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1. Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning

Author

Wessel, Maximilian J., Beanato, Elena, Popa, Traian, Windel, Fabienne, Vassiliadis, Pierre, Menoud, Pauline, Beliaeva, Valeriia, Violante, Ines R., Abderrahmane, Hedjoudje, Dzialecka, Patrycja, Park, Chang-Hyun, Maceira-Elvira, Pablo, Morishita, Takuya, Cassara, Antonino M., Steiner, Melanie, Grossman, Nir, Neufeld, Esra, and Hummel, Friedhelm C.

Published
2023
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3. Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis

Author

Rowald, Andreas, Komi, Salif, Demesmaeker, Robin, Baaklini, Edeny, Hernandez-Charpak, Sergio Daniel, Paoles, Edoardo, Montanaro, Hazael, Cassara, Antonino, Becce, Fabio, Lloyd, Bryn, Newton, Taylor, Ravier, Jimmy, Kinany, Nawal, D’Ercole, Marina, Paley, Aurélie, Hankov, Nicolas, Varescon, Camille, McCracken, Laura, Vat, Molywan, Caban, Miroslav, Watrin, Anne, Jacquet, Charlotte, Bole-Feysot, Léa, Harte, Cathal, Lorach, Henri, Galvez, Andrea, Tschopp, Manon, Herrmann, Natacha, Wacker, Moïra, Geernaert, Lionel, Fodor, Isabelle, Radevich, Valentin, Van Den Keybus, Katrien, Eberle, Grégoire, Pralong, Etienne, Roulet, Maxime, Ledoux, Jean-Baptiste, Fornari, Eleonora, Mandija, Stefano, Mattera, Loan, Martuzzi, Roberto, Nazarian, Bruno, Benkler, Stefan, Callegari, Simone, Greiner, Nathan, Fuhrer, Benjamin, Froeling, Martijn, Buse, Nik, Denison, Tim, Buschman, Rik, Wende, Christian, Ganty, Damien, Bakker, Jurriaan, Delattre, Vincent, Lambert, Hendrik, Minassian, Karen, van den Berg, Cornelis A. T., Kavounoudias, Anne, Micera, Silvestro, Van De Ville, Dimitri, Barraud, Quentin, Kurt, Erkan, Kuster, Niels, Neufeld, Esra, Capogrosso, Marco, Asboth, Leonie, Wagner, Fabien B., Bloch, Jocelyne, and Courtine, Grégoire

Published
2022
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7. Non-Invasive Deep-Brain Stimulation Using Pulsed Temporally Interfering Electric Fields for Epilepsy

Author

Acerbo, Emma, primary, Botzanowski, Boris, additional, Dellavale, Damian, additional, Stern, Matthew A., additional, Cole, Eric R., additional, Gutekunst, Claire-Anne, additional, Gantt, Miller L., additional, Steiner, Melanie, additional, Missey, Florian, additional, Cassara, Antonino, additional, Neufeld, Esra, additional, Berglund, Ken, additional, Jirsa, Viktor, additional, Gross, Robert E., additional, Drane, Daniel L., additional, Glowacki, Eric Daniel, additional, Pakhomov, Andrei G., additional, and Williamson, Adam, additional

Published
2024
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9. Non-invasive suppression of essential tremor via phase-locked disruption of its temporal coherence

Author

Li, Junheng, primary, Schreglmann, Sebastian, additional, Wang, David, additional, Peach, Robert, additional, Laurate, Anna, additional, Rhodes, Edward, additional, Panella, Emanuele, additional, Cassara, Antonino, additional, Boyden, Edward, additional, Barahona, Mauricio, additional, Rothwell, John, additional, Bhatia, Kailash, additional, and Grossman, Nir, additional

Published
2023
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10. LTP-like noninvasive striatal brain stimulation enhances striatal activity and motor skill learning in humans

