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Abstract Chronic pain, a complex and debilitating condition, poses a significant challenge to both patients and healthcare providers worldwide. Conventional pharmacological interventions often prove inadequate in delivering satisfactory relief while carrying the risks of addiction and adverse reactions. In recent years, electric neuromodulation emerged as a promising alternative in chronic pain management. This method entails the precise administration of electrical stimulation to specific nerves or regions within the central nervous system to regulate pain signals. Through mechanisms that include the alteration of neural activity and the release of endogenous pain-relieving substances, electric neuromodulation can effectively alleviate pain and improve patients' quality of life. Several modalities of electric neuromodulation, with a different grade of invasiveness, provide tailored strategies to tackle various forms and origins of chronic pain. Through an exploration of the anatomical and physiological pathways of chronic pain, encompassing neurotransmitter involvement, this narrative review offers insights into electrical therapies’ mechanisms of action, clinical utility, and future perspectives in chronic pain management.

Encoding artificial perceptions through brain stimulation, especially that of higher cognitive functions such as speech perception, is one of the most formidable challenges in brain-computer interfaces (BCI). Brain stimulation has been used for functional mapping in clinical practices for the last 70 years to treat various disorders affecting the nervous system, including epilepsy, Parkinson's disease, essential tremors, and dystonia. Recently, direct electrical stimulation has been used to evoke various forms of perception in humans, ranging from sensorimotor, auditory, and visual to speech cognition. Successfully evoking and fine-tuning artificial perceptions could revolutionize communication for individuals with speech disorders and significantly enhance the capabilities of brain-computer interface technologies. However, despite the extensive literature on encoding various perceptions and the rising popularity of speech BCIs, inducing artificial speech perception is still largely unexplored, and its potential has yet to be determined. In this paper, we examine the various stimulation techniques used to evoke complex percepts and the target brain areas for the input of speech-like information. Finally, we discuss strategies to address the challenges of speech encoding and discuss the prospects of these approaches. [ABSTRACT FROM AUTHOR]

Intraoperative neurophysiological monitoring (IONM) is a crucial advancement in neurosurgery, enhancing procedural safety and precision. This technique involves continuous real-time assessment of neurophysiological signals, aiding surgeons in timely interventions to protect neural structures. In addition to inherent limitations, IONM necessitates a detailed anesthetic plan for accurate signal recording. Given the growing importance of IONM in neurosurgery, we conducted a narrative review including the most relevant studies about the modalities and their application in different fields of neurosurgery. In particular, this review provides insights for all physicians and healthcare professionals unfamiliar with IONM, elucidating commonly used techniques in neurosurgery. In particular, it discusses the roles of IONM in various neurosurgical settings such as tumoral brain resection, neurovascular surgery, epilepsy surgery, spinal surgery, and peripheral nerve surgery. Furthermore, it offers an overview of the anesthesiologic strategies and limitations of techniques essential for the effective implementation of IONM. [ABSTRACT FROM AUTHOR]

During intraoperative neurophysiological monitoring in neurosurgery, brain electrodes are placed to record electrocorticography or to inject current for direct cortical stimulation. A low impedance electrode may improve signal quality. We review here a brain electrode (WISE Cortical Strip, WCS®), where a thin polymer strip embeds platinum nanoparticles to create conductive electrode contacts. The low impedance contacts enable a high signal-to-noise ratio, allowing for better detection of small signals such as high-frequency oscillations (HFO). The softness of the WCS may hinder sliding the electrode under the dura or advancing it to deeper structures as the hippocampus but assures conformability with the cortex even in the resection cavity. We provide an extensive review on WCS including a market overview, an introduction to the device (mechanistics, cost aspects, performance standards, safety and contraindications) and an overview of the available pre- and post-approval data. The WCS improves signal detection by lower impedance and better conformability to the cortex. The higher signal-to-noise ratio improves the detection of challenging signals. The softness of the electrode may be a disadvantage in some applications and an advantage in others. [ABSTRACT FROM AUTHOR]

Chronic pain, a complex and debilitating condition, poses a significant challenge to both patients and healthcare providers worldwide. Conventional pharmacological interventions often prove inadequate in delivering satisfactory relief while carrying the risks of addiction and adverse reactions. In recent years, electric neuromodulation emerged as a promising alternative in chronic pain management. This method entails the precise administration of electrical stimulation to specific nerves or regions within the central nervous system to regulate pain signals. Through mechanisms that include the alteration of neural activity and the release of endogenous pain-relieving substances, electric neuromodulation can effectively alleviate pain and improve patients' quality of life. Several modalities of electric neuromodulation, with a different grade of invasiveness, provide tailored strategies to tackle various forms and origins of chronic pain. Through an exploration of the anatomical and physiological pathways of chronic pain, encompassing neurotransmitter involvement, this narrative review offers insights into electrical therapies' mechanisms of action, clinical utility, and future perspectives in chronic pain management. [ABSTRACT FROM AUTHOR]

Functions of the human insula have been explored extensively with neuroimaging methods and intracranial electrical stimulation studies that have highlighted a functional segregation across its subregions. A recently developed cytoarchitectonic map of the human insula has also segregated this brain region into various areas. Our knowledge of the functional organization of this brain region at the level of these fine-parceled microstructural areas remains only partially understood. We address this gap of knowledge by applying a multimodal approach linking direct electrical stimulation and task-evoked intracranial EEG recordings with microstructural subdivisions of the human insular cortex. In 17 neurosurgical patients with 142 implanted electrodes, stimulation of 40 % of the sites induced a reportable change in the conscious experience of the subjects in visceral/autonomic, anxiety, taste/olfactory, pain/temperature as well as somatosensory domains. These subjective responses showed a topographical allocation to microstructural areas defined by probabilistic cytoarchitectonic parcellation maps of the human insula. We found the pain and thermal responses to be located in areas lg2/ld2, while non-painful/non-thermal somatosensory responses corresponded to area ld3 and visceroceptive responses to area Id6. Lastly, the stimulation of area Id7 in the dorsal anterior insula, failed to induce reportable changes to subjective experience even though intracranial EEG recordings from this region captured significant time-locked high-frequency activity (HFA). Our results provide a multimodal map of functional subdivisions within the human insular cortex at the individual brain basis and characterize their anatomical association with fine-grained cytoarchitectonic parcellations of this brain structure.

Abstract Objective Cortical stimulation is an important component of stereoelectroencephalography (SEEG). Despite this, there is currently no standardized approach and significant heterogeneity in the literature regarding cortical stimulation practices. Via an international survey of SEEG clinicians, we sought to examine the spectrum of cortical stimulation practices to reveal areas of consensus and variability. Methods A 68‐item questionnaire was developed to understand cortical stimulation practices including neurostimulation parameters, interpretation of epileptogenicity, functional and cognitive assessment and subsequent surgical decisions. Multiple recruitment pathways were pursued, with the questionnaire distributed directly to 183 clinicians. Results Responses were received from 56 clinicians across 17 countries with experience ranging from 2 to 60 years (M = 10.73, SD = 9.44). Neurostimulation parameters varied considerably, with maximum current ranging from 3 to 10 mA (M = 5.33, SD = 2.29) for 1 Hz and from 2 to 15 mA (M = 6.54, SD = 3.68) for 50 Hz stimulation. Charge density ranged from 8 to 200 μC/cm2, with up to 43% of responders utilizing charge densities higher than recommended upper safety limits, i.e. 55 μC/cm2. North American responders reported statistically significant higher maximum current (P

