Basal temporal language area revisited in Japanese language with a language function density map.

We revisited the anatomo-functional characteristics of the basal temporal language area (BTLA), first described by Lüders et al. (1986), using electrical cortical stimulation (ECS) in the context of Japanese language and semantic networks. We recruited 11 patients with focal epilepsy who underwent chronic subdural electrode implantation and ECS mapping with multiple language tasks for presurgical evaluation. A semiquantitative language function density map delineated the anatomo-functional characteristics of the BTLA (66 electrodes, mean 3.8 cm from the temporal tip). The ECS-induced impairment probability was higher in the following tasks, listed in a descending order: spoken-word picture matching, picture naming, Kanji word reading, paragraph reading, spoken-verbal command, and Kana word reading. The anterior fusiform gyrus (FG), adjacent anterior inferior temporal gyrus (ITG), and the anterior end where FG and ITG fuse, were characterized by stimulation-induced impairment during visual and auditory tasks requiring verbal output or not, whereas the middle FG was characterized mainly by visual input. The parahippocampal gyrus was the least impaired of the three gyri in the basal temporal area. We propose that the BTLA has a functional gradient, with the anterior part involved in amodal semantic processing and the posterior part, especially the middle FG in unimodal semantic processing.

Association of Cortical Superficial Siderosis with Post-Stroke Epilepsy.

OBJECTIVE: To assess whether post-stroke epilepsy (PSE) is associated with neuroimaging findings of hemosiderin in a case-control study, and whether the addition of hemosiderin markers improves the risk stratification models of PSE. METHODS: We performed a post-hoc analysis of the PROgnosis of POST-Stroke Epilepsy study enrolling PSE patients at National Cerebral and Cardiovascular Center, Osaka, Japan, from November 2014 to September 2019. PSE was diagnosed when one unprovoked seizure was experienced >7 days after the index stroke, as proposed by the International League Against Epilepsy. As controls, consecutive acute stroke patients with no history or absence of any late seizure or continuing antiseizure medications at least 3 months after stroke were retrospectively enrolled during the same study period. We examined cortical microbleeds and cortical superficial siderosis (cSS) using gradient-echo T2*-weighted images. A logistic regression model with ridge penalties was tuned using 10-fold cross-validation. We added the item of cSS to the existing models (SeLECT and CAVE) for predicting PSE and evaluated performance of new models. RESULTS: The study included 180 patients with PSE (67 women; median age 74 years) and 1,183 controls (440 women; median age 74 years). The cSS frequency was higher in PSE than control groups (48.9% vs 5.7%, p < 0.0001). Compared with the existing models, the new models with cSS (SeLECT-S and CAVE-S) demonstrated significantly better predictive performance of PSE (net reclassification improvement 0.63 [p = 0.004] for SeLECT-S and 0.88 [p = 0.001] for CAVE-S at the testing data). INTERPRETATION: Cortical superficial siderosis was associated with PSE, stratifying stroke survivors at high risk of PSE. ANN NEUROL 2023;93:357-370.

The dynamics of cortical interactions in visual recognition of object category: living versus nonliving.

Noninvasive brain imaging studies have shown that higher visual processing of objects occurs in neural populations that are separable along broad semantic categories, particularly living versus nonliving objects. However, because of their limited temporal resolution, these studies have not been able to determine whether broad semantic categories are also reflected in the dynamics of neural interactions within cortical networks. We investigated the time course of neural propagation among cortical areas activated during object naming in 12 patients implanted with subdural electrode grids prior to epilepsy surgery, with a special focus on the visual recognition phase of the task. Analysis of event-related causality revealed significantly stronger neural propagation among sites within ventral temporal lobe (VTL) at early latencies, around 250 ms, for living objects compared to nonliving objects. Differences in other features, including familiarity, visual complexity, and age of acquisition, did not significantly change the patterns of neural propagation. Our findings suggest that the visual processing of living objects relies on stronger causal interactions among sites within VTL, perhaps reflecting greater integration of visual feature processing. In turn, this may help explain the fragility of naming living objects in neurological diseases affecting VTL.

Periodic discharges plus fast activity on electroencephalogram predict worse outcomes in poststroke epilepsy.

