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Motor Rehabilitation Plasticity Hacking by Engineered stimulation of the brain dUring Sleep-wake cycle

Periodic Reporting for period 1 - MoRPHEUS (Motor Rehabilitation Plasticity Hacking by Engineered stimulation of the brain dUring Sleep-wake cycle)

Reporting period: 2022-05-16 to 2024-05-15

Brain lesions such as stroke and traumatic brain injury are a major cause of adult-onset disability. Physical therapy with robotic-aided rehabilitation is the gold standard for promoting motor recovery. Yet, half the affected individuals do not fully recover their daily living skills. Hope is provided by advanced neuroprosthetic devices, acting directly at the brain level to promote plasticity, but to date, they still fall short of producing long-lasting brain rewiring. The often neglected but close relationship between sleep, neural plasticity, pathogenesis, and motor recovery can constitute a key factor in advancing treatment. Thus, the EU-funded MoRPHEUS project aims to develop a novel neuroprosthetic approach that monitors brain activity and delivers electrical stimulation according to the sleep-wake cycle architecture.

For this, the project pursued the following specific goals:
1. Investigate how brain lesions impact the neurodynamics and electrophysiological patterns of the SWC.
2. Develop a closed-loop system to monitor SWC and deliver precisely timed ES.
3. Use ES in coordination with SWC to induce therapeutic neural plasticity and promote motor rehabilitation.

While the project remains in progress under the scope of different research programs, its scientific findings and technological advancements have been and still are being disseminated as peer-reviewed publications, contributions to open-source repositories, and communications at conferences. We expect that the technology developed in the project will benefit stakeholders in the neuroscientific and neuroengineering community, as well as physicians, medical staff, and patients in the midterm future.
MoRPHEUS was divided into working packages related to experimental procedures, technological development, dissemination of findings, and project management.

Initially, researchers conducted a series of complex chronic in vivo experiments with freely moving animals to study how ischemic lesions affect neural function, particularly sleep, revealing that such lesions impair motor function and disrupt sleep architecture and neural coordination. Analytical tools for the investigation of sleep electrophysiological signals were developed and made available to the public. Throughout this phase, the researcher received extensive training in various advanced techniques, including surgical induction of ischemic lesions, signal analysis, and machine learning, while also contributing knowledge through seminars and teaching. The theoretical background developed was published as reviews. These findings support the potential efficacy of neuroprostheses in promoting motor rehabilitation by guiding neuroplasticity.

In the sequence, researchers developed and tested the MoRPHEUS neuroprosthesis, a closed-loop system that delivers complex electrical stimulation based on specific sleep electrographic events, requiring integration with existing electrophysiology setups. The system's design involved creating and testing a custom digital signal processing framework on FPGA technology to detect and respond to neural events in real-time, while initial in vivo tests showed good tolerability of the neuromodulation strategies. The researcher received specialized training in digital circuit design and VHDL design and contributed knowledge to host institutions on advanced neuroengineering techniques.

The researcher participated in a range of training initiatives, including hands-on learning, seminars, and formal courses, which enhanced their interdisciplinary skills in neuroscience, neurology, and engineering, as well as soft and transferable skills. Additionally, they gained practical experience in project management, and grant writing, and attended key events that provided insights into research commercialization, entrepreneurship, and broader scientific and policy issues. MoRPHEUS ideas, methods, and findings were strategically disseminated through conferences, journals, lectures, and social media as the results matured, with a dedicated website created for broader public communication. Much more is expected to be released in the coming months in a gradual manner that is conditioned to issues of intellectual property exploitation.
The outcomes of the MoRPHEUS project are ready to be used by the neuroscientific and neuroengineering community as a source of knowledge in the field (published reviews on neuromodulation, neuromorphism, and closed-loop neuroengineering systems) or as tools for sleep investigation (sleep electrophysiology analysis methods and open source code deposited in free repositories). The novel findings on the pathophysiology of stroke and the neurobiological relationship between the ischemic lesion and sleep, which resulted from MoRPHEUS investigations, are currently being prepared for publication and will be available to these same stakeholders in the near future. In the same vein, in the following months, MoRPHEUS team will disseminate content related to the technological innovations on sleep neuroengineering resulting from the developments of the project, both as specialized publications and/or open source code and design in free repositories. Finally, with further investigation currently being carried out, innovations from the project have a true potential to benefit the neurotechnology industry, neurologists, and patients in the midterm future.
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