Functions of the human insula have been explored extensively with neuroimaging methods and intracranial electrical stimulation studies that have highlighted a functional segregation across its subregions. A recently developed cytoarchitectonic map of the human insula has also segregated this brain region into various areas. Our knowledge of the functional organization of this brain region at the level of these fine-parceled microstructural areas remains only partially understood. We address this gap of knowledge by applying a multimodal approach linking direct electrical stimulation and task-evoked intracranial EEG recordings with microstructural subdivisions of the human insular cortex. In 17 neurosurgical patients with 142 implanted electrodes, stimulation of 40 % of the sites induced a reportable change in the conscious experience of the subjects in visceral/autonomic, anxiety, taste/olfactory, pain/temperature as well as somatosensory domains. These subjective responses showed a topographical allocation to microstructural areas defined by probabilistic cytoarchitectonic parcellation maps of the human insula. We found the pain and thermal responses to be located in areas lg2/ld2, while non-painful/non-thermal somatosensory responses corresponded to area ld3 and visceroceptive responses to area Id6. Lastly, the stimulation of area Id7 in the dorsal anterior insula, failed to induce reportable changes to subjective experience even though intracranial EEG recordings from this region captured significant time-locked high-frequency activity (HFA). Our results provide a multimodal map of functional subdivisions within the human insular cortex at the individual brain basis and characterize their anatomical association with fine-grained cytoarchitectonic parcellations of this brain structure. • Stimulation of various insular subregions elicited regionally-specific changes in the subjective states. • These changes were topographically correlated with probabilistic cytoarchitectonic parcellation maps of insular subregions. • In the insula subregion, stimulation caused no subjective changes but higher activity was seen during salience task. [ABSTRACT FROM AUTHOR]

Intraoperative language mapping of tumor and peritumor tissue is a well-established technique for avoiding permanent neurological deficits and maximizing extent of resection. Although there are several components of language that may be tested intraoperatively (eg, naming, writing, reading, and repetition), there is a lack of consistency in how patients are tested intraoperatively as well as the techniques involved to ensure safety during an awake procedure. Here, we review appropriate patient selection, neuroanesthetic techniques, cortical and subcortical language mapping stimulation paradigms, and selection of intraoperative language tasks used during awake craniotomies. We also expand on existing language mapping reviews by considering how intensity and timing of electrical stimulation may impact interpretation of mapping results.

Early postoperative seizures (EPS) are a common complication of brain tumor surgery. EPS can lead to hemorrhage, cerebral hypoxia, increased intracranial pressure, longer hospitalization, reduced quality of life, decreased overall survival, and increased morbidity. However, there are no formal guidelines on perioperative antiseizure medication (ASM) management in patients with tumor-related epilepsy who are deemed high risk for EPS. In this study, we describe the case of a 38-year-old man with isocitrate dehydrogenase-mutant mixed glioma and two episodes of EPS manifesting with status epilepticus during prior tumor surgeries and who presented with tumor progression. The Tumor Board recommended awake craniotomy with direct electrical stimulation (DES). The patient was administered aggressive preoperative “prophylactic” ASMs by increasing the maintenance doses of lacosamide and levetiracetam by 25% 48 h before surgery. An intravenous load of fosphenytoin (20 mg/kg) was administered in the operating room before DES, followed by a maintenance dosing of 300 mg/day for 14 days. EPS did not occur, and he was discharged home on postoperative day 4. Our case illustrates that aggressive perioperative prophylactic ASM therapy beyond the maintenance ASM regimen can be considered in patients with tumor-related epilepsy at risk of EPS.

Objective: Stimulation-based language mapping relies on identifying stimulation-induced language disruptions, which preexisting speech disorders affecting the laryngeal and orofacial speech system can confound. This study ascertained the effects of preexisting stuttering on pre- and intraoperative language mapping to improve the reliability and specificity of established language mapping protocols in the context of speech fluency disorders. Method: Differentiation-ability of a speech therapist and two experienced nrTMS examiners between stuttering symptoms and stimulation-induced language errors during preoperative mappings were retrospectively compared (05/2018-01/2021). Subsequently, the impact of stuttering on intraoperative mappings was evaluated in all prospective patients (01/2021-12/2022). Results: In the first part, 4.85 % of 103 glioma patients stuttered. While both examiners had a significant agreement for misclassifying pauses in speech flow and prolongations (Κ ≥ 0.50, p ≤ 0.02, respectively), less experience resulted in more misclassified stuttering symptoms. In one awake surgery case within the second part, stuttering decreased the reliability of intraoperative language mapping.Comparison with Existing Method(s): By thoroughly differentiating speech fluency symptoms from stimulation-induced disruptions, the reliability and proportion of stuttering symptoms falsely attributed to stimulation-induced language network disruptions can be improved. This may increase the consistency and specificity of language mapping results in stuttering glioma patients. Conclusions: Preexisting stuttering negatively impacted language mapping specificity. Thus, surgical planning and the functional outcome may benefit substantially from thoroughly differentiating speech fluency symptoms from stimulation-induced disruptions by trained specialists.

Intraoperative functional mapping of tumor and peri-tumor tissue is a well-established technique for avoiding permanent neurologic deficits and maximizing extent of resection. Motor, language, and other cognitive domains may be assessed with intraoperative tasks. This article describes techniques used for motor and language mapping including awake mapping considerations in addition to less traditional intraoperative testing paradigms for cognition. It also discusses complications associated with mapping and insights into complication avoidance.

Objective: Cortical stimulation is an important component of stereoelectroencephalography (SEEG). Despite this, there is currently no standardized approach and significant heterogeneity in the literature regarding cortical stimulation practices. Via an international survey of SEEG clinicians, we sought to examine the spectrum of cortical stimulation practices to reveal areas of consensus and variability. Methods: A 68‐item questionnaire was developed to understand cortical stimulation practices including neurostimulation parameters, interpretation of epileptogenicity, functional and cognitive assessment and subsequent surgical decisions. Multiple recruitment pathways were pursued, with the questionnaire distributed directly to 183 clinicians. Results: Responses were received from 56 clinicians across 17 countries with experience ranging from 2 to 60 years (M = 10.73, SD = 9.44). Neurostimulation parameters varied considerably, with maximum current ranging from 3 to 10 mA (M = 5.33, SD = 2.29) for 1 Hz and from 2 to 15 mA (M = 6.54, SD = 3.68) for 50 Hz stimulation. Charge density ranged from 8 to 200 μC/cm2, with up to 43% of responders utilizing charge densities higher than recommended upper safety limits, i.e. 55 μC/cm2. North American responders reported statistically significant higher maximum current (P < 0.001) for 1 Hz stimulation and lower pulse width for 1 and 50 Hz stimulation (P = 0.008, P < 0.001, respectively) compared to European responders. All clinicians evaluated language, speech, and motor function during cortical stimulation; in contrast, 42% assessed visuospatial or visual function, 29% memory, and 13% executive function. Striking differences were reported in approaches to assessment, classification of positive sites, and surgical decisions guided by cortical stimulation. Patterns of consistency were observed for interpretation of the localizing capacity of stimulated electroclinical seizures and auras, with habitual electroclinical seizures induced by 1 Hz stimulation considered the most localizing. Significance: SEEG cortical stimulation practices differed vastly across clinicians internationally, highlighting the need for consensus‐based clinical guidelines. In particular, an internationally standardized approach to assessment, classification, and functional prognostication will provide a common clinical and research framework for optimizing outcomes for people with drug‐resistant epilepsy. [ABSTRACT FROM AUTHOR]

In recent years, a paradigm shift in neuroscience has been occurring from "localizationism," or the idea that the brain is organized into separately functioning modules, toward "connectomics," or the idea that interconnected nodes form networks as the underlying substrates of behavior and thought. Accordingly, our understanding of mechanisms of neurological function, dysfunction, and recovery has evolved to include connections, disconnections, and reconnections. Brain tumors provide a unique opportunity to probe large-scale neural networks with focal and sometimes reversible lesions, allowing neuroscientists the unique opportunity to directly test newly formed hypotheses about underlying brain structural-functional relationships and network properties. Moreover, if a more complete model of neurological dysfunction is to be defined as a "disconnectome," potential avenues for recovery might be mapped through a "reconnectome." Such insight may open the door to novel therapeutic approaches where previous attempts have failed. In this review, we briefly delve into the most clinically relevant neural networks and brain mapping techniques, and we examine how they are being applied to modern neurosurgical brain tumor practices. We then explore how brain tumors might teach us more about mechanisms of global brain dysfunction and recovery through pre- and postoperative longitudinal connectomic and behavioral analyses. [ABSTRACT FROM AUTHOR]