OBJECTIVE: Postseizure functional decline is a concern in poststroke epilepsy (PSE). However, data on electroencephalogram (EEG) markers associated with functional decline are scarce. Thus, we investigated whether periodic discharges (PDs) and their specific characteristics are associated with functional decline in patients with PSE. METHODS: In this observational study, patients admitted with seizures of PSE and who had scalp EEGs were included. The association between the presence or absence of PDs and postseizure short-term functional decline lasting 7 days after admission was investigated. In patients with PD, EEG markers were explored for risk stratification of short-term functional decline, according to the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology. The association between EEG markers and imaging findings and long-term functional decline at discharge and 6 months after discharge, defined as an increase in the modified Rankin Scale score compared with the baseline, was evaluated. RESULTS: In this study, 307 patients with PSE (median age = 75 years, range = 35-97 years, 64% males; hemorrhagic stroke, 47%) were enrolled. Compared with 247 patients without PDs, 60 patients with PDs were more likely to have short-term functional decline (12 [20%] vs. 8 [3.2%], p < .001), with an adjusted odds ratio (OR) of 4.26 (95% confidence interval [CI] = 1.44-12.6, p = .009). Patients with superimposed fast-activity PDs (PDs+F) had significantly more localized (rather than widespread) lesions (87% vs. 58%, p = .003), prolonged hyperperfusion (100% vs. 62%, p = .023), and a significantly higher risk of short-term functional decline than those with PDs without fast activity (adjusted OR = 22.0, 95% CI = 1.87-259.4, p = .014). Six months after discharge, PDs+F were significantly associated with long-term functional decline (adjusted OR = 4.21, 95% CI = 1.27-13.88, p = .018). SIGNIFICANCE: In PSE, PDs+F are associated with sustained neuronal excitation and hyperperfusion, which may be a predictor of postseizure short- and long-term functional decline.

Enhanced phase-amplitude coupling of human electrocorticography selectively in the posterior cortical region during rapid eye movement sleep.

The spatiotemporal dynamics of interaction between slow (delta or infraslow) waves and fast (gamma) activities during wakefulness and sleep are yet to be elucidated in human electrocorticography (ECoG). We evaluated phase-amplitude coupling (PAC), which reflects neuronal coding in information processing, using ECoG in 11 patients with intractable focal epilepsy. PAC was observed between slow waves of 0.5-0.6 Hz and gamma activities, not only during light sleep and slow-wave sleep (SWS) but even during wakefulness and rapid eye movement (REM) sleep. While PAC was high over a large region during SWS, it was stronger in the posterior cortical region around the temporoparietal junction than in the frontal cortical region during REM sleep. PAC tended to be higher in the posterior cortical region than in the frontal cortical region even during wakefulness. Our findings suggest that the posterior cortical region has a functional role in REM sleep and may contribute to the maintenance of the dreaming experience.

[Intraoperative Cortico-Cortical Evoked Potential].

In the surgery management of lesions in areas of the eloquent cortices the preservation of brain functions is required. Intraoperative electrophysiological methods are necessary to preserve the integrity of the functional network, such as motor or language areas. Cortico-cortical evoked potentials(CCEPs)have recently developed as a new intraoperative monitoring method because of advantages of a recording time of approximately 1-2 min, no requirement of patient cooperation, and high reproducibility and reliability of the data. The recent intraoperative CCEP studies have shown that CCEP can map the eloquent areas and white matter pathway, such as the dorsal language pathway, frontal aslant tract, supplementary motor area, and optic radiation. To establish intraoperative electrophysiological monitoring even under general anesthesia, further studies are required.

Distinct connectivity patterns in human medial parietal cortices: Evidence from standardized connectivity map using cortico-cortical evoked potential.

The medial parietal cortices are components of the default mode network (DMN), which are active in the resting state. The medial parietal cortices include the precuneus and the dorsal posterior cingulate cortex (dPCC). Few studies have mentioned differences in the connectivity in the medial parietal cortices, and these differences have not yet been precisely elucidated. Electrophysiological connectivity is essential for understanding cortical function or functional differences. Since little is known about electrophysiological connections from the medial parietal cortices in humans, we evaluated distinct connectivity patterns in the medial parietal cortices by constructing a standardized connectivity map using cortico-cortical evoked potential (CCEP). This study included nine patients with partial epilepsy or a brain tumor who underwent chronic intracranial electrode placement covering the medial parietal cortices. Single-pulse electrical stimuli were delivered to the medial parietal cortices (38 pairs of electrodes). Responses were standardized using the z-score of the baseline activity, and a response density map was constructed in the Montreal Neurological Institutes (MNI) space. The precuneus tended to connect with the inferior parietal lobule (IPL), the occipital cortex, superior parietal lobule (SPL), and the dorsal premotor area (PMd) (the four most active regions, in descending order), while the dPCC tended to connect to the middle cingulate cortex, SPL, precuneus, and IPL. The connectivity pattern differs significantly between the precuneus and dPCC stimulation (p<0.05). Regarding each part of the medial parietal cortices, the distributions of parts of CCEP responses resembled those of the functional connectivity database. Based on how the dPCC was connected to the medial frontal area, SPL, and IPL, its connectivity pattern could not be explained by DMN alone, but suggested a mixture of DMN and the frontoparietal cognitive network. These findings improve our understanding of the connectivity profile within the medial parietal cortices. The electrophysiological connectivity is the basis of propagation of electrical activities in patients with epilepsy. In addition, it helps us to better understand the epileptic network arising from the medial parietal cortices.

