MRI-Compatible and Conformal Electrocorticography Grids for Translational Research.

Intraoperative electrocorticography (ECoG) captures neural information from the surface of the cerebral cortex during surgeries such as resections for intractable epilepsy and tumors. Current clinical ECoG grids come in evenly spaced, millimeter-sized electrodes embedded in silicone rubber. Their mechanical rigidity and fixed electrode spatial resolution are common shortcomings reported by the surgical teams. Here, advances in soft neurotechnology are leveraged to manufacture conformable subdural, thin-film ECoG grids, and evaluate their suitability for translational research. Soft grids with 0.2 to 10 mm electrode pitch and diameter are embedded in 150 µm silicone membranes. The soft grids are compatible with surgical handling and can be folded to safely interface hidden cerebral surface such as the Sylvian fold in human cadaveric models. It is found that the thin-film conductor grids do not generate diagnostic-impeding imaging artefacts (<1 mm) nor adverse local heating within a standard 3T clinical magnetic resonance imaging scanner. Next, the ability of the soft grids to record subdural neural activity in minipigs acutely and two weeks postimplantation is validated. Taken together, these results suggest a promising future alternative to current stiff electrodes and may enable the future adoption of soft ECoG grids in translational research and ultimately in clinical settings.

Cortical Encoding of Manual Articulatory and Linguistic Features in American Sign Language.

The fluent production of a signed language requires exquisite coordination of sensory, motor, and cognitive processes. Similar to speech production, language produced with the hands by fluent signers appears effortless but reflects the precise coordination of both large-scale and local cortical networks. The organization and representational structure of sensorimotor features underlying sign language phonology in these networks remains unknown. Here, we present a unique case study of high-density electrocorticography (ECoG) recordings from the cortical surface of profoundly deaf signer during awake craniotomy. While neural activity was recorded from sensorimotor cortex, the participant produced a large variety of movements in linguistic and transitional movement contexts. We found that at both single electrode and neural population levels, high-gamma activity reflected tuning for particular hand, arm, and face movements, which were organized along dimensions that are relevant for phonology in sign language. Decoding of manual articulatory features revealed a clear functional organization and population dynamics for these highly practiced movements. Furthermore, neural activity clearly differentiated linguistic and transitional movements, demonstrating encoding of language-relevant articulatory features. These results provide a novel and unique view of the fine-scale dynamics of complex and meaningful sensorimotor actions.

Measuring the electrophysiological effects of direct electrical stimulation after awake brain surgery.

OBJECTIVE: Direct electrical stimulation (DES) at 60 Hz is used to perform real-time functional mapping of the brain, and guide tumour resection during awake neurosurgery. Nonetheless, the electrophysiological effects of DES remain largely unknown, both locally and remotely. APPROACH: In this study, we lowered the DES frequency to 1-10 Hz and we used a differential recording mode of electro-corticographic (ECoG) signals to improve the focality with a simple algorithm to remove the artefacts due to the response of the acquisition chain. MAIN RESULTS: Doing so, we were able to observe different components in the evoked potentials triggered by simulating the cortex or the subcortical white matter pathways near the recording electrodes and by stimulating the cortex remotely from the recording site. More particularly, P0 and N1 components were repeatedly observed on raw ECoG signals without the need to average the data. SIGNIFICANCE: This new methodology is important to probe the electrophysiological states and the connectivity of the brain in vivo and in real time, namely to perform electrophysiological brain mapping on human patients operated in the neurosurgical room and to better understand the electrophysiological spreading of DES.

Electrophysiologic mapping for deep brain stimulation for movement disorders.

