language function evaluation was possible before and after surgery in a total of 20 patients. Overall, the preservation rate of language function was 65.0%, and the deterioration rate was 35.0% after tumor resection with CCEP monitoring. Among those 8 patients with preoperative COWAT scores ≥ 18, 5 patients (62.5%) successfully preserved their language function, with COWAT scores > 18 after tumor resection. Among the 12 patients with preoperative deteriorated language function (COWAT score < 18), 8 patients (66.7%) showed improvement or preserved language function after surgery. Intraoperative CCEP monitoring of the arcuate fasciculus is an acceptable technology for the preservation of language function under general anesthesia in glioma surgery in patients in whom awake surgery is not feasible.

Determination of language areas in patients with epilepsy using the super-selective Wada test

The Wada test is the gold standard for determining language-dominant hemisphere. However, the precise determination of language areas in each patient requires more invasive methods, such as electrocortical stimulation. Some studies have reported the use of anesthetic injection into selective cerebral arteries to predict postoperative function. To assess the function of the anterior and posterior language areas separately, we developed an advanced test named the “super-selective Wada test” (ssWada). The ssWada procedure is as follows: an endovascular neurosurgeon identifies the arterial branches of the middle cerebral artery (MCA) perfusing the anterior language area of the inferior frontal gyrus and the posterior language area of the posterior part of the superior temporal gyrus using angiography. Behavioral neurologists assess language symptoms before and after propofol administration using a microcatheter tip in the selected arterial branch. From 30 serial patients with epilepsy who underwent ssWada test at Tohoku University Hospital, we retrospectively reviewed patients in whom multiple areas in the bilateral MCA region was examined. Eight cases were identified in this study. All eight cases had been considered for resection of the area overlapping the classical language area. Three of the eight cases were left-dominant, and the within-hemisphere distribution was also considered typical. One case was determined to be left-dominant but atypical in the intra-hemispheric functional distribution. Two cases were right-dominant, and the intra-hemispheric functional distribution was considered a mirror image of the typical pattern. The remaining two cases were considered atypical, not only in terms of bilateral language function, but also in terms of anterior-posterior functional distribution. This case series demonstrates the potential utility of ssWada in revealing separate function of the anterior and posterior language areas. The ssWada allows simulation of local surgical brain resection and detailed investigation of language function, which potentially contributes to planning the resection area. Although indications for ssWada are quite limited, it could play a complementary role to noninvasive testing because it provides information related to resection using a different approach.

Monitoring Cortico-cortical Evoked Potentials Using Only Two 6-strand Strip Electrodes for Gliomas Extending to the Dominant Side of Frontal Operculum During One-step Tumor Removal Surgery

Resection of the dominant side of gliomas extending to the frontal operculum has high risk of severe language dysfunction. Here, we report recording cortico-cortical evoked potentials (CCEP) using only two 6-strand strip electrodes to monitor language-related fibers intraoperatively. We examined whether this simple procedure is useful for removing gliomas extending to the dominant side of frontal operculum. This study included 7 cases of glioma extending to the left frontal operculum. The frontal language area (FLA) was first identified by functional mapping during awake craniotomy. Next, a 6-strand strip electrode was placed on the FLA, while on the temporal side, an electrode was placed so as to slide parallel to the sylvian fissure toward the posterior language area. Electrical stimulation was performed using the electrode on the frontal side, and CCEPs were measured from the electrode on the temporal side. CCEPs were detected in all cases. Immediately after surgery, all patients demonstrated language dysfunction to varying degree. CCEP decreased to 10% in 1 patient, who recovered language function after 24 months. CCEP decreased slightly 80% in 1, and, in the 5 other cases, CCEPs did not change. These 5 patients soon recovered language function within 2 weeks to 1 month. This study confirmed the utility of CCEP monitoring using only two 6-strand strip electrodes during one-step surgery. We believe this simple method helped in monitoring intraoperative language function and predicting its postoperative recovery in patients with gliomas extending to the dominant side of frontal operculum.

Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy.

