Functional Brain Mapping Using Depth Electrodes.

OBJECTIVE: This study investigated the neurologic symptoms and stimulus intensities in the stimulation of deep structures and subcortical fibers with the depth electrodes. METHODS: Seventeen patients with drug-refractory epilepsy who underwent functional brain mapping with the depth electrodes were enrolled. The 50 Hz electrical stimulation was applied, and the diffusion tensor image was used to identify subcortical fibers. The responsible structures and stimulus intensities for the induced neurologic symptoms were evaluated. RESULTS: Neurologic symptoms were induced in 11 of 17 patients. The opercular stimulation elicited the neurologic symptoms in 6 patients at the median threshold of 4.0 mA (visceral/face/hand sensory, hand/throat motor, negative motor and auditory symptoms). The insular stimulation induced the neurologic symptoms in 4 patients at the median threshold of 4.0 mA (auditory, negative motor, and sensory symptoms). The stimulation of subcortical fibers was induced in 5 of 9 patients at the median threshold of 4.5 mA. The thresholds of depth electrodes were significantly lower than those of subdural electrodes in 8 patients who used both subdural and depth electrodes and induced symptoms with both electrodes. CONCLUSIONS: The stimulation of depth electrodes can identify the function of deep structures and subcortical fibers with lower intensities than subdural electrodes.

An anatomo-functional study of the interactivity between the paracentral lobule and the primary motor cortex.

OBJECTIVE: The purpose of this study was to understand the anatomical and functional connections between the paracentral lobule (PCL) and the primary motor cortex (M1) of the human brain. METHODS: This retrospective study included 16 patients who underwent resection of lesions located near M1. Nine patients had lesions in the dominant hemisphere. Tractography was performed to visualize the connectivity between two regions of interest (ROIs)-the convexity and the interhemispheric fissure-that were shown by functional MRI to be activated during a finger tapping task. The number, mean length, and fractional anisotropy (FA) of the fibers between the ROIs were estimated. During surgery, subdural electrodes were placed on the brain surface, including the ROIs, using a navigation system. Cortico-cortical evoked potentials (CCEPs) were evoked by applying electrical stimuli to the hand region of M1 using electrodes placed on the convexity and were measured with electrodes placed on the interhemispheric fissure. To verify CCEP bidirectionality, electrical stimuli were applied to electrodes on the interhemispheric fissure that showed CCEP responses. Correlations of CCEP amplitudes and latencies with the number, mean length, and mean FA value obtained from tractography were determined. The correlations between these parameters and perioperative motor functions were also analyzed. RESULTS: Fibers of 14 patients were visualized by diffusion tensor imaging (DTI). Unidirectional CCEPs between the PCL and M1 were measurable in all 16 patients, and bidirectional CCEPs between them were measurable in 14 patients. There was no significant difference between the two directions in the maximum CCEP amplitude or latency (amplitude, p = 0.391; latency, p = 0.583). Neither the amplitude nor latency showed any apparent correlation with the number, mean length, or mean FA value of the fibers obtained from tractography. Pre- and postoperative motor function of the hands was not significantly correlated with CCEP amplitude or latency. The number and mean FA value of fibers obtained by DTI, as well as the maximum CCEP amplitude, varied between patients. CONCLUSIONS: This study demonstrated an anatomical connection and a bidirectional functional connection between the PCL, including the supplementary motor area, and M1 of the human brain. The observed variability between patients suggests possible motor function plasticity. These findings may serve as a foundation for further studies.

Intraoperative nerve stimulation during vagal nerve stimulator placement.

Background: Vagal nerve stimulation (VNS) is a palliative treatment for refractory epilepsy and intraoperative nerve stimulation is applied to the vagal and other nerves to prevent electrode misplacement. We evaluated these thresholds to establish intraoperative monitoring procedures for VNS surgery. Methods: Forty-six patients who underwent intraoperative nerve stimulation during VNS placement were enrolled. The vagal nerve and other exposed nerves were electrically stimulated during surgery, and muscle contraction was confirmed by electromyography of the vocal cords and visual recognition of cervical muscle contraction. The nerve thresholds and the most sensitive parts of the vagal nerve were analyzed retrospectively. Results: The stimulation of vagal nerves induced vocal cord responses in all 46 patients; the median thresholds of the most sensitive parts and all parts were 0.2 mA (range: 0.05-0.75 mA) and 0.25 mA (range: 0.15-1.5 mA), respectively. The medial middle region was identified as the most sensitive part of the vagal nerve in the majority of participants (82.5%). In 11 patients, other cervical nerves were stimulated and sternohyoid muscle contraction was induced with a median threshold of 0.35 mA (range: 0.1-0.7 mA) in eight patients, while sternocleidomastoid muscle contraction was induced with a median threshold of 0.2 mA (range: 0.1-0.2 mA) in three. Conclusion: Intraoperative stimulation of vagal nerves induces vocal cord responses with locational variations, and the middle part stimulation could minimize the stimulus intensities. The nerves innervating the sternohyoid and sternocleidomastoid muscles may be exposed during the procedure. Knowledge of these characteristics will enhance the effectiveness of this technique in future applications.

