Large-scale structural network change correlates with clinical response to rTMS in depression.

Response to repetitive transcranial magnetic stimulation (rTMS) among individuals with major depressive disorder (MDD) varies widely. The neural mechanisms underlying rTMS are thought to involve changes in large-scale networks. Whether structural network integrity and plasticity are associated with response to rTMS therapy is unclear. Structural MRIs were acquired from a series of 70 adult healthy controls and 268 persons with MDD who participated in two arms of a large randomized, non-inferiority trial, THREE-D, comparing intermittent theta-burst stimulation to high-frequency rTMS of the left dorsolateral prefrontal cortex (DLPFC). Patients were grouped according to percentage improvement on the 17-item Hamilton Depression Rating Score at treatment completion. For the entire sample and then for each treatment arm, multivariate analyses were used to characterize structural covariance networks (SCN) from cortical gray matter thickness, volume, and surface area maps from T1-weighted MRI. The association between SCNs and clinical improvement was assessed. For both study arms, cortical thickness and volume SCNs distinguished healthy controls from MDD (p = 0.005); however, post-hoc analyses did not reveal a significant association between pre-treatment SCN expression and clinical improvement. We also isolated an anticorrelated SCN between the left DLPFC rTMS target site and the subgenual anterior cingulate cortex across cortical measures (p = 0.0004). Post-treatment change in cortical thickness SCN architecture was associated with clinical improvement in treatment responders (p = 0.001), but not in non-responders. Structural network changes may underpin clinical response to rTMS, and SCNs are useful for understanding the pathophysiology of depression and neural mechanisms of plasticity and response to circuit-based treatments.

Updated scalp heuristics for localizing the dorsolateral prefrontal cortex based on convergent evidence of lesion and brain stimulation studies in depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is entering wider use as a therapeutic intervention for many psychiatric illnesses. The efficacy of this therapeutic intervention may depend on accurately localizing target brain regions. Recent work investigating whole-brain maps of circuits associated with depression and its successful treatment has identified foci of interest within the dorsolateral prefrontal cortex (DLPFC). OBJECTIVE: To create an updated scalp heuristic for localizing the DLPFC based on convergent evidence of lesion and brain stimulation studies in depression. METHODS: Using the standard MNI ICBM152 anatomical template, we localized the scalp sites at minimum Euclidean distance from target MNI coordinates and performed nasion-inion, tragus-tragus, and head-circumference measurements on the anatomical template. We then derived equations to localize these scalp sites. RESULTS: The derived equations to calculate the arc length X and Y for these new targets are as follows: [Y=((NI+TrTr)/2)×0.3167 ; X=HC×0.1359] for the left anterior DLPFC[ Y=((NI+TrTr)/2)×0.2884; X=HC×0.1352] for the right anterior DLPFC[ Y=((NI+TrTr)/2)×0.2480; X=HC×0.1847] for the left posterior DLPFC[ Y=((NI+TrTr)/2)×0.2316 ; X=HC×0.1968] for the right posterior DLPFC CONCLUSIONS: This heuristic may help localize DLPFC targets identified in previous lesion-/stimulation-mapping work. A spreadsheet calculation tool is offered to support use of this heuristic.

Optimized repetitive transcranial magnetic stimulation techniques for the treatment of major depression: A proof of concept study.

Although effective in major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) is costly and complex, limiting accessibility. To address this, we tested the feasibility of novel rTMS techniques with cost-saving opportunities, such as an open-room setting, large non-focal parabolic coils, and custom-built coil arms. We employed a low-frequency (LF) 1 Hz stimulation protocol (360 pulses per session), delivered on the most affordable FDA-approved device. MDD participants received an initial accelerated rTMS course (arTMS) of 6 sessions/day over 5 days (30 total), followed by a tapering course of daily sessions (up to 25) to decrease the odds of relapse. The self-reported Beck Depression Inventory II (BDI-II) was used to measure severity of depression. Forty-eight (48) patients completed the arTMS course. No serious adverse events occurred, and all patients reported manageable pain levels. Response and remission rates were 35.4% and 27.1% on the BDI-II, respectively, at the end of the tapering course. Repeated measures ANOVA showed significant changes of BDI-II scores over time. Even though our protocol will require further improvements, some of the concepts we introduced here could help guide the design of future trials aiming at increasing accessibility to rTMS.

