The authors have no acknowledgements.

Ethical statement: Our protocol follows the guidelines established by our institutional human research ethics committee.
1. Identification of Medically Refractory Epilepsy Patients
<ol>
	<li>Prior to invasive monitoring, evaluate allpatientswith noninvasive techniques, such as video-EEG monitoring, MRI, PET, ictalSPECT, and neuropsychological studies as described in 1 After discussion in multi-disciplinary meeting the decision whether or not to pursue invasive monitoring with SEEG must be made. 1,6,7,11,14</li>
	<li>Form a hypothesis regarding the location of the EZ. Develop a pre-implantation hypothesis of the presumed EZincorporating the ictal onset zone and regions of early (i.e., rapid) spread of epileptic (ictal) activity prior to intervention. 
	NOTE: This step can be done in conjunction with the multi-disciplinary meeting when the decision is made to pursue invasive montitoring. 
	NOTE: SEEG vs subdural grids-Based on the EZ hypothesis, decide between SEEG and subdural grid monitoring. Criteria to consider might include 1) possible deep seated EZ; 2) previous unsuccessful subdural grids monitoring; 3) indications for bilateral monitoring; 4) When non-lesional extra-temporal epilepsy is suspected. It should also be noted that additional benefit of SEEG over subdural grids includes SEEG&#39;s ability to record and stimulate critical subcortical areas when an eloquent region is hypothesized to be near the EZ.</li>
	<li>Develop an individually tailored implantation strategy based upon hypothesized EZ (Figure 1).1,7,8 
	NOTE: Adequate implantation strategy must evaluate 1) an anatomical lesion (if present); 2) structure(s) most likely to participate inictal onset; and/or 3) possible pathway(s) of seizure propagation within a functional network. In addition to anatomic considerations, logistical considerations must also be considered. For this reason, orthogonal trajectories are in general preferential in order to facilitate implantation and, later on, interpretation of the electrode positions.</li>
	<li>After developing an implantation strategy based upon the hypothesized EZ, create a plan using the robotic assistance. First, create a new encounter, by selecting &#34;new patient&#34;, then click on &#34;create trajectory&#34;, then select appropriate &#34;entry point&#34; and &#34;end point&#34; which correspond with the desired trajectory. 
	NOTE: Depending on the pre-implantation hypothesis, the number of electrodes is typically between eight and twelve. The trajectories and points of interest are typically planned using contrasted MRI or rotational angiography. These images which show not only the brain matter but the cerebral vessels allow for trajectory plans in avascular corridors to avoid vascular injury and hemorrhage.</li>
</ol>
2. Operative Procedure
<ol>
	<li>The day before surgery, obtain a contrasted, volumetric T1-weighted MRI sequence as described in by Kuzniecky et al.14 
	NOTE: This image is to be used for registration with robotic assistance and must have 1 mm slices. Then transfer the images to the stereotactic neuro-navigation software, where trajectories are planned based on previously discussed implantation strategies as described by Kuzniecky et al. 14</li>
	<li>Once in the operating room, place the patient on the surgical table in the supine position. Then obtain general anesthesia with endotracheal intubation as per anesthesiologists&#39; protocol. 
	NOTE: It is imperative that they are under general intravenous anesthesia and complete pharmacologic paralysis. Then shave the patients head, prep the skin with an antibiotic surgical application and then place the patient&#39;s head in a head neurosurgical head holder. General anesthesia differs from patient to patient.</li>
	<li>After completing the positioning attach the robotic system to the frame and complete registration. On the robotic assistance device select &#34;register&#34; and follow the prompts to complete the registration process. Complete registration using surface landmark registration based on facial features or implanted fiducial markers.</li>
	<li>Insertion (Figure 2)
	<ol>
		<li>Use a 2.5-mm drill bit to drill the skull with guidance assistance from the robotic stereotactic system. Insert the monopolar coagulator probe to open the dura mater. Screw the implantation bolt into the skull, also guided by the robotic stereotactic system.</li>
		<li>Calculate the final depth distance for the electrode (D3) using the following measurements: [(Target-Dura Distance) + (D1 - D2) = D3]. Measure the target-dura distance using the navigation system. 
		NOTE: D1 is measured as the the length of the guidance system to the dura, D2 is measured as the length of the guidance system to the end of the bolt. The D1 - D2 difference is the length of the bolt. The sum of the length of the bolt and the target-dura distance is the length of the electrode depth.</li>
		<li>Create the initial trajectory by inserting a stylette probe, guided by the implanted bolt. Then insert the electrode and secure it into the bolt. This prevents further displacement and cerebrospinal fluid (CSF) leaks.</li>
		<li>After placing and connecting all electrodes, place iodine solution soaked gauze around the bolt caps. And, then wrap the head.</li>
	</ol>
	</li>
</ol>
3. Monitoring/Recording
<ol>
	<li>Before finishing the case, connect the electrodes to the EEG recording machine to ensure proper functioning. The last step in the OR is intraoperative imaging (Figure 3). Perform Intraoperative x-rays or fluoroscopic imaging in the lateral and anterior-posterior skull. 
	NOTE: Obtain these to ensure appropriate trajectories of the electrodes. These images are not obtained to ensure stereotactic placement, rather they ensure the general correct trajectory and placement of the electrodes.</li>
	<li>After surgery, transfer the patients to the epilepsy monitoring unit Monitor the patient for seizure activity both clinically and electrographically via the SEEG electrode recording. 
	NOTE: Length of stay varies, depending on the number, quality, and ictal and interictal patterns of recordings. While monitored patients may have minor pain, treat this with acetaminophen. Typically, the length of stay is 7 days (range 3 - 28 days).</li>
	<li>Before removal of electrodes, discuss regarding the patient in a multi-disciplinary conference to review recordings and hypothesis.</li>
	<li>After recording sufficient ictal data (step 3.2) and the patient has been discussed in conference, restart the patients&#39; prior anti-epileptic medications while waiting OR for removal of electrodes.</li>
</ol>
4. Return to OR for Removal
<ol>
	<li>After recording sufficient ictal data, return the patient to the operating room for removal of the SEEG electrodes. Perform this under conscious sedation; typically 2 mg midazolam IV is sufficient.</li>
	<li>After anesthesia obtain sufficient sedation (typically with midazolam [defer dosing to anesthesiologist]), remove patients head wrap and cut the electrode wires. Monitor Patient&#39;s sedation clinically by the reported pain levels with electrode removal or suture insertion. Then prep the remaining bolt and tail of the electrode using iodinated gel.</li>
	<li>Individually, remove each bolt cap by twisting it off, followed by the electrode and lastly remove the bolt. Remove the electrodes by gently pulling them out along the axis of their insertion. Then remove the bolt by twisting it out, typically do this using fingers.</li>
	<li>Before moving on to the next electrode, close the defect left by the bolt with one stitch of nylon suture. Repeat these steps for each electrode. After removing all the electrodes, cover the stitch areas with antibiotic ointment and a loose head wrap.</li>
	<li>After removal, obtain further imaging either CT or A/P and lateral x-rays to ensure no residual hardware. 
	NOTE: Possible resection-If a surgical resection was believed to be of benefit to the patient&#39;s epilepsy then plan for a craniotomy and resection roughly 6 weeks after removal. This delay is due to infectious concerns of operating during the same hospitalization as the monitoring period.</li>
</ol>

