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Objective: To determine the optimal montage and vocalization conditions for high-gamma language mapping using stereoelectroencephalography. Methods: We studied 12 epilepsy patients who underwent invasive monitoring with depth electrodes and measurement of auditory-naming related highgamma modulations. We determined the effects of electrode montage and vocalization conditions of the response on the high-gamma (60–140  Hz) amplitudes. Results: Compared to common average reference montage, bipolar and Laplacian montages effectively reduced the degree of auditory naming-related signal deflections in the white matter during the stimulus and response phases (mixed model estimate: −21.2 to −85.4%; p  <  0.001), while maintaining those at the cortical level (−4.4 to +7.8%; p  =  0.614 to 0.085). They also reduced signal deflections outside the brain parenchyma during the response phase (−90.6 to −91.2%; p  <  0.001). Covert responses reduced signal deflections outside the brain parenchyma during the response phase (−17.0%; p  =  0.010). Conclusion: On depth electrode recording, bipolar and Laplacian montages are suitable for measuring auditory naming-related high-gamma modulations in gray matter. The covert response may highlight the gray matter activity. Significance: This study helps establish the practical guidelines for high-gamma language mapping using stereoelectroencephalography. [ABSTRACT FROM AUTHOR]

Objective: We evaluated changes in cognitive domains after neurosurgical lesioning of cortical sites with significant high‐gamma power modulations (HGM) during a visual naming task, although these sites were found language‐negative on standard‐of‐care electrical stimulation mapping (ESM). Methods: In drug‐resistant epilepsy patients who underwent resection/ablation after stereo‐electroencephalography (SEEG), we computed reliable change indices (RCIs) from a battery of presurgical and 1‐year postsurgical neuropsychological assessments. We modeled RCIs as a function of lesioning even one HGM language site, number of HGM language sites lesioned, and the magnitude of naming‐related HGM. The analyses were adjusted for 1‐year seizure freedom, operated hemispheres, and the volumes of surgical lesions. Results: In 37 patients with 4455 SEEG electrode contacts (1839 and 2616 contacts in right and left hemispheres, respectively), no ESM language sites were lesioned. Patients with lesioning of even one HGM language site showed significantly lower RCIs for Peabody Picture Vocabulary Test (PPVT), working memory, and verbal learning immediate (VLI) scores. RCI declines with higher number of HGM language sites lesioned were seen in PPVT (slope [β] = −.10), working memory (β = −.10), VLI (β = −.14), and letter–word identification (LWI; β = −.14). No neuropsychological domains improved after lesioning of HGM language sites. Significant effects of the HGM magnitude at lesioned sites were seen on working memory (β = −.31), story memory immediate (β = −.27), verbal learning recognition (β = −.18), LWI (β = −.16), spelling (β = −.49), and passage comprehension (β = −.33). Because working memory was significantly affected in all three analyses, patients with maximal working memory decline were examined post hoc, revealing that all such patients had HGM naming sites lesioned in the posterior quadrants of either hemisphere. Significance: HGM language mapping should be used as an adjunct to ESM in clinical practice and may help counsel patients/families about postsurgical cognitive deficits. [ABSTRACT FROM AUTHOR]

After recent updates to the World Health Organization pathological criteria for diagnosing and grading diffuse gliomas, all major North American and European neuro-oncology societies recommend a maximal safe resection as the initial management of a diffuse glioma. For neurosurgeons to achieve this goal, the surgical plan for both low- and high-grade gliomas should be to perform a supramaximal resection when feasible based on preoperative imaging and the patients performance status, utilizing every intraoperative adjunct to minimize postoperative neurological deficits. While the surgical approach and technique can vary, every effort must be taken to identify and preserve functional cortical and subcortical regions. In this summary statement on the current state of the field, we describe the tools and technologies that facilitate the safe removal of diffuse gliomas and highlight intraoperative and postoperative management strategies to minimize complications for these patients. Moreover, we discuss how surgical resections can go beyond cytoreduction by facilitating biological discoveries and improving the local delivery of adjuvant chemo- and radiotherapies.

• Stimulation within auditory cortex produced facial expressions and perioral motor responses in approximately one-third of patients. • Cortical sites with motor and language responses within transverse temporal gyrus and adjacent cortex (TGG+) showed different yet overlapping neurophysiologic characteristics. • TTG+ likely participates in non-verbal responses to low-level auditory and/or emotional cues during a communicative discourse. We investigated the role of transverse temporal gyrus and adjacent cortex (TTG+) in facial expressions and perioral movements. In 31 patients undergoing stereo-electroencephalography monitoring, we describe behavioral responses elicited by electrical stimulation within the TTG+. Task-induced high-gamma modulation (HGM), auditory evoked responses, and resting-state connectivity were used to investigate the cortical sites having different types of responses on electrical stimulation. Changes in facial expressions and perioral movements were elicited on electrical stimulation within TTG+ in 9 (29%) and 10 (32%) patients, respectively, in addition to the more common language responses (naming interruptions, auditory hallucinations, paraphasic errors). All functional sites showed auditory task induced HGM and evoked responses validating their location within the auditory cortex, however, motor sites showed lower peak amplitudes and longer peak latencies compared to language sites. Significant first-degree connections for motor sites included precentral, anterior cingulate, parahippocampal, and anterior insular gyri, whereas those for language sites included posterior superior temporal, posterior middle temporal, inferior frontal, supramarginal, and angular gyri. Multimodal data suggests that TTG+ may participate in auditory-motor integration. TTG+ likely participates in facial expressions in response to emotional cues during an auditory discourse. [ABSTRACT FROM AUTHOR]

• High memory loads enhance functional connectivity via occipital longitudinal tracts. • High memory loads reduce functional connectivity via arcuate, uncinate, and superior longitudinal fasciculi. • Task familiarity increases high-gamma amplitude in the inferior frontal gyrus, and its amplitude predicts successful recall. In tasks involving new visuospatial information, we rely on working memory, supported by a distributed brain network. We investigated the dynamic interplay between brain regions, including cortical and white matter structures, to understand how neural interactions change with different memory loads and trials, and their subsequent impact on working memory performance. Patients undertook a task of immediate spatial recall during intracranial EEG monitoring. We charted the dynamics of cortical high-gamma activity and associated functional connectivity modulations in white matter tracts. Elevated memory loads were linked to enhanced functional connectivity via occipital longitudinal tracts, yet decreased through arcuate, uncinate, and superior-longitudinal fasciculi. As task familiarity grew, there was increased high-gamma activity in the posterior inferior-frontal gyrus (pIFG) and diminished functional connectivity across a network encompassing frontal, parietal, and temporal lobes. Early pIFG high-gamma activity was predictive of successful recall. Including this metric in a logistic regression model yielded an accuracy of 0.76. Optimizing visuospatial working memory through practice is tied to early pIFG activation and decreased dependence on irrelevant neural pathways. This study expands our knowledge of human adaptation for visuospatial working memory, showing the spatiotemporal dynamics of cortical network modulations through white matter tracts. [ABSTRACT FROM AUTHOR]

Cognitive control processes enable the suppression of automatic behaviors and the initiation of appropriate responses. The Stroop color naming task serves as a benchmark paradigm for understanding the neurobiological model of verbal cognitive control. Previous research indicates a predominant engagement of the prefrontal and premotor cortex during the Stroop task compared to reading. We aim to further this understanding by creating a dynamic atlas of task-preferential modulations of functional connectivity through white matter. Patients undertook word-reading and Stroop tasks during intracranial EEG recording. We quantified task-related high-gamma amplitude modulations at 547 nonepileptic electrode sites, and a mixed model analysis identified regions and timeframes where these amplitudes differed between tasks. We then visualized white matter pathways with task-preferential functional connectivity enhancements at given moments. Word reading, compared to the Stroop task, exhibited enhanced functional connectivity in inter- and intra-hemispheric white matter pathways from the left occipital-temporal region 350–600 ms before response, including the posterior callosal fibers as well as the left vertical occipital, inferior longitudinal, inferior fronto-occipital, and arcuate fasciculi. The Stroop task showed enhanced functional connectivity in the pathways from the left middle-frontal pre-central gyri, involving the left frontal u-fibers and anterior callosal fibers. Automatic word reading largely utilizes the left occipital-temporal cortices and associated white matter tracts. Verbal cognitive control predominantly involves the left middle frontal and precentral gyri and its connected pathways. Our dynamic tractography atlases may serve as a novel resource providing insights into the unique neural dynamics and pathways of automatic reading and verbal cognitive control.