Clinical and imaging features of nonmotor onset seizure in poststroke epilepsy.

OBJECTIVE: Motivated by the challenges raised by diagnosing poststroke epilepsy (PSE), especially in nonmotor onset seizure (non-MOS), we aimed to investigate the features of non-MOS, including seizure sequences, patient characteristics, and electrophysiological and imaging findings in PSE. METHODS: This observational cohort study enrolled patients with PSE whose seizure onset was witnessed. According to the International League Against Epilepsy (ILAE) 2017 seizure classification, we classified seizure-onset symptoms into the non-MOS and MOS groups. We compared the different clinical characteristics between the two groups. RESULTS: Between 2011 and 2018, we enrolled 225 patients with PSE (median age, 75 years), consisting of 97 (43%) with non-MOS and 128 (57%) with MOS. Overall, 65 (67%) of the patients without MOS had no subsequent convulsions. Multivariable logistic regression analysis showed significant associations of non-MOS with absence of poststroke hemiparesis (adjusted odds ratio [OR], 1.88; 95% confidence interval [CI], 1.03-3.42), frontal stroke lobe lesions (OR, 2.11; 95% CI, 1.14-3.91), and putaminal stroke lesions (OR, 2.51; 95% CI, 1.22-5.18) as negative indicators. Postictal single-photon emission computed tomography (SPECT) detected prolonged hyperperfusion in the temporal lobe more frequently in the non-MOS than in the MOS group (48% vs 31%; p = .02). The detection rate was higher than spikes/sharp waves in scalp electroencephalography, both in the non-MOS group (72% vs 33%; p < .001) and the MOS group (68% vs 29%; p < .001). SIGNIFICANCE: This study provides the clinical features of non-MOS in patients with PSE. Compared with the patients with MOS, patients with non-MOS showed less likely subsequent convulsive seizures, highlighting the clinical challenges. Postictal perfusion imaging and negative indicators of the non-MOS type may help diagnose and stratify PSE.

Frequency-Dependent Cortical Interactions during Semantic Processing: An Electrocorticogram Cross-spectrum Analysis Using a Semantic Space Model.

Convergent evidence has demonstrated that semantics are represented by the interaction between a multimodal semantic hub at the anterior temporal lobe (ATL) and other modality-specific association cortical areas. Electrocorticogram (ECoG) recording with high spatiotemporal resolutions is efficient in evaluating such cortical interactions; however, this has not been a focus of preceding studies. The present study evaluated cortical interactions during picture naming using a novel ECoG cross-spectrum analysis, which was formulated from a computational simulation of neuronal networks and combined with a vector space model of semantics. The results clarified three types of frequency-dependent cortical networks: 1) an earlier-period (0.2-0.8 s from stimulus onset) high-gamma-band (90-150 Hz) network with a hub at the posterior fusiform gyrus, 2) a later-period (0.4-1.0 s) beta-band (15-40 Hz) network with multiple hubs at the ventral ATL and posterior middle temporal gyrus, and 3) a pre-articulation theta-band (4-7 Hz) network distributed over widely located cortical regions. These results suggest that frequency-dependent cortical interactions can characterize the underlying processes of semantic cognition, and the beta-band network with a hub at the ventral ATL is especially associated with the formation of semantic representation.

[Utility of Presurgical Evaluation Using Stereoelectroencephalography(SEEG)].

