Daily prefrontal closed-loop repetitive transcranial magnetic stimulation (rTMS) produces progressive EEG quasi-alpha phase entrainment in depressed adults

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or help smoking cessation. Research suggests that timing the delivery of TMS relative to an endogenous brain state may affect efficacy and short-term brain dyn...

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Published inBrain stimulation Vol. 15; no. 2; pp. 458 - 471
Main Authors Faller, Josef, Doose, Jayce, Sun, Xiaoxiao, Mclntosh, James R., Saber, Golbarg T., Lin, Yida, Teves, Joshua B., Blankenship, Aidan, Huffman, Sarah, Goldman, Robin I., George, Mark S., Brown, Truman R., Sajda, Paul
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LanguageEnglish
Published United States Elsevier Inc 01.03.2022
Elsevier
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Abstract Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or help smoking cessation. Research suggests that timing the delivery of TMS relative to an endogenous brain state may affect efficacy and short-term brain dynamics. To investigate whether, for a multi-week daily treatment of repetitive TMS (rTMS), there is an effect on brain dynamics that depends on the timing of the TMS relative to individuals’ prefrontal EEG quasi-alpha rhythm (between 6 and 13 Hz). We developed a novel closed-loop system that delivers personalized EEG-triggered rTMS to patients undergoing treatment for major depressive disorder. In a double blind study, patients received daily treatments of rTMS over a period of six weeks and were randomly assigned to either a synchronized or unsynchronized treatment group, where synchronization of rTMS was to their prefrontal EEG quasi-alpha rhythm. When rTMS is applied over the dorsal lateral prefrontal cortex (DLPFC) and synchronized to the patient's prefrontal quasi-alpha rhythm, patients develop strong phase entrainment over a period of weeks, both over the stimulation site as well as in a subset of areas distal to the stimulation site. In addition, at the end of the course of treatment, this group's entrainment phase shifts to be closer to the phase that optimally engages the distal target, namely the anterior cingulate cortex (ACC). These entrainment effects are not observed in the group that is given rTMS without initial EEG synchronization of each TMS train. The entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes which may have clinical consequences in depression or other diseases. •Major depressive disorder patients were treated with closed-loop EEG-triggered rTMS over DLPFC for six weeks.•Patients were randomized to rTMS triggered either synchronously or asynchronously timed to their quasi-alpha EEG oscillation.•Sync patients showed increased entrainment over sessions and decreased optimal phase difference for anterior cingulate.•Entrainment was observed both locally over the stimulation site and distally over the anterior cingulate.•The entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes.
AbstractList Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or help smoking cessation. Research suggests that timing the delivery of TMS relative to an endogenous brain state may affect efficacy and short-term brain dynamics. To investigate whether, for a multi-week daily treatment of repetitive TMS (rTMS), there is an effect on brain dynamics that depends on the timing of the TMS relative to individuals' prefrontal EEG quasi-alpha rhythm (between 6 and 13 Hz). We developed a novel closed-loop system that delivers personalized EEG-triggered rTMS to patients undergoing treatment for major depressive disorder. In a double blind study, patients received daily treatments of rTMS over a period of six weeks and were randomly assigned to either a synchronized or unsynchronized treatment group, where synchronization of rTMS was to their prefrontal EEG quasi-alpha rhythm. When rTMS is applied over the dorsal lateral prefrontal cortex (DLPFC) and synchronized to the patient's prefrontal quasi-alpha rhythm, patients develop strong phase entrainment over a period of weeks, both over the stimulation site as well as in a subset of areas distal to the stimulation site. In addition, at the end of the course of treatment, this group's entrainment phase shifts to be closer to the phase that optimally engages the distal target, namely the anterior cingulate cortex (ACC). These entrainment effects are not observed in the group that is given rTMS without initial EEG synchronization of each TMS train. The entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes which may have clinical consequences in depression or other diseases.
Background: Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or help smoking cessation. Research suggests that timing the delivery of TMS relative to an endogenous brain state may affect efficacy and short-term brain dynamics. Objective: To investigate whether, for a multi-week daily treatment of repetitive TMS (rTMS), there is an effect on brain dynamics that depends on the timing of the TMS relative to individuals’ prefrontal EEG quasi-alpha rhythm (between 6 and 13 Hz). Method: We developed a novel closed-loop system that delivers personalized EEG-triggered rTMS to patients undergoing treatment for major depressive disorder. In a double blind study, patients received daily treatments of rTMS over a period of six weeks and were randomly assigned to either a synchronized or unsynchronized treatment group, where synchronization of rTMS was to their prefrontal EEG quasi-alpha rhythm. Results: When rTMS is applied over the dorsal lateral prefrontal cortex (DLPFC) and synchronized to the patient's prefrontal quasi-alpha rhythm, patients develop strong phase entrainment over a period of weeks, both over the stimulation site as well as in a subset of areas distal to the stimulation site. In addition, at the end of the course of treatment, this group's entrainment phase shifts to be closer to the phase that optimally engages the distal target, namely the anterior cingulate cortex (ACC). These entrainment effects are not observed in the group that is given rTMS without initial EEG synchronization of each TMS train. Conclusions: The entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes which may have clinical consequences in depression or other diseases.
Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or help smoking cessation. Research suggests that timing the delivery of TMS relative to an endogenous brain state may affect efficacy and short-term brain dynamics. To investigate whether, for a multi-week daily treatment of repetitive TMS (rTMS), there is an effect on brain dynamics that depends on the timing of the TMS relative to individuals’ prefrontal EEG quasi-alpha rhythm (between 6 and 13 Hz). We developed a novel closed-loop system that delivers personalized EEG-triggered rTMS to patients undergoing treatment for major depressive disorder. In a double blind study, patients received daily treatments of rTMS over a period of six weeks and were randomly assigned to either a synchronized or unsynchronized treatment group, where synchronization of rTMS was to their prefrontal EEG quasi-alpha rhythm. When rTMS is applied over the dorsal lateral prefrontal cortex (DLPFC) and synchronized to the patient's prefrontal quasi-alpha rhythm, patients develop strong phase entrainment over a period of weeks, both over the stimulation site as well as in a subset of areas distal to the stimulation site. In addition, at the end of the course of treatment, this group's entrainment phase shifts to be closer to the phase that optimally engages the distal target, namely the anterior cingulate cortex (ACC). These entrainment effects are not observed in the group that is given rTMS without initial EEG synchronization of each TMS train. The entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes which may have clinical consequences in depression or other diseases. •Major depressive disorder patients were treated with closed-loop EEG-triggered rTMS over DLPFC for six weeks.•Patients were randomized to rTMS triggered either synchronously or asynchronously timed to their quasi-alpha EEG oscillation.•Sync patients showed increased entrainment over sessions and decreased optimal phase difference for anterior cingulate.•Entrainment was observed both locally over the stimulation site and distally over the anterior cingulate.•The entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes.
Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or help smoking cessation. Research suggests that timing the delivery of TMS relative to an endogenous brain state may affect efficacy and short-term brain dynamics.BACKGROUNDTranscranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or help smoking cessation. Research suggests that timing the delivery of TMS relative to an endogenous brain state may affect efficacy and short-term brain dynamics.To investigate whether, for a multi-week daily treatment of repetitive TMS (rTMS), there is an effect on brain dynamics that depends on the timing of the TMS relative to individuals' prefrontal EEG quasi-alpha rhythm (between 6 and 13 Hz).OBJECTIVETo investigate whether, for a multi-week daily treatment of repetitive TMS (rTMS), there is an effect on brain dynamics that depends on the timing of the TMS relative to individuals' prefrontal EEG quasi-alpha rhythm (between 6 and 13 Hz).We developed a novel closed-loop system that delivers personalized EEG-triggered rTMS to patients undergoing treatment for major depressive disorder. In a double blind study, patients received daily treatments of rTMS over a period of six weeks and were randomly assigned to either a synchronized or unsynchronized treatment group, where synchronization of rTMS was to their prefrontal EEG quasi-alpha rhythm.METHODWe developed a novel closed-loop system that delivers personalized EEG-triggered rTMS to patients undergoing treatment for major depressive disorder. In a double blind study, patients received daily treatments of rTMS over a period of six weeks and were randomly assigned to either a synchronized or unsynchronized treatment group, where synchronization of rTMS was to their prefrontal EEG quasi-alpha rhythm.When rTMS is applied over the dorsal lateral prefrontal cortex (DLPFC) and synchronized to the patient's prefrontal quasi-alpha rhythm, patients develop strong phase entrainment over a period of weeks, both over the stimulation site as well as in a subset of areas distal to the stimulation site. In addition, at the end of the course of treatment, this group's entrainment phase shifts to be closer to the phase that optimally engages the distal target, namely the anterior cingulate cortex (ACC). These entrainment effects are not observed in the group that is given rTMS without initial EEG synchronization of each TMS train.RESULTSWhen rTMS is applied over the dorsal lateral prefrontal cortex (DLPFC) and synchronized to the patient's prefrontal quasi-alpha rhythm, patients develop strong phase entrainment over a period of weeks, both over the stimulation site as well as in a subset of areas distal to the stimulation site. In addition, at the end of the course of treatment, this group's entrainment phase shifts to be closer to the phase that optimally engages the distal target, namely the anterior cingulate cortex (ACC). These entrainment effects are not observed in the group that is given rTMS without initial EEG synchronization of each TMS train.The entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes which may have clinical consequences in depression or other diseases.CONCLUSIONSThe entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes which may have clinical consequences in depression or other diseases.