Background and purpose: We analyzed the association of neuropsychological outcomes after epilepsy surgery with the intracranial electrode type (stereo electroencephalography [SEEG] and subdural electrodes [SDE]), and electrical stimulation mapping (ESM) of speech/language. Methods: Drug‐resistant epilepsy patients who underwent comprehensive neuropsychological evaluation before and 1 year after epilepsy surgery were included. SEEG and SDE subgroups were matched by age, handedness, operated hemisphere, and seizure freedom. Postsurgical neuropsychological outcomes (adjusted for presurgical scores) and reliable change indices were analyzed as functions of electrode type and ESM. Results: Ninety‐nine patients aged 6–29 years were included with similar surgical resection/ablation volumes in the SEEG and SDE subgroups. Most of the neuropsychological outcomes were comparable between SEEG and SDE subgroups; however, Working Memory and Processing Speed were significantly improved in the SEEG subgroup. Undergoing language ESM was associated with significant improvements in Spelling, Letter–Word Identification, Vocabulary, Verbal Comprehension, Verbal Learning, and Story Memory scores, but a decline in Calculation scores. Conclusions: Intracranial evaluations with SEEG and SDE are comparable in terms of long‐term postsurgical neuropsychological outcomes. Our data suggest that SEEG may be associated with improvements in working memory and processing speed, representing cognitive domains served by spatially distributed networks. Our study also supports wider use of language ESM before epilepsy surgery, preferably using other language tasks in addition to visual naming. Rather than the type of electrode, postsurgical neuropsychological outcomes are driven by whether language ESM was performed or not, with beneficial effects of language mapping. [ABSTRACT FROM AUTHOR]

Purpose: Task-based BOLD fMRI and DTI-fiber tracking have become part of the routine presurgical work-up of brain tumor patients in many institutions. However, their potential impact on both surgical treatment and neurologic outcome remains unclear, in despite of the high costs and complex implementation. Methods: We retrospectively investigated whether performing fMRI and DTI-ft preoperatively substantially impacted surgical planning and patient outcome in a series of brain tumor patients. We assessed (i) the quality of fMRI and DTI-ft results, by using a scale of 0–2 (0 = failed mapping; 1 = intermediate confidence; 2 = good confidence), (ii) whether functional planning substantially contributed to defining the surgical strategy to be undertaken (i.e., no surgery, biopsy, or resection, with or without ESM), the surgical entry point and extent of resection, and (iii) the incidence of neurological deficits post-operatively. Results: Twenty-seven patients constituted the study population. The mean confidence rating was 1.9/2 for fMRI localization of the eloquent cortex and lateralization of the language function and 1.7/2 for DTI-ft results. Treatment strategy was altered in 33% (9/27) of cases. Surgical entry point was modified in 8% (2/25) of cases. The extent of resection was modified in 40% (10/25). One patient (1/25, 4%) developed one new functional deficit post-operatively. Conclusion: Functional MR mapping — which must not be considered an alternative to ESM — has a critical role preoperatively, potentially modifying treatment strategy or increasing the neurosurgeons' confidence in the surgical approach hypothesized based on conventional imaging. [ABSTRACT FROM AUTHOR]

Background. Awake surgery is currently a safe and reliable alternative for identifying and preserving functional areas. However, this protocol has evolved over time to minimize the occurrence of electrical stimulation-induced seizures and postoperative deficits. Objective. The aim of this study is to highlight both internal and external factors influencing the language and sensorimotor thresholds of electrical stimulation mapping (ESM) during gliomas awake surgery. Material and methods. From October 2016 to April 2022, we performed a retrospective study on 74 patients underwent awake craniotomy of gliomas in two series based on ESM: group 1 and group 2. Preoperatively and three months after surgery, general performance and neurological deficits were assessed according to the type, location, and side of the tumor in correlation with ASA, BMI, Mallampati and KPS indexes. Results. The outcome shows that the median patient age was 49 years old in a range of [13-70], functional mapping was performed in language areas for 96% of patients and motor functions for 54%. In addition, 55.5% of the patients had HGG, 40.5% had LGG, and 4% had AVMs. Most lesions were in the temporal area (40.5%), followed by the frontal area (31%), 24.5% for insular area, 4% for the parietal area, and 85% of patients had left-sided lesions. The overall rate of intraoperative complications fell from 16.2% in group 2 to 1.35% in group 1. Conclusions. Under the ESM threshold of group 1, a high-quality of awake surgery can be used with optimally low complications and failure rates regardless of BMI, ASA rating, Mallampati and KPS scores or smoking status.

Background. Until the advent of new exploration techniques: functional magnetic resonance imaging (fMRI) and surgical protocols such as exeresis in awake mode, the functional recovery potential of postoperative deficits was limited by conventional tumor surgery. The use of these methods simultaneously improves the quality of life and survival medians, mainly for removing low-grade gliomas massively infiltrating subcortical networks in eloquent regions where surgery is historically not associated with high functional recovery rates. Accordingly, the results from the awake brain surgery literature motivate us to establish a new baseline on the relationship between electrical stimulation mapping (ESM) threshold, the extent of resection (EOR), neuroplastic typology, and functional recovery after intraoperative crises or postoperative care deficits using induced neuroplasticity. Materials and patients. This is a retrospective analytical study of 35 brain tumor cases of gliomas, operated by common craniotomy in awake conditions from September 2016 to July 2022. Before entering awake resection mode, all patients underwent brain mapping (ESM) by direct electrical stimulation (DES) according to standard conditions and Helsinki ethical guidelines. Analysis according to ESM was done for two groups (group 1 and group 2) of different intensities of DES. Outcomes. The ESM by threshold intensity expressed in mean ± deviation standard was: 2,45 ± 0.125 mA for sensorimotor functions against 1.35 ± 0.175 mA for cognitive mapping. These stimulation currents were optimum thresholds which allowed us during control mapping to overcome all boundary conditions, mostly false negative results. The functional recovery time (FRT) following stimulation-induced seizures was varied from 2 s to 6.26 s, marking the intraoperative neuroplasticity operated mainly by synaptic remodeling during the functional reactivation. The EOR was better for group 1 with 82.35 % gross total resection (GTR) with only 8.75% of the occurrence of transient seizures against 45.7% for group 2 and only 2.86% suffered from neurological permanent deficits in group 1 against 11.42% in group 2. Conclusions. ESM in the range of [2.35 - 2.45 mA] improved DES sensitivity without false negatives. We had a compromise of improved results between these stimulation thresholds, the duration of the craniotomy, the functional recovery time, the EOR and overall the occurrence of neurological deficits, which explain the processes involved in the success of awake surgery.

Simple Summary: Intraoperative stimulation mapping is a technique used to identify and preserve functional tissue during the surgical resection of gliomas. This form of functional brain mapping allows neurosurgeons to remove the most tumor tissue possible while minimizing the risk of a neurological deficit after surgery. The data supporting brain mapping and the technical nuances of performing these operations safely are described in this review. Gliomas are infiltrative primary brain tumors that often invade functional cortical and subcortical regions, and they mandate individualized brain mapping strategies to avoid postoperative neurological deficits. It is well known that maximal safe resection significantly improves survival, while postoperative deficits minimize the benefits associated with aggressive resections and diminish patients' quality of life. Although non-invasive imaging tools serve as useful adjuncts, intraoperative stimulation mapping (ISM) is the gold standard for identifying functional cortical and subcortical regions and minimizing morbidity during these challenging resections. Current mapping methods rely on the use of low-frequency and high-frequency stimulation, delivered with monopolar or bipolar probes either directly to the cortical surface or to the subcortical white matter structures. Stimulation effects can be monitored through patient responses during awake mapping procedures and/or with motor-evoked and somatosensory-evoked potentials in patients who are asleep. Depending on the patient's preoperative status and tumor location and size, neurosurgeons may choose to employ these mapping methods during awake or asleep craniotomies, both of which have their own benefits and challenges. Regardless of which method is used, the goal of intraoperative stimulation is to identify areas of non-functional tissue that can be safely removed to facilitate an approach trajectory to the equator, or center, of the tumor. Recent technological advances have improved ISM's utility in identifying subcortical structures and minimized the seizure risk associated with cortical stimulation. In this review, we summarize the salient technical aspects of which neurosurgeons should be aware in order to implement intraoperative stimulation mapping effectively and safely during glioma surgery. [ABSTRACT FROM AUTHOR]

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.

