Periodic Reporting for period 1 - TIMS (Deep Brain Neuromodulation using Temporal Interference Magnetic Stimulation)
Berichtszeitraum: 2022-11-01 bis 2024-04-30
Brain disorders are a leading cause of long-term disability worldwide, with conditions like stroke, multiple sclerosis, Parkinson’s, depression, ADHD, OCD, PTSD, schizophrenia, addiction, autism, and dementia affecting hundred of millions. Advances in neuroimaging have linked these disorders to abnormal brain circuit activity, but effective treatments remain limited. Current pharmacological options often have significant side effects, while psychosocial interventions like cognitive behavioral therapy (CBT) require lengthy treatment periods and may be inaccessible for severe cases. Emerging techniques like deep brain stimulation (DBS) show promise but are invasive and carry risks. Non-invasive alternatives such as transcranial electric or magnetic stimulation (TES/TMS) have shown potential but suffer from limited spatial resolution and inconsistent results due to individual anatomical differences.
Our project aims to address these limitations by developing a novel brain stimulation device based on temporal interference of magnetic fields (TIMS). This device will enable millimeter- and millisecond-precise modulation of neural activity, even in deep brain regions up to 60 mm beneath the surface. By leveraging the undistorted passage of magnetic fields through biological tissue, TIMS can achieve high precision in targeting and modulating specific neural circuits. Our envisioned device, protected by an international patent, uses phase-shifted high-carrier signals to generate a wide spectrum of waveforms, allowing for cell type-specific modulation of abnormal circuit activity—a significant breakthrough in the field. Additionally, our adaptive closed-loop system, capable of real-time targeting of brain oscillations, overcomes the challenge of stimulation artifacts through advanced techniques like Stimulation Artifact Source Separation (SASS).
This project aims to provide a non-invasive, precise, and adaptive method for brain stimulation, offering a potentially transformative treatment for a wide range of neuro-psychiatric disorders. By enabling targeted modulation of brain activity, we expect to improve treatment efficacy and reduce side effects compared to existing methods. This approach could revolutionize the management of brain disorders, making effective treatment accessible to a broader population. The integration of social sciences and humanities will ensure ethical considerations and societal impact are thoroughly addressed, promoting widespread acceptance and optimal implementation of this innovative technology.
Our project aims to address these limitations by developing a novel brain stimulation device based on temporal interference of magnetic fields (TIMS). This device will enable millimeter- and millisecond-precise modulation of neural activity, even in deep brain regions up to 60 mm beneath the surface. By leveraging the undistorted passage of magnetic fields through biological tissue, TIMS can achieve high precision in targeting and modulating specific neural circuits. Our envisioned device, protected by an international patent, uses phase-shifted high-carrier signals to generate a wide spectrum of waveforms, allowing for cell type-specific modulation of abnormal circuit activity—a significant breakthrough in the field. Additionally, our adaptive closed-loop system, capable of real-time targeting of brain oscillations, overcomes the challenge of stimulation artifacts through advanced techniques like Stimulation Artifact Source Separation (SASS).
This project aims to provide a non-invasive, precise, and adaptive method for brain stimulation, offering a potentially transformative treatment for a wide range of neuro-psychiatric disorders. By enabling targeted modulation of brain activity, we expect to improve treatment efficacy and reduce side effects compared to existing methods. This approach could revolutionize the management of brain disorders, making effective treatment accessible to a broader population. The integration of social sciences and humanities will ensure ethical considerations and societal impact are thoroughly addressed, promoting widespread acceptance and optimal implementation of this innovative technology.
The project was structured into five work packages, each aimed at achieving specific objectives essential for the proof-of-concept of the TIMS device. The first work package (WP1) focused on assembling a functional TIMS stimulator prototype. Starting from an initial blueprint, the team extended the prototype into a two-coil setup meeting the defined criteria for frequency, current, and temperature limits. A modular design was achieved, allowing for real-time control of stimulation parameters. Additionally, an algorithm was developed for the automatic calculation of optimal coil positioning to target specific brain regions.
