The study was approved by the IRB of Peking University First Hospital, and written informed consent was obtained from all participants.
NOTE: All children with intractable epilepsy who underwent frontal disconnection at the Pediatric Epilepsy Center of Peking University First Hospital from January 1, 2017, to March 1, 2022, were included and analyzed. Those who met the clinical and radiological criteria of MOGHE and whose MRI suggested that the epileptogenic lesion was confined to the frontal lobe were included. The histopathological diagnostic criteria for MOGHE have been previously described6. Semiology, ictal and interictal electroencephalography (EEG), magnetic resonance imaging (MRI), interictal 18fluorodeoxyglucose positron emission tomography (PET), and developmental assessment were performed for preoperative evaluation. Children over 7 years of age were evaluated by the Wechsler Intelligence Scale-IV, and children under 7 years of age were evaluated by the Griffith Developmental Assessment Scale. The outcome of epilepsy was evaluated by the ILAE classification, and patients with an ILAE 1 were considered seizure-free8. Semiology was divided into 3 groups (focal, spasm/generalized seizure, and mixed type). Interictal EEG was divided into focal (regional discharge), multifocal (several unilateral hemispheric regional discharges), and diffuse (contralateral involved). Ictal EEG was divided into focal (regional onset), diffuse (unilateral hemispheric onset or nonlocalizing EEG), and focal/diffuse (coexistence of 2 patterns)9. Based on the typing of MOGHE by Hartlieb et al.7, the MRI findings of the 8 patients were also classified as type 1 (Figure 1A, B) or type 2. Figure 1 shows representative intraoperative photos and pre-and postoperative images of frontal disconnection in patient 8.
1. Positioning
<ol>
	<li>Administer general anesthesia to the patient using standard techniques.</li>
	<li>Locate the Sylvian fissure, coronal suture, and central sulcus according to anatomical landmarks as a reference for drawing surgical incision lines. Make a &#34;7&#34;-shaped skin incision 1.0 cm off the midline and 2-3 cm anterior to the coronal suture. Ensure that the posterior margin of the incision includes the precentral gyrus and extends down to the pterygoid region (Figure 1D)</li>
	<li>Place the patient supine with the head turned to the opposite side. Place a shoulder pad under the shoulder to help the head turn.</li>
	<li>Maintain sterile conditions throughout the procedure by sterilely preparing the skin and draping the surgical area.</li>
</ol>
2. Opening
<ol>
	<li>Incise the scalp and muscles. Take care to cut the muscles in layers.</li>
	<li>Separate the scalp and periosteum with a scalpel. 
	NOTE: Preservation of the periosteum reduces postoperative subcutaneous hydrops.</li>
	<li>Drill three 1 cm holes using a high-speed drill of 1 cm diameter and mill down the bone flap with a 1 mm wide milling cutter. 
	NOTE: Adequate exposure of the sphenoid ridge is required to facilitate subsequent disconnection of the frontal base.</li>
	<li>Use bone wax, gelatin sponge, and bipolar cautery to achieve hemostasis.</li>
	<li>Drill 4-5 1 mm holes in the bone margin and suspend the dura to avoid epidural hematoma.</li>
	<li>Cut open the dura 0.5 cm away from the bone margin. Expose the precentral gyrus, the posterior part of the inferior frontal gyrus, and the beginning of the lateral fissure. (Figure 1E)</li>
</ol>
3. Frontal disconnection procedures
<ol>
