TY - JOUR
T1 - Day-to-day variability in motor threshold during rTMS treatment for depression
T2 - Clinical implications
AU - Cotovio, Gonçalo
AU - Oliveira-Maia, Albino J.
AU - Paul, Carter
AU - Faro Viana, Francisco
AU - Rodrigues da Silva, Daniel
AU - Seybert, Carolina
AU - Stern, Adam P.
AU - Pascual-Leone, Alvaro
AU - Press, Daniel Z.
N1 - Funding: GC was funded by Fundaçao para a Ciência e Tecnologia (FCT; Portugal) through a PhD Scholarship (SFRH/BD/130210/2017). AJOM was funded by FCT (Portugal) through a Junior Research and Career Development Award from the Harvard Medical School e Portugal Program (HMSP-ICJ/0020/2011). GC and AJO-M were supported by grant PTDC/MED-NEU/31331/2017, and AJO-M by grant PTDC/MED-NEU/30302/2017, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020 - Programa Operacional Regional de Lisboa. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the Fundaçao para a Ciência e Tecnologia, Harvard University or its affiliated academic health care centers. AJO-M was national coordinator for Portugal of a noninterventional study (EDMS-ERI-143085581, 4.0) to characterize a Treatment-Resistant Depression Cohort in Europe, sponsored by Janssen-Cilag, Ltd (2019e2020), is recipient of a grant from Schuhfried GmBH for norming and validation of cognitive tests, and is national coordinator for Portugal of trials of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd (EudraCT number 2017-003288-36 and 2020-001348- 25), and of esketamine for treatment-resistant depression, sponsored by Janssen-Cilag, Ltd (EudraCT NUMBER: 2019-002992-33). AP-L is a co-founder of Linus Health and TI Solutions AG; serves on the scientific advisory boards for Starlab Neuroscience, Neuroelectrics, Magstim Inc., Nexstim, Cognito, and MedRhythms; and is listed as an inventor on several issued and pending patents on the real-time integration of noninvasive brain stimulation with electroencephalography and magnetic resonance imaging. None of the aforementioned agencies had a role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the manuscript, nor in the decision to submit the manuscript for publication. The remaining authors have declared that they have no potential conflicts of interest involving this work, including relevant financial activities outside the submitted work and any other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing what is written.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Background: When repetitive transcranial magnetic stimulation (rTMS) is used to treat medication refractory depression, the treatment pulse intensity is individualized according to motor threshold (MT). This measure is often acquired only on the first day of treatment, as per the protocol currently approved by Food and Drug Administration. Objective: Here, we aimed to assess daily MT variability across an rTMS treatment course and simulate the effects of different schedules of MT assessment on treatment intensity. Methods: We conducted a naturalistic retrospective study with 374 patients from a therapeutic rTMS program for depression that measures MT daily. Results: For each patient, in almost half the TMS sessions, MT varied on average more than 5% as compared to the baseline MT acquired in the first treatment day. Such variability was only minimally impacted by having different TMS technicians acquiring MT in different days. In a smaller cohort of healthy individuals, we confirmed that the motor hotspot localization method, a critical step for accurate MT assessment, was stable in different days, arguing that daily MT variability reflects physiological variability, rather than an artifact of measurement error. Finally, in simulations of the effect of one-time MT measurement, we found that half of sessions would have been 5% or more above or below target intensity, with almost 5% of sessions 25% above target intensity. The simulated effects of weekly MT measurements were significantly improved. Conclusions: In conclusion, MT varies significantly across days, not fully dependent on methods of MT acquisition. This finding may have important implications for therapeutic rTMS practice regarding safety and suggests that regular MT assessments, daily or at least weekly, would ameliorate the effect.
AB - Background: When repetitive transcranial magnetic stimulation (rTMS) is used to treat medication refractory depression, the treatment pulse intensity is individualized according to motor threshold (MT). This measure is often acquired only on the first day of treatment, as per the protocol currently approved by Food and Drug Administration. Objective: Here, we aimed to assess daily MT variability across an rTMS treatment course and simulate the effects of different schedules of MT assessment on treatment intensity. Methods: We conducted a naturalistic retrospective study with 374 patients from a therapeutic rTMS program for depression that measures MT daily. Results: For each patient, in almost half the TMS sessions, MT varied on average more than 5% as compared to the baseline MT acquired in the first treatment day. Such variability was only minimally impacted by having different TMS technicians acquiring MT in different days. In a smaller cohort of healthy individuals, we confirmed that the motor hotspot localization method, a critical step for accurate MT assessment, was stable in different days, arguing that daily MT variability reflects physiological variability, rather than an artifact of measurement error. Finally, in simulations of the effect of one-time MT measurement, we found that half of sessions would have been 5% or more above or below target intensity, with almost 5% of sessions 25% above target intensity. The simulated effects of weekly MT measurements were significantly improved. Conclusions: In conclusion, MT varies significantly across days, not fully dependent on methods of MT acquisition. This finding may have important implications for therapeutic rTMS practice regarding safety and suggests that regular MT assessments, daily or at least weekly, would ameliorate the effect.
KW - Depression
KW - Resting motor threshold
KW - Transcranial magnetic stimulation
KW - Variability
UR - http://www.scopus.com/inward/record.url?scp=85111908573&partnerID=8YFLogxK
U2 - 10.1016/j.brs.2021.07.013
DO - 10.1016/j.brs.2021.07.013
M3 - Article
C2 - 34329797
AN - SCOPUS:85111908573
SN - 1935-861X
VL - 14
SP - 1118
EP - 1125
JO - Brain Stimulation
JF - Brain Stimulation
IS - 5
ER -