Electrophysiologic mapping remains an integral component of deep brain stimulation (DBS) surgical procedures, particularly in movement disorder cases where functional maps are used to guide DBS lead placement in patients with Parkinson's disease, dystonia, or tremor. Overall, the goal of the surgical procedure is to implant the distal end of a chronic, multicontact depth electrode into a specific brain region for the purpose of delivering therapeutic electrical stimulation. Regions that are currently targeted for patients with movement disorders include the subthalamic nucleus, the ventral intermediate nucleus of the thalamus, and the globus pallidus. Multiple imaging modalities are used initially to derive a stereotactic plan and guide the initial microelectrode trajectory. Changes in neuronal firing rate and pattern, both spontaneous and in response to somatosensory stimulation, are used to establish the location of the tip of the microelectrode(s), while acute stimulation can be used to estimate the proximity of neighboring brain regions. In this chapter, we will provide an overview of the microelectrode recording process as it is commonly applied to refine image-based targeting of lead placement for DBS surgery.

Quantitative Evaluation of Efficacy of Intraoperative Examination Monitor for Awake Surgery.

BACKGROUND: When brain tumors are located near the language area, a test to assess language function is required. During the test, it is practical to display combined information obtained from all the equipment so that the surgeon can confirm the patient's response to the tasks. We developed the intraoperative examination monitor for awake surgery (IEMAS) mainly to combine all information so that the language function test could be performed efficiently. The IEMAS has proved to be useful in clinical settings; however, no quantitative evaluation has been performed. This study aimed to demonstrate the clinical usefulness of the IEMAS through comparison of cases with and without IEMAS use in language function test simulation. METHODS: The language function test simulator was created to eliminate any uncertain factors, such as symptoms, which vary among patients. Neurosurgeons participated in the test, and the usefulness of the IEMAS was investigated. We analyzed test duration and number of information exchanges between surgeon and examiner. RESULTS: Total test duration with IEMAS use was significantly shorter than without IEMAS use (116.1 ± 23.1 seconds vs. 147.8 ± 48.7 seconds; P < 0.02). The number of information exchanges between surgeon and examiner was significantly lower with IEMAS use than without IEMAS use (0.2 ± 0.6 times vs. 16.1 ± 15.6 times; P < 0.02). CONCLUSIONS: We compared cases with and without IEMAS use. Total test duration decreased with IEMAS use, and number of information exchanges was reduced, thus demonstrating the usefulness of the IEMAS.

Brain Mesh: Technical Note.

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.

The Single Word Auditory Comprehension (SWAC) test: A simple method to identify receptive language areas with electrical stimulation.

OBJECTIVES: Resective surgery for medically refractory epilepsy in proximity to speech receptive areas requires balancing adequate resection of the epileptogenic zone for optimal seizure control with preservation of function. We develop a simple test (Single Word Auditory Comprehension or SWAC) to localize speech receptive areas by evaluating patients' ability to comprehend a single word. METHODS: Patients were studied during presurgical or intraoperative assessment for epilepsy with intracranial electrodes. They were asked to listen to a common word (target word) and to describe what it meant without saying the target word. Electrical stimulation (trains of biphasic 2-ms pulses, 50 Hz for 3 s) was delivered while the patient listened to the target word, not while the patient explained the meaning of the word. In six patients, SWAC test was carried out during extraoperative chronic recordings, and in one patient in the operating theater under local anesthesia. RESULTS: Among the 7 patients where the test identified deficits, 6 underwent resection (4 temporal, 1 supramarginal, and 1 occipital). Two patients showed temporary minor speech deficits after resection. No patient showed permanent speech deficits after resection. CONCLUSION/SIGNIFICANCE: The SWAC test is reliable, simple and fast to implement, and suitable for intraoperating mapping. It could be used as a simple initial test to identify receptive language areas where more complex additional tests can be performed.

Dense array EEG estimated the epileptic focus in a patient with epilepsy secondary to tuberous sclerosis complex.