Author

Wessel, Maximilian J., primary, Beanato, Elena, additional, Popa, Traian, additional, Windel, Fabienne, additional, Vassiliadis, Pierre, additional, Menoud, Pauline, additional, Beliaeva, Valeriia, additional, Violante, Ines R., additional, Abderrahmane, Hedjoudje, additional, Dzialecka, Patrycja, additional, Park, Chang-Hyun, additional, Maceira-Elvira, Pablo, additional, Morishita, Takuya, additional, Cassara, Antonino, additional, Steiner, Melanie, additional, Grossman, Nir, additional, Neufeld, Esra, additional, and Hummel, Friedhelm C., additional

Published
2022
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15. Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers

Author

Acerbo, Emma, primary, Jegou, Aude, additional, Luff, Charlotte, additional, Dzialecka, Patrycja, additional, Botzanowski, Boris, additional, Missey, Florian, additional, Ngom, Ibrahima, additional, Lagarde, Stanislas, additional, Bartolomei, Fabrice, additional, Cassara, Antonino, additional, Neufeld, Esra, additional, Jirsa, Viktor, additional, Carron, Romain, additional, Grossman, Nir, additional, and Williamson, Adam, additional

Published
2022
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16. Noninvasive Stimulation of Peripheral Nerves using Temporally-Interfering Electrical Fields

Author

Botzanowski, Boris, Donahue, Mary, Silverå Ejneby, Malin, Gallina, Alessandro L., Ngom, Ibrahima, Missey, Florian, Acerbo, Emma, Byun, Donghak, Carron, Romain, Cassara, Antonino M., Neufeld, Esra, Jirsa, Viktor, Olofsson, Peder S., Glowacki, Eric Daniel, Williamson, Adam, Botzanowski, Boris, Donahue, Mary, Silverå Ejneby, Malin, Gallina, Alessandro L., Ngom, Ibrahima, Missey, Florian, Acerbo, Emma, Byun, Donghak, Carron, Romain, Cassara, Antonino M., Neufeld, Esra, Jirsa, Viktor, Olofsson, Peder S., Glowacki, Eric Daniel, and Williamson, Adam

Abstract

Electrical stimulation of peripheral nerves is a cornerstone of bioelectronic medicine. Effective ways to accomplish peripheral nerve stimulation (PNS) noninvasively without surgically implanted devices are enabling for fundamental research and clinical translation. Here, it is demonstrated how relatively high-frequency sine-wave carriers (3 kHz) emitted by two pairs of cutaneous electrodes can temporally interfere at deep peripheral nerve targets. The effective stimulation frequency is equal to the offset frequency (0.5 - 4 Hz) between the two carriers. This principle of temporal interference nerve stimulation (TINS) in vivo using the murine sciatic nerve model is validated. Effective actuation is delivered at significantly lower current amplitudes than standard transcutaneous electrical stimulation. Further, how flexible and conformable on-skin multielectrode arrays can facilitate precise alignment of TINS onto a nerve is demonstrated. This method is simple, relying on the repurposing of existing clinically-approved hardware. TINS opens the possibility of precise noninvasive stimulation with depth and efficiency previously impossible with transcutaneous techniques., Funding Agencies|European Research Council (ERC) under the European Union [716867, 949191]; City Council of Brno, Czech Republic; European Research Council [834677]; Swedish Research Council; MedTechLabs

Published
2022
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17. Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis

Author

Computational Imaging, Cancer, Highfield Research Group, Brain, Circulatory Health, Rowald, Andreas, Komi, Salif, Demesmaeker, Robin, Baaklini, Edeny, Hernandez-Charpak, Sergio Daniel, Paoles, Edoardo, Montanaro, Hazael, Cassara, Antonino, Becce, Fabio, Lloyd, Bryn, Newton, Taylor, Ravier, Jimmy, Kinany, Nawal, D'Ercole, Marina, Paley, Aurélie, Hankov, Nicolas, Varescon, Camille, McCracken, Laura, Vat, Molywan, Caban, Miroslav, Watrin, Anne, Jacquet, Charlotte, Bole-Feysot, Léa, Harte, Cathal, Lorach, Henri, Galvez, Andrea, Tschopp, Manon, Herrmann, Natacha, Wacker, Moïra, Geernaert, Lionel, Fodor, Isabelle, Radevich, Valentin, Van Den Keybus, Katrien, Eberle, Grégoire, Pralong, Etienne, Roulet, Maxime, Ledoux, Jean-Baptiste, Fornari, Eleonora, Mandija, Stefano, Mattera, Loan, Martuzzi, Roberto, Nazarian, Bruno, Benkler, Stefan, Callegari, Simone, Greiner, Nathan, Fuhrer, Benjamin, Froeling, Martijn, Buse, Nik, Denison, Tim, Buschman, Rik, Wende, Christian, Ganty, Damien, Bakker, Jurriaan, Delattre, Vincent, Lambert, Hendrik, Minassian, Karen, van den Berg, Cornelis A T, Kavounoudias, Anne, Micera, Silvestro, Van De Ville, Dimitri, Barraud, Quentin, Kurt, Erkan, Kuster, Niels, Neufeld, Esra, Capogrosso, Marco, Asboth, Leonie, Wagner, Fabien B, Bloch, Jocelyne, Courtine, Grégoire, Computational Imaging, Cancer, Highfield Research Group, Brain, Circulatory Health, Rowald, Andreas, Komi, Salif, Demesmaeker, Robin, Baaklini, Edeny, Hernandez-Charpak, Sergio Daniel, Paoles, Edoardo, Montanaro, Hazael, Cassara, Antonino, Becce, Fabio, Lloyd, Bryn, Newton, Taylor, Ravier, Jimmy, Kinany, Nawal, D'Ercole, Marina, Paley, Aurélie, Hankov, Nicolas, Varescon, Camille, McCracken, Laura, Vat, Molywan, Caban, Miroslav, Watrin, Anne, Jacquet, Charlotte, Bole-Feysot, Léa, Harte, Cathal, Lorach, Henri, Galvez, Andrea, Tschopp, Manon, Herrmann, Natacha, Wacker, Moïra, Geernaert, Lionel, Fodor, Isabelle, Radevich, Valentin, Van Den Keybus, Katrien, Eberle, Grégoire, Pralong, Etienne, Roulet, Maxime, Ledoux, Jean-Baptiste, Fornari, Eleonora, Mandija, Stefano, Mattera, Loan, Martuzzi, Roberto, Nazarian, Bruno, Benkler, Stefan, Callegari, Simone, Greiner, Nathan, Fuhrer, Benjamin, Froeling, Martijn, Buse, Nik, Denison, Tim, Buschman, Rik, Wende, Christian, Ganty, Damien, Bakker, Jurriaan, Delattre, Vincent, Lambert, Hendrik, Minassian, Karen, van den Berg, Cornelis A T, Kavounoudias, Anne, Micera, Silvestro, Van De Ville, Dimitri, Barraud, Quentin, Kurt, Erkan, Kuster, Niels, Neufeld, Esra, Capogrosso, Marco, Asboth, Leonie, Wagner, Fabien B, Bloch, Jocelyne, and Courtine, Grégoire

Published
2022

18. Non-invasive suppression of essential tremor via phase-locked disruption of its temporal coherence

Author

Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, McGovern Institute for Brain Research at MIT, Program in Media Arts and Sciences (Massachusetts Institute of Technology), Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. Center for Neurobiological Engineering, Koch Institute for Integrative Cancer Research at MIT, Schreglmann, Sebastian R, Wang, David, Peach, Robert L, Li, Junheng, Zhang, Xu, Latorre, Anna, Rhodes, Edward, Panella, Emanuele, Cassara, Antonino M, Boyden, Edward S, Barahona, Mauricio, Santaniello, Sabato, Rothwell, John, Bhatia, Kailash P, Grossman, Nir, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, McGovern Institute for Brain Research at MIT, Program in Media Arts and Sciences (Massachusetts Institute of Technology), Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. Center for Neurobiological Engineering, Koch Institute for Integrative Cancer Research at MIT, Schreglmann, Sebastian R, Wang, David, Peach, Robert L, Li, Junheng, Zhang, Xu, Latorre, Anna, Rhodes, Edward, Panella, Emanuele, Cassara, Antonino M, Boyden, Edward S, Barahona, Mauricio, Santaniello, Sabato, Rothwell, John, Bhatia, Kailash P, and Grossman, Nir