Microbleeds Due to Reperfusion Enhance Early Seizures after Carotid Ligation in a Rat Ischemic Model.

Impaired reperfusion in ischemic brain disease is a condition that we are increasingly confronted with owing to recent advances in reperfusion therapy. In the present study, rat models of reperfusion were investigated to determine the causes of acute seizures using magnetic resonance imaging (MRI) and histopathological specimens. Rat models of bilateral common carotid artery ligation followed by reperfusion and complete occlusion were created. We compared the incidence of seizures, mortality within 24 h, MRI, and magnetic resonance spectroscopy (MRS) to evaluate ischemic or hemorrhagic changes and metabolites in the brain parenchyma. In addition, the histopathological specimens were compared with those observed on MRI. In multivariate analysis, the predictive factors of mortality were seizure (odds ratios (OR), 106.572), reperfusion or occlusion (OR, 0.056), and the apparent diffusion coefficient value of the striatum (OR, 0.396). The predictive factors of a convulsive seizure were reperfusion or occlusion (OR, 0.007) and the number of round-shaped hyposignals (RHS) on susceptibility-weighted imaging (SWI) (OR, 2.072). The incidence of convulsive seizures was significantly correlated with the number of RHS in the reperfusion model. RHS on SWI was confirmed pathologically as microbleeds in the extravasation of the brain parenchyma and was distributed around the hippocampus and cingulum bundle. MRS analysis showed that the N-acetyl aspartate level was significantly lower in the reperfusion group than in the occlusion group. In the reperfusion model, RHS on SWI was a risk factor for convulsive seizures. The location of the RHS also influenced the incidence of convulsive seizures.

Computational Fluid Dynamics Analysis Features in Aneurysm Development in Rats.

The investigation of how to control the development and growth of cerebral aneurysms is important for the prevention of subarachnoid hemorrhage. Although there have been several types of research studies on computational fluid dynamics (CFD) analysis of brain aneurysm development and growth, there has been no unified interpretation of the CFD analysis results. The purpose of this study is to clarify the characteristics of CFD analysis results related to the development of cerebral aneurysms using an animal model. Nineteen rat models of cerebral aneurysms were created, and the CFD analysis results between the cerebral aneurysm group [n = 10; the aneurysm was observed on magnetic resonance angiography (MRA) within 10 weeks after aneurysm induction surgery] and the nonaneurysm group (n = 9) were compared. All aneurysms were confirmed on the proximal segment of the left cerebral artery (P1), and the cross-sectional area and curvature of the left P1 were evaluated together. In the cerebral aneurysm group, there was a decrease in wall shear stress (WSS) that is consistent with the location of the aneurysm compared to the nonaneurysm group. The cross-sectional area of the left P1 gradually increased in the aneurysm group but not in the nonaneurysm group. The mean curvature in the entire left P1 was higher in the aneurysm group than in the nonaneurysm group. This study revealed that the development of cerebral aneurysms is due to changes in vascular morphology, namely, an increase in vessel diameter and a high curvature, and a decreased WSS consistent with the site of aneurysm development using this animal model.

Visual networks: Electric brain stimulation and diffusion tensor imaging.

OBJECTIVE: The present study investigated the networks of visual functional areas using electric brain stimulation (EBS) and diffusion tensor imaging (DTI). METHODS: Thirteen patients with intractable focal epilepsy in which visual functional areas were identified by EBS were enrolled. An electric stimulation at 50Hz was applied to electrodes during several tasks. DTI was used to identify subcortical fibers originating from the visual functional areas identified by EBS. RESULT: The electrical stimulation induced three types of visual symptoms: visual illusions (change of vision), visual hallucinations (appearance of a new object), and blurred vision. Visual illusions were associated with stimulation of lateral temporo-parieto-occipital areas, and visual hallucinations with stimulation of lateral/basal temporal areas, the occipital lobe and the precuneus. Stimulus intensities eliciting visual illusions were significantly higher than those for visual hallucinations. Tractography revealed that the superior fronto-occipital fasciculus was associated with visual illusions and the middle longitudinal fasciculus with visual hallucinations, and both symptoms shared several subcortical fibers such as the vertical occipital fasciculus, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, inferior longitudinal fasciculus, optic radiations, and commissural fibers. CONCLUSION: The present study revealed the characteristic cortical regions and networks of visual functional areas. The results obtained provide information on human visual functions and are a practical guide for electrical cortical stimulation.

