Orientation of Temporal Interference for Non-Invasive Deep Brain Stimulation in Epilepsy

AbstractIn patients with focal drug-resistant epilepsy, electrical stimulation from intracranial electrodes is frequently used for the localization of seizure onset zones and related pathological networks. The ability of electrically stimulated tissue to generate beta and gamma range oscillations, called rapid-discharges, is a frequent indication of an epileptogenic zone. However, a limit of intracranial stimulation is the fixed physical location and number of implanted electrodes, leaving numerous clinically and functionally relevant brain regions unexplored. Here, we demonstrate an alternative technique relying exclusively on nonpenetrating surface electrodes, namely an orientation-tunable form of temporally-interfering (TI) electric fields to target the CA3 of the mouse hippocampus which focally evokes seizure-like events (SLEs) having the characteristic frequencies of rapid-discharges, but without the necessity of the implanted electrodes. The orientation of the topical electrodes with respect to the orientation of the hippocampus is demonstrated to strongly control the threshold for evoking SLEs. Additionally, we demonstrate the use of square waves as an alternative to sine waves for TI stimulation. An orientation-dependent analysis of classic implanted electrodes to evoke SLEs in the hippocampus is subsequently utilized to support the results of the minimally-invasive temporally-interfering fields. The principles of orientation-tunable TI stimulation seen here can be generally applicable in a wide range of other excitable tissues and brain regions, overcoming several limitations of fixed electrodes which penetrate tissue.

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Orientation of Temporal Interference for Non-invasive Deep Brain Stimulation in Epilepsy

Frontiers in Neuroscience ◽

10.3389/fnins.2021.633988 ◽

2021 ◽

Vol 15 ◽

Author(s):

Florian Missey ◽

Evgeniia Rusina ◽

Emma Acerbo ◽

Boris Botzanowski ◽

Agnès Trébuchon ◽

...

Keyword(s):

Electric Fields ◽

Pulse Width Modulation ◽

Brain Regions ◽

Intracranial Stimulation ◽

Epileptogenic Zone ◽

Implanted Electrodes ◽

Non Invasive ◽

Gamma Range ◽

Wide Range ◽

Drug Resistant Epilepsy

In patients with focal drug-resistant epilepsy, electrical stimulation from intracranial electrodes is frequently used for the localization of seizure onset zones and related pathological networks. The ability of electrically stimulated tissue to generate beta and gamma range oscillations, called rapid-discharges, is a frequent indication of an epileptogenic zone. However, a limit of intracranial stimulation is the fixed physical location and number of implanted electrodes, leaving numerous clinically and functionally relevant brain regions unexplored. Here, we demonstrate an alternative technique relying exclusively on non-penetrating surface electrodes, namely an orientation-tunable form of temporally interfering (TI) electric fields to target the CA3 of the mouse hippocampus which focally evokes seizure-like events (SLEs) having the characteristic frequencies of rapid-discharges, but without the necessity of the implanted electrodes. The orientation of the topical electrodes with respect to the orientation of the hippocampus is demonstrated to strongly control the threshold for evoking SLEs. Additionally, we demonstrate the use of Pulse-width-modulation of square waves as an alternative to sine waves for TI stimulation. An orientation-dependent analysis of classic implanted electrodes to evoke SLEs in the hippocampus is subsequently utilized to support the results of the minimally invasive temporally interfering fields. The principles of orientation-tunable TI stimulation seen here can be generally applicable in a wide range of other excitable tissues and brain regions, overcoming several limitations of fixed electrodes which penetrate tissue and overcoming several limitations of other non-invasive stimulation methods in epilepsy, such as transcranial magnetic stimulation (TMS).

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Interindividual variability of electric fields during transcranial temporal interference stimulation (tTIS)

Scientific Reports ◽

10.1038/s41598-021-99749-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jill von Conta ◽

Florian H. Kasten ◽

Branislava Ćurčić-Blake ◽

André Aleman ◽

Axel Thielscher ◽

...

