Title: Translational Bioengineering for Neurological Disorders
Funder: Medical Research Council

Abstract: The evolution of adaptive brain stimulation is at a critical stage of translation, and several factors should be considered during the transition to the clinic. Given its potential, feedback approaches are being piloted for use in multiple disease states. Proof-of-concept experiments to improve Parkinson’s DBS with feedback control show promise, but are still restricted to short trials (order of hours) in the clinic and are burdensome to configure. In addition, attempts at feedback control for epilepsy have arguably proved disappointing, and yield modest improvement over open-loop approaches. From a control systems perspective, these initial efforts focused more on “exploitation” of existing stimulation techniques with simple feedback, versus principled application of control methods to systematically “explore” the available neuroscience parameter space. Similar issues are raised with minimally-invasive approaches like transcranial magnetic stimulation (TMS), where the optimal design of stimulation parameters still remains an open question. Due in part to this limited performance and complexity, feedback systems have thus far had limited clinical impact. The Translational Bioengineering programme aims to address these shortcomings. The inter-linked themes for the programme are 1) improving the capability of invasive “neural coprocessors” (neurostimulation systems with algorithmic capabilities embedded), 2) expanding the coprocessor concept to include minimally invasive systems, with an emphasis on brain-state dependent stimulation and synchronized integration with implants, and 3) piloting these technologies in neuroscience studies that address key gaps in translation. For both invasive and non-invasive neural coprocessors and operating systems, emphasis will be placed on 1) improving sense-stimulation performance to enhance closed-loop performance, 2) improving the data gathering and algorithm capability through advanced wireless telemetry and distributed computational methods, and 3) further advancing the research infrastructures, including regulatory and risk management, to enable collaboration and modular research tool development. To deploy and test these research systems, we will work collaboratively within the MRC BNDU to 1) pilot chronic adaptive stimulation concepts in movement disorders, epilepsy, and mood disorders in collaboration with the OpenMind consortium, 2) test brain-state dependent feedback and network plasticity methods using paired association enabled by our new instrumentation, and 3) design adaptive algorithms for modulating and improving sleep quality to address this common co-morbidity for neurological disorders. Given the emphasis on translation across multiple brain disorders, significant elements of the proposed research involve UK and US collaborators, industry partners, and regulators. The work in this proposal will follow a scaled Quality Management System compliant to key aspects of ISO13485 in a research environment, with an emphasis on IEC 60601-1 (essential safety), 60601-1-10 (physiologic control systems), 60601-2-10 (neurostimulation), and ISO14971 (risk). Data security aligns to EU General Data Protection Regulations.


Research activity codes: 5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: NEUROLOGICAL