Transcranial electrical stimulation technique for induction of unilateral motor evoked potentials.

OBJECTIVE: Transcranial electrical stimulation motor evoked potentials (TES-MEP) are widely used to monitor motor function; however, broad current spread and induced body movement are limitations of this technique. We herein report a localized stimulation technique for TES-MEP that induces unilateral MEP responses. METHODS: The stimulation of C1(+)-C4(-) or C2(+)-C3(-) was performed to induce right- or left-sided muscle contraction, respectively, in 70 patients. Electromyography was recorded by placing electrodes on the bilateral abductor pollicis brevis (APB) and abductor hallucis (AH) muscles. Stimulation conditions were regulated in the range to induce unilateral muscle contractions contralateral to the anodal stimulation. The thresholds and amplitudes of TES-MEP were retrospectively analyzed. RESULTS: The thresholds of APB were lower than those of AH in 47 patients, AH thresholds were lower than those of APB in 6 patients, and both APB and AH started to respond at the same intensity in 15 patients. This technical stimulation induced contralateral limb contractions with a suprathreshold stimulation of 129.4 ± 35.6 mA (mean ± standard deviation) in 68 patients (97%). Amplitudes in the suprathreshold stimulation of APB and AH responses were 727.5 ± 695.7 and 403.3 ± 325.7 µV, respectively. CONCLUSIONS: The C1(+)-C4/C2(+)-C3(-) stimulation in TES-MEP enables a localized stimulation to induce unilateral MEP responses. SIGNIFICANCE: Our stimulation technique enables the stable and safe monitoring of unilateral limbs, and contributes to the reliable monitoring of motor function in neurosurgery.

Deep learning for the diagnosis of mesial temporal lobe epilepsy.

OBJECTIVE: This study aimed to enable the automatic detection of the hippocampus and diagnose mesial temporal lobe epilepsy (MTLE) with the hippocampus as the epileptogenic area using artificial intelligence (AI). We compared the diagnostic accuracies of AI and neurosurgical physicians for MTLE with the hippocampus as the epileptogenic area. METHOD: In this study, we used an AI program to diagnose MTLE. The image sets were processed using a code written in Python 3.7.4. and analyzed using Open Computer Vision 4.5.1. The deep learning model, which was a fine-tuned VGG16 model, consisted of several layers. The diagnostic accuracies of AI and board-certified neurosurgeons were compared. RESULTS: AI detected the hippocampi automatically and diagnosed MTLE with the hippocampus as the epileptogenic area on both T2-weighted imaging (T2WI) and fluid-attenuated inversion recovery (FLAIR) images. The diagnostic accuracies of AI based on T2WI and FLAIR data were 99% and 89%, respectively, and those of neurosurgeons based on T2WI and FLAIR data were 94% and 95%, respectively. The diagnostic accuracy of AI was statistically higher than that of board-certified neurosurgeons based on T2WI data (p = 0.00129). CONCLUSION: The deep learning-based AI program is highly accurate and can diagnose MTLE better than some board-certified neurosurgeons. AI can maintain a certain level of output accuracy and can be a reliable assistant to doctors.

Steady-State Cortico-Cortical Evoked Potential.

PURPOSE: The present study evaluated the utility of the steady-state responses of cortico-cortical evoked potentials (SSCCEPs) and compared them with the responses of conventional CCEPs. METHODS: Eleven patients with medically intractable focal epilepsy who underwent the implantation of subdural electrodes or stereoelectroencephalography were enrolled. Conventional CCEPs were obtained by averaging responses to alternating 1-Hz electrical stimuli, and 5-Hz stimuli were delivered for recording SSCCEPs. The distribution of SSCCEPs was assessed by a frequency analysis of fast Fourier transform and compared with conventional CCEPs. RESULTS: Steady-state responses of cortico-cortical evoked potentials were successfully recorded in areas consistent with conventional CCEPs in all patients. However, SSCCEPs were more easily disturbed by the 5-Hz stimulation, and small responses had difficulty generating SSCCEPs. CONCLUSIONS: Steady-state responses of cortico-cortical evoked potentials may be a useful alternative to conventional CCEPs.