<ol>
	<li>Serletis, D., Bulacio, J., Bingaman, W., Gonzalez-Martinez, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+stereotactic+approach+for+mapping+epileptic+networks:+a+prospective+study+of+200+patients.">The stereotactic approach for mapping epileptic networks: a prospective study of 200 patients.</a> J Neurosurg. 121, 1239-1246 (2014).</li><li>Bancaud, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Epilepsy+after+60+years+of+age.+Experience+in+a+functional+neurosurgical+department.">Epilepsy after 60 years of age. Experience in a functional neurosurgical department.</a> Sem Hop. 46, 3138-3140 (1970).</li><li>Bancaud, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+stereotaxic+exploration+(SEEG)+of+epilepsy.">Functional stereotaxic exploration (SEEG) of epilepsy.</a> Electroencephalogr Clin Neurophysiol. 28, 85-86 (1970).</li><li>Talairach, J., Bancaud, J., Bonis, A., Szikla, G., Trottier, S., Vignal, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Surgical+therapy+for+frontal+epilepsies.">Surgical therapy for frontal epilepsies.</a> Adv Neurol. 57, 707-732 (1992).</li><li>Vadera, S., Mullin, J., Bulacio, J., Najm, I., Bingaman, W., Gonzalez-Martinez, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereo+electroencephalography+following+subdural+grid+placement+for+difficult+to+localize+epilepsy.">Stereo electroencephalography following subdural grid placement for difficult to localize epilepsy.</a> Neurosurgery. 72, 723-729 (2013).</li><li>Munari, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereo-electroencephalography+methodology:+advantages+and+limits.">Stereo-electroencephalography methodology: advantages and limits.</a> Acta Neurol Scand Suppl. 152, 56-69 (1994).</li><li>Gonzalez-Martinez, J., Bulacio, J., Alexopoulos, A., Jehi, L., Bingaman, W., Najm, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereoelectroencephalography+in+the+"difficult+to+localize"+refractory+focal+epilepsy+early+experience+from+a+North+American+epilepsy+center.">Stereoelectroencephalography in the "difficult to localize" refractory focal epilepsy early experience from a North American epilepsy center.</a> Epilepsia. 54, 323-330 (2013).</li><li>Gonzalez-Martinez, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereotactic+placement+of+depth+electrodes+in+medically+intractable+epilepsy.+Technicalnote.">Stereotactic placement of depth electrodes in medically intractable epilepsy. Technicalnote.</a> J Neurosurg. 120, 639-664 (2014).</li><li>Nathoo, N., Lu, M. C., Vogelbaum, M., Barnett, G. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+Touch+with+Robotics:+Neurosurgery+for+the+Future.">In Touch with Robotics: Neurosurgery for the Future.</a> Neurosurgery. 56, 421-433 (2005).</li><li>De Almeida, A. N., Olivier, A., Quesney, F., Dubeau, F., Savard, G., Andermann, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficacy+of+and+morbidity+associated+with+stereoelectroencephalography+using+computerized+tomography-or+magnetic+resonance+imaging-guided+electrode+implantation.">Efficacy of and morbidity associated with stereoelectroencephalography using computerized tomography-or magnetic resonance imaging-guided electrode implantation.</a> J Neurosurg. 104, 483-487 (2006).</li><li>Cossu, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereoelectroencephalography+in+the+presurgical+evaluation+of+focal+epilepsy+a+retrospective+analysis+of+215+procedures.">Stereoelectroencephalography in the presurgical evaluation of focal epilepsy a retrospective analysis of 215 procedures.</a> Neurosurgery. 57, 706-718 (2005).</li><li>Gonzalez-Martinez, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Robot-assisted+stereotactic+laser+ablation+in+medically+intractable+epilepsy:+operative+technique.">Robot-assisted stereotactic laser ablation in medically intractable epilepsy: operative technique.</a> Neurosurgery. 10, 167-172 (2014).</li><li>Guenot, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurophysiological+monitoring+for+epilepsy+surgery:+the+Talairach+SEEG+method.+Indications,+results,+complications+and+therapeutic+applications+in+a+series+of+100+consecutive+cases.">Neurophysiological monitoring for epilepsy surgery: the Talairach SEEG method. Indications, results, complications and therapeutic applications in a series of 100 consecutive cases.</a> Stereotact Funct Neurosurg. 77, 29-32 (2001).</li><li>Kuzniecky, R. I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multimodality+MRI+in+mesial+temporal+sclerosis:+relative+sensitivity+and+specificity.">Multimodality MRI in mesial temporal sclerosis: relative sensitivity and specificity.</a> Neurology. 49 (3), 774-778 (1997).</li><li>Cardinale, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereoelectroencephalography:+surgical+methodology,+safety,+and+stereotacticapplication+accuracy+in+500+procedures.">Stereoelectroencephalography: surgical methodology, safety, and stereotacticapplication accuracy in 500 procedures.</a> Neurosurgery. 72 (3), 353-366 (2013).</li></ol>