PURPOSE: Tuberous sclerosis complex (TSC) is a leading cause of epilepsy, with seizures affecting almost 80-90% of children. We used the concordance between magnetic resonance imaging (MRI) and dense array electroencephalography (dEEG) findings to detect epileptic focus in a patient with TSC. METHODS: A 9-year-old boy with TSC exhibited daily choking spells. As we could not detect the seizure onset area with conventional scalp electroencephalogram (EEG) and long-term video monitoring, we performed dEEG and captured his regular seizures. RESULTS: dEEG estimated that the clinical seizure activities from the right frontal region. This patient underwent focus removal, tuberectomy of the right frontal lobe, and removal of a subependymal giant cell astrocytoma. He has been seizure free for 7 years and 10 months. CONCLUSION: dEEG was useful for estimation of the placement of intracranial electrodes in a patient with TSC. This method may be useful for pre-surgical evaluation of epilepsy treatment.

Pre-Surgical Planning: Multimodality Imaging to Optimize Outcomes in Pediatric Epilepsy Surgery.

Neuroimaging is an important component of the pre-surgical planning for pediatric epilepsy. High-resolution structural magnetic resonance images are combined with advanced structural and functional imaging techniques to better define the surgical lesion and decrease morbidity postoperatively. The combination of neuroimaging, electroencephalography (EEG), and neuropsychiatric testing in a multidisciplinary epilepsy conference setting is essential for determining a plan for surgical management.

Safety and efficacy of stereoelectroencephalography in pediatric focal epilepsy: a single-center experience.

OBJECTIVE: Patients with medically refractory localization-related epilepsy (LRE) may be candidates for surgical intervention if the seizure onset zone (SOZ) can be well localized. Stereoelectroencephalography (SEEG) offers an attractive alternative to subdural grid and strip electrode implantation for seizure lateralization and localization; yet there are few series reporting the safety and efficacy of SEEG in pediatric patients. METHODS: The authors review their initial 3-year consecutive experience with SEEG in pediatric patients with LRE. SEEG coverage, SOZ localization, complications, and preliminary seizure outcomes following subsequent surgical treatments are assessed. RESULTS: Twenty-five pediatric patients underwent 30 SEEG implantations, with a total of 342 electrodes placed. Ten had prior resections or ablations. Seven had no MRI abnormalities, and 8 had multiple lesions on MRI. Based on preimplantation hypotheses, 7 investigations were extratemporal (ET), 1 was only temporal-limbic (TL), and 22 were combined ET/TL investigations. Fourteen patients underwent bilateral investigations. On average, patients were monitored for 8 days postimplant (range 3-19 days). Nearly all patients were discharged home on the day following electrode explantation. There were no major complications. Minor complications included 1 electrode deflection into the subdural space, resulting in a minor asymptomatic extraaxial hemorrhage; and 1 in-house and 1 delayed electrode superficial scalp infection, both treated with local wound care and oral antibiotics. SEEG localized the hypothetical SOZ in 23 of 25 patients (92%). To date, 18 patients have undergone definitive surgical intervention. In 2 patients, SEEG localized the SOZ near eloquent cortex and subdural grids were used to further delineate the seizure focus relative to mapped motor function just prior to resection. At last follow-up (average 21 months), 8 of 15 patients with at least 6 months of follow-up (53%) were Engel class I, and an additional 6 patients (40%) were Engel class II or III. Only 1 patient was Engel class IV. CONCLUSIONS: SEEG is a safe and effective technique for invasive SOZ localization in medically refractory LRE in the pediatric population. SEEG permits bilateral and multilobar investigations while avoiding large craniotomies. It is conducive to deep, 3D, and perilesional investigations, particularly in cases of prior resections. Patients who are not found to have focally localizable seizures are spared craniotomies.

A Computerized Microelectrode Recording to Magnetic Resonance Imaging Mapping System for Subthalamic Nucleus Deep Brain Stimulation Surgery.