• Task-preferential modulations of functional connectivity via white matter are visualized. • Task-preferential connectivity enhancement occurs hundreds of ms before overt response. • Reading preferentially enhances connectivity from left occipital-temporal areas. • Stroop task preferentially enhances connectivity from left middle frontal gyrus. Cognitive control processes enable the suppression of automatic behaviors and the initiation of appropriate responses. The Stroop color naming task serves as a benchmark paradigm for understanding the neurobiological model of verbal cognitive control. Previous research indicates a predominant engagement of the prefrontal and premotor cortex during the Stroop task compared to reading. We aim to further this understanding by creating a dynamic atlas of task-preferential modulations of functional connectivity through white matter. Patients undertook word-reading and Stroop tasks during intracranial EEG recording. We quantified task-related high-gamma amplitude modulations at 547 nonepileptic electrode sites, and a mixed model analysis identified regions and timeframes where these amplitudes differed between tasks. We then visualized white matter pathways with task-preferential functional connectivity enhancements at given moments. Word reading, compared to the Stroop task, exhibited enhanced functional connectivity in inter- and intra-hemispheric white matter pathways from the left occipital-temporal region 350–600 ms before response, including the posterior callosal fibers as well as the left vertical occipital, inferior longitudinal, inferior fronto-occipital, and arcuate fasciculi. The Stroop task showed enhanced functional connectivity in the pathways from the left middle-frontal pre-central gyri, involving the left frontal u-fibers and anterior callosal fibers. Automatic word reading largely utilizes the left occipital-temporal cortices and associated white matter tracts. Verbal cognitive control predominantly involves the left middle frontal and precentral gyri and its connected pathways. Our dynamic tractography atlases may serve as a novel resource providing insights into the unique neural dynamics and pathways of automatic reading and verbal cognitive control. [ABSTRACT FROM AUTHOR]

Background. Awake surgery is currently a safe and reliable alternative for identifying and preserving functional areas. However, this protocol has evolved over time to minimize the occurrence of electrical stimulation-induced seizures and postoperative defi cits. Objective. The aim of this study is to highlight both internal and external factors infl uencing the language and sensorimotor thresholds of electrical stimulation mapping (ESM) during gliomas awake surgery. Material and methods. From October 2016 to April 2022, we performed a retrospective study on 74 patients underwent awake craniotomy of gliomas in two series based on ESM: group 1 and group 2. Preoperatively and three months aŌ er surgery, general performance and neurological defi cits were assessed according to the type, location, and side of the tumor in correlation with ASA, BMI, Mallampatiand KPS indexes. Results. The outcome shows that the median patient age was 49 years old in a range of [13-70], functional mapping was performed in language areas for 96% of patients and motor functions for 54%. In addition, 55.5% of the patients had HGG, 40.5% had LGG, and 4% had AVMs. Most lesions were in the temporal area (40.5%), followed by the frontal area (31%), 24.5% for insular area, 4% for the parietal area, and 85% of patients had leŌ -sided lesions. The overall rate of intraoperative complications fell from 16.2% in group 2 to 1.35% in group 1. Conclusions. Under the ESM threshold of group 1, a high-quality of awake surgery can be used with optimally low complications and failure rates regardless of BMI, ASA rating, Mallampati and KPS scores or smoking status. [ABSTRACT FROM AUTHOR]

Objective: To determine the optimal montage and vocalization conditions for high-gamma language mapping using stereoelectroencephalography., Methods: We studied 12 epilepsy patients who underwent invasive monitoring with depth electrodes and measurement of auditory-naming related high-gamma modulations. We determined the effects of electrode montage and vocalization conditions of the response on the high-gamma (60-140 Hz) amplitudes., Results: Compared to common average reference montage, bipolar and Laplacian montages effectively reduced the degree of auditory naming-related signal deflections in the white matter during the stimulus and response phases (mixed model estimate: -21.2 to -85.4%; p  < 0.001), while maintaining those at the cortical level (-4.4 to +7.8%; p  = 0.614 to 0.085). They also reduced signal deflections outside the brain parenchyma during the response phase (-90.6 to -91.2%; p  < 0.001). Covert responses reduced signal deflections outside the brain parenchyma during the response phase (-17.0%; p  = 0.010)., Conclusion: On depth electrode recording, bipolar and Laplacian montages are suitable for measuring auditory naming-related high-gamma modulations in gray matter. The covert response may highlight the gray matter activity., Significance: This study helps establish the practical guidelines for high-gamma language mapping using stereoelectroencephalography., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mitsuhashi, Iimura, Suzuki, Ueda, Nishioka, Nomura, Nakajima, Sugano and Kondo.)

Mainstream cognitive neuroscience aims to build mechanistic explanations of behavior by mapping abilities described at the organismal level via the subpersonal level of computation onto specific brain networks. We provide an integrative review of these commitments and their mismatch with empirical research findings. Context-dependent neural tuning, neural reuse, degeneracy, plasticity, functional recovery, and the neural correlates of enculturated skills each show that there is a lack of stable mappings between organismal, computational, and neural levels of analysis. We furthermore highlight recent research suggesting that task context at the organismal level determines the dynamic parcellation of functional components at the neural level. Such instability prevents the establishment of specific computational descriptions of neural function, which remains a central goal of many brain mappers - including those who are sympathetic to the notion of many-to-many mappings between organismal and neural levels. This between-level instability presents a deep epistemological challenge and requires a reorientation of methodological and theoretical commitments within cognitive neuroscience. We demonstrate the need for change to brain mapping efforts in the face of instability if cognitive neuroscience is to maintain its central goal of constructing computational mechanistic explanations of behavior; we show that such explanations must be contextual at all levels. [ABSTRACT FROM AUTHOR]

Mainstream cognitive neuroscience aims to build mechanistic explanations of behavior by mapping abilities described at the organismal level via the subpersonal level of computation onto specific brain networks. We provide an integrative review of these commitments and their mismatch with empirical research findings. Context-dependent neural tuning, neural reuse, degeneracy, plasticity, functional recovery, and the neural correlates of enculturated skills each show that there is a lack of stable mappings between organismal, computational, and neural levels of analysis. We furthermore highlight recent research suggesting that task context at the organismal level determines the dynamic parcellation of functional components at the neural level. Such instability prevents the establishment of specific computational descriptions of neural function, which remains a central goal of many brain mappers – including those who are sympathetic to the notion of many-to-many mappings between organismal and neural levels. This between-level instability presents a deep epistemological challenge and requires a reorientation of methodological and theoretical commitments within cognitive neuroscience. We demonstrate the need for change to brain mapping efforts in the face of instability if cognitive neuroscience is to maintain its central goal of constructing computational mechanistic explanations of behavior; we show that such explanations must be contextual at all levels.

• During visual naming, high-gamma modulation occurs in a posteroanterior sequential pattern with overlapping temporal profiles. • Cortical activations during visual naming represent cognitive sub-components with different relative contributions from the left and right cerebral hemispheres. • Post-surgical neuropsychological deficits correlated with the location of resected parcels within the visual naming network. Cerebral spatiotemporal dynamics of visual naming were investigated in epilepsy patients undergoing stereo-electroencephalography (SEEG) monitoring. Brain networks were defined by Parcel-Activation-Resection-Symptom matching (PARS) approach by matching high-gamma (50–150 Hz) modulations (HGM) in neuroanatomic parcels during visual naming, with neuropsychological outcomes after resection/ablation of those parcels. Brain parcels with >50% electrode contacts simultaneously showing significant HGM were aligned, to delineate spatiotemporal course of naming-related HGM. In 41 epilepsy patients, neuroanatomic parcels showed sequential yet temporally overlapping HGM course during visual naming. From bilateral occipital lobes, HGM became increasingly left lateralized, coursing through limbic system. Bilateral superior temporal HGM was noted around response time, and right frontal HGM thereafter. Correlations between resected/ablated parcels, and post-surgical neuropsychological outcomes showed specific regional groupings. Convergence of data from spatiotemporal course of HGM during visual naming, and functional role of specific parcels inferred from neuropsychological deficits after resection/ablation of those parcels, support a model with six cognitive subcomponents of visual naming having overlapping temporal profiles. Cerebral substrates supporting visual naming are bilaterally distributed with relative hemispheric contribution dependent on cognitive demands at a specific time. PARS approach can be extended to study other cognitive and functional brain networks. [ABSTRACT FROM AUTHOR]