The authors have nothing to disclose.

Here is presented the technique of SEEG insertion utilizing robotic stereotactic assistance. While SEEG was originally described using other methods of frame based stereotaxis, robot-assisted SEEG offers not only similar safety but superior accuracy and efficiency. The literature reports success at localizing the EZ in over 76% of cases, which is commiserate with other previous studies using alternative techniques.6,13,.
As with any invasive intracranial procedure, SEEG is not witho...

In medically refractory epilepsy there are many non-invasive pre-surgical tools (scalp EEG., magnetic resonance imaging (MRI), functional MRI, single photon emission computed tomography, positron emission topography, and magnetoencephalography). If these non-invasive evaluations fail to sufficiently localize or define the epileptic zone (EZ) then invasive recording may be indicated. Currently, subdural grids or Stereo-electro-encephalo-graphy (SEEG) are the two most prevalent methods of invasive monitoring. SEEG was originally developed in France in the 1950's by Jean Talairach and Jean Bancaud; recently it has mostly been used for invasive monitoring of refractory epilepsy patients in France.2-4 SEEG is the consists of stereotactically inserting intracerebral electrodes into the brain parenchyma to record brain electrical activity for an extended period of time. With the intracerebral electrical recordings many patients are able to have their EZ defined to allow for surgical resection. 
Despite this long history of success SEEG remains relatively rarely used for invasive recording in America. However, SEEG does offer several significant advantages; SEEG allows for 1) recording of deep structures, 2) bihemispheric recordings, 3) another recording option if subdural grids failed, and 4) mapping of epileptic networks in three dimensions, mainly in patients where non-lesional extra-temporal epilepsy is suspected.5-7 All of these benefits are achieved without requiring a large craniotomy. A recent technologic advance in SEEG surgery is the used of robotic guidance. This sophisticated development allows for improved operative times but safer and more accurate surgical implantation of electrodes.Recently published literature reviews the results of using two different techniques for SEEG insertion; a more traditional method utilizing stereotactic frames and a newer technique using robotic assistante for SEEG insertion.1, 8,15 the results were similarly successful with each method. 
With the advent of improved robotic assistance, the SEEG insertion technique has resulted in improved operative times. The robotic system is classified as a supervisory controlled system which means the surgeon plans the operation off line and implicitly specifies the motion the robot must follow to perform the operation.9 The robotic assist results in expedient transitions from one trajectory to the next for the placement of each intracranial electrode.