Keyword(s):

Electric Fields ◽

Interindividual Variability ◽

Brain Regions ◽

Single Subject ◽

Non Invasive ◽

Left Hippocampus ◽

Potential Benefits ◽

Stimulation Technique ◽

Deep Brain ◽

Stimulation Of

AbstractTranscranial temporal interference stimulation (tTIS) is a novel non-invasive brain stimulation technique for electrical stimulation of neurons at depth. Deep brain regions are generally small in size, making precise targeting a necessity. The variability of electric fields across individual subjects resulting from the same tTIS montages is unknown so far and may be of major concern for precise tTIS targeting. Therefore, the aim of the current study is to investigate the variability of the electric fields due to tTIS across 25 subjects. To this end, the electric fields of different electrode montages consisting of two electrode pairs with different center frequencies were simulated in order to target selected regions-of-interest (ROIs) with tTIS. Moreover, we set out to compare the electric fields of tTIS with the electric fields of conventional tACS. The latter were also based on two electrode pairs, which, however, were driven in phase at a common frequency. Our results showed that the electric field strengths inside the ROIs (left hippocampus, left motor area and thalamus) during tTIS are variable on single subject level. In addition, tTIS stimulates more focally as compared to tACS with much weaker co-stimulation of cortical areas close to the stimulation electrodes. Electric fields inside the ROI were, however, comparable for both methods. Overall, our results emphasize the potential benefits of tTIS for the stimulation of deep targets, over conventional tACS. However, they also indicate a need for individualized stimulation montages to leverage the method to its fullest potential.

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Using Automated Detection and Classification of Interictal HFOs to Improve the Identification of Epileptogenic Zones in Preparation for Epilepsy Surgery

10.1101/680280 ◽

2019 ◽

Author(s):

Sina Farahmand ◽

Tiwalade Sobayo ◽

David J. Mogul

Keyword(s):

Alternative Therapy ◽

Brain Regions ◽

Automated Detection ◽

High Rate ◽

Epileptogenic Zone ◽

Analytical Methodology ◽

Automated Algorithm ◽

Energy Peak ◽

Drug Resistant Epilepsy

AbstractObjectiveFor more than 25 million drug-resistant epilepsy patients, surgical intervention aiming at resecting brain regions where seizures arise is often the only alternative therapy. However, the identification of this epileptogenic zone (EZ) is often imprecise which may affect post-surgical outcomes (PSOs). Interictal high-frequency oscillations (HFOs) have been revealed to be reliable biomarkers in delineating EZ. In this paper, an analytical methodology aiming at automated detection and classification of interictal HFOs is proposed to improve the identification of EZ. Furthermore, the detected high-rate HFO areas were compared with the seizure onset zones (SOZs) and resected areas to investigate their clinical relevance in predicting PSOs.MethodsFIR band-pass filtering as well as a combination of time-series local energy, peak, and duration analysis were utilized to identify high-rate HFO areas in interictal, multi-channel intracranial electroencephalographic (iEEG) recordings. The detected HFOs were then classified into fast-ripple (FR), ripple (R), and fast-ripple concurrent with ripple (FRandR) events.ResultsThe proposed method resulted in sensitivity of 91.08% and false discovery rate of 7.32%. Moreover, it was found that the detected HFO-FRandR areas in concordance with the SOZs would have better delineated the EZ for each patient, while limiting the area of the brain required to be resected.ConclusionTesting on a dataset of 20 patients has supported the feasibility of using this method to provide an automated algorithm to better delineate the EZ.SignificanceThe proposed methodology may significantly improve the precision by which pathological brain tissue can be identified.

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Seizures Outcome After Stereoelectroencephalography-Guided Thermocoagulations in Malformations of Cortical Development Poorly Accessible to Surgical Resection

Neurosurgery ◽

10.1227/neu.0000000000000723 ◽

2015 ◽

Vol 77 (1) ◽

pp. 9-15 ◽

Cited By ~ 30

Author(s):

Hélène Catenoix ◽

François Mauguière ◽

Alexandra Montavont ◽

Philippe Ryvlin ◽

Marc Guénot ◽

...