• Own voice perception might be a complex process including emotional, memory, somatosensory, auditory, and facial recognition processing. • Right superior temporal gyrus, transverse temporal gyrus, amygdala, hippocampus, and fusiform gyrus (FG) are likely part of the neural network subjacent to own human voice perception. • Cortico-cortical evoked potentials might help to understand neurophysiological bases of own voice perception. • Own voice perception seem to be related to facial perception as well. The neural bases for language perception have been studied elsewhere using Transcranial Magnetic Stimulation, functional Magnetic Resonance Imaging and Direct Cortical Stimulation. However, to our knowledge, there is no previous report about a patient identifying the change in his voice tone, speed, and prosody because of right temporal cortical stimulation. Nor has there been a cortico-cortical evoked potential (CCEP) assessment of the network underlying this process. We present CCEP from a patient with right focal refractory temporal lobe epilepsy of tumoral etiology who reported changes in the perception of his own speech prosody during stimulation. This report will serve as a complement to the understanding of the neural networks of language and prosody. The present report shows that right superior temporal gyrus, transverse temporal gyrus, right amygdala, hippocampus, and fusiform gyrus (FG) are part of the neural network subjacent to own human voice perception. [ABSTRACT FROM AUTHOR]

The purpose of the direct cortical and subcortical stimulation technique is to prevent false positives caused by transcranial electrical motor evoked potentials (TceMEP) in surgery on patients with brain tumors that have occurred around the motor cortex and to preserve the correct mapping of motor areas during surgery and the corticospinal tract. In addition, it reduces the trial and error that occurs during the intraoperative neurophysiological monitoring (INM) process and minimizes the test time, so that accurate information is communicated to the surgeon with quick feedback on the test results. The most important factors of this technique are, first, examination at a stimulus threshold of a certain intensity, and second, maintaining anesthesia depth at an appropriate level to prevent false positives from occurring during surgery. The third is the installation of a multi-level channel recording electrode on the opposite side of the area of operation to measure the TceMEP waveform and the response to direct cortical and subcortical stimulation in as many muscles as possible. If these conditions are maintained, it is possible to predict causes that may occur in other factors, not false positives, from the INM test.

Background: Cortico-cortical evoked potentials (CCEPs) have been used to map the frontal (FLA) and parietal (PLA) cortical regions related to language function. However, they have usually been employed as a complementary method during sleep-awake surgery. Methods: Five male and two female patients received surgery for tumors located near language areas. Six patients received general anesthesia and the sleep-awake method was used for patients with tumors located near the cortical language areas. We performed motor and somatosensory mapping with CCEPs to identify language areas and we monitored responses during surgery based on the mapping results. Electrocorticography was performed throughout the surgery. Single pulses of 1 ms duration at 5--20 mA were delivered by direct cortical stimulation using one grid at one region (e.g., FLA) and then recording using a second gird at another area (i.e., PLA). Next, reversed stimulation (from PLA to FLA) was performed. The charge density for electrical stimulation was computed. Sensibility, specificity, predictive positive values, and predicted negative values were also computed for warning alterations of CCEPs. Results: Gross tumor resection was achieved in four cases. The first postsurgical day showed language alterations in three patients, but one year later six patients remained asymptomatic and one patient showed the same symptomatology as previously. Seizures were observed in two patients that were easily jugulated. CCEPs predicted warning events with high sensibility and specificity. Postsurgical language deficits were mostly transitory. Although the latency between frontal and parietal regions showed symmetry, the amplitude and the relationship between amplitude and latency were different for FLA than for PLA. The charge density elicited by CCEPs ranged from 442 to 1768 µC/cm2. Conclusions: CCEPs have proven to be a reliable neurophysiological technique for mapping and monitoring the regions associated with language function in a small group of anesthetized patients. The high correlation between warning events and postsurgical outcomes suggested a high sensitivity and specificity and CCEPs can be used systematically in patients under general anesthesia. Nevertheless, the small number of studied patients suggests considering these results cautiously. [ABSTRACT FROM AUTHOR]

The letter to the editor expresses appreciation for an article on the WISE cortical strip for intraoperative neurophysiological monitoring. The authors highlight the capabilities of the WISE cortical strip in enhancing signal-to-noise ratio and providing real-time feedback to neurosurgeons during critical procedures. However, there are limitations to consider, such as the trade-off between electrode contact density and impedance, the need for specialized expertise, and the need for further investigation into the clinical relevance of recording high-frequency oscillations and the impact of improved electrodes on patient outcomes. The letter concludes by recommending future research and development to optimize electrode design, facilitate collaboration between specialists, and evaluate the clinical significance of recording high-frequency oscillations. Overall, the letter provides valuable insights into the potential of the WISE cortical strip for neurophysiological monitoring in neurosurgery. [Extracted from the article]

The infiltrative character of supratentorial lower grade glioma makes it possible for eloquent neural pathways to remain within tumoural tissue, which renders complete surgical resection challenging. Neuromodulation-Induced Cortical Prehabilitation (NICP) is intended to reduce the likelihood of premeditated neurologic sequelae that otherwise would have resulted in extensive rehabilitation or permanent injury following surgery. This review aims to conceptualise current approaches involving Repetitive Transcranial Magnetic Stimulation (rTMS-NICP) and extraoperative Direct Cortical Stimulation (eDCS-NICP) for the purposes of inducing cortical reorganisation prior to surgery, with considerations derived from psychiatric, rehabilitative and electrophysiologic findings related to previous reports of prehabilitation. Despite the promise of reduced risk and incidence of neurologic injury in glioma surgery, the current data indicates a broad but compelling possibility of effective cortical prehabilitation relating to perisylvian cortex, though it remains an under-explored investigational tool. Preliminary findings may prove sufficient for the continued investigation of prehabilitation in small-volume lower-grade tumour or epilepsy patients. However, considering the very low number of peer-reviewed case reports, optimal stimulation parameters and duration of therapy necessary to catalyse functional reorganisation remain equivocal. The non-invasive nature and low risk profile of rTMS-NICP may permit larger sample sizes and control groups until such time that eDCS-NICP protocols can be further elucidated. [ABSTRACT FROM AUTHOR]

Many studies have established a link between extent of resection and survival in patients with gliomas. Surgeons must optimize the oncofunctional balance by maximizing the extent of resection and minimizing postoperative neurological morbidity. Preoperative functional imaging modalities are important tools for optimizing the oncofunctional balance. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) are non-invasive imaging modalities that can be used for preoperative functional language mapping. Scarce data exist evaluating the accuracy of these preoperative modalities for language mapping compared with gold standard intraoperative data in the same cohort. This study compares the accuracy of fMRI and TMS for language mapping compared with intraoperative direct cortical stimulation (DCS). We also identified significant predictors of preoperative functional imaging accuracy, as well as significant predictors of functional outcomes. Evidence from this study could inform clinical judgment as well as provide neuroscientific insight. We used geometric distances to determine copositivity between preoperative data and intraoperative data. Twenty-eight patients were included who underwent both preoperative fMRI and TMS procedures, as well as an awake craniotomy and intraoperative language mapping. We found that TMS shows significantly superior correlation to intraoperative DCS compared with fMRI. TMS also showed significantly higher sensitivity and negative predictive value than specificity and positive predictive value. Poor cognitive baseline was associated with decreased TMS accuracy as well as increased risk for worsened aphasia postoperatively. TMS has emerged as a promising preoperative language mapping tool. Future work should be done to identify the proper role of each imaging modality in a comprehensive, multimodal approach to optimize the oncofunctional balance. [ABSTRACT FROM AUTHOR]

Many studies have established a link between extent of resection and survival in patients with gliomas. Surgeons must optimize the oncofunctional balance by maximizing the extent of resection and minimizing postoperative neurological morbidity. Preoperative functional imaging modalities are important tools for optimizing the oncofunctional balance. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) are non-invasive imaging modalities that can be used for preoperative functional language mapping. Scarce data exist evaluating the accuracy of these preoperative modalities for language mapping compared with gold standard intraoperative data in the same cohort. This study compares the accuracy of fMRI and TMS for language mapping compared with intraoperative direct cortical stimulation (DCS). We also identified significant predictors of preoperative functional imaging accuracy, as well as significant predictors of functional outcomes. Evidence from this study could inform clinical judgment as well as provide neuroscientific insight. We used geometric distances to determine copositivity between preoperative data and intraoperative data. Twenty-eight patients were included who underwent both preoperative fMRI and TMS procedures, as well as an awake craniotomy and intraoperative language mapping. We found that TMS shows significantly superior correlation to intraoperative DCS compared with fMRI. TMS also showed significantly higher sensitivity and negative predictive value than specificity and positive predictive value. Poor cognitive baseline was associated with decreased TMS accuracy as well as increased risk for worsened aphasia postoperatively. TMS has emerged as a promising preoperative language mapping tool. Future work should be done to identify the proper role of each imaging modality in a comprehensive, multimodal approach to optimize the oncofunctional balance.