Abstract

© 2021, The Author(s). Aberrant neural oscillations hallmark numerous brain disorders. Here, we first report a method to track the phase of neural oscillations in real-time via endpoint-corrected Hilbert transform (ecHT) that mitigates the characteristic Gibbs distortion. We then used ecHT to show that the aberrant neural oscillation that hallmarks essential tremor (ET) syndrome, the most common adult movement disorder, can be transiently suppressed via transcranial electrical stimulation of the cerebellum phase-locked to the tremor. The tremor suppression is sustained shortly after the end of the stimulation and can be phenomenologically predicted. Finally, we use feature-based statistical-learning and neurophysiological-modelling to show that the suppression of ET is mechanistically attributed to a disruption of the temporal coherence of the aberrant oscillations in the olivocerebellar loop, thus establishing its causal role. The suppression of aberrant neural oscillation via phase-locked driven disruption of temporal coherence may in the future represent a powerful neuromodulatory strategy to treat brain disorders.

Published
2021

20. Current directions in the auricular vagus nerve stimulation II - an engineering perspective

Author

Kaniusas, Eugenijus, Kampusch, Stefan, Tittgemeyer, Marc, Panetsos, Fivos, Fernandez Gines, Raquel, Papa, Michele, Kiss, Attila, Podesser, Bruno, Cassara, Antonino Mario, Tanghe, Emmeric, Samoudi, Amine Mohammed, Tarnaud, Thomas, Joseph, Wout, Marozas, Vaidotas, Lukosevicius, Arunas, Ištuk, Niko, Lechner, Sarah, Klonowski, Wlodzimierz, Varoneckas, Giedrius, Széles, Jozsef Constantin, Šarolić, Antonio, Frontiers, Kaniusas, Eugeniju, Kampusch, Stefan, Tittgemeyer, Marc, Panetsos, Fivo, Gines, Raquel Fernandez, Papa, Michele, Kiss, Attila, Podesser, Bruno, Cassara, Antonino Mario, Tanghe, Emmeric, Samoudi, Amine Mohammed, Tarnaud, Thoma, Joseph, Wout, Marozas, Vaidota, Lukosevicius, Aruna, Ištuk, Niko, Lechner, Sarah, Klonowski, Wlodzimierz, Varoneckas, Giedriu, Széles, Jozsef Constantin, and Šarolić, Antonio

Subjects
Technology and Engineering, stimulation optimization, stimulation patterns, General Neuroscience, vagus nerve stimulation, HEART-RATE, Review, ELECTRICAL-STIMULATION, EFFICACY, BRAIN-STEM, in silico modeling, CLOSED-LOOP, MECHANISMS, auricular nerves, auricular transillumination, personalized stimulation, MODEL, stimulation pattern, EXCITABILITY, ATRIAL-FIBRILLATION, auricular nerve, MODULATION, Neuroscience
Abstract

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging electroceutical technology in the field of bioelectronic medicine with applications in therapy. Artificial modulation of the afferent vagus nerve – a powerful entrance to the brain – affects a large number of physiological processes implicating interactions between the brain and body. Engineering aspects of aVNS determine its efficiency in application. The relevant safety and regulatory issues need to be appropriately addressed. In particular, in silico modeling acts as a tool for aVNS optimization. The evolution of personalized electroceuticals using novel architectures of the closed-loop aVNS paradigms with biofeedback can be expected to optimally meet therapy needs. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the scope of EU COST Action “European network for innovative uses of EMFs in biomedical applications (BM1309).” Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on engineering aspects – a discussion of physiological aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Published
2019

22. SPARC’s Open Online Simulation Platform for Computational Modeling of the ANS’s Physiological Role and its Modulation by Electroceutical Devices: o 2 S 2 PARC

Author

Neufeld, Esra, primary, Chavannes, Nicolas, additional, Zhuang, Katie Zhi, additional, Cassara, Antonino, additional, Lloyd, Bryn, additional, Crespo-Valero, Pedro, additional, Guidon, Manuel, additional, Maiz, Odei, additional, Anderegg, Sylvain, additional, Pascual, Ignacio, additional, Kainz, Wolfgang, additional, and Kuster, Niels, additional

Published
2020
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24. Current directions in the auricular vagus nerve stimulation I - A physiological perspective