Precise localization of the "epileptogenic zone(EZ)" is the goal of presurgical investigations in patients with drug-resistant focal epilepsy. Intracranial electroencephalography recordings are required when noninvasive evaluation results are not consistent. Although subdural grid electrodes(SDG)have been widely used in Japan, stereoelectroencephalography(SEEG)has been recently introduced. The principle of SEEG is based on anatomo-electro-clinical correlations to investigate surgical hypotheses that are primarily driven by the analysis of seizure semiology as well as other noninvasive investigations. The most important element of the SEEG methodology is to formulate preimplantation electrode trajectories considering the anatomo-electro-clinical correlations of epileptic seizures. If the preimplantation hypotheses are insufficient or incorrect, SEEG recordings will not identify the EZ. A detailed analysis of seizure semiology with respect to anatomo-electro-clinical correlates, particularly including various deep structures, such as the insular, operculum, and cingulate cortex, forms the basis of the implantation strategy for SEEG. The strategy of implantation is not to map the lobes/lobules but the epileptic networks, which usually involve multiple lobes, indicating that the theory of SEEG is completely different from that of SDG. Herein, we introduce the basics of SEEG, especially presurgical evaluations, with a representative case presentation.

Genetic Variations and Neuropathologic Features of Patients with PRKN Mutations.

BACKGROUND: Mutations in PRKN are the most common cause of autosomal recessive juvenile parkinsonism. The objective of this study was to investigate the association between genotype and pathology in patients with PRKN mutations. METHODS: We performed a sequence and copy number variation analysis of PRKN, mRNA transcripts, Parkin protein expression, and neuropathology in 8 autopsied patients. RESULTS: All the patients harbored biallelic PRKN mutations. Two patients were homozygous and heterozygous, respectively, for the missense mutation p.C431F. Seven patients had exon rearrangements, including 2 patients from a single family who harbored a homozygous deletion of exon 4, and 3 patients who carried a homozygous duplication of exons 6-7, a homozygous duplication of exons 10-11, and a heterozygous duplication of exons 2-4. In the other 2 patients, we found a compound heterozygous duplication of exon 2, deletion of exon 3, and a heterozygous duplication of exon 2. However, sequencing of cDNA prepared from mRNA revealed 2 different transcripts derived from triplication of exon 2 and deletion of exons 2-3 and from duplication of exons 2-4 and deletion of exons 3-4. Western blotting and immunohistochemistry revealed faint or no expression of Parkin in their brains. In the substantia nigra pars compacta, a subfield-specific pattern of neuronal loss and mild gliosis were evident. Lewy bodies were found in 3 patients. Peripheral sensory neuronopathy was a feature. CONCLUSIONS: Genomic and mRNA analysis is needed to identify the PRKN mutations. Variable mutations may result in no or little production of mature Parkin and the histopathologic features may be similar. © 2021 International Parkinson and Movement Disorder Society.

Connectivity Gradient in the Human Left Inferior Frontal Gyrus: Intraoperative Cortico-Cortical Evoked Potential Study.

In the dual-stream model of language processing, the exact connectivity of the ventral stream to the anterior temporal lobe remains elusive. To investigate the connectivity between the inferior frontal gyrus (IFG) and the lateral part of the temporal and parietal lobes, we integrated spatiotemporal profiles of cortico-cortical evoked potentials (CCEPs) recorded intraoperatively in 14 patients who had undergone surgical resection for a brain tumor or epileptic focus. Four-dimensional visualization of the combined CCEP data showed that the pars opercularis (Broca's area) is connected to the posterior temporal cortices and the supramarginal gyrus, whereas the pars orbitalis is connected to the anterior lateral temporal cortices and angular gyrus. Quantitative topographical analysis of CCEP connectivity confirmed an anterior-posterior gradient of connectivity from IFG stimulus sites to the temporal response sites. Reciprocality analysis indicated that the anterior part of the IFG is bidirectionally connected to the temporal or parietal area. This study shows that each IFG subdivision has different connectivity to the temporal lobe with an anterior-posterior gradient and supports the classical connectivity concept of Dejerine; that is, the frontal lobe is connected to the temporal lobe through the arcuate fasciculus and also a double fan-shaped structure anchored at the limen insulae.

Progressive length-dependent polyneuropathy in xeroderma pigmentosum group A.

BACKGROUND: In this study, we aimed to investigate the progression of peripheral nervous system involvement in xeroderma pigmentosum group A (XP-A). METHODS: We performed nerve conduction studies in 17 genetically confirmed XP-A patients and conducted follow-ups. Of these patients we also analyzed gray matter volume (GMV) using brain MRI and assessed the severity score of clinical and skin manifestation. RESULTS: We found significant reduction in the motor and sensory nerve action potential amplitude and mild reduction in conduction velocity. These findings were predominant in sensory nerves and the lower limbs, were observed since early childhood, and gradually deteriorated with age. CONCLUSIONS: The electrophysiological characteristics of XP-A patients are consistent with length-dependent axonal polyneuropathy and there is progressive deterioration from early childhood.