Accurate mapping of the seizure onset zone (SOZ) is critical to the success of epilepsy surgery outcomes. Epileptogenicity index (EI) is a statistical method that delineates hyperexcitable brain regions involved in the generation and early propagation of seizures. However, EI can overestimate the SOZ for particular electrographic seizure onset patterns. Therefore, using direct cortical stimulation (DCS) as a probing tool to identify seizure generators, we systematically evaluated the causality of the high EI nodes (>0.3) in replicating the patient's habitual seizures. Specifically, we assessed the diagnostic yield of high EI nodes, i.e., the proportion of high EI nodes that evoked habitual seizures. A retrospective single-center study that included post-stereo encephalography (SEEG) confirmed TLE patients (n = 37) that had all high EI nodes stimulated, intending to induce a seizure. We evaluated the nodal responses (true and false responder rate) to stimulation and correlated with electrographic seizure onset patterns (hypersynchronous-HYP and low amplitude fast activity patterns-LAFA) and clinically defined SOZ. The ictogenicity (i.e., the propensity to induce the patient's habitual seizure) of a high EI node was only 44.5%. The LAFA onset pattern had a significantly higher response rate to DCS (i.e., higher evoked seizures). The concordance of an evoked habitual seizure with a clinically defined SOZ with good outcomes was over 50% (p = 0.0025). These results support targeted mapping of SOZ in LAFA onset patterns by performing DCS in high EI nodes to distinguish seizure generators (true responders) from hyperexcitable nodes that may be involved in early propagation.

Accurate mapping of the seizure onset zone (SOZ) is critical to the success of epilepsy surgery outcomes. Epileptogenicity index (EI) is a statistical method that delineates hyperexcitable brain regions involved in the generation and early propagation of seizures. However, EI can overestimate the SOZ for particular electrographic seizure onset patterns. Therefore, using direct cortical stimulation (DCS) as a probing tool to identify seizure generators, we systematically evaluated the causality of the high EI nodes (>0.3) in replicating the patient's habitual seizures. Specifically, we assessed the diagnostic yield of high EI nodes, i.e., the proportion of high EI nodes that evoked habitual seizures. A retrospective single-center study that included post-stereo encephalography (SEEG) confirmed TLE patients (n = 37) that had all high EI nodes stimulated, intending to induce a seizure. We evaluated the nodal responses (true and false responder rate) to stimulation and correlated with electrographic seizure onset patterns (hypersynchronous-HYP and low amplitude fast activity patterns-LAFA) and clinically defined SOZ. The ictogenicity (i.e., the propensity to induce the patient's habitual seizure) of a high EI node was only 44.5%. The LAFA onset pattern had a significantly higher response rate to DCS (i.e., higher evoked seizures). The concordance of an evoked habitual seizure with a clinically defined SOZ with good outcomes was over 50% (p = 0.0025). These results support targeted mapping of SOZ in LAFA onset patterns by performing DCS in high EI nodes to distinguish seizure generators (true responders) from hyperexcitable nodes that may be involved in early propagation. [ABSTRACT FROM AUTHOR]

Introduction: Intraoperative neurophysiological monitoring is the golden standard for lesions located in eloquent areas of the brain. On the one hand, positive mapping offers a view of the relationship between the anatomo-functional cortical organisation of the patient and the lesion, facilitating the choice of the cerebrotomy entry point and the resection until the functional borders are found. On the other hand, negative mapping does not offer certainty that the absence of the motor response, from the operative field, is the real feedback or is the result of the false-negative response. In such a situation, a differentiation between those two must be done. Materials and methods: We evaluated the results of direct cortical stimulation of lesion located in or near the primary motor area, which were diagnosticated with contrast-enhancement head MRI and admitted to the Third Department of Neurosurgery, "Prof. Dr N. Oblu” Emergency Clinical Hospital, Iasi, Romania, between January 2014 and July 2018. Special attention was given especially to the negative mapping cases, regarding the histological type, imagistic localisation, symptoms and neurological outcome immediate postoperative, at 6 months and one-year follow-up. Results: From all 66 patients meeting the inclusion and exclusion criteria in 9,09% (6 cases) we did not obtain any motor response after direct cortical stimulation. The imagistic localisations of those cases were: 3 – Rolandic, 2 – pre-Rolandic and one retro-Rolandic. Tumors histological types were: glioblastoma, anaplastic astrocytoma, oligoastrocytoma and oligodendroglioma each one case and two cases of fibrillary astrocytoma. The intensity range was between 6 – 18mA, the mode – 12mA and the median – 10mA. Postoperatively the neurological condition of 3 patients worsened (4,54% from all the cases), while 3 had a favourable evolution with symptom remission. At 6monts and one-year follow-up in one case (1,51%), we observed no improvement in contrast with the other two, where dysfunction remission was highlighted. Conclusion: The possible technical, surgical and anesthesiologic causes of false-negative motor response must be eliminated to be able to differentiate from the real absence of the functional area from the operative field. In the first scenario, the resection may be associated with permanent postoperative neurologic deficit and major life quality alteration while in the second one the patient presents no motor dysfunction after surgery and the resection may be extensive with multiple oncological benefits.

ObjectiveLesion-based mapping of speech pathways has been possible only during invasive neurosurgical procedures using direct cortical stimulation (DCS). However, navigated transcranial magnetic stimulation (nTMS) may allow for lesion-based interrogation of language pathways noninvasively. Although not lesion-based, magnetoencephalographic imaging (MEGI) is another noninvasive modality for language mapping. In this study, we compare the accuracy of nTMS and MEGI with DCS.MethodsSubjects with lesions around cortical language areas underwent preoperative nTMS and MEGI for language mapping. nTMS maps were generated using a repetitive TMS protocol to deliver trains of stimulations during a picture naming task. MEGI activation maps were derived from adaptive spatial filtering of beta-band power decreases prior to overt speech during picture naming and verb generation tasks. The subjects subsequently underwent awake language mapping via intraoperative DCS. The language maps obtained from each of the 3 modalities were recorded and compared.ResultsnTMS and MEGI were performed on 12 subjects. nTMS yielded 21 positive language disruption sites (11 speech arrest, 5 anomia, and 5 other) while DCS yielded 10 positive sites (2 speech arrest, 5 anomia, and 3 other). MEGI isolated 32 sites of peak activation with language tasks. Positive language sites were most commonly found in the pars opercularis for all three modalities. In 9 instances the positive DCS site corresponded to a positive nTMS site, while in 1 instance it did not. In 4 instances, a positive nTMS site corresponded to a negative DCS site, while 169 instances of negative nTMS and DCS were recorded. The sensitivity of nTMS was therefore 90%, specificity was 98%, the positive predictive value was 69% and the negative predictive value was 99% as compared with intraoperative DCS. MEGI language sites for verb generation and object naming correlated with nTMS sites in 5 subjects, and with DCS sites in 2 subjects.ConclusionMaps of language function generated with nTMS correlate well with those generated by DCS. Negative nTMS mapping also correlates with negative DCS mapping. In our study, MEGI lacks the same level of correlation with intraoperative mapping; nevertheless it provides useful adjunct information in some cases. nTMS may offer a lesion-based method for noninvasively interrogating language pathways and be valuable in managing patients with peri-eloquent lesions.