Author

Kaniusas, Eugenijus, Kampusch, Stefan, Tittgemeyer, Marc, Panetsos, Fivos, Fernandez Gines, Raquel, Papa, Michele, Kiss, Attila, Podesser, Bruno, Cassara, Antonino Mario, Tanghe, Emmeric, Samoudi, Amine Mohammed, Tarnaud, Thomas, Joseph, Wout, Marozas, Vaidotas, Lukosevicius, Arunas, Istuk, Niko, Šarolić, Antonio, Lechner, Sarah, Klonowski, Wlodzimierz, Varoneckas, Giedrius, Széles, Jozsef Constantin, Kaniusas, E., Kampusch, S., Tittgemeyer, M., Panetsos, F., Gines, R. F., Papa, M., Kiss, A., Podesser, B., Cassara, A. M., Tanghe, E., Samoudi, A. M., Tarnaud, T., Joseph, W., Marozas, V., Lukosevicius, A., Istuk, N., Sarolic, A., Lechner, S., Klonowski, W., Varoneckas, G., and Szeles, J. C.

Subjects
Technology and Engineering, AUTONOMIC FUNCTION, Review, nerve stimulation, BRAIN-STEM, Clinical studie, biophysics, TRANSCUTANEOUS ELECTRICAL-STIMULATION, clinical studies, ANTIINFLAMMATORY PATHWAY, animal research, HEART-RATE-VARIABILITY, NITRIC-OXIDE, General Neuroscience, INFARCT SIZE, INFLAMMATORY RESPONSE, CONSCIOUS DOGS, Biophysic, inflammation, VAGAL, auricular vagus nerve, brain plasticity, AFFERENT MODULATION, Neuroscience
Abstract

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging technology in the field of bioelectronic medicine with applications in therapy. Modulation of the afferent vagus nerve affects a large number of physiological processes and bodily states associated with information transfer between the brain and body. These include disease mitigating effects and sustainable therapeutic applications ranging from chronic pain diseases, neurodegenerative and metabolic ailments to inflammatory and cardiovascular diseases. Given the current evidence from experimental research in animal and clinical studies we discuss basic aVNS mechanisms and their potential clinical effects. Collectively, we provide a focused review on the physiological role of the vagus nerve and formulate a biology-driven rationale for aVNS. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the framework of EU COST Action “European network for innovative uses of EMFs in biomedical applications (BM1309).” Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on physiological aspects – a discussion of engineering aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Published
2019

25. Local Multi-Channel RF Surface Coil versus Body RF Coil Transmission for Cardiac Magnetic Resonance at 3 Tesla: Which Configuration Is Winning the Game?

Author

Weinberger, Oliver, Winter, Lukas, Dieringer, Matthias A., Els, Antje, Oezerdem, Celal, Rieger, Jan, Kuehne, Andre, Cassara, Antonino M., Pfeiffer, Harald, Wetterling, Friedrich, and Niendorf, Thoralf

Subjects
Optimization, Computer and Information Sciences, Imaging Techniques, Cardiac Ventricles, Radio Waves, Materials Science, lcsh:Medicine, Research and Analysis Methods, Electromagnetism, Electromagnetic Fields, Medicine and Health Sciences, Humans, lcsh:Science, Materials by Attribute, Phantoms, Imaging, Simulation and Modeling, Physics, lcsh:R, Biology and Life Sciences, Heart, Magnetic Resonance Imaging, Benchmarking, Data Acquisition, Cardiovascular and Metabolic Diseases, Conductors, Physical Sciences, Cardiovascular Anatomy, lcsh:Q, Technology Platforms, Anatomy, Mathematics, Research Article
Abstract