Development and validation of a 3D-printed neuronavigation headset for therapeutic brain stimulation.

BACKGROUND: Accurate neuronavigation is essential for optimal outcomes in therapeutic brain stimulation. MRI-guided neuronavigation, the current gold standard, requires access to MRI and frameless stereotaxic equipment, which is not available in all settings. Scalp-based heuristics depend on operator skill, with variable reproducibility across operators and sessions. An intermediate solution would offer superior reproducibility and ease-of-use to scalp measurements, without requiring MRI and frameless stereotaxy. OBJECTIVE: We present and assess a novel neuronavigation method using commercially-available, inexpensive 3D head scanning, computer-aided design, and 3D-printing tools to fabricate form-fitted headsets for individuals that hold a stimulator, such as an rTMS coil, in the desired position over the scalp. METHODS: 20 individuals underwent scanning for fabrication of individualized headsets designed for rTMS of the left dorsolateral prefrontal cortex (DLPFC). An experienced operator then performed three trials per participant of three neuronavigation methods: MRI-guided, scalp-measurement (BeamF3 method), and headset placement, and marked the sites obtained. Accuracy (versus MRI-guidance) and reproducibility were measured for each trial of each method. RESULTS: Within-subject accuracy (against a gold-standard centroid of three MRI-guided localizations) for MRI-guided, scalp-measurement, and headset methods was 3.7 ± 1.6 mm, 14.8 ± 7.1 mm, and 9.7 ± 5.2 mm respectively, with headsets significantly more accurate (M = 5.1, p = 0.008) than scalp-measurement methods. Within-subject reproducibility (against the centroid of 3 localizations in the same modality) was 3.7 ± 1.6 mm (MRI), 4.2 ± 1.4 (scalp-measurement), and 1.4 ± 0.7 mm (headset), with headsets achieving significantly better reproducibility than either other method (p < 0.0001). CONCLUSIONS: 3D-printed headsets may offer good accuracy, superior reproducibility and greater ease-of-use for stimulator placement over DLPFC, in settings where MRI-guidance is impractical.

Concordance Between BeamF3 and MRI-neuronavigated Target Sites for Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex.

BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) is a common target for repetitive transcranial magnetic stimulation (rTMS) in major depression, but the conventional "5 cm rule" misses DLPFC in >1/3 cases. Another heuristic, BeamF3, locates the F3 EEG site from scalp measurements. MRI-guided neuronavigation is more onerous, but can target a specific DLPFC stereotaxic coordinate directly. The concordance between these two approaches has not previously been assessed. OBJECTIVE: To quantify the discrepancy in scalp site between BeamF3 versus MRI-guided neuronavigation for left DLPFC. METHODS: Using 100 pre-treatment MRIs from subjects undergoing left DLPFC-rTMS, we localized the scalp site at minimum Euclidean distance from a target MNI coordinate (X - 38 Y + 44 Z + 26) derived from our previous work. We performed nasion-inion, tragus-tragus, and head-circumference measurements on the same subjects' MRIs, and applied the BeamF3 heuristic. We then compared the distance between BeamF3 and MRI-guided scalp sites. RESULTS: BeamF3-to-MRI-guided discrepancies were <0.65 cm in 50% of subjects, <0.99 cm in 75% of subjects, and <1.36 cm in 95% of subjects. The angle from midline to the scalp site did not differ significantly using MRI-guided versus BeamF3 methods. However, the length of the radial arc from vertex to target site was slightly but significantly longer (mean 0.35 cm) with MRI-guidance versus BeamF3. CONCLUSIONS: The BeamF3 heuristic may provide a reasonable approximation to MRI-guided neuronavigation for locating left DLPFC in a majority of subjects. A minor optimization of the heuristic may yield additional concordance.