Keyword(s):

Seizure Frequency ◽

Low Voltage ◽

Cortical Development ◽

Seizure Outcome ◽

Epileptogenic Zone ◽

Drug Resistant ◽

Seizure Onset ◽

Implanted Electrodes ◽

Spontaneous Seizures ◽

Drug Resistant Epilepsy

Abstract BACKGROUND: Radiofrequency thermocoagulation (RFTC) guided by stereoelectroencephalography (SEEG) has proved to be a safe palliative method to reduce seizure frequency in patients with drug-resistant partial epilepsy. In malformation of cortical development (MCD), increasing the number of implanted electrodes over that needed for mapping of the epileptogenic zone could help to maximize RFTC efficiency. OBJECTIVE: To evaluate the benefit of SEEG-guided RFTC in 14 patients suffering from drug-resistant epilepsy related to MCD located in functional cortical areas or in regions poorly accessible to surgery. METHODS: Ten men and 4 women were treated by RFTC. Thermolesions were produced by applying a 50-V, 120-mA current for 10 to 30 seconds within the epileptogenic zone as identified by the SEEG investigation. RESULTS: An average of 25.8 ± 17.5 thermolesions were made per procedure. The median follow-up after the procedure was 41.7 months. Sixty-four percent of the patients experienced a long-term decrease in seizure frequency of >50%, of whom 6 (43%) presented long-lasting freedom from seizure. When a focal low-voltage fast activity was present at seizure onset on SEEG recordings, 87.5% of patients were responders or seizure free. All of the patients in whom electric stimulation reproduced spontaneous seizures were responders. CONCLUSION: Our results show the good benefit-risk ratio of the SEEG-guided procedure for patients suffering from MCD in whom surgery is risky. This study identifies 2 factors, focal low-voltage, high-frequency activity at seizure onset and lowered epileptogenic threshold in the coagulated area, that could be predictive of a favorable seizure outcome after RFTC.

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Magnetic Temporal Interference for Noninvasive Focal Brain Stimulation

10.1101/2022.01.10.475762 ◽

2022 ◽

Author(s):

Adam Khalifa ◽

Seyed Mahdi Abrishami ◽

Mohsen Zaeimbashi ◽

Alexander D. Tang ◽

Brian Coughlin ◽

...

Keyword(s):

Electric Fields ◽

Brain Stimulation ◽

High Frequency ◽

Low Frequency ◽

Brain Regions ◽

Strong Increase ◽

Non Invasive ◽

Frequency Magnetic Field ◽

Fos Expression ◽

The Brain

Non-invasive stimulation of deep brain regions has been a major goal for neuroscience and neuromodulation in the past three decades. Transcranial magnetic stimulation (TMS), for instance, cannot target deep regions in the brain without activating the overlying tissues and has a poor spatial resolution. In this manuscript, we propose a new concept that relies on the temporal interference of two high-frequency magnetic fields generated by two electromagnetic solenoids. To illustrate the concept, custom solenoids were fabricated and optimized to generate temporal interfering electric fields for rodent brain stimulation. C-Fos expression was used to track neuronal activation. C-Fos expression was not present in regions impacted by only one high-frequency magnetic field indicating ineffective recruitment of neural activity in non-target regions. In contrast, regions impacted by two fields that interfere to create a low-frequency envelope display a strong increase in c-Fos expression. Therefore, this magnetic temporal interference solenoid-based system provides a framework to perform further stimulation studies that would investigate the advantages it could bring over conventional TMS systems.

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Simultaneous human intracerebral stimulation and HD-EEG: ground-truth for source localization methods

10.1101/2020.02.14.948984 ◽

2020 ◽

Author(s):

Ezequiel Mikulan ◽

Simone Russo ◽

Sara Parmigiani ◽

Simone Sarasso ◽

Flavia Maria Zauli ◽

...