INTRODUCTION: The purpose of this study was to demonstrate the feasibility and efficiency of cardiac MR at 3 Tesla using local four-channel RF coil transmission and benchmark it against large volume body RF coil excitation. METHODS: Electromagnetic field simulations are conducted to detail RF power deposition, transmission field uniformity and efficiency for local and body RF coil transmission. For both excitation regimes transmission field maps are acquired in a human torso phantom. For each transmission regime flip angle distributions and blood-myocardium contrast are examined in a volunteer study of 12 subjects. The feasibility of the local transceiver RF coil array for cardiac chamber quantification at 3 Tesla is demonstrated. RESULTS: Our simulations and experiments demonstrate that cardiac MR at 3 Tesla using four-channel surface RF coil transmission is competitive versus current clinical CMR practice of large volume body RF coil transmission. The efficiency advantage of the 4TX/4RX setup facilitates shorter repetition times governed by local SAR limits versus body RF coil transmission at whole-body SAR limit. No statistically significant difference was found for cardiac chamber quantification derived with body RF coil versus four-channel surface RF coil transmission. Our simulation also show that the body RF coil exceeds local SAR limits by a factor of ~2 when driven at maximum applicable input power to reach the whole-body SAR limit. CONCLUSION: Pursuing local surface RF coil arrays for transmission in cardiac MR is a conceptually appealing alternative to body RF coil transmission, especially for patients with implants.

Published
2016

29. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. Department of Materials Science and Engineering, Massachusetts Institute of Technology. Media Laboratory, McGovern Institute for Brain Research at MIT, Picower Institute for Learning and Memory, Grossman, Nir, Bono, David C, Dedic, Nina, Kodandaramaiah, Suhasa Bangalore, Rudenko, Andrii, Suk, Ho-Jun, Tsai, Li-Huei, Boyden, Edward, Cassara, Antonino M., Neufeld, Esra, Kuster, Niels, Pascual-Leone, Alvaro, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. Department of Materials Science and Engineering, Massachusetts Institute of Technology. Media Laboratory, McGovern Institute for Brain Research at MIT, Picower Institute for Learning and Memory, Grossman, Nir, Bono, David C, Dedic, Nina, Kodandaramaiah, Suhasa Bangalore, Rudenko, Andrii, Suk, Ho-Jun, Tsai, Li-Huei, Boyden, Edward, Cassara, Antonino M., Neufeld, Esra, Kuster, Niels, and Pascual-Leone, Alvaro

Abstract

We report a noninvasive strategy for electrically stimulating neurons at depth. By delivering to the brain multiple electric fields at frequencies too high to recruit neural firing, but which differ by a frequency within the dynamic range of neural firing, we can electrically stimulate neurons throughout a region where interference between the multiple fields results in a prominent electric field envelope modulated at the difference frequency. We validated this temporal interference (TI) concept via modeling and physics experiments, and verified that neurons in the living mouse brain could follow the electric field envelope. We demonstrate the utility of TI stimulation by stimulating neurons in the hippocampus of living mice without recruiting neurons of the overlying cortex. Finally, we show that by altering the currents delivered to a set of immobile electrodes, we can steerably evoke different motor patterns in living mice., National Institutes of Health (U.S.) (Award 1DP1NS087724), National Institutes of Health (U.S.) (Award 1R01MH103910-01), National Science Foundation (U.S.) (Award CBET 1053233), National Institutes of Health (U.S.) (Grant 1RF1AG047661), National Institutes of Health (U.S.) (Grant NS051874)

Published
2017

31. Non-invasive Temporal Interference Stimulation of the Hippocampus Suppresses Epileptic Biomarkers in Patients with Epilepsy: Biophysical Differences between Kilohertz and Amplitude Modulated Stimulation.

Author

Missey F, Acerbo E, Dickey A, Trajlinek J, Studnicka O, Lubrano C, De Araujo E Silva M, Brady E, Vsiansky V, Szabo JP, Dolezalova I, Fabo D, Pail M, Gutekunst CA, Migliore R, Migliore M, Lagarde S, Carron R, Karimi F, Astorga R, Cassara A, Kuster N, Neufeld E, Bartolomei F, Pedersen NP, Gross R, Jirsa V, Drane D, Brazdil M, and Williamson A