BACKGROUND: Accurate electrode placement is critical to the success of deep brain stimulation (DBS) surgery. Suboptimal targeting may arise from poor initial target localization, frame-based targeting error, or intraoperative brain shift. These uncertainties can make DBS surgery challenging. OBJECTIVE: To develop a computerized system to guide subthalamic nucleus (STN) DBS electrode localization and to estimate the trajectory of intraoperative microelectrode recording (MER) on magnetic resonance (MR) images algorithmically during DBS surgery. METHODS: Our method is based upon the relationship between the high-frequency band (HFB; 500-2000 Hz) signal from MER and voxel intensity on MR images. The HFB profile along an MER trajectory recorded during surgery is compared to voxel intensity profiles along many potential trajectories in the region of the surgically planned trajectory. From these comparisons of HFB recordings and potential trajectories, an estimate of the MER trajectory is calculated. This calculated trajectory is then compared to actual trajectory, as estimated by postoperative high-resolution computed tomography. RESULTS: We compared 20 planned, calculated, and actual trajectories in 13 patients who underwent STN DBS surgery. Targeting errors for our calculated trajectories (2.33 mm ± 0.2 mm) were significantly less than errors for surgically planned trajectories (2.83 mm ± 0.2 mm; P = .01), improving targeting prediction in 70% of individual cases (14/20). Moreover, in 4 of 4 initial MER trajectories that missed the STN, our method correctly indicated the required direction of targeting adjustment for the DBS lead to intersect the STN. CONCLUSION: A computer-based algorithm simultaneously utilizing MER and MR information potentially eases electrode localization during STN DBS surgery.

Challenges and techniques for presurgical brain mapping with functional MRI.

Functional magnetic resonance imaging (fMRI) is increasingly used for preoperative counseling and planning, and intraoperative guidance for tumor resection in the eloquent cortex. Although there have been improvements in image resolution and artifact correction, there are still limitations of this modality. In this review, we discuss clinical fMRI's applications, limitations and potential solutions. These limitations depend on the following parameters: foundations of fMRI, physiologic effects of the disease, distinctions between clinical and research fMRI, and the design of the fMRI study. We also compare fMRI to other brain mapping modalities which should be considered as alternatives or adjuncts when appropriate, and discuss intraoperative use and validation of fMRI. These concepts direct the clinical application of fMRI in neurosurgical patients.

Presurgical language mapping using event-related high-gamma activity: The Detroit procedure.

A number of investigators have reported that event-related augmentation of high-gamma activity at 70-110 Hz on electrocorticography (ECoG) can localize functionally-important brain regions in children and adults who undergo epilepsy surgery. The advantages of ECoG-based language mapping over the gold-standard stimulation include: (i) lack of stimulation-induced seizures, (ii) better sensitivity of localization of language areas in young children, and (iii) shorter patient participant time. Despite its potential utility, ECoG-based language mapping is far less commonly practiced than stimulation mapping. Here, we have provided video presentations to explain, point-by-point, our own hardware setting and time-frequency analysis procedures. We also have provided standardized auditory stimuli, in multiple languages, ready to be used for ECoG-based language mapping. Finally, we discussed the technical aspects of ECoG-based mapping, including its pitfalls, to facilitate appropriate interpretation of the data.

An intraoperative motor tract positioning method in brain tumor surgery: technical note.

Intraoperative 3D recognition of the motor tract is indispensable to avoiding neural fiber injury in brain tumor surgery. However, precise localization of the tracts is sometimes difficult with conventional mapping methods. Thus, the authors developed a novel brain mapping method that enables the 3D recognition of the motor tract for intrinsic brain tumor surgeries. This technique was performed in 40 consecutive patients with gliomas adjacent to motor tracts that have a risk of intraoperative pyramidal tract damage. Motor tracts were electrically stimulated and identified by a handheld brain-mapping probe, the NY Tract Finder (NYTF). Sixteen-gauge plastic tubes were mounted onto the NYTF and inserted in the estimated direction of the motor tract with reference to navigational information. Only the NYTF was removed, leaving the plastic tubes in their places, immediately after muscle motor evoked potentials were recorded at the minimum stimulation current. Motor tracts were electrically identified in all cases. Three-dimensional information on the position of motor tracts was given by plastic tubes that were neurophysiologically placed. Tips of tubes showed the resection limit during tumor removal. Safe tumor resection with an arbitrary safety margin can be performed by adjusting the length of the plastic tubes. The motor tract positioning method enabled the 3D recognition of the motor tract by surgeons and provided for safe resection of tumors. Tumor resections were performed safely before damaging motor tracts, without any postoperative neurological deterioration.