Keyword(s):

Brain Activity ◽

Single Pulse ◽

Ground Truth ◽

Brain Regions ◽

Tissue Conductivity ◽

Implanted Electrodes ◽

Multiple Parameters ◽

Solution Methods ◽

Drug Resistant Epilepsy

AbstractPrecisely localizing the sources of brain activity as recorded by EEG is a fundamental procedure and a major challenge for both research and clinical practice. Even though many methods and algorithms have been proposed, their relative advantages and limitations are still not well established. Moreover, these methods involve tuning multiple parameters, for which no principled way of selection exists yet. These uncertainties are emphasized due to the lack of ground-truth for their validation and testing. Here we provide the first open dataset that comprises EEG recorded electrical activity originating from precisely known locations inside the brain of living humans. High-density EEG was recorded as single-pulse biphasic currents were delivered at intensities ranging from 0.1 to 5 mA through stereotactically implanted electrodes in diverse brain regions during pre-surgical evaluation of patients with drug-resistant epilepsy. The uses of this dataset range from the estimation of in vivo tissue conductivity to the development, validation and testing of forward and inverse solution methods.

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Spatiotemporal structure of intracranial electric fields induced by transcranial electric stimulation in human and nonhuman primates

10.1101/053892 ◽

2016 ◽

Cited By ~ 1

Author(s):

Alexander Opitz ◽

Arnaud Falchier ◽

Chao-Gan Yan ◽

Erin Yeagle ◽

Gary Linn ◽

...

Keyword(s):

Electric Field ◽

Electric Fields ◽

Electric Stimulation ◽

Brain Regions ◽

Electrode Arrays ◽

Non Invasive ◽

Crucial Information ◽

Cebus Monkeys ◽

Transcranial Electric Stimulation ◽

The Brain

AbstractTranscranial electric stimulation (TES) is an emerging technique, developed to non-invasively modulate brain function. However, the spatiotemporal distribution of the intracranial electric fields induced by TES remains poorly understood. In particular, it is unclear how much current actually reaches the brain, and how it distributes across the brain. Lack of this basic information precludes a firm mechanistic understanding of TES effects. In this study we directly measure the spatial and temporal characteristics of the electric field generated by TES using stereotactic EEG (s-EEG) electrode arrays implanted in cebus monkeys and surgical epilepsy patients. We found a small frequency dependent decrease (10%) in magnitudes of TES induced potentials and negligible phase shifts over space. Electric field strengths were strongest in superficial brain regions with maximum values of about 0.5 mV/mm. Our results provide crucial information for the interpretation of human TES studies and the optimization and design of TES stimulation protocols. In addition, our findings have broad implications concerning electric field propagation in non-invasive recording techniques such as EEG/MEG.

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Virtual resection predicts surgical outcome for drug-resistant epilepsy

Brain ◽

10.1093/brain/awz303 ◽

2019 ◽

Vol 142 (12) ◽

pp. 3892-3905 ◽

Cited By ~ 19

Author(s):

Lohith G Kini ◽

John M Bernabei ◽

Fadi Mikhail ◽

Peter Hadar ◽

Preya Shah ◽

...

Keyword(s):

Characteristic Curve ◽

Improve Patient Care ◽

Brain Regions ◽

Brain Network ◽

Drug Resistant ◽

Focal Lesions ◽

Intracranial Eeg ◽

Network Methods ◽

Drug Resistant Epilepsy ◽

Intracranial Electrodes

Abstract Patients with drug-resistant epilepsy often require surgery to become seizure-free. While laser ablation and implantable stimulation devices have lowered the morbidity of these procedures, seizure-free rates have not dramatically improved, particularly for patients without focal lesions. This is in part because it is often unclear where to intervene in these cases. To address this clinical need, several research groups have published methods to map epileptic networks but applying them to improve patient care remains a challenge. In this study we advance clinical translation of these methods by: (i) presenting and sharing a robust pipeline to rigorously quantify the boundaries of the resection zone and determining which intracranial EEG electrodes lie within it; (ii) validating a brain network model on a retrospective cohort of 28 patients with drug-resistant epilepsy implanted with intracranial electrodes prior to surgical resection; and (iii) sharing all neuroimaging, annotated electrophysiology, and clinical metadata to facilitate future collaboration. Our network methods accurately forecast whether patients are likely to benefit from surgical intervention based on synchronizability of intracranial EEG (area under the receiver operating characteristic curve of 0.89) and provide novel information that traditional electrographic features do not. We further report that removing synchronizing brain regions is associated with improved clinical outcome, and postulate that sparing desynchronizing regions may further be beneficial. Our findings suggest that data-driven network-based methods can identify patients likely to benefit from resective or ablative therapy, and perhaps prevent invasive interventions in those unlikely to do so.