Cognitive impairment is a common comorbidity of epilepsy and adversely impacts people with both frontal lobe (FLE) and temporal lobe (TLE) epilepsy. While its neural substrates have been investigated extensively in TLE, functional imaging studies in FLE are scarce. In this study, we profiled the neural processes underlying cognitive impairment in FLE and directly compared FLE and TLE to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE and 52 controls) using neuropsychological tests and four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-seizure medication load. We devised a multiscale approach to map brain activation and deactivation during cognition and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional systems; and (ii) the principal functional connectivity gradient, which encodes a continuous transition of regional connectivity profiles, anchoring lower-level sensory and transmodal brain areas at the opposite ends of a spectrum. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, as well as reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. The imaging signatures of dysfunction in FLE are broadly similar to those in TLE, but some patterns are syndrome-specific: altered default-mode deactivation is more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands is more marked in TLE. Functional abnormalities in FLE and TLE appear overall modulated by disease load. On balance, our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies and sheds light on system behaviour that may be amenable to future remediation strategies.

Feasibility, Contrast Sensitivity and Network Specificity of Language fMRI in Presurgical Evaluation for Epilepsy and Brain Tumor Surgery.

Language fMRI has become an integral part of the planning process in brain surgery. However, fMRI may suffer from confounding factors both on the patient side, as well as on the provider side. In this study, we investigate how patient-related confounds affect the ability of the patient to perform language fMRI tasks (feasibility), the task sensitivity from an image contrast point of view, and the anatomical specificity of expressive and receptive language fMRI protocols. 104 patients were referred for language fMRI in the context of presurgical procedures for epilepsy and brain tumor surgery. Four tasks were used: (1) a verbal fluency (VF) task to map vocabulary use, (2) a semantic description (SD) task to map sentence formation/semantic integration skills, (3) a reading comprehension (RC) task and (4) a listening comprehension (LC) task. Feasibility was excellent in the LC task (100%), but in the acceptable to mediocre range for the rest of the tasks (SD: 87.50%, RC: 85.57%, VF: 67.30%). Feasibility was significantly confounded by age (p = 0.020) and education level (p = 0.003) in VF, by education level (p = 0.004) and lesion laterality (p = 0.019) in SD and by age (p = 0.001), lesion laterality (p = 0.007) and lesion severity (p = 0.048) in RC. All tasks were comparable regarding sensitivity in generating statistically significant image contrast (VF: 90.00%, SD: 92.30%, RC: 93.25%, LC: 88.46%). The lobe of the lesion (p = 0.005) and the age (p = 0.009) confounded contrast sensitivity in the VF and SD tasks respectively. Both VF and LC tasks demonstrated unilateral lateralization of posterior language areas; only the LC task showed unilateral lateralization of anterior language areas. Our study highlights the effects of patient-related confounding factors on language fMRI and proposes LC as the most feasible, less confounded, and efficiently lateralizing task in the clinical presurgical context.

Intraoperative Corticocortical Evoked Potentials for Language Monitoring in Epilepsy Surgery

To evaluate the applicability of corticocortical evoked potentials (CCEP) for intraoperative monitoring of the language network in epilepsy surgery under general anesthesia. To investigate the clinical relevance on language functions of intraoperative changes of CCEP recorded under these conditions. CCEP monitoring was performed in 14 epileptic patients (6 females, 4 children) during resections in the left perisylvian region under general anesthesia. Electrode strips were placed on the anterior language area (AL) and posterior language area (PL), identified by structural and functional magnetic resonance imaging. Single-pulse electric stimulations were delivered to pairs of adjacent contacts in a bipolar fashion. During resection, we monitored the integrity of the dorsal language pathway by stimulating either AL by recording CCEP from PL or vice versa, depending on stability and reproducibility of CCEP. We evaluated the first negative (N1) component of CCEP before, during, and after resection. All procedures were successfully completed without adverse events. The best response was obtained from AL during stimulation of PL in 8 patients and from PL during stimulation of AL in 6 patients. None of 12 patients with a postresection N1 amplitude decrease of 0%-15% from baseline presented postoperative language impairment. Decreases of 28% and 24%, respectively, of the N1 amplitude were observed in 2 patients who developed transient postoperative speech disturbances. The application of CCEP monitoring is possible and safe in epilepsy surgery under general anesthesia. Putative AL and PL can be identified using noninvasive presurgical neuroimaging. Decrease of N1 amplitude >15% from baseline may predict postoperative language deficits.

Language Mapping Using Stereo Electroencephalography: A Review and Expert Opinion.