Evaluation of Pleasure-Displeasure Induced by Use of Lipsticks with Near-Infrared Spectroscopy (NIRS): Usefulness of 2-Channel NIRS in Neuromarketing.

In order to examine whether near-infrared spectroscopy (NIRS) would be a useful neuromarketing tool, we employed NIRS to evaluate the difference of pleasure-displeasure in women, induced by the use of different types of lipsticks. The subjects used lipsticks A and B; A is softer than B. Concentration changes of oxy-Hb were measured in the bilateral prefrontal cortex (PFC) during use of lipsticks A and B. We evaluated the right and left dominancy of PFC activity by calculating the Laterality Index (LI) (LI = leftΔoxy-Hb - rightΔoxy-Hb); positive LI indicates left-dominant activity while negative LI indicate right-dominant activity. We found a significant interaction between the use of lipsticks A and B, using a two-way factorial analysis of variance [F(1,13) = 9.63, p < 0.01]; Δoxy-Hb in the left PFC was larger than that in the right PFC during the use of lipstick A, while Δoxy-Hb in the right PFC tended to be larger than that in the left PFC during the use of lipstick B (p < 0.1). The LI of lipstick A was larger than that of lipstick B (paired T-test, p = 0.0083). We suggest that lipstick A caused a more positive emotional response than lipstick B, since greater left than right frontal cortical activity is associated with positive affect. These results suggest that 2-channel NIRS may be a useful neuromarketing tool, since it allows objective assessment of pleasure-unpleasure.

Insula and somatosensory cortical myelination and iron markers underlie individual differences in empathy.

Empathy is a key component of our ability to engage and interact with others. In recent years, the neural mechanisms underlying affective and cognitive empathy have garnered intense interest. This work demonstrates that empathy for others depends upon a distributed network of regions such as the insula, parietal cortex, and somatosensory areas, which are also activated when we ourselves experience an empathized-with emotion (e.g., pain). Individuals vary markedly in their ability to empathize with others, which predicts the tendency to help others and relates to individual differences in the neuroanatomy of these areas. Here, we use a newly developed, high-resolution (800 µm isotropic), quantitative MRI technique to better elucidate the neuroanatomical underpinnings of individual differences in empathy. Our findings extend previous studies of the neuroanatomical correlates of cognitive and affective empathy. In particular, individual differences in cognitive empathy were associated with markers of myeloarchitectural integrity of the insular cortex, while affective empathy was predicted by a marker of iron content in second somatosensory cortex. These results indicate potential novel biomarkers of trait empathy, suggesting that microstructural features of an empathy and body-related network are crucial for understanding the mental and emotional states of others.

Optical Neuronavigation without Rigid Head Fixation During Awake Surgery.