Introduction: Intraoperative neurophysiological monitoring is the golden standard for lesions located in eloquent areas of the brain. On the one hand, positive mapping offers a view of the relationship between the anatomo-functional cortical organisation of the patient and the lesion, facilitating the choice of the cerebrotomy entry point and the resection until the functional borders are found. On the other hand, negative mapping does not offer certainty that the absence of the motor response, from the operative field, is the real feedback or is the result of the falsenegative response. In such a situation, a differentiation between those two must be done. Materials and methods: We evaluated the results of direct cortical stimulation of lesion located in or near the primary motor area, which were diagnosticated with contrast-enhancement head MRI and admitted to the Third Department of Neurosurgery, "Prof. Dr N. Oblu" Emergency Clinical Hospital, Iasi, Romania, between January 2014 and July 2018. Special attention was given especially to the negative mapping cases, regarding the histological type, imagistic localisation, symptoms and neurological outcome immediate postoperative, at 6 months and one-year follow-up. Results: From all 66 patients meeting the inclusion and exclusion criteria in 9,09% (6 cases) we did not obtain any motor response after direct cortical stimulation. The imagistic localisations of those cases were: 3 - Rolandic, 2 - pre-Rolandic and one retro-Rolandic. Tumors histological types were: glioblastoma, anaplastic astrocytoma, oligoastrocytoma and oligodendroglioma each one case and two cases of fibrillary astrocytoma. The intensity range was between 6 - 18mA, the mode - 12mA and the median - 10mA. Postoperatively the neurological condition of 3 patients worsened (4,54% from all the cases), while 3 had a favourable evolution with symptom remission. At 6monts and one-year follow-up in one case (1,51%), we observed no improvement in contrast with the other two, where dysfunction remission was highlighted. Conclusion: The possible technical, surgical and anesthesiologic causes of falsenegative motor response must be eliminated to be able to differentiate from the real absence of the functional area from the operative field. In the first scenario, the resection may be associated with permanent postoperative neurologic deficit and major life quality alteration while in the second one the patient presents no motor dysfunction after surgery and the resection may be extensive with multiple oncological benefits. [ABSTRACT FROM AUTHOR]

Background: The dilemma of neuro-oncological surgery involving suspected eloquent cortex is to maximize the extent of resection while minimizing neurological morbidity, referred to as the "onco-functional balance." Diffuse lower-grade gliomas are capable of infiltrating or displacing neural function within cortical regions and subcortical white matter tracts, which can render classical anatomic associations of eloquent function misleading., Observations: This study employed presurgical navigated transcranial magnetic stimulation (nTMS) to determine the motor eloquence of a diffuse lower-grade glioma at the superior frontal gyrus extending and intrinsic to the primary motor cortex in a 45-year-old female. Positive nTMS findings were confirmed intraoperatively with high-frequency direct cortico-subcortical stimulation (HF-DCS). Modification of the HF-DCS train count from train-of-five to train-of-two permitted resection beyond classic anatomical boundaries and conventional HF-DCS safe stopping criteria., Lessons: Anatomical correlates of function can inaccurately inform the surgical management of diffuse lower-grade glioma, which represents the utmost opportunity for progression-free survival. Integrating an individually tailored nTMS-DCS surgical strategy contributed to complete resection, negating the requirement for adjuvant therapy. Serial nTMS follow-up may assist with the characterization of tumor-induced functional reorganization. https://thejns.org/doi/10.3171/CASE24197.

ObjectDirect cortical stimulation (DCS) is the gold-standard technique for motor mapping during craniotomy. However, preoperative noninvasive motor mapping is becoming increasingly accurate. Two such noninvasive modalities are navigated transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) imaging. While MEG imaging has already been extensively validated as an accurate modality of noninvasive motor mapping, TMS is less well studied. In this study, the authors compared the accuracy of TMS to both DCS and MEG imaging.MethodsPatients with tumors in proximity to primary motor cortex underwent preoperative TMS and MEG imaging for motor mapping. The patients subsequently underwent motor mapping via intraoperative DCS. The loci of maximal response were recorded from each modality and compared. Motor strength was assessed at 3 months postoperatively.ResultsTranscranial magnetic stimulation and MEG imaging were performed on 24 patients. Intraoperative DCS yielded 8 positive motor sites in 5 patients. The median distance ± SEM between TMS and DCS motor sites was 2.13 ± 0.29 mm, and between TMS and MEG imaging motor sites was 4.71 ± 1.08 mm. In no patients did DCS motor mapping reveal a motor site that was unrecognized by TMS. Three of 24 patients developed new, early neurological deficit in the form of upper-extremity paresis. At the 3-month follow-up evaluation, 2 of these patients were significantly improved, experiencing difficulty only with fine motor tasks; the remaining patient had improvement to 4/5 strength. There were no deaths over the course of the study.ConclusionsMaps of the motor system generated with TMS correlate well with those generated by both MEG imaging and DCS. Negative TMS mapping also correlates with negative DCS mapping. Navigated TMS is an accurate modality for noninvasively generating preoperative motor maps.

Objectives. The genesis of tumors is unknown in our days. Surgery represents an effective treatment of this disorder. According to many studies of brain tumor surgery, a motor deficit rate of 30% has been observed, postoperatively, after surgeries on brain tumors in the motor areas. The aim of the study was to evaluate the direct cortical stimulation in the surgical treatment of glial brain tumors, in motor areas. Material and Methods. The examination group included 35 patients with brain tumors, localized in the parasilvian region. Direct cortical stimulation was used intraoperatively, in order to establish the motor areas. For the evaluation of the neurological deficit, a comparative analysis of the pre- and postoperative motor deficit was performed. Results. Direct cortical stimulation was performed in 35 patients. During its stimulation, the motor areas were detected in 32 patients. Under the control of Direct Cortical Stimulation, subtotal and partial tumor resection was performed in 31 patients and, due to the location of the tumor in the motor area, biopsy was performed in 1 patient. The worsening of the postoperative motor deficit was recorded in the partial ablation for 2 patients and biopsy for 1 patient, where the tumor was directly localized in the motor area. Direct cortical stimulation, in the extent of total and subtotal ablation, prevented postoperative motor deficit at discharge in 22 patients. Conclusions. In order to avoid postoperative neurological consequences and improve the patients' quality of life, it is appropriate to use intraoperative direct cortical stimulation.

Transcranial electrical stimulation-motor evoked potential (TES-MEP) is a valuable intraoperative monitoring technique during brain tumor surgery. However, TES can stimulate deep subcortical areas located far from the motor cortex. There is a concern about false-negative results from the use of TES-MEP during resection of those tumors adjacent to the primary motor cortex. Our study reports three cases of TES-MEP monitoring with false-negative results due to deep axonal stimulation during brain tumor resection. Although no significant change in TES-MEP was observed during surgery, study subjects experienced muscle weakness after surgery. Deep axonal stimulation of TES could give false-negative results. Therefore, a combined method of TES-MEP and direct cortical stimulation-motor evoked potential (DCS-MEP) or direct subcortical stimulation should be considered to overcome the limitation of TES-MEP.