A score to map the lateral nonprimary motor area: Multispectrum intrinsic brain activity versus cortical stimulation.

OBJECTIVE: Multispectrum electrocorticographic components are critical for mapping the nonprimary motor area (NPMA). The objective of this study was to derive and validate a reliable scoring system for electrocorticography-based NPMA mapping (NPMA score) to replace electrical cortical stimulation (ECS) during brain surgery. METHODS: We analyzed 14 consecutive epilepsy patients with subdural electrodes implanted in the frontal lobe at Kyoto University Hospital. The NPMA score was retrospectively derived from multivariate analysis in the derivation group (patients = 7, electrodes = 713, during 2010-2013) and validated in the validation group (patients = 7, electrodes = 772, during 2014-2017). We assessed the accuracy and reliability of the score relative to ECS in determining the NPMA and predicting postoperative functional outcomes. RESULTS: Multivariate analysis in the derivation group led to an 8-point score for predicting ECS-based NPMA (1 point for anatomical localization of the electrode and 1 or 2 points for movement-related electrocorticographic components regardless of somatotopy in very slow cortical potential shifts [<0.5 Hz], 40-80-Hz band power increase, and 8-24-Hz band power decrease), which was validated in the validation group. The area under the receiver operating characteristic curve (AUC) was 0.89 in the derivation group. Good prediction (specificity = 94%, sensitivity = 100%) and discrimination (AUC = 0.87) were reproduced in the validation group. Overall, higher NPMA scores identified 2 patients with postoperative deficits after frontal lobe resection. SIGNIFICANCE: The NPMA score is reliable for NPMA mapping, potentially replacing ECS. It is a potential prognostic marker for postoperative functional deficits.

A rational, multispectral mapping algorithm for primary motor cortex: A primary step before cortical stimulation.

OBJECTIVE: For future artificial intelligence-based brain mapping, development of a rational and safe scoring system for a brain motor mapping algorithm using electrocorticography (ECoG score), which contains various spectral, purely intrinsic brain activities, is necessary for either before or in the absence of electrical cortical stimulation (ECS). METHODS: We evaluated 1114 electrodes of 10 consecutive focal epilepsy patients who underwent subdural electrode implantation before epilepsy surgery at Kyoto University Hospital during 2011-2017. Data from ECoG-based mapping (bandpass filter of 0.016-300/600 Hz) to define the primary motor area (M1) localization were used to create an ECoG score (range = 0-4) by assigning 1 point each for the occurrence of ECoG components: very slow movement-related cortical potentials (<0.5-1.0 Hz), event-related synchronization (76-100 Hz or 100-200 Hz), and event-related desynchronization (8-12 Hz or 12-24 Hz). The ECoG score was assessed by calculating the sensitivity, specificity, and cutoff values of the score for localization concordance with M1 defined using only ECS as a reference. RESULTS: With an area under the receiver operating characteristic curve (AUC) of 0.76, cutoffs of scores of 4 and 1 showed high specificity (94%) and sensitivity (98%) in concordance with ECS-based mapping, respectively. The ECoG score for mapping M1 of the upper limb achieved greater accuracy (AUC = 0.85) compared to that of the face (AUC = 0.64). SIGNIFICANCE: The ECoG score proposed in the present study is rational, simple, and useful to define M1, and it is spatially concordant with ECS. Although ECS is still widely employed for presurgical examination, our proposed application of the ECoG score may be suitable for future brain M1 mapping, and possibly beyond M1 mapping, independently of ECS.

Critique of the 2017 epileptic seizure and epilepsy classifications.

This article critiques the International League Against Epilepsy (ILAE) 2015-2017 classifications of epilepsy, epileptic seizures, and status epilepticus. It points out the following shortcomings of the ILAE classifications: (1) they mix semiological terms with epileptogenic zone terminology; (2) simple and widely accepted terminology has been replaced by complex terminology containing less information; (3) seizure evolution cannot be described in any detail; (4) in the four-level epilepsy classification, level two (epilepsy category) overlaps almost 100% with diagnostic level one (seizure type); and (5) the design of different classifications with distinct frameworks for newborns, adults, and patients in status epilepticus is confusing. The authors stress the importance of validating the new ILAE classifications and feel that the decision of Epilepsia to accept only manuscripts that use the ILAE classifications is premature and regrettable.