• Optical imaging is particularly adapted for intraoperative translational works. • The brain activity can be monitored with the quantification of cortical hemoglobin. • A functional model was implemented to identify the activated cortical areas. • Patient's cortical activity is monitored in real time (during data acquisition). Intraoperative optical imaging is a localization technique for the functional areas of the human brain cortex during neurosurgical procedures. However, it still lacks robustness to be used as a clinical standard. In particular new biomarkers of brain functionality with improved sensitivity and specificity are needed. We present a method for the real time identification of the activated cortical areas based on the analysis of the cortical hemodynamic using a RGB camera and a white light source. We measure the quantitative oxy and deoxy-hemoglobin concentration changes in the human brain cortex with the modified Beer-Lambert law and Monte Carlo simulations. A functional model has been implemented to define in real time a binary biomarker of the cortical activation following neuronal activation by physiological stimuli. The results show a good correlation between the computed activation maps and the brain areas localized by electrical brain stimulation. We demonstrate that a RGB camera combined with a quantitative modeling of brain hemodynamics biomarkers can evaluate in real time the functional areas during neurosurgery and serve as a tool of choice to complement electrical brain stimulation. [ABSTRACT FROM AUTHOR]

Face recognition is impaired in patients with prosopagnosia, which may occur as a side effect of neurosurgical procedures. Face selective regions on the ventral temporal cortex have been localized with electrical cortical stimulation (ECS), electrocorticography (ECoG), and functional magnetic resonance imagining (fMRI). This is the first group study using within-patient comparisons to validate face selective regions mapping, utilizing the aforementioned modalities. Five patients underwent surgical treatment of intractable epilepsy and joined the study. Subdural grid electrodes were implanted on their ventral temporal cortices to localize seizure foci and face selective regions as part of the functional mapping protocol. Face selective regions were identified in all patients with fMRI, four patients with ECoG, and two patients with ECS. From 177 tested electrode locations in the region of interest (ROI), which is defined by the fusiform gyrus and the inferior temporal gyrus, 54 face locations were identified by at least one modality in all patients. fMRI mapping showed the highest detection rate, revealing 70.4% for face selective locations, whereas ECoG and ECS identified 64.8 and 31.5%, respectively. Thus, 28 face locations were co-localized by at least two modalities, with detection rates of 89.3% for fMRI, 85.7% for ECoG and 53.6 % for ECS. All five patients had no face recognition deficits after surgery, even though five of the face selective locations, one obtained by ECoG and the other four by fMRI, were within 10 mm to the resected volumes. Moreover, fMRI included a quite large volume artifact on the ventral temporal cortex in the ROI from the anatomical structures of the temporal base. In conclusion, ECS was not sensitive in several patients, whereas ECoG and fMRI even showed activation within 10 mm to the resected volumes. Considering the potential signal drop-out in fMRI makes ECoG the most reliable tool to identify face selective locations in this study. A multimodal approach can improve the specificity of ECoG and fMRI, while simultaneously minimizing the number of required ECS sessions. Hence, all modalities should be considered in a clinical mapping protocol entailing combined results of co-localized face selective locations.

Face recognition is impaired in patients with prosopagnosia, which may occur as a side effect of neurosurgical procedures. Face selective regions on the ventral temporal cortex have been localized with electrical cortical stimulation (ECS), electrocorticography (ECoG), and functional magnetic resonance imagining (fMRI). This is the first group study using within-patient comparisons to validate face selective regions mapping, utilizing the aforementioned modalities. Five patients underwent surgical treatment of intractable epilepsy and joined the study. Subdural grid electrodes were implanted on their ventral temporal cortices to localize seizure foci and face selective regions as part of the functional mapping protocol. Face selective regions were identified in all patients with fMRI, four patients with ECoG, and two patients with ECS. From 177 tested electrode locations in the region of interest (ROI), which is defined by the fusiform gyrus and the inferior temporal gyrus, 54 face locations were identified by at least one modality in all patients. fMRI mapping showed the highest detection rate, revealing 70.4% for face selective locations, whereas ECoG and ECS identified 64.8 and 31.5%, respectively. Thus, 28 face locations were co-localized by at least two modalities, with detection rates of 89.3% for fMRI, 85.7% for ECoG and 53.6 % for ECS. All five patients had no face recognition deficits after surgery, even though five of the face selective locations, one obtained by ECoG and the other four by fMRI, were within 10 mm to the resected volumes. Moreover, fMRI included a quite large volume artifact on the ventral temporal cortex in the ROI from the anatomical structures of the temporal base. In conclusion, ECS was not sensitive in several patients, whereas ECoG and fMRI even showed activation within 10 mm to the resected volumes. Considering the potential signal drop-out in fMRI makes ECoG the most reliable tool to identify face selective locations in this study. A multimodal approach can improve the specificity of ECoG and fMRI, while simultaneously minimizing the number of required ECS sessions. Hence, all modalities should be considered in a clinical mapping protocol entailing combined results of co-localized face selective locations. [ABSTRACT FROM AUTHOR]

Prolonged seizures in children with focal epilepsy (FE) may impair language functions and often reoccur after surgical intervention. This study is aimed at developing a novel deep relational reasoning network to investigate whether conventional diffusion-weighted imaging connectome analysis can be improved when predicting expressive and receptive scores of preoperative language impairments and classifying postoperative seizure outcomes (seizure freedom or recurrence) in individual FE children. To deeply reason the dependencies of axonal connections that are sparsely distributed in the whole brain, this study proposes the “dilated CNN + RN”, a dilated convolutional neural network (CNN) combined with a relation network (RN). The performance of the dilated CNN + RN was evaluated using whole brain connectome data from 51 FE children. It was found that when compared with other state-of-the-art algorithms, the dilated CNN + RN led to an average improvement of 90.2% and 97.3% in predicting expressive and receptive language scores, and 2.2% and 4% improvement in classifying seizure freedom and seizure recurrence, respectively. These improvements were independent of the prefixed connectome densities. Also, the dilated CNN + RN could provide an explainable artificial intelligence (AI) model by computing gradient-based regression/classification activation maps. This mapping analysis revealed left superior-medial frontal cortex, bilateral hippocampi, and cerebellum as crucial hubs, facilitating important connections that were most predictive of language function and seizure refractoriness after surgery. [ABSTRACT FROM AUTHOR]

Despite technological and interpretative advances, the non-invasive modalities used for pre-surgical evaluation of patients with drug-resistant epilepsy (DRE), fail to generate a concordant anatomo-electroclinical hypothesis for the location of the seizure onset zone in many patients. This requires chronic monitoring with intracranial electroencephalography (EEG), which facilitates better localization of the seizure onset zone, and allows evaluation of the functional significance of cortical regions-of-interest by electrical stimulation mapping (ESM). There are two principal modalities for intracranial EEG, namely subdural electrodes and stereotactic depth electrodes (stereo-EEG). Although ESM is considered the gold standard for functional mapping with subdural electrodes, there have been concerns about its utility with stereo-EEG. This is mainly because subdural electrodes allow contiguous sampling of the dorsolateral convexity of cerebral hemispheres, and permit delineation of the extent of eloquent functional areas on the cortical surface. Stereo-EEG, while having relatively sparse sampling on the cortical surface, offers the ability to access the depth of sulci, mesial and basal surfaces of cerebral hemispheres, and deep structures such as the insula, which are largely inaccessible to subdural electrodes. As stereo-EEG is increasingly the preferred modality for intracranial monitoring, we find it opportune to summarize the literature for ESM with stereo-EEG in this narrative review. Emerging evidence shows that ESM for defining functional neuroanatomy is feasible with stereo-EEG, but probably requires a different approach for interpretation and clinical decision making compared to ESM with subdural electrodes. We have also compared ESM with stereo-EEG and subdural electrodes, for current thresholds required to evoke desired functional responses vs. unwanted after-discharges. In this regard, there is preliminary evidence that ESM with stereo-EEG may be safer than ESM with subdural grids. Finally, we have highlighted important unanswered clinical and scientific questions for ESM with stereo-EEG in the hope to encourage future research and collaborative efforts.