<table><tbody><tr><td>ROSA</td><td>ROSA</td><td></td><td>robotic implantation system</td></tr><tr><td>electrodes</td><td>adtech</td><td></td><td></td></tr></tbody></table>

stereo-electro-encephalo-graphy (seeg) with robotic assistance in the presurgical evaluation of medical refractory epilepsy: a technical note

SEEG is a method and technique which is used for accurate, invasive recording of seizure activity via three dimensional recordings. In epilepsy patients who are deemed appropriate candidates for invasive recordings, the decision to monitor is made between the subdural grids versus SEEG. Invasive neuromonitoring for epilepsy is pursued in patients with complex, medically refractory epilepsy. The goal of invasive monitoring is to offer resective surgery with the hope of allowing seizure freedom. SEEG&#39;s advantages include access to deep cortical structures, an ability to localize the epileptogenic zone (EZ) when subdural grids have failed to do so, and in patients with non-lesional extra-temporal epilepsies. In this manuscript, we present a succinct historical overview of the SEEG and report on our experience with frameless stereotaxy under robotic. An imperative step of SEEG insertion is planning the electrode trajectories. In order to most effectively record ictal activity via SEEG trajectories should be planned based upon a hypothesis of where the seizure activity originates the presumed epileptogenic zone (EZ). The EZ hypothesis is based on a standardized preoperative workup including video-EEG monitoring, MRI (magnetic resonance imaging), PET (positron emission tomography), ictal SPECT (Single-photon emission computed tomography), and neuropsychological assessment. Using a suspected EZ, SEEG electrodes can be placed minimally invasively yet maintain accuracy and precision. Clinical results showed the ability to localize the EZ in 78% of difficult to localize epileptic patients.1

Recent results indicate that in one consecutive series of 78 patients who underwent SEEG insertion via robotic assistance had successful localization of the EZ in 76.2% of patients.1 That same study showed of the patients who went on to have surgical resection of EZ had grade 1 Engel seizure freedom in 67.8% of patients (Figure 4). Morbidity rate is 2.5%. Permanent morbidity was noticed is 1 patient (1.2%). Per electrode, it was shown to have a wound infection ...

Watch this Scientific Journal Video about Stereo-Electro-Encephalo-Graphy SEEG With Robotic Assistance in the Presurgical Evaluation of Medical Refractory Epilepsy: A Technical Note at JoVE.com

Stereo-Electro-Encephalo-Graphy SEEG With Robotic Assistance in the Presurgical Evaluation of Medical Refractory Epilepsy: A Technical Note

Stereo-electroencephalography (SEEG) aids in localization of epileptogenic zones, however, remains relatively underutilized in the United States. The goal of this abstract is to provide a brief introduction to the technique of SEEG and further a detailed technique of using robotic assistance in the placement of SEEG electrodes.

Stereo-Electro-Encephalo-Graphy (SEEG) With Robotic Assistance in the Presurgical Evaluation of Medical Refractory Epilepsy: A Technical Note

SEEG is a method and technique which is used for accurate, invasive recording of seizure activity via three dimensional recordings. In epilepsy patients ...

stereo-electro-encephalo-graphy-seeg-with-robotic-assistance

Research

JoVE Journal

Medicine

17.1K Views.  Cleveland Clinic. Stereo-electroencephalography (SEEG) aids in localization of epileptogenic zones, however, remains relatively underutilized in the United States. The goal of this abstract is to provide a brief introduction to the technique of SEEG and further a detailed technique of using robotic assistance in the placement of SEEG electrodes. 

Video: Stereo-Electro-Encephalo-Graphy SEEG With Robotic Assistance in the Presurgical Evaluation of Medical Refractory Epilepsy: A Technical Note

Performing Behavioral Tasks in Subjects with Intracranial Electrodes

Patients having stereo-electroencephalography (SEEG) electrode, subdural grid or depth electrode implants have a multitude of electrodes implanted in different areas of their brain for the localization of their seizure focus and eloquent areas. After implantation, the patient must remain in the hospital until the pathological area of brain is found and possibly resected. During this time, these patients offer a unique opportunity to the research community because any number of behavioral paradigms can be performed to uncover the neural correlates that guide behavior. Here we present a method for recording brain activity from intracranial implants as subjects perform a behavioral task designed to assess decision-making and reward encoding. All electrophysiological data from the intracranial electrodes are recorded during the behavioral task, allowing for the examination of the many brain areas involved in a single function at time scales relevant to behavior. Moreover, and unlike animal studies, human patients can learn a wide variety of behavioral tasks quickly, allowing for the ability to perform more than one task in the same subject or for performing controls. Despite the many advantages of this technique for understanding human brain function, there are also methodological limitations that we discuss, including environmental factors, analgesic effects, time constraints and recordings from diseased tissue. This method may be easily implemented by any institution that performs intracranial assessments; providing the opportunity to directly examine human brain function during behavior.