Stereo-electroencephalography (sEEG) is a method that uses stereotactically implanted depth electrodes for extra-operative mapping of epileptogenic and functional networks. sEEG derived functional mapping is achieved using electrical cortical stimulations (ECS) that are currently the gold standard for delineating eloquent cortex. As this stands true especially for primary cortices (e.g., visual, sensitive, motor, etc.), ECS applied to higher order brain areas determine more subtle behavioral responses. While anterior and posterior language areas in the dorsal language stream seem to share characteristics with primary cortices, basal temporal language area (BTLA) in the ventral temporal cortex (VTC) behaves as a highly associative cortex. After a short introduction and considerations about methodological aspects of ECS using sEEG, we review the sEEG language mapping literature in this perspective. We first establish the validity of this technique to map indispensable language cortices in the dorsal language stream. Second, we highlight the contrast between the growing empirical ECS experience and the lack of understanding regarding the fundamental mechanisms underlying ECS behavioral effects, especially concerning the dispensable language cortex in the VTC. Evidences for considering network architecture as determinant for ECS behavioral response complexities are discussed. Further, we address the importance of designing new research in network organization of language as this could enhance ECS ability to map interindividual variability, pathology driven reorganization, and ultimately identify network resilience markers in order to better predict post-operative language deficit. Finally, based on a whole body of available studies, we believe there is strong evidence to consider sEEG as a valid, safe and reliable method for defining eloquent language cortices although there have been no proper comparisons between surgical resections with or without extra-operative or intra-operative language mapping.

Abstract P356: Wernicke’s Vertical Occipital Fasciculus in Post-Stroke Reading

Introduction: The vertical-occipital fasciculus (VOF), which was initially described by Wernicke more than a century ago but recently rediscovered, connects visual association cortices to the posterior language areas. We hypothesized that the vertical-occipital fasciculus plays a critical role in reading. Methods: Thirty-two participants with subacute to chronic left hemispheric stroke leading to varying degrees of aphasia were enrolled in the study and underwent concurrent diffusion tensor imaging (DTI) and language assessment. Assessments included the Boston Diagnostic Aphasia Examination (BDAE) to assess oral reading and reading comprehension and the Boston Naming Test to assess picture naming. Two major cortico-cortical projection pathways, VOF, connected with posterior language cortices and frontal aslant tract (FAT), connecting anterior language areas, were mapped with deterministic tractography and quantified bilaterally. We conducted partial correlations between fractional anisotropy (FA) values of the tracts and reading and picture naming scores, controlling for age, education, and total lesion load. We corrected for multiple comparisons at the false discovery rate (FDR) (p&lt;0.05). Results: FA of left VOF was found to be significantly correlated with BDAE total reading scores (r=0.49, p=0.004), and this remained significant after FDR correction (p=0.03). Although a significant correlation was seen between picture naming and left VOF FA (r=0.41, p=0.02), and right VOF FA (r=0.37, p=0.04), these associations were not significant after FDR correction (p&gt;0.05). FAT FA values were not significantly associated with oral reading or picture naming tests. Conclusion: This study provides preliminary evidence that left VOF plays a potential role in reading after left hemispheric stroke.

A concordance study determining language dominance between navigated transcranial magnetic stimulation and the Wada test in patients with drug-resistant epilepsy

ObjectiveIt remains unclear whether transcranial magnetic stimulation (TMS) can replace the Wada test to determine language hemisphere dominance (HD). Using the Wada test as the gold standard, this study aimed to investigate the accuracy of navigated TMS (nTMS) in determining language HD. MethodsThis study enrolled nine right-handed patients with drug-resistant epilepsy. We hypothesized that application of nTMS to language-related areas of the language-dominant hemisphere would induce positive manifestation of language dysfunction (LD). To test our hypothesis, the patients were instructed to perform a visual object-naming task while nTMS was applied to the anterior (e.g., Broca’s area) and posterior (e.g., Wernicke’s area) regions, which are closely related to language processing. The Wada test result was used as the gold standard, and the diagnostic value of nTMS was assessed using the Kappa consistency test. ResultsThe nTMS-induced LD positive rate for the bilateral anterior language areas (85.7%) was higher than that for the posterior language areas (57.1%). There was high consistency between nTMS stimulation of the left anterior and posterior language areas and the Wada test results for determining language HD. In contrast, the consistency of stimulation of the right anterior and posterior transfer sites was moderate (Kappa value = 0.545, P = 0.171) and low, respectively. For the latter, no statistical calculation was performed because stimulation of the right posterior speech area was negative in all patients compared with the Wada test results. ConclusionsOur findings revealed that using nTMS to stimulate language-related left anterior and posterior areas could predict language HD with high accuracy. When the stimulation performance of these areas is positive, nTMS and the Wada test are equally accurate. Observing only negative performance may indicate that language HD has been transferred to the right side.