Usefulness of Intraoperative Electrocorticography for the Localization of Epileptogenic Zones.

Intraoperative electrocorticography (iECoG) is widely performed to identify irritative zones in the cortex during brain surgery; however, several limitations (e.g., short recording times and the effects of general anesthesia) reduce its effectiveness. The present study aimed to evaluate the utility of iECoG for localizing epileptogenic zones. We compared the results of iECoG and chronic electrocorticography (cECoG) in 25 patients with refractory epilepsy. Subdural electrodes were implanted with iECoG under general anesthesia (2% sevoflurane). cECoG recordings were performed for 3-14 days. The distribution of iECoG spikes was compared with cECoG spike, seizure onset zone, and resection areas. The concordance patterns of each distribution were classified into four patterns: Group 1: No spike in iECoG, Group 2: concordant (2a: iECoG smaller, 2b: iECoG larger, Group 3: discordant >50%). The concordance rate of interictal spikes, seizure onset zones, and resection areas were 88.0% (Group 2a: 72.0%, Group 2b: 16.0%), 70.0% (Group 2a: 25.0%, Group 2b: 45.0%), and 81.0% (Group 2a: 42.9%, Group 2b: 38.1%), respectively. The resection of iECoG spike areas significantly correlated with good surgical outcomes. The indication and limitations of iECoG need to be realized, and the complementary use of iECoG and cECoG may enhance clinical utility.

Comparison of Thresholds between Bipolar and Monopolar Electrical Cortical Stimulation.

Electrical cortical stimulation is widely performed and is the gold standard for functional mapping in intractable epilepsy patients; however, a standard protocol has not yet been established. With respect to stimulation methods, two techniques can be applied: monopolar and bipolar stimulation. We compared the threshold to induce clinical symptoms between these two stimulation techniques. Twenty patients with intractable epilepsy who underwent electrical cortical stimulation for functional mapping were retrospectively investigated. We evaluated the stimulation intensity thresholds required to induce motor, sensory, and language symptoms. A total of 114 electrodes in 20 patients were used to investigate motor, sensory, and language symptoms. The thresholds required to induce motor (median value, bipolar: 4 mA, monopolar: 5 mA, p < 0.05) and language symptoms (bipolar: 8 mA, monopolar: 10 mA, p < 0.0005) were significantly higher for monopolar stimulation than those for bipolar stimulation. However, for sensory symptoms, no significant differences were found in the required thresholds between monopolar and bipolar stimulation (bipolar: 4 mA, monopolar: 4 mA, p = 0.474). Bipolar cortical stimulation required lower intensities to produce clinical motor and language symptoms and thus would be safe and suitable for screening of the eloquent area in functional mapping.

Effect of Early Surgical Intervention for Brain Tumors Associated with Epilepsy on the Improvement in Memory Performance.

We evaluated the effect of early surgical intervention on the change in memory performance of patients with low-grade brain tumors associated with epilepsy. Twenty-three adult patients with low-grade brain tumors and epilepsy who underwent surgery at our institution between 2010 and 2019 were included. The Wechsler Memory Scale-Revised (WMS-R) was used to assess cognitive memory performance. Memory performance before and after surgery was retrospectively evaluated. In addition, the relationships among preoperative memory function, postoperative seizure outcome, preoperative seizure control, temporal lobe lesion, and change in memory function were examined. There were statistically significant improvements from median preoperative to postoperative WMS-R subscale scores for verbal memory, general memory, and delayed recall (p<0.001, p<0.001, and p=0.0055, respectively) regardless of preoperative sores and tumor location. Good postsurgical seizure control was associated with significant improvements in postoperative WMS-R performance. Our results indicated that early surgical intervention might improve postoperative memory function in patients with low-grade brain tumors and epilepsy.

Motor Mapping with Functional Magnetic Resonance Imaging: Comparison with Electrical Cortical Stimulation.

