Multimodal approach for highly selective nerve stimulation

Peripheral nerve stimulation (PNS) has been increasing used in treatment of a number of health conditions. These include treatment resistant epilepsy, obesity, pain, and incontinence. One of the main obstacles in wider and more efficient use of PNS is the lack of stimulation selectivity in terms of activating only relevant fibres that produce a desired effect and avoiding activation of non-targeted fibres that can lead to serious side effects. Attaining precision in neuromodulation can be achieved through fibre selective PNS. This can be realized by using specific parameters in the electrical stimulation (either offline or in real-time) such as to selectively target certain fibre types, while avoiding others. This is the current standard in Vagal Nerve Stimulation (VNS) for epilepsy. However, fibre type-selectivity alone cannot always provide adequate control of PNS effects. Hence, spatially selective PNS would need to be deployed. The knowledge of the anatomical arrangement of fibre populations in the PNS can be used to derive multiple-contact cuff electrode (MCE) device capable of delivering PNS to a single compartment of the nerve, rather than the entire nerve. Spatial targeting of specific fibre populations in a nerve, especially those that lie in the interior, may require special stimulation waveforms and cathode/anode arrangements in to produce clinically meaningful selectivity. For example, temporal interference stimulation (IS) is such a method that allows targeting of neural targets in greater distances from the stimulation electrode. Similarly, focused ultrasound stimulation (FUS) has also shown potential in targeting specific neural tissue within a larger neural mass, including the ones deeper in the nerve structure, suggesting potentially better selectivity compared to electrical stimulation. Combining the two modalities can open new avenues, not only in the ways how the stimulation can be delivered more precisely to the targeted nerve fibres but also in providing new methods of more precise interaction with neurons given differences in the physiological effects produced by these two modalities.  

The goal of this PhD research will be to explore how ultrasound stimulation can be combined with electrical stimulation to achieve better spatial and fiber type selectivity. The work will build up on state-of-the-art technology in the domain of IS and FUS and know how in the two domains. The focus is on creating the setup that can simultaneously deliver both stimuli and allow for the adaptation of parameters that can facilitate steering of stimulation focus and identifying optimal configurations. Hence, understanding of the underlying stimulation effects for both modalities is required and the ability to translate existing models of stimulation effects into the system settings and experimental designs needed to understand the phenomena observed in vitro and potentially in vivo. The design challenge of integrating both modalities in a form factor of an implant is not of primary goal but providing the requirements for such a system is.

In the first phase of the project, the PhD candidate will be asked to theoretically devise a method of selective stimulation using electrical and ultrasound stimuli, based on literature and multi-modal modelling results. The student will describe the method of steering the stimulation towards desired area and activating only the targeted fibers. The methods will be used to design and develop a system capable or rendering this multimodal stimulation. The second phase will be focused on exploring the effectiveness of the devised method, using the developed system, and improving both the method and the system. The experiments carried our will involve phantom models, living tissue and optionally animal experiments. Requirements specifications towards an implantable solution should be devised after the validation experiments.

Skills and background:

• Electrical engineering, with special affinity for biomedical applications and physics
• System design and implementation
• Ability to devise creative solutions based on and going beyond the state of the art
• Affiliation with CMOS processes and transducer technology
• Simulations, prototyping and proof-of-principle experiments