Utility of Intraoperative Cortico-Cortical Evoked Potentials for the Evaluation of Language Function During Brain Tumor Resection

The cortico-cortical evoked potentials (CCEP) are a relatively recent intraoperative monitoring tool that has shown high reliability in detecting the functional language area and its connections. In this work we describe a patient with a tumor located in the language area who underwent tumor resection. A neurophysiological intraoperative mapping of the frontal and posterior language area with the anesthetized patient was carried out. Then the patient was awaked. To demonstrate the relationship between language function and CCEP, the Ojemann’s stimulation technique was used in the same electrodes were CCEPs were obtained. An alteration in the emission of language had been found on the electrodes where CCEP was obtained and in adjacent electrodes. During tumor resection we used a double check for language function: neurological evaluation and CCEPs. We obtained a biunivocal relationship between warning criteria in the CCEP and immediate language impairment on neurological examination. We always observed a significant decrease in the CCEP associated with language impairment. The CCEP are able to obtain information in real time with a good spatial resolution of the language function. Future studies should be carried out in order to analyse the robustness of this technique to perform it in anesthetized patients.

Multitask preoperative language mapping in epilepsy surgery: A combination of navigated transcranial magnetic stimulation and extra-operative electrical cortical stimulation

Navigated transcranial magnetic stimulation (nTMS) is increasingly applied in language mapping. However, the application mode and task selection of nTMS are not standardized. The aim of this study was to assessed the necessity and validity of multitask nTMS language mapping by comparing results with extraoperative electrical cortical stimulation (eoECS). In this study, sixteen epilepsy surgery patients were examined by nTMS and eoECS language mapping, and the two results were compared. The mapping results were validated with pre- to postoperative language assessments. Compared with eoECS, nTMS showed the overall sensitivity of 82.4%, specificity of 95.1%, positive predictive value of 66.7%, and negative predictive value of 97.8%. Spontaneous speech was the most sensitive task in the frontal area, naming was the sensitive task in both frontal and temporal areas. The false responses were mainly located in the perisylvian region. Multitask nTMS helps to reduce missing language relevant cortex preoperatively. Selecting spontaneous speech and naming tasks in frontal area, comprehension and naming tasks in temporal and posterior language area would strike the balance between the validity and efficiency of the mapping procedure. These results manifested the necessity of applying multitask in nTMS language mapping. Our study highlighted the importance of the nTMS evaluation mode and task selection for epilepsy patients.

Interhemispheric and Intrahemispheric Connectivity From the Left Pars Opercularis Within the Language Network Is Modulated by Transcranial Stimulation in Healthy Subjects.

Neural activity related to language can be modulated within widespread networks following learning or in response to disruption—including the experimental application of noninvasive brain stimulation. However, the spatiotemporal characteristics of such modulation remain insufficiently explored. The present study combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to explore the modulation of activity across the language network following continuous theta-burst stimulation (cTBS) of the left pars opercularis. In 10 healthy subjects (21 ± 2 years old, four females), neuronavigated cTBS was delivered over the left pars opercularis of the frontal operculum (part of the traditional Broca’s area) at 80% of active motor threshold (AMT) stimulation intensity. Real cTBS and sham cTBS were performed in two different visits separated by at least 48 h. Before, immediately, and 10 min after cTBS, 30 single pulses of TMS were delivered to the left pars opercularis at 80% of the resting motor threshold (RMT), whereas EEG was simultaneously recorded. We examined the cTBS-induced modulation of phase locking values (PLVs) between the TMS-evoked potentials (TEPs) recorded over the pars opercularis and those recorded over its right-hemispheric homolog area, the left supramarginal area, and the left superior temporal area in different EEG frequency bands and different time windows following cTBS. cTBS to the left pars opercularis induced within the gamma band: (1) a significant increase in TEP phase synchronization between the left and right pars opercularis at an early time window (250–350 ms) following cTBS; and (2) significantly increased PLV with the left supramarginal area and the left superior temporal area at a later time window (600–700 ms). In the theta and delta band, cTBS to the left pars opercularis induced significantly increased phase synchronization of TEPs between the left pars opercularis and the posterior left hemispheric language areas at a late time window. In sham condition, there was a significant decrease in TEP phase synchronization of the high beta band between left pars opercularis and left superior temporal area at 200–300 ms. These results contribute to characterize the dynamics of the language network and may have implications in the development of noninvasive stimulation protocols to promote the language rehabilitation in aphasia patients.