• 4D tractography animated single-pulse electrical stimulation (SPES)-related neural propagations via white matter pathways. • SPES-related neural propagations took place via the corpus callosum. • SPES-related neural propagations also took place via the anterior commissure. To visualize and validate the dynamics of interhemispheric neural propagations induced by single-pulse electrical stimulation (SPES). This methodological study included three patients with drug-resistant focal epilepsy who underwent measurement of cortico-cortical spectral responses (CCSRs) during bilateral stereo-electroencephalography recording. We delivered SPES to 83 electrode pairs and analyzed CCSRs recorded at 268 nonepileptic electrode sites. Diffusion-weighted imaging (DWI) tractography localized the interhemispheric white matter pathways as streamlines directly connecting two electrode sites. We localized and visualized the putative SPES-related fiber activation, at each 1-ms time window, based on the propagation velocity defined as the DWI-based streamline length divided by the early CCSR peak latency. The resulting movie, herein referred to as four-dimensional tractography, delineated the spatiotemporal dynamics of fiber activation via the corpus callosum and anterior commissure. Longer streamline length was associated with delayed peak latency and smaller amplitude of CCSRs. The cortical regions adjacent to each fiber activation site indeed exhibited CCSRs at the same time window. Our four-dimensional tractography successfully animated neural propagations via distinct interhemispheric pathways. Our novel animation method has the potential to help investigators in addressing the mechanistic significance of the interhemispheric network dynamics supporting physiological function. [ABSTRACT FROM AUTHOR]

Despite technological and interpretative advances, the non-invasive modalities used for pre-surgical evaluation of patients with drug-resistant epilepsy (DRE), fail to generate a concordant anatomo-electroclinical hypothesis for the location of the seizure onset zone in many patients. This requires chronic monitoring with intracranial electroencephalography (EEG), which facilitates better localization of the seizure onset zone, and allows evaluation of the functional significance of cortical regions-of-interest by electrical stimulation mapping (ESM). There are two principal modalities for intracranial EEG, namely subdural electrodes and stereotactic depth electrodes (stereo-EEG). Although ESM is considered the gold standard for functional mapping with subdural electrodes, there have been concerns about its utility with stereo-EEG. This is mainly because subdural electrodes allow contiguous sampling of the dorsolateral convexity of cerebral hemispheres, and permit delineation of the extent of eloquent functional areas on the cortical surface. Stereo-EEG, while having relatively sparse sampling on the cortical surface, offers the ability to access the depth of sulci, mesial and basal surfaces of cerebral hemispheres, and deep structures such as the insula, which are largely inaccessible to subdural electrodes. As stereo-EEG is increasingly the preferred modality for intracranial monitoring, we find it opportune to summarize the literature for ESM with stereo-EEG in this narrative review. Emerging evidence shows that ESM for defining functional neuroanatomy is feasible with stereo-EEG, but probably requires a different approach for interpretation and clinical decision making compared to ESM with subdural electrodes. We have also compared ESM with stereo-EEG and subdural electrodes, for current thresholds required to evoke desired functional responses vs. unwanted after-discharges. In this regard, there is preliminary evidence that ESM with stereo-EEG may be safer than ESM with subdural grids. Finally, we have highlighted important unanswered clinical and scientific questions for ESM with stereo-EEG in the hope to encourage future research and collaborative efforts. [ABSTRACT FROM AUTHOR]

• We measured neuronal responses to single-pulse electrical stimulation (SPES). • Bipolar and Laplacian montages record near-field responses on depth electrodes. • Subcortical SPES elicited neuronal responses at large numbers of contacts. To determine the optimal depth electrode montages for the assessment of effective connectivity based on single-pulse electrical stimulation (SPES). To determine the effect of SPES locations on the extent of resulting neuronal propagations. We studied 14 epilepsy patients who underwent invasive monitoring with depth electrodes and measurement of cortico-cortical evoked potentials (CCEPs) and cortico-cortical spectral responses (CCSRs). We determined the effects of electrode montage and stimulus sites on the CCEP/CCSR amplitudes. Bipolar and Laplacian montages effectively reduced the degree of SPES-related signal deflections at extra-cortical levels, including outside the brain, while maintaining those at the cortical level. SPES of structures more proximal to the deep white matter, compared to the cortical surface, elicited greater CCEPs and CCSRs. On depth electrode recording, bipolar and Laplacian montages are suitable for measurement of near-field CCEPs and CCSRs. SPES of the white matter axons may induce neuronal propagations to extensive regions of the cerebral cortex. This study helps to establish the practical guidelines on the diagnostic use of CCEPs/CCSRs. [ABSTRACT FROM AUTHOR]

Introduction: Cortico-cortical evoked potentials (CCEPs) are utilized to identify effective networks in the human brain. Following single-pulse electrical stimulation of cortical electrodes, evoked responses are recorded from distant cortical areas. A negative deflection (N1) which occurs 10–50 ​ms post-stimulus is considered to be a marker for direct cortico-cortical connectivity. However, with CCEPs alone it is not possible to observe the white matter pathways that conduct the signal or accurately predict N1 amplitude and latency at downstream recoding sites. Here, we develop a new approach, termed “dynamic tractography,” which integrates CCEP data with diffusion-weighted imaging (DWI) data collected from the same patients. This innovative method allows greater insights into cortico-cortical networks than provided by each method alone and may improve the understanding of large-scale networks that support cognitive functions. The dynamic tractography model produces several fundamental hypotheses which we investigate: 1) DWI-based pathlength predicts N1 latency; 2) DWI-based pathlength negatively predicts N1 voltage; and 3) fractional anisotropy (FA) along the white matter path predicts N1 propagation velocity. Methods: Twenty-three neurosurgical patients with drug-resistant epilepsy underwent both extraoperative CCEP recordings and preoperative DWI scans. Subdural grids of 3 ​mm diameter electrodes were used for stimulation and recording, with 98–128 eligible electrodes per patient. CCEPs were elicited by trains of 1 ​Hz stimuli with an intensity of 5 ​mA and recorded at a sample rate of 1 ​kHz. N1 peak and latency were defined as the maximum of a negative deflection within 10–50 ​ms post-stimulus with a z-score > 5 relative to baseline. Electrodes and DWI were coregistered to construct electrode connectomes for white matter quantification. Results: Clinical variables (age, sex, number of anti-epileptic drugs, handedness, and stimulated hemisphere) did not correlate with the key outcome measures (N1 peak amplitude, latency, velocity, or DWI pathlength). All subjects and electrodes were therefore pooled into a group-level analysis to determine overall patterns. As hypothesized, DWI path length positively predicted N1 latency (R2 ​= ​0.81, β ​= ​1.51, p ​= ​4.76e-16) and negatively predicted N1 voltage (R2 ​= ​0.79, β ​= ​−0.094, p ​= ​9.30e-15), while FA predicted N1 propagation velocity (R2 ​= ​0.35, β ​= ​48.0, p ​= ​0.001). Conclusion: We have demonstrated that the strength and timing of the CCEP N1 is dependent on the properties of the underlying white matter network. Integrated CCEP and DWI visualization allows robust localization of intact axonal pathways which effectively interconnect eloquent cortex.

Purpose: Multiple system atrophy (MSA) is an atypical parkinsonian syndrome and often difficult to discriminate clinically from progressive supranuclear palsy (PSP) and Parkinson's disease (PD) in early stages. Although a characteristic metabolic brain network has been reported for MSA, it is unknown whether this network can provide a clinically useful biomarker in different centers. This study was aimed to identify and cross-validate MSA-related brain network and assess its ability for differential diagnosis and clinical correlations in Chinese and American patient cohorts. Methods: We included 18F-FDG PET scans retrospectively from 128 clinically diagnosed parkinsonian patients (34 MSA, 34 PSP and 60 PD) and 40 normal subjects in China and in the USA. Using PET images from 20 moderate-stage MSA patients of parkinsonian subtype and 20 normal subjects in both centers, we reproduced MSA-related pattern (MSAPRP) of spatial covariance and estimated its reliability. MSAPRP scores were evaluated in assessing differential diagnosis among moderate- and early-stage MSA, PSP or PD patients and clinical correlations with disease severity. Regional metabolic differences were detected using statistical parameter mapping analysis. MSA-related network and regional topographies of metabolic abnormality were cross-validated between the Chinese and American cohorts. Results: We generated a highly reliable MSAPRP characterized by decreased loading in inferior frontal cortex, striatum and cerebellum, and increased loading in sensorimotor, parietal and occipital cortices. MSAPRP scores discriminated between normal, MSA, PSP and PD subjects and correlated with standardized ratings of clinical stages and motor symptoms in MSA. High similarities in MSAPRPs, network scores and corresponding maps of metabolic abnormality were observed between two different cohorts. Conclusion: We have demonstrated reproducible metabolic topographies associated with MSA at both network and regional levels in two independent patient cohorts. Moreover, MSAPRP scores are sensitive for evaluating disease discrimination and clinical correlates. This study supports differential diagnosis of MSA regardless of different patient populations, PET scanners and imaging protocols.