Direct cortical stimulation (DCS) in epilepsy surgery patients has a long history of functional brain mapping and seizure triggering. Here, we review its findings when applied to the insula in order to map the insular functions, evaluate its local and distant connections, and trigger seizures. Clinical responses to insular DCS are frequent and diverse, showing a partial segregation with spatial overlap, including a posterior somatosensory, auditory, and vestibular part, a central olfactory-gustatory region, and an anterior visceral and cognitive-emotional portion. The study of cortico-cortical evoked potentials (CCEPs) has shown that the anterior (resp. posterior) insula has a higher connectivity rate with itself than with the posterior (resp. anterior) insula, and that both the anterior and posterior insula are closely connected, notably between the homologous insular subdivisions. All insular gyri show extensive and complex ipsilateral and contralateral extra-insular connections, more anteriorly for the anterior insula and more posteriorly for the posterior insula. As a rule, CCEPs propagate first and with a higher probability around the insular DCS site, then to the homologous region, and later to more distal regions with fast cortico-cortical axonal conduction delays. Seizures elicited by insular DCS have rarely been specifically studied, but their rate does not seem to differ from those of other DCS studies. They are mainly provoked from the insular seizure onset zone but can also be triggered by stimulating intra- and extra-insular early propagation zones. Overall, in line with the neuroimaging studies, insular DCS studies converge on the view that the insula is a multimodal functional hub with a fast propagation of information, whose organization helps understand where insular seizures start and how they propagate.

Background: Monitoring of motor function during surgery for supratentorial tumors under general anesthesia applies either transcranial electrical stimulation (TES) or direct cortical stimulation (DCS) to elicit motor-evoked potentials. To date, there is no guideline that favor one method over the other. Therefore, we designed this randomized study to compare between both methods regarding the prediction of postoperative motor deficits and extent of tumor resection. Methods: This is a multicenter (six centers in Germany and one in Switzerland), double blind, parallel group, exploratory, randomized controlled clinical trial. Patients without or with mild paresis, who are scheduled for surgical resection of motor-eloquent brain tumors under general anesthesia will be randomized to surgical resection under TES or surgical resection under DCS. The primary endpoint is sensitivity and specificity in prognosis of motor function 7 days after surgery. The main secondary endpoint is the extent of tumor resection. The study is planned to include 120 patients within 2 years. Discussion: The present exploratory study should compare TES and DCS regarding sensitivity and specificity in predicting postoperative motor deficit and extent of tumor resection to calculate the required number of patients in a confirmatory trial to test the superiority of one method over the other.

BackgroundInvasive cortical stimulation (ICS) is a neuromodulation method in which electrodes are implanted on the cortex to deliver chronic stimulation. ICS has been used to treat neurological disorders such as neuropathic pain, epilepsy, movement disorders and tinnitus. Noninvasive neuromodulation methods such as transcranial magnetic stimulation and transcranial electrical stimulation (TES) show great promise in treating some neurological disorders and require no surgery. However, only acute stimulation can be delivered. Epicranial current stimulation (ECS) is a novel concept for delivering chronic neuromodulation through subcutaneous electrodes implanted on the skull. The use of concentric-ring ECS electrodes may allow spatially focused stimulation and offer a less invasive alternative to ICS.ObjectivesDemonstrate ECS proof-of-concept using concentric-ring electrodes in rats and then use a computational model to explore the feasibility and limitations of ECS in humans.MethodsECS concentric-ring electrodes were implanted in 6 rats and pulsatile stimulation delivered to the motor cortex. An MRI based electro-anatomical human head model was used to explore different ECS concentric-ring electrode designs and these were compared with ICS and TES.ResultsConcentric-ring ECS electrodes can selectively stimulate the rat motor cortex. The computational model showed that the concentric-ring ECS electrode design can be optimized to achieve focused cortical stimulation. In general, focality was less than ICS but greater than noninvasive transcranial current stimulation.ConclusionECS could be a promising minimally invasive alternative to ICS. Further work in large animal models and patients is needed to demonstrate feasibility and long-term stability.

Background: During brain tumor resection, neurophysiological mapping and monitoring help surgeons locate, characterize, and functionally assess eloquent brain areas in real time. The selection of mapping and monitoring targets has implications for successful surgery. Here, the authors compare direct cortical stimulation (DCS) as suggested by median nerve (MN) with posterior tibial nerve (PTN) cortical sensory mapping (SM) during mesial lesion resection., Observations: Recordings from a 6-contact cortical strip served to generate an MN and a PTN sensory map, which indicated the strip was anterior to the central sulcus. Responses exhibited an amplitude gradient with no phase reversal (PR). DCS, elicited through a stimulus probe or contact(s) of the strip, yielded larger responses from the corresponding sensory mapped limb; that is, PTN SM resulted in larger lower limb muscle responses than those suggested by MN SM., Lessons: SM of the MN and PTN is effective for localizing eloquent cortical areas wherein the PTN is favored in surgery for mesial cortical tumors. The recorded amplitude of the cortical somatosensory evoked potential is a valuable criterion for defining the optimal location for DCS, despite an absent PR. The pathway at risk dictates the specifics of SM, which subsequently defines the optimal location for DCS.

Introduction: Direct cortical stimulation has been used for brain mapping and localization of eloquent areas in awake patients. This simplified technique is to provide the positive areas, which can be preserved if the tumor or lesions are involved eloquent areas., Objective: The main objective of this study is to determine whether direct cortical stimulation in awake brain mapping for low-grade glioma patients increases the rate of resection or not., Method: The authors present a retrospective study between 2020 to 2022 that includes 35 cases in a single center, to get higher resection rate, and their consequences in awake craniotomy in low-grade glioma patients. Here, two neurosurgeons were involved and the minimum follow-up was 12 months., Results: The authors achieved 80% removal of tumors. To get higher resection rate we emphasized negative mapping with prior anatomical analysis to understand functional realignment. Stimulation-related complications will be thoroughly discussed with a potential future direction to minimize the issues. The authors used PROMIS score to measure patients physical and mental health status and kernofsky score to measure performance status before and after successful surgery. The authors found three cases of transient deficit in repetitive stimulation. Repeated stimulation to identify the eloquent areas with low voltage frequency is a good option. Numbness in the face related to stimulation may continue for 6 weeks., Conclusion: Functional realignment in shifted brain and edema can be seen while doing cortical and subcortical stimulation. Most of the stimulation from low to high for language mapping may vary from patient to patient. For safe removal of low-grade glioma a steep learning curve is needed to find out the negative areas, though the authors emphasize positive mapping of areas to secure the maximum eloquence., Competing Interests: There are no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Invasive cortical stimulation (ICS) is a neuromodulation method in which electrodes are implanted on the cortex to deliver chronic stimulation. ICS has been used to treat neurological disorders such as neuropathic pain, epilepsy, movement disorders and tinnitus. Noninvasive neuromodulation methods such as transcranial magnetic stimulation and transcranial electrical stimulation (TES) show great promise in treating some neurological disorders and require no surgery. However, only acute stimulation can be delivered. Epicranial current stimulation (ECS) is a novel concept for delivering chronic neuromodulation through subcutaneous electrodes implanted on the skull. The use of concentric-ring ECS electrodes may allow spatially focused stimulation and offer a less invasive alternative to ICS. Objectives: Demonstrate ECS proof-of-concept using concentric-ring electrodes in rats and then use a computational model to explore the feasibility and limitations of ECS in humans. Methods: ECS concentric-ring electrodes were implanted in 6 rats and pulsatile stimulation delivered to the motor cortex. An MRI based electro-anatomical human head model was used to explore different ECS concentric-ring electrode designs and these were compared with ICS and TES. Results: Concentric-ring ECS electrodes can selectively stimulate the rat motor cortex. The computational model showed that the concentric-ring ECS electrode design can be optimized to achieve focused cortical stimulation. In general, focality was less than ICS but greater than noninvasive transcranial current stimulation. Conclusion: ECS could be a promising minimally invasive alternative to ICS. Further work in large animal models and patients is needed to demonstrate feasibility and long-term stability. [ABSTRACT FROM AUTHOR]

