CaltechAUTHORS
Published August 21, 2023 | Version Published
Journal Article Open

Toward personalized circuit-based closed-loop brain-interventions in psychiatry: using symptom provocation to extract EEG-markers of brain circuit activity

Creators

  • 1. ROR icon Centre for Addiction and Mental Health
  • 2. ROR icon University of Toronto
  • 3. ROR icon University of Tübingen
  • 4. ROR icon University of Pennsylvania
  • 5. ROR icon University of California, Los Angeles
  • 6. ROR icon UCLA Health
  • 7. ROR icon California Institute of Technology
  • 8. ROR icon Karolinska Institute

Abstract

Symptom provocation is a well-established component of psychiatric research and therapy. It is hypothesized that specific activation of those brain circuits involved in the symptomatic expression of a brain pathology makes the relevant neural substrate accessible as a target for therapeutic interventions. For example, in the treatment of obsessive-compulsive disorder (OCD), symptom provocation is an important part of psychotherapy and is also performed prior to therapeutic brain stimulation with transcranial magnetic stimulation (TMS). Here, we discuss the potential of symptom provocation to isolate neurophysiological biomarkers reflecting the fluctuating activity of relevant brain networks with the goal of subsequently using these markers as targets to guide therapy. We put forward a general experimental framework based on the rapid switching between psychiatric symptom states. This enable neurophysiological measures to be derived from EEG and/or TMS-evoked EEG measures of brain activity during both states. By subtracting the data recorded during the baseline state from that recorded during the provoked state, the resulting contrast would ideally isolate the specific neural circuits differentially activated during the expression of symptoms. A similar approach enables the design of effective classifiers of brain activity from EEG data in Brain-Computer Interfaces (BCI). To obtain reliable contrast data, psychiatric state switching needs to be achieved multiple times during a continuous recording so that slow changes of brain activity affect both conditions equally. This is achieved easily for conditions that can be controlled intentionally, such as motor imagery, attention, or memory retention. With regard to psychiatric symptoms, an increase can often be provoked effectively relatively easily, however, it can be difficult to reliably and rapidly return to a baseline state. Here, we review different approaches to return from a provoked state to a baseline state and how these may be applied to different symptoms occurring in different psychiatric disorders.

Copyright and License

© 2023 Zrenner, Zrenner, Balderston, Blumberger, Kloiber, Laposa, Tadayonnejad, Trevizol, Zai and Feusner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Funding

DB receives research support from the Canadian Institutes of Health Research (CIHR), NIH, Brain Canada, and the Temerty Family through the CAMH Foundation. SK reports grants from the Labatt Family Innovation Fund in Brain Health (Department of Psychiatry, University of Toronto), the Max Bell Foundation, the Canadian Centre on Substance Use and Addiction, the Ontario Ministry of Health and Long-Term Care (MOHLTC), and CIHR. JF receives research support from the NIH, the Klarman Family Foundation, and the CAMH Discovery Fund. BZ receives research support from CIHR. CZ receives research support from CIHR and the Brain Canada Foundation.

Contributions

BZ, CZ, DB, and JF contributed to the conception and design of the work. BZ and JF wrote the first draft of the manuscript. CZ, NB, DB, SK, JL, RT, AT, and GZ wrote sections of the manuscript. All authors contributed to the manuscript revision and read and approved the submitted version.

Data Availability

The original contributions presented in this study are included in this article/supplementary material, further inquiries can be directed to the corresponding author.

Conflict of Interest

BZ and CZ are shareholders in sync2brain GmbH (Tübingen, Germany) a University of Tübingen spin-off start-up company developing technology for personalized therapeutic TMS. BZ reports part-time salary support from sync2brain GmbH, unrelated to this work. DB received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and has been the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. DB also received in-kind equipment support from MagVenture for 3 investigator-initiated studies. DB received medication supplies for an investigator-initiated trial from Indivior. DB has participated in one Scientific Advisory Board Meeting for Janssen and one meeting for Welcony Inc. SK has received honorarium for past consultation for EmpowerPharm.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Files

fncir-17-1208930.pdf

Files (815.8 kB)

Name Size Download all
md5:e455bc82af26f8a30987e15c3bc7f213
815.8 kB Preview Download

Additional details

Identifiers

PMCID
PMC10475600

Funding

Canadian Institutes of Health Research
National Institutes of Health
Brain Canada Foundation
Centre for Addiction and Mental Health
University of Toronto
Max Bell Foundation
Canadian Centre on Substance Use and Addiction
Ministry of Health and Long Term Care
Klarman Family Foundation