Direct recordings of neuronal circuit responses during transcranial magnetic stimulation in rodents

• Applicant: Dr. Alia Benali
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 416792011

Over the last three decades, transcranial magnetic stimulation (TMS), a non-invasive brain stimulation method based on electromagnetic induction, has gained considerable interest in experimental and clinical neuroscience for its capability of non-invasively activating cortical neuronal populations and inducing plasticity. Despite its widespread application, most of our current understanding of the physiological mechanisms underlying various TMS effects is based on inferences from indirect observations. The neurophysiological mechanisms of TMS are still largely unknown. It is, therefore, important to address this critical limitation in order to facilitate TMS research and further exploit the therapeutic potential of this highly promising technique. The aim of this project is to make the direct link between a TMS pulse and its induced neuronal activation at the neuronal level, in vivo, using laboratory rodents. A giant obstacle that prevented the direct investigation of TMS neurophysiology was the large TMS-induced electromagnetic interference. However, with our recent successful development of a method for concurrent TMS and extracellular electrophysiology (EEP), the direct, near artifact-free (<1 ms) investigation of TMS effects at the level of single neurons in laboratory rodents has become possible. For this project, first, we plan to upgrade the newly developed methodology from a single-channel to a multichannel system to enable recording of TMS-induced responses simultaneously in a large number of neurons across multiple brain areas. Then, we will use high-density microelectrode arrays to record, under TMS, single neuron activities over multiple cortical columns in anesthetized rodents to study the spatial and temporal dynamics of TMS neuro-activation and its relations with cortical outputs. Next, we will employ optophysiological methods to gain a deeper understanding of how TMS modulates the activities of local cortical networks and what are the contributions of different neuron classes to this modulation. We believe that by making a direct link between TMS and its neuronal activations, the proposed project establish the much-needed physiological foundation of TMS and has far-reaching implications in therapeutics as well as in neuroscience research.

• DFG Programme: Research Grants
• Major Instrumentation: Magventure TMS system
• Instrumentation Group: 3400 Nervenreizgeräte