Prefrontal rTMS for treating depression: location and intensity results from the OPT-TMS multi-site clinical trial

Abstract

Background: Motor cortex localization and motor threshold determination often guide Transcranial Magnetic Stimulation (TMS) placement and intensity settings for non-motor brain stimulation. However, anatomic variability results in variability of placement and effective intensity.

Objective: Post-study analysis of the OPT-TMS Study reviewed both the final positioning and the effective intensity of stimulation (accounting for relative prefrontal scalp-cortex distances).

Methods: We acquired MRI scans of 185 patients in a multi-site trial of left prefrontal TMS for depression. Scans had marked motor sites (localized with TMS) and marked prefrontal sites (5 cm anterior of motor cortex by the "5 cm rule"). Based on a visual determination made before the first treatment, TMS therapy occurred either at the 5 cm location or was adjusted 1 cm forward. Stimulation intensity was 120% of resting motor threshold.

Results: The "5 cm rule" would have placed stimulation in premotor cortex for 9% of patients, which was reduced to 4% with adjustments. We did not find a statistically significant effect of positioning on remission, but no patients with premotor stimulation achieved remission (0/7). Effective stimulation ranged from 93 to 156% of motor threshold, and no seizures were induced across this range. Patients experienced remission with effective stimulation intensity ranging from 93 to 146% of motor threshold, and we did not find a significant effect of effective intensity on remission.

Conclusions: Our data indicates that individualized positioning methods are useful to reduce variability in placement. Stimulation at 120% of motor threshold, unadjusted for scalp-cortex distances, appears safe for a broad range of patients.

Copyright © 2013 Elsevier Inc. All rights reserved.

Figures

Figure 1

Brain images of motor and prefrontal localization (by the 5 cm, VIM, and 5 cm+1 cm methods) Points of motor and prefrontal localization (by the 5 cm, VIM, and 5 cm+1 cm methods) in MNI space are overlaid on a template brain. Points are smoothed to portray relative density of localization (dark red = few scans, bright red = many scans).

Figure 2

MNI Distribution of VIM determinations of “No Adjustment” or “Move Forward”. for the marked 5 cm prefrontal sites, distributions in the MNI y-axis are shown for either VIM determinations of “No Adjustment” or “Move Forward”. Distributions indicate mean (vertical gray lines), standard deviation (white rectangles), and range (thin white horizontal line). Brodmann Area 6 (red) and 8 (blue) are displayed on the template brain for reference.

Figure 3

Effective stimulation by remission status for each Brodmann area The y-axis is effective stimulation in terms of motor threshold (adjusted for scalp-cortex distance) in each Brodmann area (BA 6, 8, 9, 44, 45, 46, and all areas combined), separated into two columns for patients not achieving remission (NR) and patients achieving remission (R). The effective stimulation is displayed as an “x” and appears bolded or blurred for patients with equal or overlapping effective stimulation in a column. No patients achieved remission in BA 6, so only one column is seen for BA 6. No statistical significant differences of TMS intensity were found between patients not achieving remission and patients achieving remission (independent sample t-tests of BA8, BA 9, and also of all patients combined, p > .05).