Gonçalo Cotovio1, Albino J Oliveira-Maia2, Carter Paul3, Francisco Faro Viana4, Daniel Rodrigues da Silva4, Carolina Seybert4, Adam P Stern5, Alvaro Pascual-Leone6, Daniel Z Press7. 1. Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 02215, MA, USA; Champalimaud Research & Clinical Centre, Champalimaud Centre for the Unknown, Lisbon, Portugal; Department of Psychiatry and Mental Health, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal; NOVA Medical School, NMS, Universidade Nova de Lisboa, Lisbon, Portugal. 2. Champalimaud Research & Clinical Centre, Champalimaud Centre for the Unknown, Lisbon, Portugal; Department of Psychiatry and Mental Health, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal; NOVA Medical School, NMS, Universidade Nova de Lisboa, Lisbon, Portugal. 3. Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 02215, MA, USA. 4. Champalimaud Research & Clinical Centre, Champalimaud Centre for the Unknown, Lisbon, Portugal. 5. Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 02215, MA, USA; Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 02215, MA, USA. 6. Department of Neurology, Harvard Medical School, Boston, MA, USA; Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Aging Research, Hebrew SeniorLife, Boston, MA, USA; Institut Guttmann de Neurorehabilitación, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain. 7. Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 02215, MA, USA. Electronic address: dpress@bidmc.harvard.edu.
Abstract
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.
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.