1. Development of Micro-magnetic stimulation.
Electrical stimulation is currently used to treat a wide range of cardiovascular, sensory and neurological diseases. Despite its success, there are significant limitations to its application, including incompatibility with magnetic resonance imaging, limited control of electric fields and decreased performance associated with tissue inflammation. Magnetic stimulation overcomes these limitations but existing devices (that is, transcranial magnetic stimulation) are large, reducing their translation to chronic applications. In addition, existing devices are not effective for deeper, sub-cortical targets.
To overcome such limitations, we developed a sub-millimeter coil and demonstrate that magnetic stimulation arising from this small coil can activate neurons in the rabbit retina. Interestingly, the results of both modelling and physiological experiments suggest that different spatial orientations of the coils relative to the retinal tissue can be used to generate specific neural responses. These results raise the possibility that micro-magnetic stimulation coils, small enough to be implanted within the brain parenchyma, may prove to be an effective alternative to existing stimulation devices (Bonmassar et al. Nat Commun 2012; Lee et al. US patent application 2014).
We have since shown that stimulation from such a coil can activate neurons of the sub-thalamic nucleus which is the major target of DBS for treatment of Parkinson’s disease (Lee et al. IEEE TNSRE 2015) and can also strongly activate cortical pyramidal neurons of the prefrontal cortex (PFC) which are the major target of transcranial magnetic stimulation (TMS) for treatment of depression (Lee et al. IEEE TNSRE 2016).
We are now developing a novel coil design that is much smaller but more effective than that of the existing micro-coil so as to implement a 3-D high density coil array that can be used as a the high-resolution cortical prosthetic device. In preliminary testing, we have found that the new design is working well in both in vitro and in vivo animal experiments (Lee et al. Sci Adv 2016). As the result of our recent work, we are now beginning several collaborations with both US and international laboratories to assess the clinical effectiveness of this new coil.
2. Optimization of micro-coil designs for precise activation of primary visual cortex.
Electrical stimulation via cortically-implanted electrodes has been proposed to treat a wide range of neurological disorders. Effectiveness has been limited however, in part due to the inability of conventional electrodes to activate specific types of neurons while avoiding other types. Recent demonstrations that magnetic stimulation from a micro-coil can selectively activate pyramidal neurons (PNs) while avoiding passing axons suggest the possibility that such an approach can overcome this limitation. To explore this further, we used computer simulations to determine how micro-coil design influences the threshold and selectivity with which pyramidal neurons are activated. A computational model was developed to predict the magnetic and electric fields induced by conventional electrodes as well as by rectangular-, V- and W-shaped coil designs. The more promising designs (V- and W-shapes) were fabricated for use in electrophysiological experiments including in vitro patch-clamp recording & calcium imaging (GCaMP6f) of mouse brain slices. Both V- and W-shaped coils reliably activated layer 5 (L5) PNs but V-coils were more effective while W-coils were more selective. Activation thresholds with double-loop coils were approximately one-half those of single-loop coils, regardless of the design. Calcium imaging revealed that both V- and W-coils better confine activation than rectangular coils or electrodes. Taken together, our results suggest that individual design features of micro-coils can influence both their strength as well as their selectivity. Further, our results also suggest that computer simulations based on electromagnetic theory can provide accurate predictions of physiological results. In summary, our results show how coil design influences the response of cortical neurons to stimulation and are an important step towards the development of next-generation cortical prostheses.
3. Selective activation of cortical columns using multichannel magnetic stimulation with a bent flat microwire array.
Cortical neural prostheses that aim to restore useful vision, hearing, and tactile sensations require the ability to selectively target different cortical regions simultaneously. Electrical stimulation via intracortical electrodes has been used to create spatial patterns of cortical activation. However, their efficacy remains limited due to the inability of conventional electrodes to confine activation to specific cortical regions around each electrode. Magnetic stimulation from single bent wires can selectively activate pyramidal neurons while avoiding passing axons, thereby confining activation to small cortical regions. This work presents a novel bent flat microwire array and demonstrates its effectiveness for selective activation of cortical columns in mouse brain slices.
A computational model was developed to compare the spatial resolution of magnetic stimulation from bent wire arrays with 280 and 530 µm tip spacings. The same array designs were fabricated for use in electrophysiological experiments, i.e., calcium imaging (GCaMP6s) of mouse brain slices.
All fabricated array designs reliably produced spatially discrete cortical activations at low stimulus amplitudes, but the 280-µm-spacing produced strong interference (constructive or destructive) at high stimulus amplitudes, thereby resulting in single strong activations or two asymmetric activations. 4-channel bent wire arrays with spacing of 340 µm avoided the interference and produced clearer spatial patterns of activation than electrodes.
Bent wire array designs can influence the strength and the spatial resolution of multichannel magnetic stimulation. These results suggest that bent microwire arrays can enhance the selectivity of multichannel stimulation of brain and therefore may help to develop reliable and effective cortical neural prostheses.
- Lee SW*. Selective activation of cortical columns using multichannel magnetic stimulation with a bent flat microwire array. IEEE Trans Biomed Eng. 2021 July; Vol. 68, no. 7, PubMed PMID: 33095707.
- Lee SW*, Thyagarajan K, Fried SI. Micro-coil design influences the spatial extent of responses to intracortical magnetic stimulation. IEEE Trans Biomed Eng. 2019 June; Vol. 66, no. 6, PubMed PMID: 30369434.
- Lee SW, Fallegger F, Casse BD, Fried SI. Implantable microcoils for intracortical magnetic stimulation. Sci Adv. 2016 Dec;2(12):e1600889. PubMed PMID: 27957537; PubMed Central PMCID: PMC5148213.
- Lee SW, Fried S. Enhanced control of cortical pyramidal neurons with micro-magnetic stimulation. IEEE Trans Neural Syst Rehabil Eng. 2016 Nov 22;PubMed PMID: 27893396.
- Lee SW, Fried SI. Suppression of subthalamic nucleus activity by micromagnetic stimulation. IEEE Trans Neural Syst Rehabil Eng. 2015 Jan;23(1):116-27. PubMed PMID: 25163063; PubMed Central PMCID: PMC4467829.
- Bonmassar G, Lee SW, Freeman DK, Polasek M, Fried SI, Gale JT. Microscopic magnetic stimulation of neural tissue. Nat Commun. 2012 Jun 26;3:921. PubMed PMID: 22735449; PubMed Central PMCID: PMC3621430.