An EIC Pathfinder project developing wireless deep-brain stimulation with engineered magnetic nanomaterials. Thermal, mechanical and electrical effects are combined to excite or inhibit selected neurons, with experimental evaluation in models of Fragile X syndrome.
Project abstract
BRAINSTORM will introduce an innovative, scalable, wireless, multimodal nanoinvasive neuromodulation technology suitable for independent and switchable excitation and inhibition of deep brain neurons. BRAINSTORM breakthrough relies on novel smart anisotropic magnetic nanomaterials (SMNs) acting both as nanoscale ‘heaters’ and as ‘torquers’ by leveraging eith…Read the full abstractCollapse abstract
BRAINSTORM will introduce an innovative, scalable, wireless, multimodal nanoinvasive neuromodulation technology suitable for independent and switchable excitation and inhibition of deep brain neurons. BRAINSTORM breakthrough relies on novel smart anisotropic magnetic nanomaterials (SMNs) acting both as nanoscale ‘heaters’ and as ‘torquers’ by leveraging either hysteretic losses under kHz frequencies or transitions from vortex to in-plane magnetization under Hz frequencies. Intrinsic bimodal functionality that permits direct control of thermosensitive or mechanosenitive neurons, will be boosted by advanced polymer functionalization to transfer torques to electrical signals trough piezoelectric coating, and to enable transport and delivery of viral vectors to targeted neurons for genetic targeting with sensory channels. SMNs will also be steered to endogenous sensory channels relying on antibody targeting. Selected actuation of ion channels that respond to thermal or mechanical stimulus will permit selective activation or inhibition of targeted neuronal populations identifiable by magnetic resonance imaging. Advanced driving electronics will include to metamaterial solenoid coils for rapid frequency switch for control of ‘mechanical’ or ‘thermal’ functionality while focused ultrasound will facilitate non invasive delivery of SMNs in the targeted brain area. The ability of the BRAINSTORM platform to shape behaviour and demonstrate therapeutic potential by modulating the excitation/inhibition balance through thermal/mechanical/electrical modalities will be demonstrated in mouse models of Fragile X syndrome.
Research connections
Publications
2026
Journal of nanobiotechnology
Neuromodulation techniques have emerged as transformative tools for treating several neurological and psychiatric disorders, offering alternatives to traditional pharmacological approaches often hindered by the blood-brain barrier and off-target effects. While conventional modalities like deep brain stimulation, transcranial magnetic stimulation, and optogen…Read the full abstractCollapse abstract
Neuromodulation techniques have emerged as transformative tools for treating several neurological and psychiatric disorders, offering alternatives to traditional pharmacological approaches often hindered by the blood-brain barrier and off-target effects. While conventional modalities like deep brain stimulation, transcranial magnetic stimulation, and optogenetics have shown promise, they each face limitations in invasiveness, spatial resolution, or clinical applicability. In recent years, low-intensity ultrasound has gained attention as a noninvasive, deep-penetrating modality capable of modulating brain circuits with millimeter-sized spatial precision. This review explores the synergistic integration of ultrasound with engineered nanosystems to achieve multimodal neuromodulation such as electrical, mechanical, optical, and chemical via acoustic energy. We describe how nanoscale materials can transduce ultrasound into localized bioelectric signals, mechanical stress, light emission, or controlled drug release. These interactions enable precise, on-demand stimulation or inhibition of neuronal activity, including in deep brain regions. Experimental studies have demonstrated neuromodulatory effects across a variety of models, with applications ranging from optogenetics and drug delivery to behavioral modulation in rodents and primates. The review concludes with a critical assessment of the translational challenges such as nanoparticle delivery, biocompatibility, long-term clearance, and safety thresholds for human use while outlining promising strategies like cell-based delivery, biodegradable materials, and closed-loop control systems. These innovations highlight the potential of ultrasound-assisted nanosystems as transformative tools for precise neuromodulation in both experimental neuroscience and clinical applications.
2020
Frontiers in Physics
Focused ultrasound (FUS) neuromodulation has shown that mechanical waves can interact with cell membranes and mechanosensitive ion channels, causing changes in neuronal activity. However, the thorough understanding of the mechanisms involved in these interactions are hindered by different experimental conditions for a variety of animal scales and models. Whi…Read the full abstractCollapse abstract
Focused ultrasound (FUS) neuromodulation has shown that mechanical waves can interact with cell membranes and mechanosensitive ion channels, causing changes in neuronal activity. However, the thorough understanding of the mechanisms involved in these interactions are hindered by different experimental conditions for a variety of animal scales and models. While the lack of complete understanding of FUS neuromodulation mechanisms does not impede benefiting from the current known advantages and potential of this technique, a precise characterization of its mechanisms of action and their dependence on experimental setup (e.g., tuning acoustic parameters and characterizing safety ranges) has the potential to exponentially improve its efficacy as well as spatial and functional selectivity. This could potentially reach the cell type specificity typical of other, more invasive techniques e.g., opto- and chemogenetics or at least orientation-specific selectivity afforded by transcranial magnetic stimulation. Here, the mechanisms and their potential overlap are reviewed along with discussions on the potential insights into mechanisms that magnetic resonance imaging sequences along with a multimodal stimulation approach involving electrical, magnetic, chemical, light, and mechanical stimuli can provide.