| 1. |
- Botzanowski, Boris, et al.
(författare)
-
Noninvasive Stimulation of Peripheral Nerves using Temporally-Interfering Electrical Fields
- 2022
-
Ingår i: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659. ; 11:17
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
- Missey, Florian, et al.
(författare)
-
Laser-Driven Wireless Deep Brain Stimulation using Temporal Interference and Organic Electrolytic Photocapacitors
- 2022
-
Ingår i: Advanced Functional Materials. - : WILEY-V C H VERLAG GMBH. - 1616-301X .- 1616-3028. ; 32:33
-
Tidskriftsartikel (refereegranskat)abstract
- Deep brain stimulation (DBS) is a technique commonly used both in clinical and fundamental neurosciences. Classically, brain stimulation requires an implanted and wired electrode system to deliver stimulation directly to the target area. Although techniques such as temporal interference (TI) can provide stimulation at depth without involving any implanted electrodes, these methods still rely on a wired apparatus which limits free movement. Herein organic photocapacitors as untethered light-driven electrodes which convert deep-red light into electric current are reported. Pairs of these ultrathin devices can be driven using lasers at two different frequencies to deliver stimulation at depth via temporally interfering fields. This concept of laser TI stimulation using numerical modeling, tests with phantom brain samples, and finally in vivo tests is validated. Wireless organic photocapacitors are placed on the cortex and elicit stimulation in the hippocampus, while not delivering off-target stimulation in the cortex. This laser-driven wireless TI evokes a neuronal response at depth that is comparable to control experiments induced with deep brain stimulation protocols using implanted electrodes. This work shows that a combination of these two techniques-temporal interference and organic electrolytic photocapacitors-provides a reliable way to target brain structures requiring neither deeply implanted electrodes nor tethered stimulator devices. The laser TI protocol demonstrated here addresses two of the most important drawbacks in the field of DBS and thus holds potential to solve many issues in freely moving animal experiments or for clinical chronic therapy application.
|
|
| 3. |
- Missey, Florian, et al.
(författare)
-
Obstructive sleep apnea improves with non-invasive hypoglossal nerve stimulation using temporal interference
- 2023
-
Ingår i: Bioelectronic Medicine. - : BioMed Central (BMC). - 2332-8886. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Peripheral nerve stimulation is used in both clinical and fundamental research for therapy and exploration. At present, non-invasive peripheral nerve stimulation still lacks the penetration depth to reach deep nerve targets and the stimulation focality to offer selectivity. It is therefore rarely employed as the primary selected nerve stimulation method. We have previously demonstrated that a new stimulation technique, temporal interference stimulation, can overcome depth and focality issues.Methods: Here, we implement a novel form of temporal interference, bilateral temporal interference stimulation, for bilateral hypoglossal nerve stimulation in rodents and humans. Pairs of electrodes are placed alongside both hypoglossal nerves to stimulate them synchronously and thus decrease the stimulation amplitude required to activate hypoglossal-nerve-controlled tongue movement.Results: Comparing bilateral temporal interference stimulation with unilateral temporal interference stimulation, we show that it can elicit the same behavioral and electrophysiological responses at a reduced stimulation amplitude. Traditional transcutaneous stimulation evokes no response with equivalent amplitudes of stimulation.Conclusions: During first-in-man studies, temporal interference stimulation was found to be well-tolerated, and to clinically reduce apnea-hypopnea events in a subgroup of female patients with obstructive sleep apnea. These results suggest a high clinical potential for the use of temporal interference in the treatment of obstructive sleep apnea and other diseases as a safe, effective, and patient-friendly approach.Trial registration: The protocol was conducted with the agreement of the International Conference on Harmonisation Good Clinical Practice (ICH GCP), applicable United States Code of Federal Regulations (CFR) and followed the approved BRANY IRB File # 22-02-636-1279.
|
|
| 4. |
- Missey, Florian, et al.
(författare)
-
Organic electrolytic photocapacitors for stimulation of the mouse somatosensory cortex
- 2021
-
Ingår i: Journal of Neural Engineering. - : IOP Publishing Ltd. - 1741-2560 .- 1741-2552. ; 18:6
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. For decades electrical stimulation has been used in neuroscience to investigate brain networks and been deployed clinically as a mode of therapy. Classically, all methods of electrical stimulation require implanted electrodes to be connected in some manner to an apparatus which provides power for the stimulation itself. Approach. We show the use of novel organic electronic devices, specifically organic electrolytic photocapacitors (OEPCs), which can be activated when illuminated with deep-red wavelengths of light and correspondingly do not require connections with external wires or power supplies when implanted at various depths in vivo. Main results. We stimulated cortical brain tissue of mice with devices implanted subcutaneously, as well as beneath both the skin and skull to demonstrate a wireless stimulation of the whisker motor cortex. Devices induced both a behavior response (whisker movement) and a sensory response in the corresponding sensory cortex. Additionally, we showed that coating OEPCs with a thin layer of a conducting polymer formulation (PEDOT:PSS) significantly increases their charge storage capacity, and can be used to further optimize the applied photoelectrical stimulation. Significance. Overall, this new technology can provide an on-demand electrical stimulation by simply using an OEPC and a deep-red wavelength illumination. Wires and interconnects to provide power to implanted neurostimulation electrodes are often problematic in freely-moving animal research and with implanted electrodes for long-term therapy in patients. Our wireless brain stimulation opens new perspectives for wireless electrical stimulation for applications in fundamental neurostimulation and in chronic therapy.
|
|
| 5. |
- Missey, Florian, et al.
(författare)
-
Orientation of Temporal Interference for Non-invasive Deep Brain Stimulation in Epilepsy
- 2021
-
Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 15
-
Tidskriftsartikel (refereegranskat)abstract
- 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).
|
|