In WP2, the project aimed to validate the technical capabilities of the TIMS stimulator. A spherical phantom-head setup was constructed to measure the magnetic and electric fields induced by the TIMS with high spatial resolution.
The objective of WP3 was to demonstrate the closed-loop operation and artifact suppression of TIMS. A phantom-head setup was constructed for EEG measurements, and TIMS-related artifacts were characterized. An advanced artifact rejection algorithm was developed and validated, enabling simultaneous real-time TIMS and EEG integration. A proof-of-concept closed-loop system was implemented, successfully synchronizing TIMS phases with simulated brain activity, thus showcasing the adaptive capabilities of the system.
WP4 investigated the potential of TIMS to target specific cell types. In silico characterization revealed the sensitivity of hippocampal cell types to TIMS. Experimental validation was conducted on rodent hippocampal slices, demonstrating differential effects of TIMS through immunohistochemical analysis. The final work package, WP5, focused on intellectual property protection, market analysis, and dissemination of results. A comprehensive market analysis was performed, identifying potential applications in medical, research, and consumer markets. Intellectual property rights were secured in collaboration with Charité BIH Innovations. The project results were prepared for dissemination through presentations at international conferences, scientific publications, and public outreach activities involving stakeholders, policy makers, and patient advocacy groups.
The project successfully developed and validated a TIMS stimulator prototype, demonstrating precise control over neural modulation. Technical validation confirmed significant advantages over existing methods, and the closed-loop system effectively synchronized stimulation with target oscillations. Experiments confirmed the potential for cell type-specific modulation. These advancements establish TIMS as a promising non-invasive tool to treat neuropsychiatric disorders, with future development and application supported by extensive dissemination and intellectual property protection.
In WP2, the project aimed to validate the technical capabilities of the TIMS stimulator. A spherical phantom-head setup was constructed to measure the magnetic and electric fields induced by the TIMS with high spatial resolution.
The objective of WP3 was to demonstrate the closed-loop operation and artifact suppression of TIMS. A phantom-head setup was constructed for EEG measurements, and TIMS-related artifacts were characterized. An advanced artifact rejection algorithm was developed and validated, enabling simultaneous real-time TIMS and EEG integration. A proof-of-concept closed-loop system was implemented, successfully synchronizing TIMS phases with simulated brain activity, thus showcasing the adaptive capabilities of the system.
WP4 investigated the potential of TIMS to target specific cell types. In silico characterization revealed the sensitivity of hippocampal cell types to TIMS. Experimental validation was conducted on rodent hippocampal slices, demonstrating differential effects of TIMS through immunohistochemical analysis. The final work package, WP5, focused on intellectual property protection, market analysis, and dissemination of results. A comprehensive market analysis was performed, identifying potential applications in medical, research, and consumer markets. Intellectual property rights were secured in collaboration with Charité BIH Innovations. The project results were prepared for dissemination through presentations at international conferences, scientific publications, and public outreach activities involving stakeholders, policy makers, and patient advocacy groups.
The project successfully developed and validated a TIMS stimulator prototype, demonstrating precise control over neural modulation. Technical validation confirmed significant advantages over existing methods, and the closed-loop system effectively synchronized stimulation with target oscillations. Experiments confirmed the potential for cell type-specific modulation. These advancements establish TIMS as a promising non-invasive tool to treat neuropsychiatric disorders, with future development and application supported by extensive dissemination and intellectual property protection.
The TIMS project developed a precise, non-invasive brain stimulation prototype with superior depth selectivity and spatial resolution compared to conventional state-of-the-art methods. Key achievements include successful closed-loop operation and testing for cell type-specific modulation. To ensure further success, continued research, clinical trials, demonstration projects, market access, IPR support, international partnerships, and regulatory compliance will be essential. These steps will facilitate the commercialization and global adoption of TIMS for treating neuro-psychiatric disorders.