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. 2022 Mar 15:434:120121.
doi: 10.1016/j.jns.2021.120121. Epub 2021 Dec 28.

Physiologically informed neuromodulation

Karen Wendt  1 , Timothy Denison  2 , Gaynor Foster  3 , Lothar Krinke  4 , Alix Thomson  3 , Saydra Wilson  5 , Alik S Widge  6
Affiliations

Physiologically informed neuromodulation

Karen Wendt et al. J Neurol Sci. .

Abstract

The rapid evolution of neuromodulation techniques includes an increasing amount of research into stimulation paradigms that are guided by patients' neurophysiology, to increase efficacy and responder rates. Treatment personalisation and target engagement have shown to be effective in fields such as Parkinson's disease, and closed-loop paradigms have been successfully implemented in cardiac defibrillators. Promising avenues are being explored for physiologically informed neuromodulation in psychiatry. Matching the stimulation frequency to individual brain rhythms has shown some promise in transcranial magnetic stimulation (TMS). Matching the phase of those rhythms may further enhance neuroplasticity, for instance when combining TMS with electroencephalographic (EEG) recordings. Resting-state EEG and event-related potentials may be useful to demonstrate connectivity between stimulation sites and connected areas. These techniques are available today to the psychiatrist to diagnose underlying sleep disorders, epilepsy, or lesions as contributing factors to the cause of depression. These technologies may also be useful in assessing the patient's brain network status prior to deciding on treatment options. Ongoing research using invasive recordings may allow for future identification of mood biomarkers and network structure. A core limitation is that biomarker research may currently be limited by the internal heterogeneity of psychiatric disorders according to the current DSM-based classifications. New approaches are being developed and may soon be validated. Finally, care must be taken when incorporating closed-loop capabilities into neuromodulation systems, by ensuring the safe operation of the system and understanding the physiological dynamics. Neurophysiological tools are rapidly evolving and will likely define the next generation of neuromodulation therapies.

Keywords: Biomarkers in psychiatry; Brain-state dependent stimulation; Deep brain stimulation; Electroencephalography; Neuromodulation; Transcranial magnetic stimulation.

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Conflict of interest statement

Lothar Krinke is currently the CEO of Welcony Inc. Welcony Inc. is commercializing Electroencephalography, Transcranial Magnetic Stimulation and other Medical and Research Devices under the Magstim, EGI, Neurosign and Technomed brands and businesses. He also used to be an employee of Medtronic and holds Medtronic stock. Gaynor Foster and Alix Thomson are employed by Welcony Inc.

Alik Widge has multiple granted and pending patent applications in the use of physiologic markers to optimize neurostimulation, including for oscillation-related neurostimulation. None of these is licensed to any entity. He receives device donations from Medtronic, Inc., which previously employed Drs. Krinke and Denison.

Tim Denison has multiple granted and pending patent applications in the use of physiologic markers to optimize neurostimulation; the patents relevant for this work are licensed to Medtronic. He has consulted for Synchron, Cortec Neuro, Inspire, and Medtronic. He has research collaborations with and stock ownership in Bioinduction Ltd., research grants and collaborations with Magstim Ltd., and is a co-founder of Amber Therapeutics and Verity VR. These activities are managed with a conflict-of-interest plan at the University of Oxford. Tim Denison and Karen Wendt have received materials for research from Magstim Ltd.

Saydra Wilson has current grant funding to use physiologic markers to optimize neuromodulation supported by the University of Minnesota's MnDRIVE (Minnesota's Discovery, Research and Innovation Economy) initiative.

Tim Denison, Karen Wendt, Alik Widge and Saydra Wilson received no direct financial support for the authorship of this article.

Figures

Fig. 1
Fig. 1
Modeling open-loop, closed-loop and feed-forward control of the neurostimulator. The highlighted arrows capture the future state where devices respond to temporal rhythms, as a digital chronotherapy.
See this image and copyright information in PMC

References

    1. Premarket Approval of NEUROPACE RNS SYSTEM. 2013. Food and Drug Administration.https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100026 (accessed June 2021)
    1. Fisher R.S., et al. Automatic vagus nerve stimulation triggered by ictal tachycardia: clinical outcomes and device performance—the U.S. E-37 trial. Neuromodulation: Technol. Neural Interf. 2016;19(2):188–195. doi: 10.1111/ner.12376. 2016/02/01. - DOI - PMC - PubMed
    1. Premarket Approval of Percept Deep Brain Stimulation Therapy System. 2021. Food and Drug Administration.https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P960... (accessed June 2021)
    1. Lambez B., Harwood-Gross A., Golumbic E.Z., Rassovsky Y. Non-pharmacological interventions for cognitive difficulties in ADHD: a systematic review and meta-analysis. J. Psychiatr. Res. 2020;120:40–55. doi: 10.1016/j.jpsychires.2019.10.007. 2020/01/01/ - DOI - PubMed
    1. Darling K.E., Benore E.R., Webster E.E. Biofeedback in pediatric populations: a systematic review and meta-analysis of treatment outcomes. Transl. Behav. Med. 2020;10(6):1436–1449. doi: 10.1093/tbm/ibz124. - DOI - PubMed