[Initial Experience of Stereotactic EEG Insertion with Anchor Bolt:Problem Extraction and Improvement of Insertion Accuracy].

In recent years, stereotactic electroencephalography(SEEG)has been focused on as a new invasive method for epileptic focus detection. Although the covering area of the brain surface is smaller than the invasive estimation with subdural electrodes, SEEG can evaluate foci that are deeply seated, noncontiguous leaves, and/or bilateral hemispheres. In addition, SEEG can capture consecutive changes in seizure activity in three dimensions. Due to the development of neuroimaging, computer-assisted, and robotic surgery technology, SEEG insertion began to be commonly used worldwide. Although the approximate complication rates of SEEG are estimated as 1% to 3%, which is lower than that of subdural electrode implantation, the risks of major complications, such as permanent neurological deficit and death, are equivalent. Therefore, meticulous procedure must be needed. To introduce SEEG for intractable partial epilepsy, we acquired approval from the institutional review board and concurrently imported surgical devices and electrodes from the manufacturer in the United States for two surgical candidates. We safely performed SEEG insertion, focal identification, and brain functional mapping by cortical electrical stimulation in two cases. Insertion was difficult for some electrodes, which could be due to the lack of adequate surgical device and large skull angle. Hopefully, the official installation of SEEG will be planned in the near future. We hereby reported tips and pitfalls of SEEG implantation through our own experience in a single institute.

Neural pattern similarity between contra- and ipsilateral movements in high-frequency band of human electrocorticograms.

The cortical motor areas are activated not only during contralateral limb movements but also during ipsilateral limb movements. Although these ipsilateral activities have been observed in several brain imaging studies, their functional role is poorly understood. Due to its high temporal resolution and low susceptibility to artifacts from body movements, the electrocorticogram (ECoG) is an advantageous measurement method for assessing the human brain function of motor behaviors. Here, we demonstrate that contra- and ipsilateral movements share a similarity in the high-frequency band of human ECoG signals. The ECoG signals were measured from the unilateral sensorimotor cortex while patients conducted self-paced movements of different body parts, contra- or ipsilateral to the measurement side. The movement categories (wrist, shoulder, or ankle) of ipsilateral movements were decoded as accurately as those of contralateral movements from spatial patterns of the high-frequency band of the precentral motor area (the primary motor and premotor areas). The decoder, trained in the high-frequency band of ipsilateral movements generalized to contralateral movements, and vice versa, confirmed that the activity patterns related to ipsilateral limb movements were similar to contralateral ones in the precentral motor area. Our results suggest that the high-frequency band activity patterns of ipsilateral and contralateral movements might be functionally coupled to control limbs, even during unilateral movements.

Clinical impact of intraoperative CCEP monitoring in evaluating the dorsal language white matter pathway.

In order to preserve postoperative language function, we recently proposed a new intraoperative method to monitor the integrity of the dorsal language pathway (arcuate fasciculus; AF) using cortico-cortical evoked potentials (CCEPs). Based on further investigations (20 patients, 21 CCEP investigations), including patients who were not suitable for awake surgery (five CCEP investigations) or those without preoperative neuroimaging data (eight CCEP investigations including four with untraceable tractography due to brain edema), we attempted to clarify the clinical impact of this new intraoperative method. We monitored the integrity of AF by stimulating the anterior perisylvian language area (AL) by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. After tumor resection, single-pulse electrical stimuli were also applied to the floor of the removal cavity to record subcortico-cortical evoked potentials (SCEPs) at AL and PL in 12 patients (12 SCEP investigations). We demonstrated that (1) intraoperative dorsal language network monitoring was feasible even when patients were not suitable for awake surgery or without preoperative neuroimaging studies, (2) CCEP is a dynamic marker of functional connectivity or integrity of AF, and CCEP N1 amplitude could even become larger after reduction of brain edema, (3) a 50% CCEP N1 amplitude decline might be a cut-off value to prevent permanent language dysfunction due to impairment of AF, (4) a correspondence (<2.0 ms difference) of N1 onset latencies between CCEP and the sum of SCEPs indicates close proximity of the subcortical stimulus site to AF (<3.0 mm). Hum Brain Mapp 38:1977-1991, 2017. © 2017 Wiley Periodicals, Inc.