Functional MRI Task Comparison for Language Mapping in Neurosurgical Patients.

Language task-based functional MRI (fMRI) is increasingly used for presurgical planning in patients with brain lesions. Different paradigms elicit activations of different components of the language network. The aim of this study is to optimize fMRI clinical usage by comparing the effectiveness of three language tasks for language lateralization and localization in a large group of patients with brain lesions. We analyzed fMRI data from a sequential retrospective cohort of 51 patients with brain lesions who underwent presurgical fMRI language mapping. We compared the effectiveness of three language tasks (Antonym Generation, Sentence Completion (SC), and Auditory Naming) for lateralizing language function and for activating cortex within patient-specific regions-of-interest representing eloquent language areas, and assessed the degree of spatial overlap of the areas of activation elicited by each task. The tasks were similarly effective for lateralizing language within the anterior language areas. The SC task produced higher laterality indices within the posterior language areas and had a significantly higher agreement with the clinical report. Dice coefficients between the task pairs were in the range of .351-.458, confirming substantial variation in the components of the language network activated by each task. SC task consistently produced large activations within the dominant hemisphere and was more effective for lateralizing language within the posterior language areas. The low degree of spatial overlap among the tasks strongly supports the practice of using a battery of tasks to help the surgeon to avoid eloquent language areas.

Relationship Between EEG Electrode and Functional Cortex in the International 10 to 20 System.

In this study, we attempted to define the variability in the anatomical relationship between scalp EEG electrodes and eloquent cortical function, as inferred from fMRI. MRI-compatible fiducial markers were positioned at locations of CZ, C3 and C4, T3 and T4, and F7 and F8 in 10 healthy subjects. Well-validated fMRI paradigms were administered to activate primary motor cortex and language regions, and the distance between these brain regions and fiducial markers was measured. C3/C4, Cz, F8/F7, and T3/T4 were located 16 to 42 mm from the BOLD signal in the primary motor cortex for the contralateral hand and foot, and anterior and posterior language areas, 11 to 21 mm of which was the distance from the skin to the underlying cortex. There is considerable variation in the distance between the fMRI-defined primary motor and language cortex and the most contiguous electrode. This distance likely underestimates the true variability of electrode placement in relation to eloquent cortex in people with epilepsy or structural brain disorders. Because the evidence indicates that spikes on scalp EEG reflect discharges from the cortex that is of the order of 3 cm by 3 cm or greater in size, the demonstrated variability of electrode placement in relation to the cortex may be clinically and surgically important in individual patients.

Location and Threshold of Electrical Cortical Stimulation for Functional Brain Mapping

Although many studies have investigated functional localization by electrical stimulation, the threshold to identify each area remains controversial. The present study aimed to elucidate the threshold of a cortical stimulation for functional mapping. We analyzed data from 17 patients with medically intractable epilepsy who underwent a 50-Hz electrical cortical stimulation for functional mapping between October 2013 and May 2017. The symptoms induced by the stimulation and the thresholds of the stimulation for these responses were evaluated. Motor responses were observed after the stimulation of the primary motor cortex, supplementary motor area, and frontal eye field, and sensory responses after the stimulation of the primary and secondary sensory cortex. Regarding negative responses, language impairment was observed after the stimulation of the anterior, posterior, and basal temporal language areas, negative motor responses after the stimulation of the premotor cortex, posterior parietal cortex, and the pre- supplementary motor area, and an impairment in spatial recognition after the stimulation of the right posterior parietal cortex. Negative or positive auditory symptoms were observed with the stimulation of the posterior superior temporal gyrus. The thresholds for positive phenomena were significantly lower than those for negative phenomena (Mann-Whitney U test, P < 0.01), and sensory responses were induced at significantly lower intensities than motor responses (P < 0.01). Positive and sensory effects are induced by lower intensities than negative and motor responses, respectively. The present results provide not only a practical guide for functional mapping, but also a hierarchal concept of processing in the brain.