Biology subjects

ACERBO, E.

Publications and source records attributed to ACERBO, E..

5 recordsLinked to original sources

bioRxiv2024

Improved Temporal and Spatial Focality of Non-invasive Deep-brain Stimulation using Multipolar Single-pulse Temporal Interference with Applications in Epilepsy

Temporal Interference (TI) is an emerging method to non-invasively stimulate deep brain structures. This innovative technique is increasingly recognized for its potential applications in the treatment of various neurological disorders, including epilepsy, depression, and Alzheimers disease. However, several drawbacks to the TI method exist that we aim to improve upon. To begin, the applied electric field in the TI target is not much higher than what non-invasive transcranial alternating current stimulation (TACS) provides in the cortex. Additionally, the TI stimulation onset is dependent on the envelope of the amplitude modulated (AM) signal, where for example 1 Hz and 100 Hz envelopes have significantly different rise times to reach maximum envelope amplitude - unlike square biphasic pulses. This limitation in turn prevents classic TI, from applying bursts of pulses. Finally, the electric field intensity of TI cannot be increased or decreased at the target without dramatically altering the spatial profile of the stimulation focus. In the work presented here, we efficiently address all three of these limitations. First, we performed two-photon calcium imaging to show that individual neurons selectively respond to the TI envelope frequency, providing evidence that TI modulates neural activity with temporal specificity. This marks a significant advancement, representing the first empirical demonstration of neuronal activation at the {Delta}f frequency within the context of TI and in an imaging modality. Subsequently, we compared the AM signals of TI with phase-shift keying (PSK) modulated signals to highlight the superior effectiveness of noninvasive pulses in contrast to the traditional TI method, particularly in inducing epileptic activity (after-discharges) in mice. We also added a multipolar configuration to create a significant increase in the electric field at the target without significantly altering the spatial profile and applied Fourier components to replicate classic biphasic bursts of square pulses - all transcranially, without the use of penetrating electrodes. These innovations aim to enhance the precision and efficacy of TI stimulation, to advance its application in neurological research and therapy. Key Points / HighlightsO_LINon-invasive temporal interference stimulation modulates the activity of individual neurons at the envelope frequency. C_LIO_LIA non-invasive multi-pulse TI stimulation paradigm improves both temporal and spatial focality in the deep target neural tissue when compared to traditional continuous wave (amplitude-modulated) TI stimulation. C_LIO_LIPulse TI paradigms can stimulate deep neural targets with reduced amplitude of the topical high-frequency stimulation, decreasing off-target stimulation when compared to continuous wave TI patterns. As a consequence, pulse TI stimulation reduces the risk of undesired side effects such as high-frequency conduction block in off-target tissues or cortical areas. C_LIO_LIBoth temporal and spatial focality of the TI stimulation pattern positively correlate with the efficacy of the stimulation to induce seizures in the mouse hippocampus. C_LI

neuroscience↗

bioRxiv2023

Controlling focality and intensity of non-invasive deep brain stimulation using multipolar temporal interference in non-human primates and rodents

Temporal interference (TI) is a method of non-invasive brain stimulation using transcutaneous electrodes that allows the targeting and modulation of deeper brain structures, not normally associated with non-invasive simulation, while avoiding unwanted stimulation of shallower cortical structures. The properties of TI have been previously demonstrated, however, the problem of decoupling stimulation focality from stimulation intensity has not been addressed. In this paper, we provide a possible novel solution, multipolar TI (mTI), which allows increased independent control over both the size of the stimulated region and the stimulation intensity. The mTI method uses multiple carrier frequencies to create multiple overlapping amplitude-modulated envelopes, rather than using one envelope as in standard TI. The study presents an explanation of the concept of mTI along with experimental data gathered from Rhesus macaques and mice. We improved the focality at depth in anesthetized mice and monkeys, and using the new focality in awake monkeys, evoked targeted activity at depth in the superior colliculus. The mTI method could be an interesting and potentially useful new tool alongside other forms of non-invasive brain stimulation. Teaser: Multipolar Temporal Interference Stimulation can produce a more focal brain stimulation at depth compared to Temporal Interference.

neuroscience↗

bioRxiv2023

Obstructive Sleep Apnea Improves with Non-invasive Hypoglossal Nerve Stimulation using Temporal Interference

BackgroundPeripheral 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. MethodsHere, 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. ResultsComparing 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. ConclusionsDuring 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 registrationThe 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.

neuroscience↗

bioRxiv2021

Laser-driven Wireless Deep Brain Stimulation using Temporal Interference and Organic Electrolytic Photocapacitors

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 we report organic photocapacitors as untethered light-driven electrodes which convert deep-red light into electric current. Pairs of these ultrathin devices can be driven using lasers at two different frequencies to deliver stimulation at depth via temporally interfering fields. We validate this concept of laser TI stimulation using numerical modeling, ex vivo tests with phantom samples, and finally in vivo tests. 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 evoked a neuronal response at depth that is comparable to control experiments induced with deep brain stimulation protocols using implanted electrodes. Our 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 address two of the most important drawbacks in the field of deep brain stimulation and thus holds potential to solve many issues in freely-moving animal experiments or for clinical chronic therapy application.

bioengineering↗

bioRxiv2021

Organic electrolytic photocapacitors for stimulation of the mouse somatosensory cortex

ObjectiveFor 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. ApproachWe 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 resultsWe 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. SignificanceOverall, 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.

bioengineering↗