	<li>Use the stereotactic system software for surgical planning before surgery. Import the 3D T1, flair weighted images, and PET data into the software for registration and 3D reconstruction10. 
	NOTE: The precentral sulcus was delineated by a 3D coregistration. Intraoperative mapping of the central gyrus was not performed (Figure 1C).</li>
	<li>Select the area with the most severe abnormality on preoperative imaging for histological examination.</li>
	<li>Resect the posterior part of the inferior frontal gyrus to fully expose the 1 and 2 short gyri of the insula. 
	NOTE: In children under 5 years of age with suspected frontal MOGHE, preservation of the speech area is not considered in order to maximize the extent of disconnection of the epileptogenic zone.</li>
	<li>Disconnect the base of the frontal lobe and the fibers along the anterior insula to the sphenoid ridge and then to the midline. 
	NOTE: The anterior cerebral artery and the olfactory triangle are landmarks of the posterior boundary of the disconnection. The gyrus rectus is located medial to the olfactory nerve, and the disconnection of the base of the frontal lobe needs to reach the midline pia. The contralateral brain tissue must be well preserved.</li>
	<li>Dissect the gray and white matter along the precentral sulcus. The boundary of disconnection at the midline is the cerebral falx, and down to the cingulate gyrus, disconnect it accordingly.
	<ol>
		<li>When performing intrafrontal disconnection along the precentral sulcus, disconnect the white matter under the bottom of the sulcus slightly forward to make the pyramidal tract intact.</li>
		<li>On the other hand, because MOGHE is a white matter lesion with blurred gray-white matter boundaries, perform a sufficiently deep resection/disconnection to achieve the highest chance of seizure freedom.</li>
	</ol>
	</li>
	<li>Incise the corpus callosum to open the ipsilateral ventricles, dissect the arcuate fibers completely along the top of the ventricles to the anterior horn, and then meet the frontal base disconnection line. 
	NOTE: The entire anterior lateral ventricle is completely open so far.</li>
	<li>Disconnect the anterior corpus callosum to the anterior commissure within the lateral ventricles, where the posterior portion of the frontobasal disconnection reaches the level of the callosal disconnection.</li>
	<li>Expose the anterior cerebral artery, which can be an anatomical landmark in the disconnection of the corpus callosum. Finally, resect the paraterminal gyrus and posterior gyrus rectus behind the anterior cerebral artery with suction. 
	NOTE: The frontobasal disconnection should be complete, including the paraterminal gyrus and posterior gyrus rectus; otherwise, the seizure outcome will be greatly affected. Frontal disconnection is frequently accompanied by resection of the 1 or/and 2 insular short gyri according to the preoperative evaluation, thereby facilitating a more comprehensive excision of the epileptogenic zone. The photos after disconnection and postoperative MRI are shown in Figure 1. Resection of the 1 and 2 short insular gyri should be actively considered, especially if preoperative MRI and PET suggest abnormalities.</li>
</ol>
4. Closure
<ol>
	<li>Suture the dura with 4-0 absorbable sutures to achieve a tight closure.</li>
	<li>Place an epidural drain for 2 days.</li>
	<li>Fix the bone using 3 absorbable cranial bone locks.</li>
	<li>Close the subcutaneous layer with 4-0 subcuticular sutures.</li>
	<li>Suture the skin with a stapler.</li>
</ol>