• Stereo-EEG sensorimotor mapping was prospectively compared with reference neuroanatomy. • Electrical stimulation mapping localized anatomic sensorimotor parcels with high accuracy. • Sensorimotor thresholds below after-discharge thresholds suggest safety of stereo-EEG ESM. We evaluated stereo-EEG electrical stimulation mapping (ESM) for localization of anatomic sensorimotor parcels in pediatric patients with drug-resistant epilepsy. We also analyzed sensorimotor and after-discharge thresholds, and the somatotopy of sensorimotor responses. ESM was performed with 50 Hz, biphasic, 2–3 s trains, using 1–9 mA current. Pre- and post-implant neuroimaging was co-registered and intersected with Neurosynth reference, to classify each electrode contact as lying within/outside an anatomic sensorimotor parcel. Indices of diagnostic performance were computed. Sensorimotor and after-discharge thresholds were analyzed using multivariable linear mixed models. In 15 patients (6 females), aged 5.5–21.2 years, ESM showed high accuracy (0.80), high specificity (0.86), and diagnostic odds ratio (11.4, p < 0.0001) for localization of sensorimotor parcels. Mean sensorimotor threshold (3.4 mA) was below mean after-discharge threshold (4.2 mA, p = 0.0004). Sensorimotor and after-discharge thresholds showed a significant decrease with increasing intelligence quotient. Somatotopy of sensorimotor responses was mapped to standardized brain parcels. We provide evidence for diagnostic validity and safety of stereo-EEG sensorimotor ESM. The somatotopy of sensorimotor responses elicited with electrical stimulation provide new insights into mechanisms of motor control and sensory perception. [ABSTRACT FROM AUTHOR]

Purpose: We studied the association between electrical stimulation mapping (ESM) with a visual naming task and post-operative neuropsychological outcomes after pediatric epilepsy surgery.Methods: Children who underwent epilepsy surgery, having pre- and 1-year post-surgery neuropsychological evaluation (NPE) available, were included. NPE scores were transformed using principal components (PC) analysis. The relationship between post-surgical PC scores, adjusted for pre-surgery PC scores, and ESM was analyzed. Clinical variables influencing this relationship were also sought.Results: One hundred and four children (89 patients >5 years-old, and 15 patients 3-5 years-old) were included. Among children >5 years-of-age, a significant effect of language ESM was observed on all 3 post-surgery PC scores adjusted for respective pre-surgery PC scores. Specifically, only 30 % patients who underwent language ESM had a decrease in PC1 scores ≥1-year after epilepsy surgery, compared to 68 % those who did not undergo language ESM (p = 0.001). Seizure outcomes, age at the time of surgery, predominant seizure type, and family history of epilepsy were other significant determinants of post-surgical PC scores including a change in PC scores from pre-surgery baseline. Combinations of pre-surgical variables were able to predict post-surgical PC scores with high specificity. In children aged 3-5 years, no significant effect of language ESM was seen on post-surgery PC scores adjusted for respective pre-surgery PC scores.Conclusions: Speech/language ESM should be performed more widely in patients >5 years-of-age undergoing epilepsy surgery. Also, more efficient brain mapping techniques and language paradigms are needed for younger children. [ABSTRACT FROM AUTHOR]

Support vector machine (SVM)‐based multivariate pattern analysis (MVPA) has delivered promising performance in decoding specific task states based on functional magnetic resonance imaging (fMRI) of the human brain. Conventionally, the SVM‐MVPA requires careful feature selection/extraction according to expert knowledge. In this study, we propose a deep neural network (DNN) for directly decoding multiple brain task states from fMRI signals of the brain without any burden for feature handcrafts. We trained and tested the DNN classifier using task fMRI data from the Human Connectome Project's S1200 dataset (N = 1,034). In tests to verify its performance, the proposed classification method identified seven tasks with an average accuracy of 93.7%. We also showed the general applicability of the DNN for transfer learning to small datasets (N = 43), a situation encountered in typical neuroscience research. The proposed method achieved an average accuracy of 89.0 and 94.7% on a working memory task and a motor classification task, respectively, higher than the accuracy of 69.2 and 68.6% obtained by the SVM‐MVPA. A network visualization analysis showed that the DNN automatically detected features from areas of the brain related to each task. Without incurring the burden of handcrafting the features, the proposed deep decoding method can classify brain task states highly accurately, and is a powerful tool for fMRI researchers. [ABSTRACT FROM AUTHOR]

Brief-pulse stimulation at 50 Hz has been shown to terminate afterdischarges observed in epilepsy patients. However, the optimal pulse stimulation parameters for terminating cortical electrical stimulation-induced afterdischarges remain unclear. In the present study, we examined the effects of different brief-pulse stimulation frequencies (5, 50 and 100 Hz) on cortical electrical stimulation-induced afterdischarges in 10 patients with refractory epilepsy. Results demonstrated that brief-pulse stimulation could terminate cortical electrical stimulation-induced afterdischarges in refractory epilepsy patients. In conclusion, (1) a brief-pulse stimulation was more effective when the afterdischarge did not extend to the surrounding brain area. (2) A higher brief-pulse stimulation frequency (especially 100 Hz) was more likely to terminate an afterdischarge. (3) A low current intensity of brief-pulse stimulation was more likely to terminate an afterdischarge

BCI2000 has been a popular platform for development of real-time brain computer interfaces (BCIs). Since BCI2000's initial release, web browsers have evolved considerably, enabling rapid development of internet-enabled applications and interactive visualizations. Linking the amplifier abstraction and signal processing native to BCI2000 with the host of technologies and ease of development afforded by modern web browsers could enable a new generation of browser-based BCIs and visualizations. We developed a server and filter module called BCI2000Web providing an HTTP connection capable of escalation into an RFC6455 WebSocket, which enables direct communication between a browser and a BCI2000 distribution in real-time, facilitating a number of novel applications. We also present a JavaScript module, bci2k.js, that allows web developers to create paradigms and visualizations using this interface in an easy-to-use and intuitive manner. To illustrate the utility of BCI2000Web, we demonstrate a browser-based implementation of a real-time electrocorticographic (ECoG) functional mapping suite called WebFM. We also explore how the unique characteristics of our browser-based framework make BCI2000Web an attractive tool for future BCI applications. BCI2000Web leverages the advances of BCI2000 to provide real-time browser-based interactions with human neurophysiological recordings, allowing for web-based BCIs and other applications, including real-time functional brain mapping. Both BCI2000 and WebFM are provided under open source licenses. Enabling a powerful BCI suite to communicate with today's most technologically progressive software empowers a new cohort of developers to engage with BCI technology, and could serve as a platform for internet-enabled BCIs.