Intraoperative neurophysiological monitoring during brain surgery uses direct cortical stimulation to map the motor cortex by recording muscle activity induced by the excitation of alpha motor neurons (MNs). Computational models have been used to understand local brain stimulation. However, a computational model revealing the stimulation process from the cortex to MNs has not yet been proposed. Thus, the aim of the current study was to develop a corticomotoneuronal (CMN) model to investigate intraoperative stimulation during surgery. The CMN combined the following three processes into one system for the first time: (1) induction of an electric field in the brain based on a volume conductor model; (2) activation of pyramidal neuron (PNs) with a compartment model; and (3) formation of presynaptic connections of the PNs to MNs using a conductance-based synaptic model coupled with a spiking model. The implemented volume conductor model coupled with the axon model agreed with experimental strength-duration curves. Additionally, temporal/spatial and facilitation effects of CMN synapses were implemented and verified. Finally, the integrated CMN model was verified with experimental data. The results demonstrated that our model was necessary to describe the interaction between frequency and pulses to assess the difference between low-frequency and multi-pulse high-frequency stimulation in cortical stimulation. The proposed model can be used to investigate the effect of stimulation parameters on the cortex to optimize intraoperative monitoring. [ABSTRACT FROM AUTHOR]

Summary: Objective: Navigated transcranial magnetic stimulation (nTMS) is becoming increasingly popular in noninvasive preoperative language mapping, as its results correlate well enough with those obtained by direct cortical stimulation (DCS) during awake surgery in adult patients with tumor. Reports in the context of epilepsy surgery or extraoperative DCS in adults are, however, sparse, and validation of nTMS with DCS in children is lacking. Furthermore, little is known about the risk of inducing epileptic seizures with nTMS in pediatric epilepsy patients. We provide the largest validation study to date in an epilepsy surgery population. Methods: We compared language mapping with nTMS and extraoperative DCS in 20 epilepsy surgery patients (age range 9‐32 years; 14 children and adolescents). Results: In comparison with DCS, sensitivity of nTMS was 68%, specificity 76%, positive predictive value 27%, and negative predictive value 95%. Age, location of ictal‐onset zone near or within DCS‐mapped language areas or severity of cognitive deficits had no significant effect on these values. None of our patients had seizures during nTMS. Significance: Our study suggests that nTMS language mapping is clinically useful and safe in epilepsy surgery patients, including school‐aged children and patients with extensive cognitive dysfunction. Similar to in tumor surgery, mapping results in the frontal region are most reliable. False negative findings may be slightly more likely in epilepsy than in tumor surgery patients. Mapping results should always be verified by other methods in individual patients. [ABSTRACT FROM AUTHOR]

Transcranial alternating current stimulation (tACS) uses sinusoidal, subthreshold, electric fields to modulate cortical processing. Cortical processing depends on a fine balance between excitation and inhibition and tACS acts on both excitatory and inhibitory cortical neurons. Given this, it is not clear whether tACS should increase or decrease cortical excitability. We investigated this using transcranial current stimulation of the rat (all males) motor cortex consisting of a continuous subthreshold sine wave with short bursts of suprathreshold pulse-trains inserted at different phases to probe cortical excitability. We found that when a low-rate, long-duration, suprathreshold pulse-train was used, subthreshold cathodal tACS decreased cortical excitability and anodal tACS increased excitability. However, when a high-rate, short-duration, suprathreshold pulse-train was used this pattern was inverted. An integrate-and-fire model incorporating biophysical differences between cortical excitatory and inhibitory neurons could predict the experimental data and helped interpret these results. The model indicated that low-rate suprathreshold pulse-trains preferentially stimulate excitatory cortical neurons, whereas high-rate suprathreshold pulse-trains stimulate both excitatory and inhibitory neurons. If correct, this indicates that suprathreshold pulse-train stimulation maybe able to selectively control the excitation-inhibition balance within a cortical network. The excitation-inhibition balance then likely plays an important role in determining whether subthreshold tACS will increase or decrease cortical excitability. [ABSTRACT FROM AUTHOR]

Electrically stimulating early visual cortex results in a visual percept known as a phosphene. Although phosphenes can be evoked by a wide range of electrode sizes and current amplitudes, they are invariably described as small. To better understand this observation, we electrically stimulated 93 electrodes implanted in the visual cortex of 13 human subjects who reported phosphene size while stimulation current was varied. Phosphene size increased as the stimulation current was initially raised above threshold, but then rapidly reached saturation. Phosphene size also depended on the location of the stimulated site, with size increasing with distance from the foveal representation. We developed a model relating phosphene size to the amount of activated cortex and its location within the retinotopic map. First, a sigmoidal curve was used to predict the amount of activated cortex at a given current. Second, the amount of active cortex was converted to degrees of visual angle by multiplying by the inverse cortical magnification factor for that retinotopic location. This simple model accurately predicted phosphene size for a broad range of stimulation currents and cortical locations. The unexpected saturation in phosphene sizes suggests that the functional architecture of cerebral cortex may impose fundamental restrictions on the spread of artificially evoked activity and this may be an important consideration in the design of cortical prosthetic devices. [ABSTRACT FROM AUTHOR]

Object: Preoperative functional magnetic resonance imaging (fMRI) remains a promising method to aid in the surgical management of patients diagnosed with brain tumors. For patients that are candidates for awake craniotomies, surgical decisions can potentially be improved by fMRI but this depends on the level of concordance between preoperative brain maps and the maps provided by the gold standard intraoperative method, direct cortical stimulation (DCS). There have been numerous studies of the concordance between fMRI and DCS using sensitivity and specificity measures, however the results are variable across studies and the key factors influencing variability are not well understood. Thus, the present work addresses the influence of technical factors on fMRI and DCS concordance. Methods: Motor and language mapping data were collected for a group of glioma patients (n = 14) who underwent both preoperative fMRI and intraoperative DCS in an awake craniotomy procedure for tumor removal. Normative fMRI data were also acquired in a healthy control group (n = 12). The fMRI and DCS mapping data were co-registered; true positive (TP), true negative (TN), false positive (FP) and false negative (FN) occurrences were tabulated over the exposed brain surface. Sensitivity and specificity were measured for the total group, and the motor and language sub-groups. The influence of grid placement, fMRI statistical thresholding, and task standardization were assessed. Correlations between proportions of agreement and error were carefully scrutinized to evaluate concordance more in-depth. Results: Concordance was significantly better for motor versus language mapping. There was an inverse relationship between TP and TN with increasing statistical threshold, and FP dominated the total error. Sensitivity and specificity were reduced when tasks were not standardized across fMRI and DCS. Conclusions: Although the agreement between fMRI and DCS is good, variability is introduced by technical factors that can diminish the quality of patient data. Neurosurgeons should evaluate the usefulness of fMRI data while considering that a) discordance arises primarily from FP fMRI results; b) there is an inherent trade-off between sensitivity and specificity with fMRI statistical threshold; and c) best results are achieved using batteries of tasks that are standardized across both mapping methods.

Objective: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging-derived tractography (DTI-t) contribute to the localization of language areas, but their accuracy remains controversial. This study aimed to investigate the diagnostic performance of preoperative fMRI and DTI-t obtained with a simultaneous multi-slice technique using intraoperative direct cortical stimulation (DCS) or corticocortical evoked potential (CCEP) as reference standards., Materials and Methods: This prospective study included 26 patients (23-74 years; male:female, 13:13) with tumors in the vicinity of Broca's area who underwent preoperative fMRI and DTI-t. A site-by-site comparison between preoperative (fMRI and DTI-t) and intraoperative language mapping (DCS or CCEP) was performed for 226 cortical sites to calculate the sensitivity and specificity of fMRI and DTI-t for mapping Broca's areas. For sites with positive signals on fMRI or DTI-t, the true-positive rate (TPR) was calculated based on the concordance and discordance between fMRI and DTI-t., Results: Among 226 cortical sites, DCS was performed in 100 sites and CCEP was performed in 166 sites. The specificities of fMRI and DTI-t ranged from 72.4% (63/87) to 96.8% (122/126), respectively. The sensitivities of fMRI (except for verb generation) and DTI-t were 69.2% (9/13) to 92.3% (12/13) with DCS as the reference standard, and 40.0% (16/40) or lower with CCEP as the reference standard. For sites with preoperative fMRI or DTI-t positivity (n = 82), the TPR was high when fMRI and DTI-t were concordant (81.2% and 100% using DCS and CCEP, respectively, as the reference standards) and low when fMRI and DTI-t were discordant (≤ 24.2%)., Conclusion: fMRI and DTI-t are sensitive and specific for mapping Broca's area compared with DCS and specific but insensitive compared with CCEP. A site with a positive signal on both fMRI and DTI-t represents a high probability of being an essential language area., Competing Interests: Seung Hong Choi, a contributing editor of the Korean Journal of Radiology, was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Korean Society of Radiology.)