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Modeling intracranial electrodes

10.1101/2021.04.28.441828 ◽

2021 ◽

Author(s):

Alejandro Blenkmann ◽

Anne-Kristin Solbakk ◽

Jugoslav Ivanovic ◽

Pål Gunnar Larsson ◽

Robert T. Knight ◽

...

Keyword(s):

Electrode Array ◽

Localization Algorithm ◽

Electrode Arrays ◽

Implanted Electrodes ◽

Brain Functions ◽

Brain Surface ◽

Depth Electrodes ◽

Surgical Evaluation ◽

Drug Resistant Epilepsy ◽

Intracranial Electrodes

AbstractBackgroundIntracranial electrodes are implanted in patients with drug-resistant epilepsy as part of their pre-surgical evaluation. This allows investigation of normal and pathological brain functions with excellent spatial and temporal resolution. The spatial resolution relies on methods that precisely localize the implanted electrodes in the cerebral cortex, which is critical for drawing valid anatomical inferences about brain function.Multiple methods have been developed to localize implanted electrodes, mainly relying on pre-implantation MRI and post-implantation CT images. However, there is no standard approach to quantify the performance of these methods systematically.The purpose of our work is to model intracranial electrodes to simulate realistic implantation scenarios, thereby providing methods to optimize localization algorithm performance.ResultsWe implemented novel methods to model the coordinates of implanted grids, strips, and depth electrodes, as well as the CT artifacts produced by these.We successfully modeled a large number of realistic implantation “scenarios”, including different sizes, inter-electrode distances, and brain areas. In total, more than 3300 grids and strips were fitted over the brain surface, and more than 850 depth electrode arrays penetrating the cortical tissue were modeled. More than 37000 simulations of electrode array CT artifacts were performed in these “scenarios”, mimicking the intensity profile and orientation of real artifactual voxels. Realistic artifacts were simulated by introducing different noise levels, as well as overlapping electrodes.ConclusionsWe successfully developed the first platform to model implanted intracranial grids, strips, and depth electrodes and realistically simulate CT artifacts and noise.These methods set the basis for developing more complex models, while simulations allow the performance evaluation of electrode localization techniques systematically.The methods described in this article, and the results obtained from the simulations, are freely available via open repositories. A graphical user interface implementation is also accessible via the open-source iElectrodes toolbox.

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Group-Level Analysis of Induced Electric Field in Deep Brain Regions by Different TMS Coils

10.1101/786459 ◽

2019 ◽

Cited By ~ 1

Author(s):

Jose Gomez-Tames ◽

Atsushi Hamasaka ◽

Akimasa Hirata ◽

Ilkka Laakso ◽

Mai Lu ◽

...

Keyword(s):

Electric Fields ◽

Brain Regions ◽

Invasive Technique ◽

Group Level ◽

Registration Method ◽

Non Invasive ◽

Consistent Group ◽

Coil Performance ◽

Deep Brain Region ◽

Deep Brain

AbstractDeep transcranial magnetic stimulation (dTMS) is a non-invasive technique used in treating depression. In this study, we computationally evaluate group-level dosage during dTMS with the aim of characterizing targeted deep brain regions to overcome the limitation of using individualized head models to characterize coil performance in a population.We use an inter-subject registration method adapted to deep brain regions that enable projection of computed electric fields (EFs) from individual realistic head models (n= 18) to the average space of deep brain regions. The computational results showed consistent group-level hotspots of the EF in deep brain region with intensities between 20%-50% of the maximum EF in the cortex. Large co-activation in other brain regions was confirmed while half-value penetration depth from the cortical surface was smaller than 2 cm. The halo figure-8 assembly and halo circular assembly coils induced the highest EFs for caudate, putamen, and hippocampus.Generalized induced EF maps of deep regions show target regions despite inter-individual difference. This is the first study that visualizes generalized target regions during dTMS and provides a method for making informed decisions during dTMS interventions in clinical practice.

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