MOGHE and Epilepsy: Outcomes of Frontal Disconnection Surgery 

<ol>
	<li>Oegema, R., 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=International+consensus+recommendations+on+the+diagnostic+work-up+for+malformations+of+cortical+development.">International consensus recommendations on the diagnostic work-up for malformations of cortical development.</a> Nat Rev Neurol. 16 (11), 618-635 (2020).</li><li>Najm, 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=The+ilae+consensus+classification+of+focal+cortical+dysplasia:+An+update+proposed+by+an+ad+hoc+task+force+of+the+ILAE+diagnostic+methods+commission.">The ilae consensus classification of focal cortical dysplasia: An update proposed by an ad hoc task force of the ILAE diagnostic methods commission.</a> Epilepsia. 63 (8), 1899-1919 (2022).</li><li>Coras, R., 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=Proliferative+oligodendroglial+hyperplasia+in+epilepsy+(poghe):+A+novel+diagnostic+entity.">Proliferative oligodendroglial hyperplasia in epilepsy (poghe): A novel diagnostic entity.</a> Epilepsia. 54, 318-318 (2013).</li><li>Schurr, 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=Mild+malformation+of+cortical+development+with+oligodendroglial+hyperplasia+in+frontal+lobe+epilepsy:+A+new+clinico-pathological+entity.">Mild malformation of cortical development with oligodendroglial hyperplasia in frontal lobe epilepsy: A new clinico-pathological entity.</a> Brain Pathol. 27 (1), 26-35 (2017).</li><li>Garganis, K., 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=Temporal+lobe+&amp;#34;plus&amp;#34;+epilepsy+associated+with+oligodendroglial+hyperplasia+(MOGHE).">Temporal lobe &amp;#34;plus&amp;#34; epilepsy associated with oligodendroglial hyperplasia (MOGHE).</a> Acta Neurol Scand. 140 (4), 296-300 (2019).</li><li>Liu, X. Y., 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=Clinical+characteristics+and+surgical+outcomes+in+children+with+mild+malformation+of+cortical+development+and+oligodendroglial+hyperplasia+in+epilepsy.">Clinical characteristics and surgical outcomes in children with mild malformation of cortical development and oligodendroglial hyperplasia in epilepsy.</a> Epilepsia Open. 8 (3), 898-911 (2023).</li><li>Hartlieb, T., 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=Age-related+MR+characteristics+in+mild+malformation+of+cortical+development+with+oligodendroglial+hyperplasia+and+epilepsy+(MOGHE).">Age-related MR characteristics in mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE).</a> Epilepsy Behav. 91, 68-74 (2019).</li><li>Wieser, H. G., 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=Proposal+for+a+new+classification+of+outcome+with+respect+to+epileptic+seizures+following+epilepsy+surgery.">Proposal for a new classification of outcome with respect to epileptic seizures following epilepsy surgery.</a> Epilepsia. 42 (2), 282-286 (2001).</li><li>Wang, Y., 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=Disconnection+surgery+in+pediatric+epilepsy:+A+single+center's+experience+with+185+cases.">Disconnection surgery in pediatric epilepsy: A single center's experience with 185 cases.</a> Neurosurgery. 93 (6), 1251-1258 (2023).</li><li>Wang, Y., 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=Seizure+and+cognitive+outcomes+of+posterior+quadrantic+disconnection:+A+series+of+12+pediatric+patients.">Seizure and cognitive outcomes of posterior quadrantic disconnection: A series of 12 pediatric patients.</a> Br J Neurosurg. 34 (6), 677-682 (2020).</li><li>Gaballa, A., 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=Clinical+characteristics+and+postoperative+seizure+outcome+in+patients+with+mild+malformation+of+cortical+development+and+oligodendroglial+hyperplasia.">Clinical characteristics and postoperative seizure outcome in patients with mild malformation of cortical development and oligodendroglial hyperplasia.</a> Epilepsia. 62 (12), 2920-2931 (2021).</li><li>Barba, 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=Clinical+features,+neuropathology,+and+surgical+outcome+in+patients+with+refractory+epilepsy+and+brain+somatic+variants+in+the+slc35a2+gene.">Clinical features, neuropathology, and surgical outcome in patients with refractory epilepsy and brain somatic variants in the slc35a2 gene.</a> Neurology. 100 (5), e528-e542 (2023).</li><li>Garganis, K., 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=Frontal+lobe+epilepsy+and+mild+malformation+with+oligodendroglial+hyperplasia:+Further+observations+on+electroclinical+and+imaging+phenotypes,+and+surgical+perspectives.">Frontal lobe epilepsy and mild malformation with oligodendroglial hyperplasia: Further observations on electroclinical and imaging phenotypes, and surgical perspectives.</a> Epileptic Disord. 25 (3), 343-359 (2023).</li><li>Willard, A., 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=Seizure+outcome+after+surgery+for+mri-diagnosed+focal+cortical+dysplasia:+A+systematic+review+and+meta-analysis.">Seizure outcome after surgery for mri-diagnosed focal cortical dysplasia: A systematic review and meta-analysis.</a> Neurology. 98 (3), e236-e248 (2022).</li><li>Kalbhenn, T., 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=Operative+posterior+disconnection+in+epilepsy+surgery:+Experience+with+29+patients.">Operative posterior disconnection in epilepsy surgery: Experience with 29 patients.</a> Epilepsia. 60 (9), 1973-1983 (2019).</li><li>Devlin, A. 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=Clinical+outcomes+of+hemispherectomy+for+epilepsy+in+childhood+and+adolescence.">Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence.</a> Brain. 126 (Pt 3), 556-566 (2003).</li><li>Marras, C. E., 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=Hemispherotomy+and+functional+hemispherectomy:+Indications+and+outcome.">Hemispherotomy and functional hemispherectomy: Indications and outcome.</a> Epilepsy Res. 89 (1), 104-112 (2010).</li><li>Castagno, S., 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=Seizure+outcomes+of+large+volume+temporo-parieto-occipital+and+frontal+surgery+in+children+with+drug-resistant+epilepsy.">Seizure outcomes of large volume temporo-parieto-occipital and frontal surgery in children with drug-resistant epilepsy.</a> Epilepsy Res. 177, 106769 (2021).</li><li>Kamalboor, H., Alhindi, H., Alotaibi, F., Althubaiti, I., Alkhateeb, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Frontal+disconnection+surgery+for+drug-resistant+epilepsy:+Outcome+in+a+series+of+16+patients.">Frontal disconnection surgery for drug-resistant epilepsy: Outcome in a series of 16 patients.</a> Epilepsia Open. 5 (3), 475-486 (2020).</li></ol>