Summary Electrical brain stimulation (EBS) complements neural measurements by probing the causal relationship between brain and perception, cognition, and action. Many fundamental questions about EBS remain unanswered, including the spatial extent of cortex responsive to stimulation, and the relationship between the circuitry engaged by EBS and the types of neural responses elicited by sensory stimulation. Here, we measured neural responses and the effects of EBS in primary visual cortex in four patients implanted with intracranial electrodes. Using stimulation, behavior, and retinotopic mapping, we show the relationship between the size of affected cortical area and the magnitude of electrical charge. Furthermore, we show that the spatial location of electrically induced visual sensations is matched to the receptive field of the cortical site measured with broadband field potentials, and less so with event related potentials. Together, these findings broaden our knowledge about the mechanism of EBS and the neuromodulation of the human brain. [ABSTRACT FROM AUTHOR]

Summary An enduring puzzle in the neuroscience of voluntary action is the origin of the remarkably wide dispersion of the reaction time distribution, an interval far greater than is explained by synaptic or signal transductive noise [ 1, 2 ]. That we are able to change our planned actions—a key criterion of volition [ 3 ]—so close to the time of their onset implies decision-making must reach deep into the execution of action itself [ 4–6 ]. It has been influentially suggested the reaction time distribution therefore reflects deliberate neural procrastination [ 7 ], giving alternative response tendencies sufficient time for fair competition in pursuing a decision threshold that determines which one is behaviorally manifest: a race model, where action selection and execution are closely interrelated [ 8–11 ]. Although the medial frontal cortex exhibits a sensitivity to reaction time on functional imaging that is consistent with such a mechanism [ 12–14 ], direct evidence from disruptive studies has hitherto been lacking. If movement-generating and movement-delaying neural substrates are closely co-localized here, a large-scale lesion will inevitably mask any acceleration, for the movement itself could be disrupted. Circumventing this problem, here we observed focal intracranial electrical disruption of the medial frontal wall in the context of the pre-surgical evaluation of two patients with epilepsy temporarily reversing such hypothesized procrastination. Effector-specific behavioral acceleration, time-locked to the period of electrical disruption, occurred exclusively at a specific locus at the ventral border of the pre-supplementary motor area. A cardinal prediction of race models of voluntary action is thereby substantiated in the human brain. [ABSTRACT FROM AUTHOR]

Object: Preoperative functional magnetic resonance imaging (fMRI) remains a promising method to aid in the surgical management of patients diagnosed with brain tumors. For patients that are candidates for awake craniotomies, surgical decisions can potentially be improved by fMRI but this depends on the level of concordance between preoperative brain maps and the maps provided by the gold standard intraoperative method, direct cortical stimulation (DCS). There have been numerous studies of the concordance between fMRI and DCS using sensitivity and specificity measures, however the results are variable across studies and the key factors influencing variability are not well understood. Thus, the present work addresses the influence of technical factors on fMRI and DCS concordance. Methods: Motor and language mapping data were collected for a group of glioma patients (n = 14) who underwent both preoperative fMRI and intraoperative DCS in an awake craniotomy procedure for tumor removal. Normative fMRI data were also acquired in a healthy control group (n = 12). The fMRI and DCS mapping data were co-registered; true positive (TP), true negative (TN), false positive (FP), and false negative (FN) occurrences were tabulated over the exposed brain surface. Sensitivity and specificity were measured for the total group, and for the motor and language sub-groups. The influence of grid placement, fMRI statistical thresholding, and task standardization were assessed. Correlations between proportions of agreement and error were also carefully scrutinized to evaluate concordance in more detail. Results: Concordance was significantly better for motor vs. language mapping. There was an inverse relationship between TP and TN with increasing statistical threshold, and FP dominated the total error. Sensitivity and specificity were reduced when tasks were not standardized across fMRI and DCS. Conclusions: Although the agreement between fMRI and DCS is good, variability is introduced by technical factors that can diminish the quality of patient data. Neurosurgeons should evaluate the usefulness of fMRI data while considering that (a) discordance arises primarily from FP fMRI results; (b) there is an inherent trade-off between sensitivity and specificity with fMRI statistical threshold; and (c) best results are achieved using batteries of tasks that are standardized across both mapping methods. [ABSTRACT FROM AUTHOR]

Vertigo is a common neurological complaint, which can result in significant morbidity and decreased quality of life. While pathology to peripheral and subtentorial brain structures is a well-established cause of vertigo, cortical lesions have also been linked to vertigo and may lend insight into relevant neuroanatomy. Here, we investigate the supratentorial lesion locations associated with vertigo and test whether they map to a common brain network. We performed a systematic literature search and identified 23 cases of supratentorial brain lesions associated with vertigo. We mapped the lesion locations to a standard brain template and computed the network of brain regions functionally connected to each lesion location, using a 'wiring diagram' of the human brain termed the human connectome ( n = 1000). Sensitivity was assessed by identifying the most common connection to lesion locations associated with vertigo, and specificity was assessed through comparison with control lesions associated with symptoms other than vertigo ( n = 68). We found that functional connectivity between lesion locations and the bilateral ventral posterior insula was both sensitive (22/23 lesions) and specific (voxel-wise family-wise error-corrected P < 0.05) for lesion-induced vertigo. We computed connectivity with this hub region to define a lesion-based vertigo network, which included regions in the bilateral insula, somatosensory cortex, higher-level visual areas, cingulate sulcus, thalamus and multiple cerebellar regions in the territory of the posterior inferior cerebellar artery. Next, we used stereo-electroencephalography (80 stimulation sites across 17 patients) to test whether stimulation sites associated with vertigo mapped to this same network. We found that 36/42 (86%) of stimulation sites eliciting vertigo fell within the lesion-based vertigo network in contrast to 16/39 (41%) of stimulation sites that did not elicit vertigo. Connectivity between stimulation sites and our lesion-based hub in the ventral posterior insula was also significantly associated with vertigo ( P < 0.0001). We conclude that cortical lesions and direct electrical stimulation sites associated with vertigo map to a common brain network, offering insights into the causal neuroanatomical substrate of vertigo., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is used for resection planning in patients suffering from brain lesions within regions known to be involved in language function. Yet we also need data that show whether patients benefit clinically from preoperative rTMS for language mapping. Methods: We enrolled 25 patients with language eloquently located brain lesions undergoing preoperative rTMS language mapping (GROUP 1, 2011–2013), with the mapping results not being available for the surgeon, and we matched these patients with 25 subjects who also underwent preoperative rTMS (GROUP 2, 2013–2014), but the mapping results were taken into account during tumor resection. Additionally, cortical language maps were generated by analyzing preoperative rTMS and intraoperative direct cortical stimulation (DCS) data. Results: Mean anterior-posterior (ap) craniotomy extents and overall craniotomy sizes were significantly smaller for the patients in GROUP 2 (Ap: p = 0.0117; overall size: p = 0.0373), and postoperative language deficits were found significantly more frequently for the patients in GROUP 1 (p = 0.0153), although the preoperative language status did not differ between groups (p = 0.7576). Additionally, there was a trend towards fewer unexpected tumor residuals, shorter surgery duration, less peri- or postoperative complications, shorter inpatient stay, and higher postoperative Karnofsky performance status scale (KPS) for the patients in GROUP 2. Conclusions: The present study provides a first hint that the clinical course of patients suffering from brain tumors might be improved by preoperative rTMS language mapping. However, a significant difference between both groups was only found for craniotomy extents and postoperative deficits, but not for other clinical parameters, which only showed a trend toward better results in GROUP 2. Therefore, multicenter trials with higher sample sizes are needed to further investigate the distinct impact of rTMS language mapping on the clinical course of brain tumor patients. [ABSTRACT FROM AUTHOR]