Patients implanted with intracranial electrodes provide a unique opportunity to record neurological data from multiple areas of the brain while the patient performs behavioral tasks. Here, we present a method of recording from implanted patients that can be reproducible at other institutions with access to this patient population.

Patients having stereo-electroencephalography (SEEG) electrode, subdural grid or depth electrode implants have a multitude of electrodes implanted in ...

Behavior

Recording Human Electrocorticographic (ECoG) Signals for Neuroscientific Research and Real-time Functional Cortical Mapping

Neuroimaging studies of human cognitive, sensory, and motor processes are usually based on noninvasive techniques such as electroencephalography (EEG), magnetoencephalography or functional magnetic-resonance imaging. These techniques have either inherently low temporal or low spatial resolution, and suffer from low signal-to-noise ratio and/or poor high-frequency sensitivity. Thus, they are suboptimal for exploring the short-lived spatio-temporal dynamics of many of the underlying brain processes. In contrast, the invasive technique of electrocorticography (ECoG) provides brain signals that have an exceptionally high signal-to-noise ratio, less susceptibility to artifacts than EEG, and a high spatial and temporal resolution (i.e., &lt;1 cm/&lt;1 millisecond, respectively). ECoG involves measurement of electrical brain signals using electrodes that are implanted subdurally on the surface of the brain. Recent studies have shown that ECoG amplitudes in certain frequency bands carry substantial information about task-related activity, such as motor execution and planning1, auditory processing2 and visual-spatial attention3. Most of this information is captured in the high gamma range (around 70-110 Hz). Thus, gamma activity has been proposed as a robust and general indicator of local cortical function1-5. ECoG can also reveal functional connectivity and resolve finer task-related spatial-temporal dynamics, thereby advancing our understanding of large-scale cortical processes. It has especially proven useful for advancing brain-computer interfacing (BCI) technology for decoding a user's intentions to enhance or improve communication6 and control7. Nevertheless, human ECoG data are often hard to obtain because of the risks and limitations of the invasive procedures involved, and the need to record within the constraints of clinical settings. Still, clinical monitoring to localize epileptic foci offers a unique and valuable opportunity to collect human ECoG data. We describe our methods for collecting recording ECoG, and demonstrate how to use these signals for important real-time applications such as clinical mapping and brain-computer interfacing. Our example uses the BCI2000 software platform8,9 and the SIGFRIED10 method, an application for real-time mapping of brain functions. This procedure yields information that clinicians can subsequently use to guide the complex and laborious process of functional mapping by electrical stimulation.
Prerequisites and Planning:
Patients with drug-resistant partial epilepsy may be candidates for resective surgery of an epileptic focus to minimize the frequency of seizures. Prior to resection, the patients undergo monitoring using subdural electrodes for two purposes: first, to localize the epileptic focus, and second, to identify nearby critical brain areas (i.e., eloquent cortex) where resection could result in long-term functional deficits. To implant electrodes, a craniotomy is performed to open the skull. Then, electrode grids and/or strips are placed on the cortex, usually beneath the dura. A typical grid has a set of 8 x 8 platinum-iridium electrodes of 4 mm diameter (2.3 mm exposed surface) embedded in silicon with an inter-electrode distance of 1cm. A strip typically contains 4 or 6 such electrodes in a single line. The locations for these grids/strips are planned by a team of neurologists and neurosurgeons, and are based on previous EEG monitoring, on a structural MRI of the patient's brain, and on relevant factors of the patient's history. Continuous recording over a period of 5-12 days serves to localize epileptic foci, and electrical stimulation via the implanted electrodes allows clinicians to map eloquent cortex. At the end of the monitoring period, explantation of the electrodes and therapeutic resection are performed together in one procedure.
In addition to its primary clinical purpose, invasive monitoring also provides a unique opportunity to acquire human ECoG data for neuroscientific research. The decision to include a prospective patient in the research is based on the planned location of their electrodes, on the patient's performance scores on neuropsychological assessments, and on their informed consent, which is predicated on their understanding that participation in research is optional and is not related to their treatment. As with all research involving human subjects, the research protocol must be approved by the hospital's institutional review board. The decision to perform individual experimental tasks is made day-by-day, and is contingent on the patient's endurance and willingness to participate. Some or all of the experiments may be prevented by problems with the clinical state of the patient, such as post-operative facial swelling, temporary aphasia, frequent seizures, post-ictal fatigue and confusion, and more general pain or discomfort.
At the Epilepsy Monitoring Unit at Albany Medical Center in Albany, New York, clinical monitoring is implemented around the clock using a 192-channel Nihon-Kohden Neurofax monitoring system. Research recordings are made in collaboration with the Wadsworth Center of the New York State Department of Health in Albany. Signals from the ECoG electrodes are fed simultaneously to the research and the clinical systems via splitter connectors. To ensure that the clinical and research systems do not interfere with each other, the two systems typically use separate grounds. In fact, an epidural strip of electrodes is sometimes implanted to provide a ground for the clinical system. Whether research or clinical recording system, the grounding electrode is chosen to be distant from the predicted epileptic focus and from cortical areas of interest for the research. Our research system consists of eight synchronized 16-channel g.USBamp amplifier/digitizer units (g.tec, Graz, Austria). These were chosen because they are safety-rated and FDA-approved for invasive recordings, they have a very low noise-floor in the high-frequency range in which the signals of interest are found, and they come with an SDK that allows them to be integrated with custom-written research software. In order to capture the high-gamma signal accurately, we acquire signals at 1200Hz sampling rate-considerably higher than that of the typical EEG experiment or that of many clinical monitoring systems. A built-in low-pass filter automatically prevents aliasing of signals higher than the digitizer can capture. The patient's eye gaze is tracked using a monitor with a built-in Tobii T-60 eye-tracking system (Tobii Tech., Stockholm, Sweden). Additional accessories such as joystick, bluetooth Wiimote (Nintendo Co.), data-glove (5th Dimension Technologies), keyboard, microphone, headphones, or video camera are connected depending on the requirements of the particular experiment.
Data collection, stimulus presentation, synchronization with the different input/output accessories, and real-time analysis and visualization are accomplished using our BCI2000 software8,9. BCI2000 is a freely available general-purpose software system for real-time biosignal data acquisition, processing and feedback. It includes an array of pre-built modules that can be flexibly configured for many different purposes, and that can be extended by researchers' own code in C++, MATLAB or Python. BCI2000 consists of four modules that communicate with each other via a network-capable protocol: a Source module that handles the acquisition of brain signals from one of 19 different hardware systems from different manufacturers; a Signal Processing module that extracts relevant ECoG features and translates them into output signals; an Application module that delivers stimuli and feedback to the subject; and the Operator module that provides a graphical interface to the investigator.
A number of different experiments may be conducted with any given patient. The priority of experiments will be determined by the location of the particular patient's electrodes. However, we usually begin our experimentation using the SIGFRIED (SIGnal modeling For Realtime Identification and Event Detection) mapping method, which detects and displays significant task-related activity in real time. The resulting functional map allows us to further tailor subsequent experimental protocols and may also prove as a useful starting point for traditional mapping by electrocortical stimulation (ECS).
Although ECS mapping remains the gold standard for predicting the clinical outcome of resection, the process of ECS mapping is time consuming and also has other problems, such as after-discharges or seizures. Thus, a passive functional mapping technique may prove valuable in providing an initial estimate of the locus of eloquent cortex, which may then be confirmed and refined by ECS. The results from our passive SIGFRIED mapping technique have been shown to exhibit substantial concurrence with the results derived using ECS mapping10.
The protocol described in this paper establishes a general methodology for gathering human ECoG data, before proceeding to illustrate how experiments can be initiated using the BCI2000 software platform. Finally, as a specific example, we describe how to perform passive functional mapping using the BCI2000-based SIGFRIED system.

