Periodic Reporting for period 1 - MEMOPROSTHETICS (Neuroprosthetic Modulation of Large-Scale Brain Networks for Treating Memory Disorders)
Période du rapport: 2022-10-01 au 2025-03-31
The MEMOPROSTHETICS project aims at developing a neuroprosthesis of the neural networks underlying memory processes using electrical stimulation of these structures, with the overall goal to improve learning and memory in neurological disorders. This is a basic science research project still at a pre-clinical stage in non-human primates, but with potential therapeutic applications in brain injury or neurodegenerative diseases such as Alzheimer’s disease. In Alzheimer’s disease for example, it is difficult to create new memories because of a deficit in memory encoding capabilities. This encoding is done electrically because the neurons communicate with each other via nerve impulses which are electrical signals. Within the framework of MEMOPROSTHETICS, we are implanting several electrodes in different brain regions in order to carry out electrical stimulations inspired by the way the brain naturally works, and thus mitigate neuronal and cognitive deficits. The neuroprosthesis will record and analyse the brain’s neurophysiological signals thanks to several dozens of electrodes, and will then carry out targeted electrical stimulations modulated accordingly, i.e. with stimulation frequencies and amplitudes adjusted in a precise and personalized manner. Similarly to the way a pacemaker affects heart rhythms, but applied to very complex brain circuits. Overall, three areas of the brain will be implanted: the hippocampus, the main area underlying memory processes, the entorhinal cortex, also involved in memory mechanisms and Alzheimer’s disease, and the prefrontal cortex, which is the substrate of higher cognitive functions. Ultimately, we expect this project to lead to a new generation of neuromodulation devices for improving cognitive function in neurological disorders.
The MEMOPROSTHETICS project focuses on advancing our understanding of learning and memory, and the potential for neurostimulation to enhance cognitive functions in non-human primates with and without cognitive impairments. In a first objective, we investigate the neural oscillations (electrical signals that oscillate at specific frequencies and are characteristic of a particular brain area and and / neurological function) that mediate learning and memory in three brain areas: the hippocampus, entorhinal cortex, and prefrontal cortex. To this end, we first developed custom brain implants for precise neural recordings and stimulation, as well as methods based on magnetic resonance imaging and optical tracking for targeting these areas with a submillimetric precision. Our preliminary results have identified changes in neural signals that are correlated with a memory task. In our next objectives, we examine whether electrical stimulation of these areas, so-called deep brain stimulation (DBS), can enhance or disrupt the creation of new memories. While applying stimulation parameters that had been previously used in patients with epilepsy, we have found that stimulating the hippocampus or the entorhinal cortex at certain amplitudes deteriorates memory performance. We are now exploring various stimulation parameters to understand conflicting results in the existing literature and develop robust protocols for improving memory. These objectives are conducted both in a state without cognitive deficits, and in a state where temporary cognitive impairments are induced by a pharmacological intervention. Finally, our last objective will attempt to miniaturize our current system to make it fully implantable and pave the way to future clinical studies. Overall, the project integrates innovative technologies to explore the intricate relationship between stimulation parameters, neural activity, and learning and memory processes, with implications for treating neurological disorders such as Alzheimer’s disease.
MEMOPROSTHETICS still requires further research, which will be conducted in the next 3 years of the project, to determine stimulation parameters with a potentially beneficial effect on memory encoding. If successful, our results may be patentable and lead to opportunities for future industrial transfer and clinical studies. Meanwhile, our project has already led to methods and datasets that can be useful to the community working on neurophysiology and neuroimaging in non-human primates. These methods have been sent or will be sent soon for publications in peer-reviewed journals. Some of the associated datasets have already been uploaded to public repositories to facilitate data sharing in the community.