The authors have nothing to disclose.

MOGHE is a new white matter entity predominantly at the GM/WM boundaries but shows no cortical layer disorganization as is typical for FCDs2. The untypical semiology and extensive EEG make it very difficult to determine the location of the epileptogenic zone using traditional methods of anatomo-electro-clinical evaluation, which creates difficulties in surgical decision-making. Previous studies reported that patients with MOGHE achieved good outcomes after wide resection6<s...

Malformation of cortical development (MCD) is an important cause of drug-resistant epilepsy and developmental delay in young children. There are many types of MCD, among which FCD is the most common type1. According to the latest updated FCD classification in 2022, MOGHE is described and classified as a predominantly white matter lesion in contrast to juxta-cortical localized FCD2 that was primarily described as proliferative&#8195;oligodendroglial&#8195;hyperplasia&#8195;with&#8195;epilepsy&#8195;(POGHE) in 20133 and first proposed in 20174. MOGHE is defined by an increase in heterotopic neurons in the white matter and deep cortical layers above 2200 Olig2-immunoreactive cells/mm2 in specimen2,4,5.
Clinically, MOGHE is most commonly observed in the frontal lobe, and epileptic spasms are the most common initial seizure type6. The interictal EEG pattern was usually multifocal or widespread in young children6. In younger children, MRI showed an increased laminar signal at the gray-white matter junction. In older children, reduced subcortical T2/FLAIR signals and blurring at the gray-white matter transition were observed7. An accurate delineation of MOGHE is very difficult in clinical practice. Therefore, the traditional concept and strategy of preoperative evaluation to determine the extent of the epileptogenic zone by comprehensive anatomo-electro-clinical evaluation is difficult to implement. Herein, a pediatric cohort with MOGHE in the frontal lobe was analyzed to extend the knowledge of surgical treatment for MOGHE.

<table><tbody><tr><td>Absorbable cranial bone lock</td><td>Braun Inc.</td><td>FF016</td><td></td></tr><tr><td>Drainage</td><td>Branden Inc.</td><td>Fr12</td><td></td></tr><tr><td>High-speed drill</td><td>Stryker</td><td>5400-050-000</td><td></td></tr><tr><td>Microscope</td><td>Leica Inc.</td><td>M525F40</td><td></td></tr><tr><td>NIHON KOHDAN EEG system</td><td>NIHON KOHDAN Inc.</td><td>EEG-1200C</td><td>EEG&amp;nbsp;</td></tr><tr><td>Philips PET-CT system</td><td>Philips Inc.</td><td>Gemini GXL</td><td>PET-CT</td></tr><tr><td>Sinovation Stereotactic system</td><td>Sinovation Inc.</td><td>SR1</td><td>3D construction</td></tr></tbody></table>

frontal disconnection for treating mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (moghe) in the frontal lobe

Malformation of cortical development is an important cause of drug-resistant epilepsy in young children. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) has been added to the last focal cortical dysplasia (FCD) classification and commonly involves the frontal lobe. The semiology at the onset of epilepsy is dominated by non-lateralizing infantile spasm; the boundaries of the malformation are usually difficult to determine by magnetic resonance imaging (MRI) and positron emission tomography (PET), and electroencephalography (EEG) findings are often widespread. Therefore, the traditional concept and strategy of preoperative evaluation to determine the extent of the epileptogenic zone by comprehensive anatomo-electro-clinical methods are difficult to implement. 
Frontal disconnection is an effective surgical method for the treatment of epilepsy, but there are few related reports. A total of 8 children with histo-pathologically confirmed MOGHE were retrospectively studied. MOGHE was located in the frontal lobe in all patients, and frontal disconnection was performed. The periinsular approach was used in the disconnective procedures, divided into several surgical steps: the partial inferior frontal gyrus resection, the frontobasal and intrafrontal disconnection, and the anterior corpus callosotomy. 
One patient presented with a short-term postoperative speech disorder, while another patient exhibited transient postoperative limb weakness. No long-term postoperative complications were observed. At 2 years after surgery, 75% of patients were seizure-free, with cognitive improvement in half of them. This finding suggested that frontal disconnection is an effective and safe surgical procedure for the treatment of MOGHE instead of extensive resection in the frontal lobe.