Recording Human Electrocorticographic ECoG Signals for Neuroscientific Research and Real-time Functional Cortical Mapping

We present a method for collecting electrocorticographic signals for research purposes from humans who are undergoing invasive epilepsy monitoring. We show how to use the BCI2000 software platform for data collection, signal processing and stimulus presentation. Specifically, we demonstrate SIGFRIED, a BCI2000-based tool for real-time functional brain mapping.

Neuroimaging studies of human cognitive, sensory, and motor processes are usually based on noninvasive techniques such as electroencephalography (EEG), ...

Neuroscience

Technical Aspects of the Mouse Aortocaval Fistula

Technical aspects of creating an arteriovenous fistula in the mouse are discussed. Under general anesthesia, an abdominal incision is made, and the aorta and inferior vena cava (IVC) are exposed. The proximal infrarenal aorta and the distal aorta are dissected for clamp placement and needle puncture, respectively. Special attention is paid to avoid dissection between the aorta and the IVC. After clamping the aorta, a 25 G needle is used to puncture both walls of the aorta into the IVC. The surrounding connective tissue is used for hemostatic compression. Successful creation of the AVF will show pulsatile arterial blood flow in the IVC. Further confirmation of successful AVF can be achieved by post-operative Doppler ultrasound.

The goal is to produce an arteriovenous fistula that is simple and reproducible. This method does not use sutures or glue adhesive. Therefore the samples can be used with the least amount of foreign materials for analysis.

Technical aspects of creating an arteriovenous fistula in the mouse are discussed. Under general anesthesia, an abdominal incision is made, and the aorta ...