OBJECTIVE: Optical neuronavigation without rigid pin fixation of the head may lead to inaccurate results because of the patient's movements during awake surgery. In this study, we report our results using a skull-mounted reference array for optical tracking in patients undergoing awake craniotomy for eloquent gliomas. METHODS: Between March 2013 and December 2014, 18 consecutive patients (10 men, 8 women) with frontotemporal (n = 16) or frontoparietal (perirolandic; n = 2) lesions underwent awake craniotomy without rigid pin fixation. All patients had a skull-mounted reference array for optical tracking placed on the forehead. Accuracy of navigation was determined with pointer tip deviation measurements on superficial and bony anatomic structures. Good accuracy was defined as a tip deviation <2 mm. RESULTS: Gross total resection (>98%) was achieved in 7 patients (38%); >90% of tumor was resected in 8 patients (44%). In 3 patients, only subtotal resection or biopsy was performed secondary to stimulation results. In all patients, good accuracy of the optical neuronavigation system could be demonstrated without intraoperative peculiarities or complications. The reference array had to be repositioned because of loosening in 1 patient. Neuronavigation could be reliably applied to support stimulation-based resection. CONCLUSIONS: A skull-mounted reference array is a simple and safe method for optical neuronavigation tracking without rigid pin fixation of the patient's head.

Classification and Prediction of Clinical Improvement in Deep Brain Stimulation From Intraoperative Microelectrode Recordings.

We present a random forest (RF) classification and regression technique to predict, intraoperatively, the unified Parkinson's disease rating scale (UPDRS) improvement after deep brain stimulation (DBS). We hypothesized that a data-informed combination of features extracted from intraoperative microelectrode recordings (MERs) can predict the motor improvement of Parkinson's disease patients undergoing DBS surgery. We modified the employed RFs to account for unbalanced datasets and multiple observations per patient, and showed, for the first time, that only five neurophysiologically interpretable MER signal features are sufficient for predicting UPDRS improvement. This finding suggests that subthalamic nucleus (STN) electrophysiological signal characteristics are strongly correlated to the extent of motor behavior improvement observed in STN-DBS.

Registering imaged ECoG electrodes to human cortex: A geometry-based technique.

BACKGROUND: The accurate localization of implanted ECoG electrodes over the brain is of critical importance to invasive diagnostic work-up for the surgical treatment of intractable epileptic seizures. The implantation of subdural electrodes is an invasive procedure which typically introduces non-uniform deformations of a subject's brain, increasing the difficulty of determining the precise location of the electrodes vis-à-vis cortex. Formalization of this problem is used to define a novel solution for the optimal localization of subdural electrodes. NEW METHOD: We demonstrate that nonlinear transformation is required to accurately register the implanted electrodes to the non-deformed pre-surgical cortical surface, and that this problem is accommodated by utilizing known features of electrode geometry. Techniques to register chronically implanted subdural electrodes to the undistorted brain image are described and evaluated using simulated and clinical data. RESULTS: Principal Axis, our novel analysis method that estimates an electrode's orientation by the moment of inertia of the solid electrode volume, proved to be the most reliable measure in both the simulated and clinical datasets. COMPARISON WITH EXISTING METHODS: This method of electrode translation along its principal axis is an improvement over other techniques, such as the limited view provided by intraoperative photography, and the image degradation inherent in post-operative MRI. CONCLUSIONS: This technique compensates for alterations due to post-operative brain edema, and translates subdural electrodes to their original location on pre-operative MRI 3D models. This is helpful in the correct localization of seizure foci and functional mapping of epilepsy patients.

Evaluation of a pre-surgical functional MRI workflow: From data acquisition to reporting.

PURPOSE: Present and assess clinical protocols and associated automated workflow for pre-surgical functional magnetic resonance imaging in brain tumor patients. METHODS: Protocols were validated using a single-subject reliability approach based on 10 healthy control subjects. Results from the automated workflow were evaluated in 9 patients with brain tumors, comparing fMRI results to direct electrical stimulation (DES) of the cortex. RESULTS: Using a new approach to compute single-subject fMRI reliability in controls, we show that not all tasks are suitable in the clinical context, even if they show meaningful results at the group level. Comparison of the fMRI results from patients to DES showed good correspondence between techniques (odds ratio 36). CONCLUSION: Providing that validated and reliable fMRI protocols are used, fMRI can accurately delineate eloquent areas, thus providing an aid to medical decision regarding brain tumor surgery.