According to the inclusion criteria, a total of 8 eligible patients were included in the analysis. The group consisted of 8 boys. The age of onset was 4-28 months (median 6 months), and the age of surgery ranged from 17-135 months (median 38 months). The duration of epilepsy ranged from 13 to 121 months (median 32 months). The semiology of 4 patients was epileptic spasms, 3 had focal seizures, and 1 had mixed seizures. Interictal EEG indicated focal in 3 patients, multifocal in 3 patients, and diffuse in 2 patients. Icta...

Author Spotlight: Studying Clinical Characters and Epilepsy Outcomes After Frontal Disconnection in Patients with MOGHE

Here, we present a protocol to describe the epilepsy outcome and complications of 8 patients with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) in the frontal lobe after frontal disconnection. The procedure is characterized by its simplicity, user-friendliness, and fewer postoperative complications.

Frontal Disconnection for Treating Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE) in the Frontal Lobe

Malformation of cortical development is an important cause of drug-resistant epilepsy in young children. Mild malformation of cortical development with ...

frontal-disconnection-for-treating-mild-malformation-cortical

Research

JoVE Journal

Medicine

737 Views.  Peking University First Hospital. We bestudeerden de postoperatieve epilepsie-uitkomst voor MOGHE. Vanwege de klinische kenmerken van MOGHE zijn het traditionele concept en de strategie van preoperatieve evaluatie om de omvang van de epileptogene zone te bepalen moeilijk te implementeren. We proberen de uitkomst van epilepsie en de complicaties na het loskoppelen van de frontale kwab van MOGHE in de frontale kwab te analyseren.Voor patiënten met MOGHE moet de omvang van de resectie re...

Video: Auteur in de schijnwerpers: klinische karakters en epilepsie-resultaten bestuderen na frontale ontkoppeling bij patiënten met MOGHE

Network Analysis of the Default Mode Network Using Functional Connectivity MRI in Temporal Lobe Epilepsy

Functional connectivity MRI (fcMRI) is an fMRI method that examines the connectivity of different brain areas based on the correlation of BOLD signal fluctuations over time. Temporal Lobe Epilepsy (TLE) is the most common type of adult epilepsy and involves multiple brain networks. The default mode network (DMN) is involved in conscious, resting state cognition and is thought to be affected in TLE where seizures cause impairment of consciousness. The DMN in epilepsy was examined using seed based fcMRI. The anterior and posterior hubs of the DMN were used as seeds in this analysis. The results show a disconnection between the anterior and posterior hubs of the DMN in TLE during the basal state. In addition, increased DMN connectivity to other brain regions in left TLE along with decreased connectivity in right TLE is revealed. The analysis demonstrates how seed-based fcMRI can be used to probe cerebral networks in brain disorders such as TLE.

The Default Mode Network (DMN) in Temporal Lobe Epilepsy (TLE) is analyzed in the resting state of the brain using seed-based functional connectivity MRI (fcMRI).

Functional connectivity MRI (fcMRI) is an fMRI method that examines the connectivity of different brain areas based on the correlation of BOLD signal ...

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 ...

