E-field Orientation in Theta Burst Stimulation Modulates Changes in Motor Evoked Potential Amplitude

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Abstract Submission 

Silas Preis¹, Constanze Ramschütz², Sandro Krieg³, Claus Zimmer⁴, Bernhard Meyer⁵, Nico Sollmann⁶, Severin Schramm⁷

¹Technical University of Munich, Munich, Bavaria, ²Technical University of Munich, München, Germany, ³Department of Neurosurgery, Universitätsklinikum Heidelberg, Heidelberg, Germany, ⁴Dep. of Neuroradiology, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Bavaria, ⁵Dep. of Neurosurgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Bavaria, ⁶Dep. of Diagnostic and Interventional Radiology, University Hospital Ulm, Munich, Bavaria, ⁷Department of Diagnostic and Interventional Neuroradiology, School of Medicine, Munich, Bavaria

Silas Preis  
Technical University of Munich
Munich, Bavaria

Constanze Ramschütz  
Technical University of Munich
München, Germany

Sandro Krieg  
Department of Neurosurgery, Universitätsklinikum Heidelberg
Heidelberg, Germany

Claus Zimmer, Prof. Dr.  
Dep. of Neuroradiology, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich
Munich, Bavaria

Bernhard Meyer, Prof. Dr.  
Dep. of Neurosurgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich
Munich, Bavaria

Nico Sollmann, PD Dr. Dr. med  
Dep. of Diagnostic and Interventional Radiology, University Hospital Ulm
Munich, Bavaria

Severin Schramm, Dr. med. sci  
Department of Diagnostic and Interventional Neuroradiology, School of Medicine
Munich, Bavaria

Transcranial magnetic stimulation (TMS) is a noninvasive method for brain stimulation employed in an increasing range of diagnostic and therapeutic settings (Krieg, 2017; Lefaucheur et al., 2020). Although TMS-based neuromodulation (NM) protocols are utilized in the treatment of neuropsychiatric and other conditions, the underlying neurophysiological processes remain insufficiently understood (Goldsworthy, Hordacre et al. 2021). One thus far unexamined factor to optimize TMS NM outcomes is the orientation of the stimulating coil relative to individual cortical anatomy, which has been recognized as a relevant factor in single-pulse stimulation (Raffin, Pellegrino et al. 2015). We present preliminary findings from healthy participants in whom we investigated the impact of e-field orientation during continuous theta burst stimulation (cTBS) on NM regarding motor evoked potentials (MEPs).

8 healthy participants (average age: 23 ± 3 years, 4 females) underwent T1-weighted (T1w) imaging at 3 Tesla to obtain images for neuronavigated TMS (nTMS). Three nTMS sessions separated by at least 14 days were conducted per subject to assess the impact of the e-field orientation during cTBS on the MEP amplitude. After identification of the abductor pollicis brevis muscle hotspot and the coil orientation for maximum MEP generation within the dominant hemisphere, the resting motor threshold (rMT) was determined and 30 MEPs were elicited at 150% rMT (M. Goldsworthy, Hordacre, & Ridding, 2016; Hordacre et al., 2017). Afterwards, cTBS with conventional parameters (40 s, 600 stimuli, 3 stimuli with 50 Hz every 200 ms) (Huang, Edwards et al. 2005) was performed at 70 % rMT (M. Goldsworthy et al., 2016; Hordacre et al., 2017) at the same site using one out of three protocols (OPT: stimulation with optimal coil direction; 90°: anterior coil end rotated 90° upwards from OPT; SHAM: stimulation with a 7.3-cm spacer). Subsequently, we elicited 3 sets of 30 MEPs at increasing intervals after cTBS (0-5 min, 5-10 min, 10-15 min). The MEPs were analyzed to evaluate the influence of the e-field orientation on MEP amplitudes.

After adjusting for a family-wise error rate, MEP amplitudes pre- and post-TBS differed significantly between the measured time points, with the observed differences varying by e-field orientation of cTBS (Figure 1A-C). On a group level, cTBS in both OPT and SHAM conditions demonstrated heightened MEPs compared to baseline (OPT: post-cTBS 3553±1999 µV vs. pre-cTBS 2923±2460 µV, p<0.05; Figure 1A; SHAM: post-cTBS 3174±2160 µV vs. pre-cTBS 2235±1703 µV, p<0.0001; Figure 1C). Here, SHAM demonstrated significantly higher increases of MEP amplitudes compared to the other two conditions (SHAM-cTBS 698±1249 µV vs. OPT-cTBS 321±1293 µV vs. 90°-cTBS 293±1240 µV, p<0.05; Figure 1E). Results on the group level did not reflect pronounced and heterogenous NM effects as observed on the single-subject level (Figure 1G-J).

On a group level, counter to the classical assumption of MEP suppression, we observed MEP facilitation following cTBS in both OPT and SHAM conditions, potentially highlighting the need to further elucidate sham-derived effects in TMS NM (Boucher et al., 2021). These findings add to research questioning the consistency of TMS NM (M. R. Goldsworthy, Hordacre, Rothwell, & Ridding, 2021). Changes in NM response based on e-field orientation were more pronounced for some subjects compared to others (Figure 1G-J), stressing the inter-individual variability in NM responses (M. R. Goldsworthy et al., 2021). Our results may underscore the complexity and variability of cTBS effects on cortical excitability. Additionally, we provide first evidence implying e-field orientation during TMS NM as a factor influencing NM outcome. Individual optimization of e-field orientation could improve NM outcomes in other settings, e.g. therapeutic applications.

Non-invasive Magnetic/TMS ¹

Methods Development ²

ADULTS

Cortex

Development

Motor

MRI

Transcranial Magnetic Stimulation (TMS)

Treatment