The aim of the present study was to evaluate motor area mapping using functional magnetic resonance imaging (fMRI) compared with electrical cortical stimulation (ECS). Motor mapping with fMRI and ECS were retrospectively compared in seven patients with refractory epilepsy in which the primary motor (M1) areas were identified by fMRI and ECS mapping between 2012 and 2019. A right finger tapping task was used for fMRI motor mapping. Blood oxygen level-dependent activation was detected in the left precentral gyrus (PreCG)/postcentral gyrus (PostCG) along the "hand knob" of the central sulcus in all seven patients. Bilateral supplementary motor areas (SMAs) were also activated (n = 6), and the cerebellar hemisphere showed activation on the right side (n = 3) and bilateral side (n = 4). Furthermore, the premotor area (PM) and posterior parietal cortex (PPC) were also activated on the left side (n = 1) and bilateral sides (n = 2). The M1 and sensory area (S1) detected by ECS included fMRI-activated PreCG/PostCG areas with broader extent. This study showed that fMRI motor mapping was locationally well correlated to the activation of M1/S1 by ECS, but the spatial extent was not concordant. In addition, the involvement of SMA, PM/PPC, and the cerebellum in simple voluntary movement was also suggested. Combination analysis of fMRI and ECS motor mapping contributes to precise localization of M1/S1.

Cortical regions and networks of hyperkinetic seizures: Electrocorticography and diffusion tensor imaging study.

OBJECTIVE: The present study investigated the cortical areas and networks responsible for hyperkinetic seizures by analyzing invasive recordings and diffusion tensor imaging (DTI) tractography. METHODS: Seven patients with intractable focal epilepsy in whom hyperkinetic seizures were recorded during an invasive evaluation at Sapporo Medical University between January 2012 and March 2020 were enrolled in the present study. Intracranial recordings were analyzed to localize seizure-onset zones (SOZs) and symptomatogenic zones (spread areas at clinical onset). DTI was used to identify the subcortical fibers originating from SOZs. RESULTS: Ten SOZs were located in four areas: (1) the inferior parietal lobule (two SOZs in two patients), (2) temporo-occipital junction (three SOZs in two patients), (3) medial temporal area (three SOZs in three patients) and (4) medial/lateral frontal lobe (two SOZs in two patients). Symptomatogenic zones appeared to be the premotor area, basal temporal area, temporo-occipital junction, and the postcentral gyrus/supramarginal gyrus. The tractographic analysis revealed that the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), middle longitudinal fasciculus (MLF), arcuate fasciculus (AF)/superior longitudinal fasciculus (SLF) II, III, and cingulum bundle may be associated with hyperkinetic seizures. CONCLUSION: The present results suggest the cortical areas (the inferior parietal lobule, temporo-occipital junction, medial temporal area, and medial/lateral frontal lobe) and subcortical fibers (IFOF, ILF, MLF, AF/SLFII, III, and the cingulum bundle) responsible for generating hyperkinetic seizures.

Effects of polarity of bipolar sensorimotor direct cortical stimulation on intraoperative motor evoked potentials.

OBJECTIVE: The present study investigated the effects of the stimulus polarity and location of motor evoked potential (MEP) to establish a stimulation protocol. METHODS: Nineteen patients who intraoperatively underwent MEP in bipolar direct cortical stimulation were enrolled in the present study. Somatosensory evoked potentials (SEP) of the contralateral median nerve stimulation were recorded to determine stimulation sites. MEP was performed under two settings in all patients: 1. Anodal bipolar stimulation: an anode on the precentral gyrus and a cathode on the postcentral gyrus, 2. Cathodal bipolar stimulation: a cathode on the precentral gyrus and an anode on the postcentral gyrus. MEP amplitudes and the coefficient of variation (CV) at a stimulation intensity of 25 mA and the thresholds of induced MEP were compared between the two settings. RESULTS: An electrical stimulation at 25 mA induced a significantly higher amplitude in cathodal bipolar stimulation than in anodal bipolar stimulation. Cathodal bipolar stimulation also showed significantly lower thresholds than anodal stimulation. CV did not significantly differ between the two groups. CONCLUSIONS: These results indicate that cathodal bipolar stimulation is superior to anodal bipolar stimulation for intraoperative MEP monitoring. SIGNIFICANCE: MEP in cathodal bipolar cortical stimulation may be used in a safe and useful evaluation method of motor fiber damage that combines sensitivity and specificity.

A case of paroxysmal kinesigenic dyskinesia suspected to be reflex epilepsy.

An 11-year-old male patient developed weakness or right arm elevation after sudden movement at the age of eight. Reflex epilepsy was initially suspected; however, magnetic resonance imaging and electroencephalography (EEG) revealed no abnormality. Video-EEG monitoring was performed, but no change was noted during attacks of weakness. He was diagnosed with paroxysmal kinesigenic dyskinesia (PKD) and carbamazepine has stopped his attacks. PKD is a rare neurological disorder characterized by brief attacks of involuntary movement triggered by sudden voluntary movements, which may be confused with reflex epilepsy. PKD should be considered as a differential diagnosis of reflex epilepsy.