Neuroscience

Direct-current Stimulation and Multi-electrode Array Recording of Seizure-like Activity in Mice Brain Slice Preparation

Cathodal transcranial direct-current stimulation (tDCS) induces suppressive effects on drug-resistant seizures. To perform effective actions, the stimulation parameters (e.g., orientation, field strength, and stimulation duration) need to be examined in mice brain slice preparations. Testing and arranging the orientation of the electrode relative to the position of the mice brain slice are feasible. The present method preserves the thalamocingulate pathway to evaluate the effect of DCS on anterior cingulate cortex seizure-like activities. The results of the multichannel array recordings indicated that cathodal DCS significantly decreased the amplitude of the stimulation-evoked responses and duration of 4-aminopyridine and bicuculline-induced seizure-like activity. This study also found that cathodal DCS applications at 15 min caused long-term depression in the thalamocingulate pathway. The present study investigates the effects of DCS on thalamocingulate synaptic plasticity and acute seizure-like activities. The current procedure can test the optimal stimulation parameters including orientation, field strength, and stimulation duration in an in vitro mouse model. Also, the method can evaluate the effects of DCS on cortical seizure-like activities at both the cellular and network levels.

Studies have shown that cathodal transcranial direct-current stimulation can produce suppressive effects on drug-resistant seizures. In this study, an in vitro experimental setup was devised in which the direct-current stimulation and multielectrode array recording of seizure-like activity were evaluated in mice brain slice preparation. The direct-current stimulation parameters were evaluated.

Cathodal transcranial direct-current stimulation (tDCS) induces suppressive effects on drug-resistant seizures. To perform effective actions, the ...

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 ...

Comprehensive Endovascular and Open Surgical Management of Cerebral Arteriovenous Malformations

Arteriovenious malformations (AVMs) are associated with significant morbidity and mortality, and have a rupture risk of ~3% per year. Treatment of AVMs must be tailored specifically to the lesion, with surgical resection being the gold standard for small, accessible lesions. Pre-operative embolization of AVMs can reduce nidal blood flow and remove high-risk AVM features such as intranidal or venous aneurysms, thereby simplifying a challenging neurosurgical procedure. Herein, we describe our approach for the staged endovascular embolization and open resection of AVMs, and highlight the advantages of having a comprehensively trained neurovascular surgeon leading a multi-disciplinary clinical team. This includes planning the craniotomy and resection to immediately follow the final embolization stage, thereby using a single session of anesthesia for aggressive embolization, and rapid resection. Finally, we provide a representative case of a 22-year-old female with an unruptured right frontal AVM diagnosed during a seizure workup, who was successfully treated via staged embolizations followed by open surgical resection.

Surgery is the gold standard for accessible arteriovenious malformations (AVMs), and pre-operative embolization can simplify this procedure. We describe our approach for staged endovascular embolization and open resection of AVMs, and provide a representative clinical example highlighting the advantages of a comprehensively trained neurovascular surgeon leading a multi-disciplinary clinical team.

Arteriovenious malformations (AVMs) are associated with significant morbidity and mortality, and have a rupture risk of ~3% per year. Treatment of AVMs ...

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 ...

Interictal High Frequency Oscillations Detected with Simultaneous Magnetoencephalography and Electroencephalography as Biomarker of Pediatric Epilepsy

Crucial to the success of epilepsy surgery is the availability of a robust biomarker that identifies the Epileptogenic Zone (EZ). High Frequency Oscillations (HFOs) have emerged as potential presurgical biomarkers for the identification of the EZ in addition to Interictal Epileptiform Discharges (IEDs) and ictal activity. Although they are promising to localize the EZ, they are not yet suited for the diagnosis or monitoring of epilepsy in clinical practice. Primary barriers remain: the lack of a formal and global definition for HFOs; the consequent heterogeneity of methodological approaches used for their study; and the practical difficulties to detect and localize them noninvasively from scalp recordings. Here, we present a methodology for the recording, detection, and localization of interictal HFOs from pediatric patients with refractory epilepsy. We report representative data of HFOs detected noninvasively from interictal scalp EEG and MEG from two children undergoing surgery.
The underlying generators of HFOs were localized by solving the inverse problem and their localization was compared to the Seizure Onset Zone (SOZ) as this was defined by the epileptologists. For both patients, Interictal Epileptogenic Discharges (IEDs) and HFOs were localized with source imaging at concordant locations. For one patient, intracranial EEG (iEEG) data were also available. For this patient, we found that the HFOs localization was concordant between noninvasive and invasive methods. The comparison of iEEG with the results from scalp recordings served to validate these findings. To our best knowledge, this is the first study that presents the source localization of scalp HFOs from simultaneous EEG and MEG recordings comparing the results with invasive recordings. These findings suggest that HFOs can be reliably detected and localized noninvasively with scalp EEG and MEG. We conclude that the noninvasive localization of interictal HFOs could significantly improve the presurgical evaluation for pediatric patients with epilepsy.