• Picture naming-specific high-gamma augmentation was noted in the bilateral occipital-fusiform pathways. • Auditory naming-specific high-gamma augmentation was noted in the bilateral superior temporal gyrus. • Auditory naming-specific high-gamma augmentation was noted in the left perisylvian network regions. To characterize the spatiotemporal dynamics of auditory and picture naming-related cortical activation in Japanese-speaking patients. Ten patients were assigned auditory naming and picture naming tasks during extraoperative intracranial EEG recording in a tertiary epilepsy center. Time-frequency analysis determined at what electrode sites and at what time windows during each task the amplitude of high-gamma activity (65–95 Hz) was modulated. The superior-temporal gyrus on each hemisphere showed high-gamma augmentation during sentence listening, whereas the left middle-temporal and inferior-frontal gyri showed high-gamma augmentation peaking around stimulus offset. Auditory naming-specific high-gamma augmentation was noted in the bilateral superior-temporal gyri as well as left frontal-parietal-temporal perisylvian network regions, whereas picture naming-specific augmentation was noted in the occipital-fusiform regions, bilaterally. The inferior pre- and postcentral gyri on each hemisphere showed modality-common high-gamma augmentation time-locked to overt responses. The spatiotemporal dynamics of auditory and picture naming-related high-gamma augmentation in Japanese-speaking patients were qualitatively similar to those previously reported in studies of English-speaking patients. The cortical dynamics for auditory sentence recognition are at least partly shared by cohorts speaking two distinct languages. Multicenter studies regarding the clinical utility of high-gamma language mapping across Eastern and Western hemispheres may be feasible. [ABSTRACT FROM AUTHOR]

The nature of abstract and concrete semantics and differences between them have remained a debated issue in psycholinguistic and cognitive studies for decades. Most of the available behavioral and neuroimaging studies reveal distinctions between these two types of semantics, typically associated with a so-called "concreteness effect." Many attempts have been made to explain these differences using various approaches, from purely theoretical linguistic and cognitive frameworks to neuroimaging experiments. In this brief overview, we will try to provide a snapshot of these diverse views and relationships between them and highlight the crucial issues preventing this problem from being solved. We will argue that one potentially beneficial way forward is to identify the neural mechanisms underpinning acquisition of the different types of semantics (e.g., by using neurostimulation techniques to establish causal relationships), which may help explain the distinctions found between the processing of concrete and abstract semantics. [ABSTRACT FROM AUTHOR]

Standard electrostimulation cortical mapping includes application of electrical current to the explored areas through an electrode and marking of functional zones by means of paper tags with different symbols. This approach has several disadvantages. First, the electrode is moved randomly. It leads to overlooking of some zones, which causes mapping deficiency, and restimulation of others, which can trigger epileptic seizures. Second, the tags easily shift and close the marked structures. We describe a new simple device that provides precise cortical mapping without indicated problems and the technique to apply it. The device is a flexible polymer mesh with square pores of a certain size. The neurosurgeon applies the mesh onto the brain cortex and sequentially stimulates it through the pores. The functional areas are labeled. Pores corresponding to the lesion are cut out, and the lesion is removed through the cutout without removing the mesh. After operation, the mesh is removed. Using this technique, we operated on a patient with a glioma located near the primary motor cortex. The accessible cortical area was accurately mapped, and the tumor was resected without any complications. The mesh allowed us to significantly streamline the mapping process. Our case illustrates that the proposed invention can be successfully used in neurosurgical operations for precise electrostimulation mapping of the brain cortex. [ABSTRACT FROM AUTHOR]

Highlights • Resection of HGM language sites is associated with worse neuropsychological outcomes. • Working memory was significantly worse in patients with resection of HGM naming sites. • Neuropsychological evaluation of children with epilepsy should include multiple cognitive and language domains. Abstract Background Language mapping with high-gamma modulation (HGM) has compared well with electrical cortical stimulation mapping (ESM). However, there is limited prospective data about its functional validity. We compared changes in neuropsychological evaluation (NPE) performed before and 1-year after epilepsy surgery, between patients with/without resection of cortical sites showing HGM during a visual naming task. Methods Pediatric drug-resistant epilepsy (DRE) patients underwent pre-surgical language localization with ESM and HGM using a visual naming task. Surgical decisions were based solely on ESM results. NPE difference scores were compared between patients with/without resection of HGM naming sites using principal component (PC) analysis. Follow-up NPE scores were modeled with resection group as main effect and respective pre-surgical score as a covariate, using analysis of covariance. Results Seventeen native English speakers (12 females), aged 6.5–20.2 years, were included. One year after epilepsy surgery, first PC score increased by (mean ± standard deviation) 14.4 ± 16.5 points in patients without resection, whereas it decreased by 7.6 ± 24.6 points in those with resection of HGM naming sites (p = 0.040). This PC score represented verbal comprehension, working memory, perceptual reasoning (Wechsler subscales); Woodcock-Johnson Tests of Achievement; and Peabody Picture Vocabulary Test. Subsequent analysis showed significant difference in working memory score between patients with/without resection of HGM naming sites (−15.2 points, 95% confidence limits −29.7 to −0.7, p = 0.041). Conclusion We highlight the functional consequences of resecting HGM language sites, and suggest that NPE of DRE patients should include comprehensive assessment of multiple linguistic and cognitive domains besides naming ability. [ABSTRACT FROM AUTHOR]

BCI2000 has been a popular platform for development of real-time brain computer interfaces (BCIs). Since BCI2000's initial release, web browsers have evolved considerably, enabling rapid development of internet-enabled applications and interactive visualizations. Linking the amplifier abstraction and signal processing native to BCI2000 with the host of technologies and ease of development afforded by modern web browsers could enable a new generation of browser-based BCIs and visualizations. We developed a server and filter module called BCI2000Web providing an HTTP connection capable of escalation into an RFC6455 WebSocket, which enables direct communication between a browser and a BCI2000 distribution in real-time, facilitating a number of novel applications. We also present a JavaScript module, bci2k.js, that allows web developers to create paradigms and visualizations using this interface in an easy-to-use and intuitive manner. To illustrate the utility of BCI2000Web, we demonstrate a browser-based implementation of a real-time electrocorticographic (ECoG) functional mapping suite called WebFM. We also explore how the unique characteristics of our browser-based framework make BCI2000Web an attractive tool for future BCI applications. BCI2000Web leverages the advances of BCI2000 to provide real-time browser-based interactions with human neurophysiological recordings, allowing for web-based BCIs and other applications, including real-time functional brain mapping. Both BCI2000 and WebFM are provided under open source licenses. Enabling a powerful BCI suite to communicate with today's most technologically progressive software empowers a new cohort of developers to engage with BCI technology, and could serve as a platform for internet-enabled BCIs. [ABSTRACT FROM AUTHOR]

Localized evoked activity of the human cortex produces fast changes in optical properties that can be detected noninvasively (event-related optical signal, or EROS). In the present study a fast EROS response (latency approximately 100 ms) elicited in the occipital cortex by visual stimuli showed spatial congruence with fMRI signals and temporal correspondence with VEPs, thus combining subcentimeter spatial localization with subsecond temporal resolution. fMRI signals were recorded from striate and extrastriate cortex. Both areas showed EROS peaks, but at different latencies after stimulation (100 and 200-300 ms, respectively). These results suggest that EROS manifests localized neuronal activity associated with information processing. The temporal resolution and spatial localization of this signal make it a promising tool for studying the time course of activity in localized brain areas and for bridging the gap between electrical and hemodynamic imaging methods.

Objectives: Functional brain mapping and precise localization are essential for the resection of centrally located tumors. We describe our initial experience with awake craniotomy for sensorimotor tumors in 15 patients using synthesized surface anatomy scanning (SSAS), intraoperative functional brain mapping, and an infrared-based navigation system (INS) without fixation of the patient’s head. Methods: Craniotomy positioning was planned using the images created by SSAS. Fiducial markers were placed along the skin incision line for intraoperative registration of an INS. The resection of the tumor was performed under local anesthesia using both intraoperative functional brain mapping and an INS. In or near the motor cortex or the descending motor pathway, the extent of the resection was determined by the stimulation induced motor response and the intraoperative neurologic findings. Results: Appropriately centered craniotomies were obtained in all cases using the presurgical planning images of SSAS. Reliable functional localization was identified with direct cortical and subcortical stimulation. The location of the tumors was detected within 3.5 mm of that predicted by the computation (target registration error). Postoperative computed tomography scans showed grossly total resection of the tumor in 13 of 15 cases and subtotal resection in 2 cases. Although 10 patients had mild to severe neurologic deficits in the immediate postoperative period, there were no permanent deficits. Conclusions: Sensorimotor tumors can be resected effectively with the combined use of SSAS, stimulation cortical mapping and an INS with clinical acceptable morbidity.