Pitfalls of Commonly Used Ischemic and Dementia Models Due to Early Seizure by Carotid Ligation.

While the bilateral common carotid artery (CCA) ligation model is widely used in cerebrovascular disease and dementia studies, it can frequently cause seizures. We examined the validity of seizure as an experimental model of ischemia. Eight-week-old male Wistar and Sprague-Dawley (SD) rats were implanted with electrocorticography (ECoG) electrodes and bilateral CCA ligation was performed and compared to the sham groups. ECoG monitoring was used to confirm the seizure discharge and count the number of spikes in the interictal phase 2 h after ligation, followed by power spectral analysis. Magnetic resonance imaging (MRI) was performed 6 h after bilateral CCA ligation to assess fractional anisotropy (FA), apparent diffusion coefficient (ADC), and cerebral blood flow (CBF) values. Magnetic resonance spectroscopy (MRS) was also performed and the ischemic parameters and electrophysiological changes were compared. The Wistar rat group had significantly higher mortality, frequency of seizures, incidence of non-convulsive seizures, and number of spikes in the interictal period compared to those in the SD rat group. Power spectral analysis showed increased power in the delta band in both Wistar and SD rat groups. MRI, after CCA ligation, showed significantly lower ADC values, lower glutamine and glutamate levels, and higher lactate values in Wistar rats, although there was no difference in FA values. Metabolic and electrophysiological changes after CCA ligation differed according to the rat strain. Wistar rats were prone to increased lactate and decreased glutamine and glutamate levels and the development of status epilepticus. Seizures can affect the results of ischemic experiments.

Eye Movement Network Originating from Frontal Eye Field: Electric Cortical Stimulation and Diffusion Tensor Imaging.

This study investigated the networks originating from frontal eye fields (FEFs) using electric cortical stimulation and diffusion tensor imaging (DTI). Seven patients with intractable focal epilepsy, in which FEFs were identified by electrical cortical stimulation, were enrolled in this study. Electric stimulation at 50 Hz was applied to the electrodes for functional mapping. DTI was used to identify the subcortical fibers originating from the FEFs with two regions of interests (ROIs) in the FEF and contralateral paramedian pontine reticular formation (PPRF). FEFs were found in the superior precentral sulcus (pre-CS) in six patients and superior frontal gyrus (SFG) in three patients. DTI detected fibers connecting FEFs and contralateral PPRFs, passing within the internal capsule. The fibers were located close to the lateral antero-superior border of the subthalamic nucleus (STN) and medial posterior border of the globus pallidus internus (GPi). This study found the characteristic subcortical networks of the FEF. These tracts should be noted to prevent complications of deep brain stimulation (DBS) of the STN or GPi.

Preoperative Prediction of Communication Difficulties during Awake Craniotomy in Glioma Patients: A Retrospective Evaluation of 136 Cases at a Single Institution.

Awake craniotomy has been widely performed in patients with glioma in eloquent areas to minimize postoperative brain dysfunction. However, neurological examination in awake craniotomy is sometimes problematic due to communication difficulties during the intraoperative awake period. We evaluated preoperative predictors of these difficulties in awake craniotomy for patients with glioma. In all, 136 patients with glioma who underwent awake craniotomy at our institution between January 2012 and January 2020 were retrospectively evaluated. Patients were divided into two groups (appropriately awake group and inappropriately awake group) depending on their state during the intraoperative awake period, and the relationship between communication difficulties in awake craniotomy and both clinical and radiological characteristics were assessed. The appropriately awake group included 110 patients, and the inappropriately awake group included 26 patients. Reasons for inclusion in the inappropriately awake group were insufficient wakefulness in 15 patients, restless state in 6, and intraoperative seizures in 5. In multivariate analysis, the likelihood of being inappropriately awake was inversely correlated with preoperative seizures (odds ratio [OR], 0.23; 95% confidence interval [CI], 0.06-0.89; p = 0.033) and positively correlated with left-sided lesions (OR, 7.31; 95% CI, 1.54-34.62; p = 0.012). Both lack of preoperative seizures and left-sided lesions were identified as risk factors for intraoperative difficulties in awake craniotomy for patients with glioma. Understanding these risk factors may lead to more appropriate determination of eligibility for awake craniotomy.