High Frequency Oscillations (HFOs) have emerged as presurgical biomarkers for the identification of the epileptogenic zone in pediatric patients with medically refractory epilepsy. A methodology for the noninvasive recording, detection, and localization of HFOs with simultaneous scalp electroencephalography (EEG) and magnetoencephalography (MEG) is presented.

Crucial to the success of epilepsy surgery is the availability of a robust biomarker that identifies the Epileptogenic Zone (EZ). High Frequency ...

MRI-guided Focused Ultrasound Thalamotomy for Patients with Medically-refractory Essential Tremor

Essential tremor (ET) is the most common type of tremor in adults. While ET does not result in decreased life expectancy, the disabilities associated with ET can have a significant impact on quality of life, mood, functional activities, and socialization. Patients suffering from ET not sufficiently treated with first line medications may be eligible for alternative strategies such as deep brain stimulation, radiofrequency ablation, and MRI guided focused ultrasound (MRgFUS). High-intensity MRgFUS is an emerging modality to treat ET, its attraction for patients being that it is noninvasive and associated with short recovery time, as patients are home the day after treatment. While MRgFUS centers are still limited, it will become important for clinicians to consider MRgFUS as a treatment alternative, particularly in the case of a patient for whom open surgery is contraindicated. This article outlines the steps of patient selection, equipment setup, sonication, and post-treatment follow-up, as well as critical steps to be aware of when performing a MRgFUS procedure.

High-intensity MRI guided focused ultrasound is an emerging noninvasive technique to precisely ablate brain tissue. It has been shown to be safe and effective in treating medically-refractory essential tremor. This article describes the protocol for thalamotomy from patient selection to equipment setup to post-treatment follow-up.

Essential tremor (ET) is the most common type of tremor in adults. While ET does not result in decreased life expectancy, the disabilities associated with ...

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 ...

Improving Outcomes in Anteromesial Temporal Lobe Resections - A Demonstration of Resecting the Temporal Piriform Cortex

Anteromesial temporal lobe resection (ATLR) is a useful treatment option for drug-resistant mesial temporal lobe epilepsy (DRmTLE). Growing evidence suggests the piriform cortex plays a crucial role in the generation and propagation of seizures in DRmTLE - and that the resection of the temporal portion of the piriform cortex is associated with significantly improved rates of seizure freedom. 
Here, we present the resection of the temporal portion of the piriform cortex in ATLR, using high-resolution preoperative probabilistic tractography algorithms and fused anatomical masks of the structures of interest into the intraoperative neuronavigation and microscope head-up display (HUD). 
All patients undergoing comprehensive preoperative assessment and investigations for DRmTLE provided informed, written consent to record an intraoperative video of the procedure. Patients were identified by an expert multidisciplinary team of epileptologists, epilepsy neurosurgeons, neuropsychologists, neuropsychiatrists, and electrophysiologists at a large epilepsy surgery center. The preoperative imaging pipeline included the delineation of critical structures. This included the temporal piriform cortex, and high-resolution probabilistic tractography for essential tracts at risk (e.g., optic radiation and inferior fronto-occipital fasciculus). These were co-registered to the preoperative volumetric neuronavigation scan and uploaded to the intra-operative neuronavigation system. 
Presented here is a step-by-step procedure of ATLR, including the resection of the temporal portion of the piriform cortex. The protocol combines Advanced structural and diffusion MR imaging and intraoperative visual aids to integrate anatomical masks of critical grey matter structures and white matter tracts into the surgical workflow in the operating room.

Here, we demonstrate an approach to intraoperative neurosurgical guidance in anteromesial temporal lobe resections, specifically highlighting the use of tractography and anatomical masks to aid safe resection of the temporal portion of the piriform cortex - an area increasingly regarded as a crucial surgical target in drug-resistant mesial temporal lobe epilepsy.

Anteromesial temporal lobe resection (ATLR) is a useful treatment option for drug-resistant mesial temporal lobe epilepsy (DRmTLE). Growing evidence ...

Frontal Disconnection for Treating Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Epilepsy (MOGHE) in the Frontal Lobe

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