Sensory TRP channels as key transducers in body homeostasis

Summary Currently, no medical intervention effectively protects cognitive function in people with dementia. A number of converging lines of research indicate a potentially transformative role for neuromodulation. We are developing a minimally invasive way to electrically stimulate the brain in order to preserve neurons in brain regions that are involved in cognitive functioning. This will delay functional decline in patients with neurodegenerative diseases and significantly improve their quality of life. Transcranial Alternating Current Stimulation (tACS) is a noninvasive neuromodulation method that causes weak entrainment in neural populations in the cortex. It may improve working memory in elderly subjects, but it is difficult to reach deeper brain structures and deliver continuous stimulation with clinically significant effects. Recently, transcranial stimulation using temporally interfering electric field stimulation has been proposed as a noninvasive method for stimulating deep brain structures such as the hippocampus in mice. Temporal Interference (TI) stimulation has great potential for inducing neuroprotection in patients with mild cognitive impairment, but there remain obstacles for optimal translation. There is currently no portable hardware that allows chronic stimulation of deep brain structures in humans in a minimally invasive way. In the present project, we want to fill this knowledge gap to optimize the neuroprotective effects of brain stimulation in nonhuman primates. We want to apply electrical stimulation in nonhuman primates during a memory task and during electrophysiological recordings in deep brain structures. We also want to develop a fully implantable ‘behind the ear’ stimulator, which will allow us to advance our minimally invasive solution by performing chronic TI stimulation and further adjusting the parameters in human subjects. Ultimately, this device will allow us to make epicranial TI stimulation a safe and relatively low-cost intervention that can be applied in large numbers of patients also in the home environment.