Non-invasive modulation of the brain with transcranial magnetic stimulation (TMS) has demonstrated good results and been approved widely for clinical use and insurance coverage.  However, with the current technology, the locus (position) of the stimulation can only be changed slowly and real-time information of electrical brain-state is not taken into account, limiting the therapies, in practice, to a single brain site and open-loop stimulation. The goal in the multinational and multidisciplinary ConnectToBrain project is to develop and prepare for wide clinical use a multi-locus closed-loop TMS technique.

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The synergistic project consists of three main areas of development:

1)      Multilocus TMS (mTMS) coil array covering most of the cortical mantle and allowing real-time high-precision control over the locus, direction, intensity, and timing of the stimulation pulses

2)      Real-time analysis of brain activity and connectivity by using high-density electroencephalography and prior information from magnetic resonance imaging and magnetoencephalography for brain-state-dependent and closed-loop stimulation

3)      Demonstration of feasibility, safety, and effects of the developed techniques and methods, and their therapeutic utility in dysfunctional brain networks in Alzheimer’s disease and motor stroke

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By the end of the project, we expect to have developed new technology capable of correcting dysfunctional brain networks in several brain disorders with better therapeutic efficacy than current state-of-the-art techniques and the potential to induce a major paradigm shift in therapeutic neuromodulation. If successful and widely transferred for clinical use, ConnectToBrain will eventually lead to a substantial reduction in the suffering and economic burden caused by brain disorders.

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Key publications:

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• Basti, A., Chella, F., Guidotti, R., Ermolova, M., D'Andrea, A., Stenroos, M., Romani, G. L., Pizzella, V., & Marzetti, L. (2022). Looking through the windows: a study about the dependency of phase-coupling estimates on the data length. Journal of Neural Engineering 19, 016039. https://doi.org/10.1088/1741-2552/ac52d3
• Basti, A., Nili, H., Hauk, O., Marzetti, L., & Henson, R. N. (2020). Multi-dimensional connectivity: a conceptual and mathematical review. NeuroImage, 117179. https://doi.org/10.1016/j.neuroimage.2020.117179
• Baur, D., Galevska, D., Hussain, S., Cohen, L. G., Ziemann, U., & Zrenner, C. (2020). Induction of LTD-like corticospinal plasticity by low-frequency rTMS depends on pre-stimulus phase of sensorimotor μ-rhythm. Brain Stimulation, 13(6), 1580-1587. https://doi.org/10.1016/j.brs.2020.09.005
• Gordon, P. C., Belardinelli, P., Stenroos, M., Ziemann, U., & Zrenner, C. (2022). Prefrontal theta phase-dependent rTMS-induced plasticity of cortical and behavioral responses in human cortex. Brain Stimulation, 15(2), 391–402. https://doi.org/10.1016/j.brs.2022.02.006
• Gordon, P. C., Jovellar, D. B., Song, Y., Zrenner, C., Belardinelli, P., Siebner, H. R., & Ziemann, U. (2021). Recording brain responses to TMS of primary motor cortex by EEG - utility of an optimized sham procedure. NeuroImage, 245, 118708. https://doi.org/10.1016/j.neuroimage.2021.118708
• Nieminen, J.O. , Sinisalo, H., Souza, V.H., Malmi, M., Yuryev, M., Tervo, A.E., Stenroos, M., Milardovich, D., Korhonen, J.T., Koponen, L.M. & Ilmoniemi, R.J. (2022). Multi-locus transcranial magnetic stimulation system for electronically targeted brain stimulation, Brain Stimulation 15(1), 116-124. https://doi.org/10.1016/j.brs.2021.11.014
• Tervo, A. E., Metsomaa, J., Nieminen, J. O., Sarvas, J., & Ilmoniemi, R. J. (2020). Automated search of stimulation targets with closed-loop transcranial magnetic stimulation. NeuroImage, 117082. https://doi.org/10.1016/j.neuroimage.2020.117082
• Tervo, A.E., Nieminen, J.O., Lioumis, P., Metsomaa, J., Souza, V.H., Sinisalo, H., Stenroos, M., Sarvas J., Ilmoniemi, R.J. (2022). Closed-loop optimization of transcranial magnetic stimulation with electroencephalography feedback. Brain Stimulation, 15(2). https://doi.org/10.1016/j.brs.2022.01.016
• Zrenner, C., Galevska, D., Nieminen, J. O., Baur, D., Stefanou, M. I., & Ziemann, U. (2020). The shaky ground truth of real-time phase estimation. NeuroImage, 116761. https://doi.org/10.1016/j.neuroimage.2020.116761
• ‍Stefanou, M. I., Galevska, D., Zrenner, C., Ziemann, U., & Nieminen, J. O. (2020). Interhemispheric symmetry of µ-rhythm phase-dependency of corticospinal excitability. Scientific Reports, 10(1), 1-9. https://doi.org/10.1038/s41598-020-64390-w

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