Animal models of psychopathology are particularly useful for studying the neurobiology of depression and characterising the subtypes. Recently, our group was the first to identify a possible relationship between the LPA1 receptor and a mixed anxiety-depression phenotype. Specifically, maLPA1-null mice exhibited a phenotype characterised by depressive and anxious features. However, the constitutive lack of the gene encoding the LPA1 receptor (Lpar1) can induce compensatory mechanisms that might have resulted in the observed deficits. Therefore, in the present study, we have compared the impact of permanent loss and acute pharmacological inhibition of the LPA1 receptor on despair-like behaviours and on the functional brain map associated with these behaviours, as well as on the degree of functional connectivity among structures. Although the antagonist (intracerebroventricularly administered Ki16425) mimicked some, but not all, effects of genetic deletion of the LPA1 receptor on the results of behavioural tests and engaged different brain circuits, both treatments induced depression-like behaviours with an agitation component that was linked to functional changes in key brain regions involved in the stress response and emotional regulation. In addition, both Ki16425 treatment and LPA1 receptor deletion modified the functional brain maps in a way similar to the changes observed in depressed patients. In summary, the pharmacological and genetic approaches could ultimately assist in dissecting the function of the LPA1 receptor in emotional regulation and brain responses, and a combination of those approaches might provide researchers with an opportunity to develop useful drugs that target the LPA1 receptor as treatments for depression, mainly the anxious subtype. This article has an associated First Person interview with the first author of the paper.

Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson's disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4 weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [14C]-iodoantipyrine 1 week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate–putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function.

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

Highlights • We newly developed a stereotaxic recording system for awake marmosets. • Neuronal activities in the cerebral cortex and deep brain structures were recorded. • The system is well suited for functional brain mapping. • It also can be used for recording during task, two-photon imaging and optogenetics. Abstract The common marmoset has been proposed as a potential alternative to macaque monkey as a primate model for neuroscience and medical research. Here, we have newly developed a stereotaxic neuronal recording system for awake marmosets under the head-fixed condition by modifying that for macaque monkeys. Using this system, we recorded neuronal activity in the cerebral cortex of awake marmosets and successfully identified the primary motor cortex by intracortical microstimulation. Neuronal activities of deep brain structures, such as the basal ganglia, thalamus, and cerebellum, in awake marmosets were also successfully recorded referring to magnetic resonance images. Our system is suitable for functional mapping of the brain, since the large recording chamber allows access to arbitrary regions over almost the entire brain, and the recording electrode can be easily moved stereotaxically from one site to another. In addition, our system is desirable for neuronal recording during task performance to assess motor skills and cognitive function, as the marmoset sits in the marmoset chair and can freely use its hands. Moreover, our system can be used in combination with cutting-edge techniques, such as two-photon imaging and optogenetic manipulation. This recording system will contribute to boosting neuroscience and medical research using marmosets. [ABSTRACT FROM AUTHOR]

Highlights • The present study investigated the threshold and distribution of afterdischarges (ADs). • The thresholds of ADs induction were not affected by lobar differences and epileptogenicity. • The stimulation of premotor areas appeared to induce ADs in remote cortices. Abstract Objective The present study aimed to investigate the threshold and distribution of afterdischarges (ADs) with cortical electrical stimulation for functional brain mapping. Method We retrospectively analyzed data from 11 patients with medically intractable epilepsy who underwent 50-Hz cortical electrical stimulation for functional mapping followed by resection. These patients became seizure free for more than six months. The threshold and distribution of ADs induced by the stimulation were evaluated. Results The median threshold was 6 mA (range: 2–15 mA) for the frontal lobe, 8 mA (3–15 mA) for the temporal lobe, 6 mA (2–15 mA) for the parietal lobe, and 6 mA (4–12 mA) for the occipital lobe. No significant interlobar differences were observed in AD thresholds. No significant differences were noted between within and outside epileptogenic zones. The distribution of ADs, remote spread was observed in all patients, reflecting fronto-parieto-temporal connections, as well as contiguous spread. The stimulation of premotor areas, the inferior parietal lobule, supplementary motor area, and basal temporal areas appeared to induce ADs in remote cortices. Conclusion While no locational differences were observed in AD thresholds, each brain region showed a characteristic pattern for AD spread. Remote AD spread needs to be considered for safe functional mapping. [ABSTRACT FROM AUTHOR]

Objective This meta-analysis compared diagnostic validity of electrocorticographic (ECoG) high-γ modulation (HGM) with electrical stimulation mapping (ESM) for presurgical language localization. Methods From a structured literature search, studies with electrode level data comparing ECoG HGM and ESM for language localization were included in the meta-analysis. Outcomes included global measures of diagnostic validity: area under the summary receiver operating characteristic (SROC) curve (AUC), and diagnostic odds ratio (DOR); as well as pooled estimates of sensitivity and specificity. Clinical and technical determinants of sensitivity/specificity were explored. Results Fifteen studies were included in qualitative synthesis, and 10 studies included in the meta-analysis (number of patients 1–17, mean age 10.3–53.6 years). Overt picture naming was the most commonly used task for language mapping with either method. Electrocorticographic high-γ modulation was analyzed at 50–400 Hz with different bandwidths in individual studies. For ESM, pulse duration, train duration, and maximum current varied greatly among studies. Sensitivity (0.23–0.99), specificity (0.48–0.96), and DOR (1.45–376.28) varied widely across studies. The pooled estimates are: sensitivity 0.61 (95% CI 0.44, 0.76), specificity 0.79 (95% CI 0.68, 0.88), and DOR 6.44 (95% CI 3.47, 11.94). Area under the SROC curve was 0.77. Results of bivariate meta-regression were limited by small samples for individual variables. Conclusion Electrocorticographic high-γ modulation is a specific but not sensitive method for language localization compared with gold-standard ESM. Given the pooled DOR of 6.44 and AUC of 0.77, ECoG HGM can fairly reliably ascertain electrodes overlying ESM cortical language sites. [ABSTRACT FROM AUTHOR]

Purpose We studied the effect of fosphenytoin (FOS) pre-medication on the incidence and thresholds of after-discharges (ADs), seizures, and functional responses during electrical stimulation mapping (ESM). Methods As individualized by the attending epileptologist, FOS was given intravenously at 2 mg-phenytoin-equivalents (PE)/kg/min or 150 mg-PE/min (whichever slower). Patients who received and did not receive FOS were compared for the incidence and thresholds of ADs, seizures, and functional responses. Results Before ESM, 40 and 82 patients respectively were pre-medicated/not pre-medicated with FOS. The incidence of ESM-induced seizures was significantly lower in FOS pre-medicated patients (22.5% vs. 42.7%, p = 0.044), whereas temporal language threshold was higher (9.2 vs. 6.5 mA, p = 0.032). FOS was more efficacious in preventing ESM-induced seizures in patients with symptomatogenic zone ipsilateral to the side of ESM. Although FOS dose had no significant effect on minimum language, minimum motor, or AD thresholds; seizure and temporal language thresholds showed trends approaching significance, intersecting at 12.2 mg-PE/kg. The incidence of ESM-induced seizures was significantly lower in those who received FOS at a dose of ≤12 mg/kg (9.1%) compared to those who did not receive any FOS (42.7%, p = 0.046), while the temporal language thresholds were not significantly different (6.3 vs. 6.5 mA, p = 0.897). Conclusions This study provides class III evidence that FOS pre-medication before ESM decreases the incidence of ESM-induced seizures, but increases temporal language threshold. FOS pre-medication may thus be considered before ESM. Future studies should prospectively verify these observations and characterize dose-response relationships. [ABSTRACT FROM AUTHOR]

Blood oxygen level-dependent ( BOLD) functional magnetic resonance imaging ( fMRI) studies of patients with cerebrovascular disease have largely ignored the confounds associated with abnormal cerebral blood flow, vascular reactivity and neurovascular coupling. We studied BOLD fMRI activation and cerebrovascular reactivity in moyamoya disease. To characterize the impact of remote vascular demands on BOLD fMRI measurements, we varied the vascular territories engaged by manipulating the experimental task performed by the participants. Vascular territories affected by disease were identified using BOLD cerebrovascular reactivity. Preliminary evidence from two patients pre- and postrevascularization surgery and four controls indicates that neurovascular coupling in affected brain regions can be modulated by the task-related vascular demands in unaffected regions. In one patient studied, we observed that brain regions with improved cerebrovascular reactivity after surgery demonstrated normalized neurovascular coupling, that is the degree to which neurovascular coupling was modulated by task-related vascular demands was decreased. We propose that variations in task-dependent neurovascular coupling in patients with moyamoya disease are likely related to vascular steal. While preliminary, our findings are a proof of concept of the limitations of BOLD fMRI in cerebrovascular disease and suggest a role for assessment of cerebrovascular reactivity to improve interpretation of task-related BOLD fMRI activation. [ABSTRACT FROM AUTHOR]