Operative Technique and Nuances for the Stereoelectroencephalographic (SEEG) Methodology Utilizing a Robotic Stereotactic Guidance System

The SEEG methodology has gained favor in North America over the last decade as a means of localizing the epileptogenic zone (EZ) prior to epilepsy surgery. Recently, the application of a robotic stereotactic guidance system for implantation of SEEG electrodes has become more popular in many epilepsy centers. The technique for the use of the robot requires extreme precision in the pre-surgical planning phase and then the technique is streamlined during the operative portion of the methodology, as the robot and surgeon work in concert to implant the electrodes. Herein is detailed precise operative methodology of using the robot to guide implantation of SEEG electrodes. A major limitation of the procedure, namely its heavy reliance on the ability to register the patient to a preoperative volumetric magnetic resonance image (MRI), is also discussed. Overall, this procedure has been shown to have a low morbidity rate and an extremely low mortality rate. The use of a robotic stereotactic guidance system for the implantation of SEEG electrodes is an efficient, fast, safe, and accurate alternative to conventional manual implantation strategies.

Operative Technique and Nuances for the Stereoelectroencephalographic SEEG Methodology Utilizing a Robotic Stereotactic Guidance System

The SEEG methodology is simplified and made faster with a stereotactic robot. Careful attention must be paid to the registration of the preoperative volumetric MRI to the patient prior to use of the robot in the OR. The robot streamlines the procedure, leading to decreased operative times and accurate implantations.

The SEEG methodology has gained favor in North America over the last decade as a means of localizing the epileptogenic zone (EZ) prior to epilepsy ...

Investigating the Function of Deep Cortical and Subcortical Structures Using Stereotactic Electroencephalography: Lessons from the Anterior Cingulate Cortex

Stereotactic Electroencephalography (SEEG) is a technique used to localize seizure foci in patients with medically intractable epilepsy. This procedure involves the chronic placement of multiple depth electrodes into regions of the brain typically inaccessible via subdural grid electrode placement. SEEG thus provides a unique opportunity to investigate brain function. In this paper we demonstrate how SEEG can be used to investigate the role of the dorsal anterior cingulate cortex (dACC) in cognitive control. We include a description of the SEEG procedure, demonstrating the surgical placement of the electrodes. We describe the components and process required to record local field potential (LFP) data from consenting subjects while they are engaged in a behavioral task. In the example provided, subjects play a cognitive interference task, and we demonstrate how signals are recorded and analyzed from electrodes in the dorsal anterior cingulate cortex, an area intimately involved in decision-making. We conclude with further suggestions of ways in which this method can be used for investigating human cognitive processes.

Stereotactic Electroencephalography (SEEG) is an operative technique used in epilepsy surgery to help localize seizure foci. It also affords a unique opportunity to investigate brain function. Here we describe how SEEG can be used to investigate cognitive processes in human subjects.

Stereotactic Electroencephalography (SEEG) is a technique used to localize seizure foci in patients with medically intractable epilepsy. This procedure ...

A Pipeline for 3D Multimodality Image Integration and Computer-assisted Planning in Epilepsy Surgery

Epilepsy surgery is challenging and the use of 3D multimodality image integration (3DMMI) to aid presurgical planning is well-established. Multimodality image integration can be technically demanding, and is underutilised in clinical practice. We have developed a single software platform for image integration, 3D visualization and surgical planning. Here, our pipeline is described in step-by-step fashion, starting with image acquisition, proceeding through image co-registration, manual segmentation, brain and vessel extraction, 3D visualization and manual planning of stereoEEG (SEEG) implantations. With dissemination of the software this pipeline can be reproduced in other centres, allowing other groups to benefit from 3DMMI. We also describe the use of an automated, multi-trajectory planner to generate stereoEEG implantation plans. Preliminary studies suggest this is a rapid, safe and efficacious adjunct for planning SEEG implantations. Finally, a simple solution for the export of plans and models to commercial neuronavigation systems for implementation of plans in the operating theater is described. This software is a valuable tool that can support clinical decision making throughout the epilepsy surgery pathway.

We describe the steps to use our custom designed software for image integration, visualization and planning in epilepsy surgery.

Epilepsy surgery is challenging and the use of 3D multimodality image integration (3DMMI) to aid presurgical planning is well-established. Multimodality ...

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases.

Resting-state functional-connectivity MRI has identified abnormalities in patients with a wide range of neuropsychiatric disorders, including epilepsy due to malformations of cortical development. Transcranial Magnetic Stimulation in combination with EEG can demonstrate that patients with epilepsy have cortical hyperexcitability in regions with abnormal connectivity.

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations ...

Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control seizures. However, a significant minority of patients continues to exhibit post-operative seizures, even in those cases in which the suspected source of seizures has been correctly localized and resected. The protocol presented here combines a clinical procedure routinely employed during the pre-operative evaluation of temporal lobe epilepsy (TLE) patients with a novel technique for network analysis. The method allows for the evaluation of the temporal evolution of mesial network parameters. The bilateral insertion of foramen ovale electrodes (FOE) into the ambient cistern simultaneously records electrocortical activity at several mesial areas in the temporal lobe. Furthermore, network methodology applied to the recorded time series tracks the temporal evolution of the mesial networks both interictally and during the seizures. In this way, the presented protocol offers a unique way to visualize and quantify measures that considers the relationships between several mesial areas instead of a single area.

This protocol describes a procedure to track the evolution of mesial network measures in temporal lobe epilepsy (TLE) patients. It is based on the combination of intracranial recordings with a novel numerical technique for data analysis. Specifically, we present a protocol for network analyses of foramen ovale recordings.

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control ...

Equipment Setup and Artifact Removal for Simultaneous Electroencephalogram and Functional Magnetic Resonance Imaging for Clinical Review in Epilepsy

Simultaneous electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) is a unique combined technique that provides synergy in the understanding and localization of seizure onset in epilepsy. However, reported experimental protocols for EEG-fMRI recordings fail to address details about conducting such procedures on epilepsy patients. In addition, these protocols are limited solely to research settings. To fill the gap between patient monitoring in an epilepsy monitoring unit (EMU) and conducting research with an epilepsy patient, we introduce a unique EEG-fMRI recording protocol of epilepsy during the interictal period. The use of an MR conditional electrode set, which can also be used in the EMU for a simultaneous scalp EEG and video recording, allows an easy transition of EEG recordings from the EMU to the scanning room for concurrent EEG-fMRI recordings. Details on the recording procedures using this specific MR conditional electrode set are provided. In addition, the study explains step-by-step EEG processing procedures to remove the imaging artifacts, which can then be used for clinical review. This experimental protocol promotes an amendment to the conventional EEG-fMRI recording for enhanced applicability in both clinical (i.e., EMU) and research settings. Furthermore, this protocol provides the potential to expand this modality to postictal EEG-fMRI recordings in the clinical setting.

This article details simultaneous electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) recording procedures that can be used in both clinical and research settings. EEG processing procedures to remove imaging artifacts for clinical review are also included. This study focuses on the example of epilepsy during the interictal period.

Simultaneous electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) is a unique combined technique that provides synergy in the ...

Bioengineering

Integrating MEG and HD-EEG in Pediatric Epilepsy Localization

Electromagnetic Source Imaging in Presurgical Evaluation of Children with Drug-Resistant Epilepsy

For children with drug-resistant epilepsy (DRE), seizure freedom relies on the delineation and resection (or ablation/disconnection) of the epileptogenic zone (EZ) while preserving the eloquent brain areas. The development of a reliable and noninvasive localization method that provides clinically useful information for the localization of the EZ is, therefore, crucial to achieving successful surgical outcomes. Electric and magnetic source imaging (ESI and MSI) have been increasingly utilized in the presurgical evaluation of these patients showing promising findings in the delineation of epileptogenic as well as eloquent brain areas. Moreover, the combination of ESI and MSI into a single solution, namely electromagnetic source imaging (EMSI), performed on simultaneous high-density electroencephalography (HD-EEG) and magnetoencephalography (MEG) recordings has shown higher source localization accuracy than either modality alone. Despite these encouraging findings, such techniques are performed in only a few tertiary epilepsy centers, are rarely recorded simultaneously, and are underutilized in pediatric cohorts. This study illustrates the experimental setup for recording simultaneous MEG and HD-EEG data as well as the methodological framework for analyzing these data aiming to localize the irritative zone, the seizure onset zone, and eloquent brain areas in children with DRE. More specifically, the experimental setups are presented for (i) recording and localizing interictal and ictal epileptiform activity during sleep and (ii) recording visual-, motor-, auditory-, and somatosensory-evoked responses and mapping relevant eloquent brain areas (i.e., visual, motor, auditory, and somatosensory) during visuomotor task, as well as auditory and somatosensory stimulations. Detailed steps of the data analysis pipeline are further presented for performing EMSI as well as individual ESI and MSI using equivalent current dipole (ECD) and dynamic statistical parametric mapping (dSPM).

Author Spotlight: Advancing Pediatric Epilepsy Surgery in Children Through Novel Biomarkers and Enhanced Localization

Magnetoencephalography (MEG) and high-density electroencephalography (HD-EEG) are rarely recorded simultaneously, although they yield confirmatory and complementary information. Here, we illustrate the experimental setup for recording simultaneous MEG and HD-EEG and the methodology for analyzing these data aiming to localize epileptogenic and eloquent brain areas in children with drug-resistant epilepsy.

For children with drug-resistant epilepsy (DRE), seizure freedom relies on the delineation and resection (or ablation/disconnection) of the epileptogenic ...