Abstract

Medication refractory focal epilepsy creates a significant challenge, with approximately 30% of patients ineligible for surgery due to the involvement of eloquent cortex in the epileptogenic network. For such patients with limited surgical options, electrical neuromodulation represents a promising alternative therapy. In this study, we investigate the potential of non-invasive temporal interference (TI) electrical stimulation to reduce epileptic biomarkers in patients with epilepsy by comparing intracerebral recordings obtained before, during, and after TI stimulation, to recordings during low and high kHz frequency (HF) sham stimulation. Thirteen patients with symptoms of mesiotemporal epilepsy (MTLE) and implanted with stereoelectroencephalography (sEEG) depth electrodes received TI stimulation with an amplitude modulation (AM) frequency of 130Hz (df), where the AM was delivered with lower frequency kHz carriers (1kHz + 1.13kHz), or higher frequency carriers (9kHz + 9.13kHz), targeting the hippocampus, a common epileptic focus and consequently stimulation target in MTLE. Our results show that TI stimulation yields a statistically significant decrease in interictal epileptiform discharges (IEDs) and pathological high-frequency oscillations (HFOs) specifically fast ripples (FR), where the suppression is apparent in the hippocampal focus and propagation from the focus is reduced brain-wide. HF sham stimulation at 1kHz frequency also impacted the IED rate in the cortex, but without reaching the hippocampal focus. The HF sham effect diminished with increasing frequencies (2, 5, and 9kHz, respectively), specifically as a function of depth into the cortex. This depth dependence was not observed with the TI, independent of the employed carrier frequency (low or high kHz). Furthermore, a strong carry-over effect, i.e., suppression of epileptic biomarkers for a period of time after the end of stimulation, was observed for TI but not for kHz. Our findings underscore the possible application of TI in epilepsy, as an additional non-invasive brain stimulation tool, potentially offering opportunities to assess brain region response to electrical neuromodulation before committing to a deep brain stimulation (DBS) or responsive neurostimulation (RNS) implants. Our results further demonstrate distinct biophysical differences between kHz and focal AM stimulation.

Published
2025
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32. Current Directions in the Auricular Vagus Nerve Stimulation I - A Physiological Perspective.

Author

Kaniusas E, Kampusch S, Tittgemeyer M, Panetsos F, Gines RF, Papa M, Kiss A, Podesser B, Cassara AM, Tanghe E, Samoudi AM, Tarnaud T, Joseph W, Marozas V, Lukosevicius A, Ištuk N, Šarolić A, Lechner S, Klonowski W, Varoneckas G, and Széles JC

Abstract

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging technology in the field of bioelectronic medicine with applications in therapy. Modulation of the afferent vagus nerve affects a large number of physiological processes and bodily states associated with information transfer between the brain and body. These include disease mitigating effects and sustainable therapeutic applications ranging from chronic pain diseases, neurodegenerative and metabolic ailments to inflammatory and cardiovascular diseases. Given the current evidence from experimental research in animal and clinical studies we discuss basic aVNS mechanisms and their potential clinical effects. Collectively, we provide a focused review on the physiological role of the vagus nerve and formulate a biology-driven rationale for aVNS. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the framework of EU COST Action "European network for innovative uses of EMFs in biomedical applications (BM1309)." Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on physiological aspects - a discussion of engineering aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Published
2019
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33. Current Directions in the Auricular Vagus Nerve Stimulation II - An Engineering Perspective.

Author

Kaniusas E, Kampusch S, Tittgemeyer M, Panetsos F, Gines RF, Papa M, Kiss A, Podesser B, Cassara AM, Tanghe E, Samoudi AM, Tarnaud T, Joseph W, Marozas V, Lukosevicius A, Ištuk N, Lechner S, Klonowski W, Varoneckas G, Széles JC, and Šarolić A

Abstract

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging electroceutical technology in the field of bioelectronic medicine with applications in therapy. Artificial modulation of the afferent vagus nerve - a powerful entrance to the brain - affects a large number of physiological processes implicating interactions between the brain and body. Engineering aspects of aVNS determine its efficiency in application. The relevant safety and regulatory issues need to be appropriately addressed. In particular, in silico modeling acts as a tool for aVNS optimization. The evolution of personalized electroceuticals using novel architectures of the closed-loop aVNS paradigms with biofeedback can be expected to optimally meet therapy needs. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the scope of EU COST Action "European network for innovative uses of EMFs in biomedical applications (BM1309)." Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on engineering aspects - a discussion of physiological aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Published
2019
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