Author Huffman, Sarah
Saber, Golbarg T.
Faller, Josef
Sajda, Paul
Goldman, Robin I.
Doose, Jayce
Lin, Yida
Teves, Joshua B.
George, Mark S.
Sun, Xiaoxiao
Mclntosh, James R.
Blankenship, Aidan
Brown, Truman R.
AuthorAffiliation 1 Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
3 US DEVCOM Army Research Laboratory, Aberdeen Proving Ground, MD 20115, USA
5 Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC 29425, USA
4 Department of Orthopaedic Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA
6 Department of Neurology, University of Chicago, Chicago, IL 60637, USA
2 Center for Biomedical Imaging, Medical University of South Carolina, Charleston, SC 29425, USA
10 Ralph H. Johnson VA Medical Center, Charleston, SC 29401, USA
9 Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI 53705, USA
7 Department of Computer Science, Columbia University, New York, NY 10027, USA
12 Department of Electrical Engineering, Columbia University, New York, NY 10027, USA
8 Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC 29425, USA
13 Data Science Institute, Co
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Issue 2
Keywords Closed-loop neurostimulation
Electroencephalography (EEG)
Repetitive transcranial magnetic stimulation (rTMS)
Inter-trial phase coherence (ITPC)
Major depressive disorder (MDD)
Language English
License This is an open access article under the CC BY-NC-ND license.
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
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Josef Faller: conceptualization, methodology, software, writing-original draft
All persons who meet authorship criteria are listed as authors, and all authors certify that they have participated sufficiently in the work to take public responsibility for the content, including participation in the concept, design, analysis, writing, or revision of the manuscript.
Golbarg T.Saber: conceptualization, methodology, data curation
Joshua B. Teves: investigation, data curation
Aidan Blankenship: investigation, data curation
Mark S. George: conceptualization, methodology, writing-review & editing, funding acquisition, project administration, supervision
Paul Sajda: conceptualization, methodology, writing-original draft, writing-review & editing, funding acquisition, project administration, supervision
Robin Goldman: conceptualization, methodology, writing-review & editing, funding acquisition, project administration, supervision
Jayce Doose: conceptualization, investigation, data curation, writing-original draft, writing-review & editing
Xiaoxiao Sun: methodology, formal analysis, writing-original draft, writing-review & editing, Visualization
James Mclntosh: conceptualization, methodology, software, data curation, writing-review & editing
contributed equally
Yida Lin: software
Truman R. Brown: conceptualization, methodology, writing-review & editing, funding acquisition, project administration, supervision
Sarah Huffman: investigation
ORCID 0000-0002-9738-1342
0000-0002-0366-0253
0000-0002-1961-7284
0000-0001-6100-2067
0000-0002-4957-2486
0000-0002-3970-1619
0000-0001-5789-7638
OpenAccessLink https://www.sciencedirect.com/science/article/pii/S1935861X22000365
PMID 35231608
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crossref_primary_10_1016_j_brs_2022_02_008
pubmed_primary_35231608
elsevier_sciencedirect_doi_10_1016_j_brs_2022_02_008
PublicationCentury 2000
PublicationDate 2022-03-01
PublicationDateYYYYMMDD 2022-03-01
PublicationDate_xml – month: 03
  year: 2022
  text: 2022-03-01
  day: 01
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle Brain stimulation
PublicationTitleAlternate Brain Stimul
PublicationYear 2022
Publisher Elsevier Inc
Elsevier
Publisher_xml – name: Elsevier Inc
– name: Elsevier
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Snippet Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or help smoking...
Background: Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or...
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StartPage 458
SubjectTerms Adult
Alpha Rhythm
Brain
Closed-loop neurostimulation
Depressive Disorder, Major - therapy
Electroencephalography (EEG)
Humans
Inter-trial phase coherence (ITPC)
Major depressive disorder (MDD)
Prefrontal Cortex - physiology
Repetitive transcranial magnetic stimulation (rTMS)
Transcranial Magnetic Stimulation - adverse effects
Treatment Outcome
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Title Daily prefrontal closed-loop repetitive transcranial magnetic stimulation (rTMS) produces progressive EEG quasi-alpha phase entrainment in depressed adults
URI https://dx.doi.org/10.1016/j.brs.2022.02.008
https://www.ncbi.nlm.nih.gov/pubmed/35231608
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