Dose-dependent target engagement of a clinical iTBS protocol: An interleaved TMS-fMRI study in healthy subjects.

concurrent TMS-fMRI depression treatment functional MRI (fMRI) interleaved iTBS-fMRI neuromodulation transcranial magnetic stimulation (TMS)

Journal

Biological psychiatry. Cognitive neuroscience and neuroimaging
ISSN: 2451-9030
Titre abrégé: Biol Psychiatry Cogn Neurosci Neuroimaging
Pays: United States
ID NLM: 101671285

Informations de publication

Date de publication:
23 Aug 2024
Historique:
received: 29 04 2024
revised: 08 08 2024
accepted: 12 08 2024
medline: 26 8 2024
pubmed: 26 8 2024
entrez: 25 8 2024
Statut: aheadofprint

Résumé

Intermittent theta burst stimulation (iTBS) of the dorsolateral prefrontal cortex (DLPFC) is widely applied as therapeutic intervention in mental health, however understanding of its mechanisms is still incomplete. Prior MRI studies have mainly used offline iTBS or short sequences in concurrent TMS-fMRI. This study investigated a full 600 stimuli iTBS protocol using interleaved TMS-fMRI in comparison with two control conditions in healthy subjects. In a crossover design, 18 participants underwent three sessions of interleaved iTBS-fMRI: 1) left DLPFC at 40% resting motor threshold (rMT) intensity, 2) left DLPFC at 80% rMT intensity, and 3) left primary motor cortex (M1) at 80% rMT intensity. We compared immediate blood-oxygen-level-dependent (BOLD) responses during interleaved iTBS-fMRI across these conditions including correlations between individual fMRI BOLD activation and iTBS induced electric field (E-field) strength at the target sites. Whole-brain analysis showed increased activation in several regions following iTBS. Specifically, left DLPFC, as well as bilateral M1, anterior cingulate cortex, and insula showed increased activation during 80% rMT left DLPFC stimulation. Increased BOLD activity in the left DLPFC was not observed with 40% rMT left DLPFC stimulation nor left M1 80% rMT iTBS, whereas activation in other regions was found to overlap between conditions. Of note, BOLD activation and E-field intensities were only correlated for M1 stimulation, but not for the DLPFC conditions. The study showed dosage and target specific BOLD activation during interleaved TMS-fMRI with 600 stimuli iTBS in healthy subjects. Future studies may use our approach for demonstrating target engagement.

Sections du résumé

BACKGROUND BACKGROUND
Intermittent theta burst stimulation (iTBS) of the dorsolateral prefrontal cortex (DLPFC) is widely applied as therapeutic intervention in mental health, however understanding of its mechanisms is still incomplete. Prior MRI studies have mainly used offline iTBS or short sequences in concurrent TMS-fMRI. This study investigated a full 600 stimuli iTBS protocol using interleaved TMS-fMRI in comparison with two control conditions in healthy subjects.
METHODS METHODS
In a crossover design, 18 participants underwent three sessions of interleaved iTBS-fMRI: 1) left DLPFC at 40% resting motor threshold (rMT) intensity, 2) left DLPFC at 80% rMT intensity, and 3) left primary motor cortex (M1) at 80% rMT intensity. We compared immediate blood-oxygen-level-dependent (BOLD) responses during interleaved iTBS-fMRI across these conditions including correlations between individual fMRI BOLD activation and iTBS induced electric field (E-field) strength at the target sites.
RESULTS RESULTS
Whole-brain analysis showed increased activation in several regions following iTBS. Specifically, left DLPFC, as well as bilateral M1, anterior cingulate cortex, and insula showed increased activation during 80% rMT left DLPFC stimulation. Increased BOLD activity in the left DLPFC was not observed with 40% rMT left DLPFC stimulation nor left M1 80% rMT iTBS, whereas activation in other regions was found to overlap between conditions. Of note, BOLD activation and E-field intensities were only correlated for M1 stimulation, but not for the DLPFC conditions.
CONCLUSIONS CONCLUSIONS
The study showed dosage and target specific BOLD activation during interleaved TMS-fMRI with 600 stimuli iTBS in healthy subjects. Future studies may use our approach for demonstrating target engagement.

Identifiants

pubmed: 39182723
pii: S2451-9022(24)00244-1
doi: 10.1016/j.bpsc.2024.08.009
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Kai-Yen Chang (KY)

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany; Neuroimaging Core Unit Munich - NICUM, University Hospital LMU, Munich, Germany; DZPG (German Center for Mental Health), partner site Munich-Augsburg, Germany.

Martin Tik (M)

High Field MR Center, Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria; Brain Stimulation Lab, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, USA.

Yuki Mizutani-Tiebel (Y)

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany; Neuroimaging Core Unit Munich - NICUM, University Hospital LMU, Munich, Germany; DZPG (German Center for Mental Health), partner site Munich-Augsburg, Germany.

Paul Taylor (P)

Department of Psychology, LMU Munich, Munich, Germany.

Timo van Hattem (T)

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany; Neuroimaging Core Unit Munich - NICUM, University Hospital LMU, Munich, Germany; DZPG (German Center for Mental Health), partner site Munich-Augsburg, Germany.

Peter Falkai (P)

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany; Neuroimaging Core Unit Munich - NICUM, University Hospital LMU, Munich, Germany; DZPG (German Center for Mental Health), partner site Munich-Augsburg, Germany.

Frank Padberg (F)

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany; Neuroimaging Core Unit Munich - NICUM, University Hospital LMU, Munich, Germany; DZPG (German Center for Mental Health), partner site Munich-Augsburg, Germany. Electronic address: Frank.Padberg@med.uni-muenchen.de.

Lucia Bulubas (L)

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany; Neuroimaging Core Unit Munich - NICUM, University Hospital LMU, Munich, Germany; DZPG (German Center for Mental Health), partner site Munich-Augsburg, Germany.

Daniel Keeser (D)

Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany; Neuroimaging Core Unit Munich - NICUM, University Hospital LMU, Munich, Germany; DZPG (German Center for Mental Health), partner site Munich-Augsburg, Germany.

Classifications MeSH