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R01 Mag Stim - Coggle Diagram

- - - - TMS generates heat and sound, but neither is likely responsible for the evoked responses - tissue heating from TMS is negligible and the click sound can't explain a few ms latency.
      - There are some puzzling reports, though.
        
        Threshold discrepancy: Human data suggest 33–70 V/m, while theoretical calculations predict 175–430 V/m.
        
        Clinical outcomes also vary considerably.
        
        But at least activation is reliable. It's the downstream effects that are unpredictable, as is often the case with other stimulation methods.
      - The coil sits outside the head and the scalp and skull insulate, so there is no galvanic path, and leakage is excluded by design.
        
        Overall, TMS provides evidence beyond reasonable doubt that magnetic neurostimulation is real, and suggests that unreliability is not inherent to mStim,
        
        Although a more precise understanding of its mechanisms of action would still be beneficial. Let's think about what are the real issue with TMS, and how can it be improved by studying mechanism later.
    - - Support
        
        Published physiological demonstration
        
        Our group
        
        Mostly half-turn coil: unreliable neural activation, and we cannot confidently rule out the possibility of current leakage.
        
        Bonmassar group
        
        • Park HJ, Bonmassar G, Kaltenbach JA, Machado AG, Manzoor NF, Gale JT (2013). "Activation of the central nervous system induced by micro-magnetic stimulation." Nat Commun 4:2463.
        
        Keywords: Panasonic coil, dorsal cochlear nucleus (DCN) stimulation, IC recording, single monophasic rectangular pulse
        The IC responses are real neural responses, but it isn't clear whether they were driven magnetically, by a non-magnetic electric field from the coil, or acoustically. Latencies seem a bit too long for CN stimulation. No comparison is made with electrically or acoustically evoked IC responses. No orientation test.
        
        • Golestanirad L et al. (2018). "Solenoidal micromagnetic stimulation enables activation of axons with specific orientation."
        
        Keywords: Panasonic coil, dorsal cochlear nucleus (DCN) stimulation, IC recording, single monophasic rectangular pulse
        Same preparation as Park 2013, with coil orientation as the one added variable. No stimulus amplitude or pulse width reported for the animal experiments. The quality of the work invites scrutiny: thin data presentation, numbers that don't reconcile, and several misattributed citations.
        
        • Serano P, Angelone LM, Katnani H, Eskandar E, Bonmassar G (2015). "A novel brain stimulation technology provides compatibility with MRI." Sci Rep 5:9805.
        
        ISMRM 2025 abstract (Marturano et al.) reporting localized activation and glutamate changes in rats.
        
        Hui Ye's lab
        
        • Ye H, Chen VC-F, Helon J, Apostolopoulos N (2020). "Focal suppression of epileptiform activity in the hippocampus by a high-frequency magnetic field." Neuroscience
        
        • Skach J, Conway C, Barrett L, Ye H (2020). "Axonal blockage with microscopic magnetic stimulation." Sci Rep 10.
        
        "Somatic inhibition by microscopic magnetic stimulation." Sci Rep 11.
        
        • Ye H, Chen V, Hendee J. (2022) "Cellular mechanisms underlying state-dependent neural inhibition with magnetic stimulation." Sci Rep.
        
        Wang Lab
        
        • Saha R, Faramarzi S, Bloom RP, Benally OJ, Wu K, di Girolamo A, Tonini D, Keirstead SA, Low WC, Netoff TI, Wang J-P (2022). "Strength-frequency curve for micromagnetic neurostimulation through excitatory postsynaptic potentials (EPSPs) on rat hippocampal neurons and numerical modeling of magnetic microcoil (μcoil)."
        
        Bhatti Group
        
        • Mukesh S, Blake DT, McKinnon BJ, Bhatti PT. "Modeling intracochlear magnetic stimulation: a finite-element analysis." IEEE TNSRE, pp. 1353–1362.
        
        • Sarreal RRS, Blake DT, Bhatti PT (2022). "Development and characterization of a micromagnetic alternative to cochlear implant electrode arrays." IEEE TNSRE 30:2116–2125.
        
        Tateno Group
        
        • Minusa S, Osanai H, Tateno T. "Micromagnetic stimulation of the mouse auditory cortex in vivo using an implantable solenoid system."
        
        • Osanai H, Minusa S, Tateno T. "Micro-coil-induced inhomogeneous electric field produces sound-driven-like neural responses in microcircuits of the mouse auditory cortex in vivo."
        
        • Minusa S, Muramatsu S, Osanai H, Tateno T. "A multichannel magnetic stimulation system using submillimeter-sized coils: system development and experimental application to rodent brain in vivo."
        
        • "Temporal and spatial profiles of evoked activity induced by magnetic stimulation using millimeter-sized coils in the mouse auditory cortex in vivo."
        
        Sohee Kim's lab
        
        • Lee KJ, Jang J-W, Kim S. "Magnetic stimulation of the sciatic nerve using an implantable high-inductance coil with low-intensity current."
        
        • Lee KJ, Jang J-W, Kim JS, Kim S (2024). "Epidural magnetic stimulation of the motor cortex using an implantable coil." Brain Stimul 17(5):1157–1166.
        
        • Park J, Lee KJ, et al., Kim S, Lee S. "Optimized coil design for enhanced electric field induction in peripheral nerve stimulation."
      - Doubts
- - - - 🔴 To explain the mechanism, he used computational modeling, but he scaled up the modeling results by at least three orders of magnitude and reported the scaled values in the manuscript without explaining the adjustment. He told me that a modeling expert had suggested this approach. 🟠 I don't clearly remember the rationale, but I think he said the modeling results were very noisy, with many sharp peaks, so he connected the highest peaks rather than averaging them out.
        
        🟡 These kinds of behaviors, which I’ve either heard about or experienced firsthand, have made me question the reliability of his other results as well.
      - 🟠 When SB was conducting in vivo monkey experiments with SW, he expressed some concerns about the results. SW became quite upset and accused SB of sabotaging the project.
    - - 🔴 Also, even when I observed responses, I couldn't detect any orientation-dependent effects.
    - - But honestly, 🟡 I wonder whether they were as scientifically lax as SW or, like me, had doubts about potential confounding factors but chose not to voice them.