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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.

Objective: We investigated the role of transverse temporal gyrus and adjacent cortex (TTG+) in facial expressions and perioral movements., Methods: 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., Results: 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., Conclusions: Multimodal data suggests that TTG+ may participate in auditory-motor integration., Significance: TTG+ likely participates in facial expressions in response to emotional cues during an auditory discourse., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: 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., Methods: 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., Results: 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., Conclusions: Optimizing visuospatial working memory through practice is tied to early pIFG activation and decreased dependence on irrelevant neural pathways., Significance: This study expands our knowledge of human adaptation for visuospatial working memory, showing the spatiotemporal dynamics of cortical network modulations through white matter tracts., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

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.

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.

Objective: This systematic review and meta-analysis evaluated the diagnostic validity of functional magnetic resonance imaging (fMRI) compared to electrical stimulation mapping (ESM) for pre-surgical language mapping., Methods: A structured literature search was performed and studies with electrode-level data comparing fMRI and ESM for language localization were analyzed. Outcome measures included pooled estimates of diagnostic odds ratio (DOR), sensitivity, and specificity. Sources of heterogeneity were explored with a meta-regression framework., Results: Nine studies were included in the analysis having 5-40 patients with mean age 11.3-43.4 years. Verb generation and picture naming were the most common fMRI tasks, while picture naming was the most common ESM task. Sensitivity (0.37-0.95), specificity (0.36-0.97), and DOR (1.9-44.6) for fMRI compared to ESM varied widely across studies with statistically significant heterogeneities. Pooled estimates were: sensitivity 0.71 (95% confidence interval 0.54, 0.83), specificity 0.74 (0.58, 0.85), and DOR 7.0 (3.5, 13.8), from a valid meta-analysis (area under the summary receiver-operating-curve 0.78). fMRI was noted to have higher sensitivity in studies using higher maximal ESM currents. fMRI variables could not be included in the meta-regression because of substantial methodological differences among studies., Conclusions: fMRI is moderately sensitive and moderately specific for language localization compared to ESM in well-designed studies. However, because the confidence limits for sensitivity and DOR are close to the line of no effect, and there is high unmeasured heterogeneity, fMRI cannot perhaps be used as the only modality for language localization to inform neurosurgical decisions at present., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Cerebral spatiotemporal dynamics of visual naming were investigated in epilepsy patients undergoing stereo-electroencephalography (SEEG) monitoring., Methods: 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., Results: 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., Conclusions: 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., Significance: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: To visualize and validate the dynamics of interhemispheric neural propagations induced by single-pulse electrical stimulation (SPES)., Methods: 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., Results: 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., Conclusions: Our four-dimensional tractography successfully animated neural propagations via distinct interhemispheric pathways., Significance: Our novel animation method has the potential to help investigators in addressing the mechanistic significance of the interhemispheric network dynamics supporting physiological function., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: 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., Methods: 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., Results: 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., Conclusions: 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., Significance: This study helps to establish the practical guidelines on the diagnostic use of CCEPs/CCSRs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: 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., Methods: 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., Results: 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., Conclusions: We provide evidence for diagnostic validity and safety of stereo-EEG sensorimotor ESM., Significance: The somatotopy of sensorimotor responses elicited with electrical stimulation provide new insights into mechanisms of motor control and sensory perception., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

