Magnetic Micro-coils

* Our results strongly support the viability of implantable microcoils as an attractive alternative to conventional electrode implants
* New microcoils can effectively drive neuronal circuits in vivo
* Strong similarities in behavioral responses to magnetic versus electric stimulation suggest that the underlying neuronal responses may be similar for the two modalities
* Coil design influences the response of cortical neurons to stimulation and are an important step toward the development of next-generation cortical prostheses
* Enhanced selectivity of microcoil-based magnetic stimulation will be especially useful for visual prostheses as well as for many brain-computer interface applications that require precise activation of the cortex
* Magnetic fields extend in specific directions, allowing selective targeting of neurons with the same orientation while simultaneously avoiding the activation of other neurons
* Micro-coil array could be developed whereby neural activity at different locations in single cortical columns could be independently and precisely controlled
* Implanted coils can be used to drive responses associated with the targeted neurons
* Coil design shapes the spatial extent of cortical activation
* Specific design features of micro-coils can greatly influence the strength and selectivity of neuronal activation in cortex
* Multi-loop coils enhance the strength of stimulation but not the selectivity
* V-shaped coils enhance selective activation of vertical pyramidal neurons (PNs) over horizontal axons
* W-shape enhances selectivity even further, but slightly reduces the strength of stimulation
* Addition of multiple loops to the coil increases the strength of stimulation over that of single-loop coils, thereby enabling the reduction of activation thresholds

* Successful activation of PNs in vitro
* Can effectively activate neurons in vitro and also drive neural circuits in vivo
* Stimulation of cortical pyramidal neurons in brain slices in vitro was reliable and could be confined to spatially narrow regions (<60 μm)
* In vitro calcium fluorescence imaging revealed that the V and W-coils both produced spatially-confined activation in cortex relative to that of conventional electrodes, but the W-coil was more selective in a manner that was consistent with the model predictions

* In vitro brain slice
* Electrophysiological recordings were performed using brain slices prepared from 17- to 30-day-old mice
* Measured the response of L5 PNs from the prefrontal (PFC) and primary motor (M1) cortices to stimulation from a micro-coil in the in vitro mouse brain slice
* In vivo animal experiments
* 2 to 4 months old mice

* Mice

* Smaller size
* In vivo implantation was safe and resulted in consistent and predictable behavioral responses
* Eliminates variability of electrode impedance following implantation allowed coils to be safely inserted into the cortex
* Comparable in size to electrodes that are routinely implanted into the cortex
* Electric fields that arise from magnetic stimulation are spatially asymmetric and can therefore be harnessed to selectively activate some neuronal subpopulations while simultaneously avoiding others
* Ability to activate vertically oriented pyramidal neurons (PNs) without activating horizontally oriented passing axons in the cortex
* Coils can be completely insulated with soft biocompatible materials that have been shown to mitigate the cortical response to implantation
* Microcoils could safely be implanted into the brains of anesthetized mice
* This level of activation with micro-coils would also be potentially advantageous for studies with small laboratory animals as it allows for very precise targeting of specific neurons within a focal region
* Magnetic activation does not require direct contact between metal electrode and neural tissue, the potential for adverse interactions is greatly reduced
* Coil-based stimulation less prone to the numerous problems that can arise at the brain-electrode interface
* Combination of selective targeting, increased reliability, and power levels
* Ability to penetrate scar tissue; Since the magnetic signal can pass through biocompatible insulating material, direct contact between neural tissue and the metal coil is eliminated, further reducing the potential for damage to the coil
* Microcoil stimulation can activate cortical neurons but also that specific types of neurons can be selectively targeted
* High permeability of magnetic fields to biological substances may yield another important advantage because it suggests that encapsulation and other adverse effects of implantation will not diminish coil performance over time, as happens to electrodes
* Individual design features can influence both the strength as well as the selectivity of micro-coils and can be accurately predicted by computer simulations

* Electrical artifact arising from the stimulus
* High levels of current (> 178 mA) were necessary to induce the fields required for activation and thus the power levels associated with magnetic stimulation from micro-coils are greater than those associated with electric stimulation
* The maximum stimulus rate that could be delivered with this coil was limited to 10 Hz. While this may be sufficient to reproduce some elements of physiological signaling, the rates used previously to induce phosphenes and/or saccades during electric stimulation were considerably higher

* Lee et al. 2016, Implantable microcoils for intracortical magnetic stimulation, Science Advances 2: e1600889

* https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5148213/

* Lee and Fried 2017, Enhanced Control of Cortical Pyramidal Neurons With Micromagnetic Stimulation, IEEE Trans Neural Syst Rehabil Eng 25:1375-1386.

* Lee et al. 2019, Micro-Coil Design Influences the Spatial Extent of Responses to Intracortical Magnetic Stimulation, IEEE Trans Biomed Eng 66:1680-1694

* Lee and Fried 2014, The Response of L5 Pyramidal Neurons of the PFC to Magnetic Stimulation From a Micro-Coil, Conf Proc IEEE Eng Med Biol Soc 2014: 6125-8. Lee et al. 2016, Implantable microcoils for intracortical magnetic stimulation

* https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498237/
* https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561646/
* https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5148213/

* Custom software, written in MATLAB, was used to calculate the spatial gradient of induced electric fields (E-fields) that arose from the flow of current through a microcoil