BrainMag

We will systematically test the cellular effects of a new safer form of non-invasive brain stimulation, focal low-intensity rTMS (LI-rTMS), which is at an intensity too low to directly activate neuronal firing. We will use use multiple experimental approaches, from short-term effects on neuronal excitability and synaptic activity to more durable effects on neuron morphology, and extending to modification of network function including inter-regional synchrony and brain oscillations including studies on human cortical excitability. Our results will provide important fundamental information necessary for future therapeutic applications. The effects of magnetic stimulation on neuronal excitability depend critically on stimulation parameters such as frequency, pattern and duration, which are limited in high intensity rTMS for technical and safety reasons. LI-rTMS can be administered over a wide range of frequencies/patterns, allowing identification of stimulation parameters that optimally modulate neuronal and network excitability in different brain areas containing different neuronal types. Our specific research questions are: 1) How does LI-rTMS acutely impact neuronal and synaptic function? 2) How does chronic LI-rTMS treatment alter neuronal circuitry? 3) How does LI-rTMS affect activity in the human brain? Based on our preliminary results, we anticipate the outcomes of the BrainMag study will show that LI-rTMS induces immediate changes to neuronal function which consolidate with repeated stimulation sessions to structural changes in neurons and their circuits that modulate brain function, and that these changes will be different in different brain regions. Understanding these effects will provide important information for optimising future therapeutic applications. This program is only possible due to the combination of complementary expertise within the consortium. While the Sherrard team has experience of LI-rTMS in vitro and in the visual system, it needs the expertise of the Charpier team to investigate acute effects on cortical neuron excitability, an advance which is necessary before LI-rTMS can seriously be considered for human application, which is highly cortico-centric. In turn, magnetic stimulation is new for the Charpier team. Importantly the presence of the Valero-Cabré team means that translation to humans is feasible. He has extensive experience in the application of different types of brain stimulation in human subjects and patient cohorts, which opens the possibility of undertaking preliminary proof-of-principle assessment of LI-rTMS effects on the human brain. The added value of this research program is that we will identify fundamental effects of low-intensity magnetic stimulation including, for the first time, in humans. This will facilitate the transfer of this brain stimulation approach to clinical treatment. The importance of low intensity, as opposed to high-intensity, stimulation is that it is safe and runs on domestic electricity or batteries, making it suitable for home treatment – a therapeutic advance completely unavailable at present.