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 18 F-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., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To characterize the spatiotemporal dynamics of auditory and picture naming-related cortical activation in Japanese-speaking patients., Methods: 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., Results: 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., Conclusions: 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., Significance: 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., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: Our case illustrates that the proposed invention can be successfully used in neurosurgical operations for precise electrostimulation mapping of the brain cortex., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To examine current thresholds and their determinants for language and motor mapping with extra-operative electrical cortical stimulation (ECS)., Methods: ECS electrocorticograph recordings were reviewed to determine functional thresholds. Predictors of functional thresholds were found with multivariable analyses., Results: In 122 patients (age 11.9±5.4years), average minimum, frontal, and temporal language thresholds were 7.4 (± 3.0), 7.8 (± 3.0), and 7.4 (± 3.1) mA respectively. Average minimum, face, upper and lower extremity motor thresholds were 5.4 (± 2.8), 6.1 (± 2.8), 4.9 (± 2.3), and 5.3 (± 3.3) mA respectively. Functional and after-discharge (AD)/seizure thresholds were significantly related. Minimum, frontal, and temporal language thresholds were higher than AD thresholds at all ages. Minimum motor threshold was higher than minimum AD threshold up to 8.0years of age, face motor threshold was higher than frontal AD threshold up to 11.8years age, and lower subsequently. UE motor thresholds remained below frontal AD thresholds throughout the age range., Conclusions: Functional thresholds are frequently above AD thresholds in younger children., Significance: These findings raise concerns about safety and neurophysiologic validity of ECS mapping. Functional and AD/seizure thresholds relationships suggest individual differences in cortical excitability which cannot be explained by clinical variables., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: This study examined the incidence, thresholds, and determinants of electrical cortical stimulation (ECS)-induced after-discharges (ADs) and seizures., Methods: Electrocorticograph recordings were reviewed to determine incidence of ECS-induced ADs and seizures. Multivariable analyses for predictors of AD/seizure occurrence and their thresholds were performed., Results: In 122 patients, the incidence of ADs and seizures was 77% (94/122) and 35% (43/122) respectively. Males (odds ratio [OR] 2.92, 95% CI 1.21-7.38, p=0.02) and MRI-negative patients (OR 3.69, 95% CI 1.24-13.7, p=0.03) were found to have higher odds of ECS-induced ADs. A significant trend for decreasing AD thresholds with age was seen (regression co-efficient -0.151, 95% CI -0.267 to -0.035, p=0.011). ECS-induced seizures were more likely in patients with lateralized functional imaging (OR 6.62, 95% CI 1.36-55.56, p=0.036, for positron emission tomography) and presence of ADs (OR 3.50, 95% CI 1.12-13.36, p=0.043)., Conclusions: ECS is associated with a high incidence of ADs and seizures. With age, current thresholds decrease and the probability for AD/seizure occurrence increases., Significance: ADs and seizures during ECS brain mapping are potentially hazardous and affect its functional validity. Thus, safer method(s) for brain mapping with improved neurophysiologic validity are desirable., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Intra-stimulation discharges (IDs) can occur during language mapping, are largely unrecognized, and may precede the occurrence of after-discharges (ADs) and seizures. This study aimed to identify predictors of ID occurrence and determine whether IDs increase the probability of triggered ADs., Methods: A total of 332 stimulation events performed during language mapping were analyzed in 3 patients who underwent intracranial EEG recordings during evaluations for epilepsy surgery. IDs were identified in 76 stimulation events. The relationships between IDs and the stimulus current intensity, stimulation duration, and proximity to regions of abnormal cortical excitability [characterized by the presence of baseline epileptiform discharges (BEDs)] were determined using regression analysis., Results: The presence of BEDs in close proximity to stimulation, an increase in stimulus intensity by 1 mA, and an increase in stimulation duration by 1s independently increased the odds of triggering IDs by 7.40, 1.37, and 1.39 times, respectively. All IDs were triggered during stimulations in the temporal lobe. The occurrence of IDs increased the odds of triggering ADs 5-fold., Conclusions: Longer stimulations, higher currents, and the presence of BEDs at the stimulation site increase the probability of ID occurrence, which in turn increases the probability of triggering ADs., Significance: Attention to IDs may improve the safety and precision of neurophysiologic mapping., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: We investigated intracranially-recorded gamma activity during calculation tasks to better understand the cortical dynamics of calculation., Methods: We studied 11 patients with focal epilepsy (age range: 9-28years) who underwent measurement of calculation- and naming-related gamma-augmentation during extraoperative electrocorticography (ECoG). The patients were instructed to overtly verbalize a one-word answer in response to auditorily-delivered calculation and naming questions. The assigned calculation tasks were addition and subtraction involving integers between 1 and 17., Results: Out of the 1001 analyzed cortical electrode sites, 63 showed gamma-augmentation at 50-120Hz elicited by both tasks, 88 specifically during naming, and 7 specifically during calculation. Common gamma-augmentation mainly took place in the Rolandic regions. Calculation-specific gamma-augmentation, involving the period between the question-offset and response-onset, was noted in the middle-temporal, inferior-parietal, inferior post-central, middle-frontal, and premotor regions of the left hemisphere. Calculation-specific gamma-augmentation in the middle-temporal, inferior-parietal, and inferior post-central regions peaked around the question offset, while that in the frontal lobe peaked after the question offset and before the response onset. This study failed to detect a significant difference in calculation-specific gamma amplitude between easy trials and difficult ones requiring multi-digit operations., Conclusions: Auditorily-delivered stimuli can elicit calculation-specific gamma-augmentation in multiple regions of the left hemisphere including the parietal region. However, the additive diagnostic value of measurement of gamma-augmentation related to a simple calculation task appears modest., Significance: Further studies are warranted to determine the functional significance of calculation-specific gamma-augmentation in each site, and to establish the optimal protocol for mapping mental calculation., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Focality in electro-clinical or neuroimaging data often motivates epileptologists to consider epilepsy surgery in patients with medically-uncontrolled seizures, while not all focal findings are causally associated with the generation of epileptic seizures. With the help of Hill's criteria, we have discussed how to establish causality in the context of the presurgical evaluation of epilepsy. The strengths of EEG include the ability to determine the temporal relationship between cerebral activities and clinical events; thus, scalp video-EEG is necessary in the evaluation of the majority of surgical candidates. The presence of associated ictal discharges can confirm the epileptic nature of a particular spell and whether an observed neuroimaging abnormality is causally associated with the epileptic seizure. Conversely, one should be aware that scalp EEG has a limited spatial resolution and sometimes exhibits propagated epileptiform discharges more predominantly than in situ discharges generated at the seizure-onset zone. Intraoperative or extraoperative electrocorticography (ECoG) is utilized when noninvasive presurgical evaluation, including anatomical and functional neuroimaging, fails to determine the margin between the presumed epileptogenic zone and eloquent cortex. Retrospective as well as prospective studies have reported that complete resection of the seizure-onset zone on ECoG was associated with a better seizure outcome, but not all patients became seizure-free following such resective surgery. Some retrospective studies suggested that resection of sites showing high-frequency oscillations (HFOs) at >80Hz on interictal or ictal ECoG was associated with a better seizure outcome. Others reported that functionally-important areas may generate HFOs of a physiological nature during rest as well as sensorimotor and cognitive tasks. Resection of sites showing task-related augmentation of HFOs has been reported to indeed result in functional loss following surgery. Thus, some but not all sites showing interictal HFOs are causally associated with seizure generation. Furthermore, evidence suggests that some task-related HFOs can be transiently suppressed by the prior occurrence of interictal spikes. The significance of interictal HFOs should be assessed by taking into account the eloquent cortex, seizure-onset zone, and cortical lesions. Video-EEG and ECoG generally provide useful but still limited information to establish causality in presurgical evaluation. A comprehensive assessment of data derived from multiple modalities is ultimately required for successful management., (Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)