Connectivity-guided intermittent theta burst versus repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled trial.

Disruption in reciprocal connectivity between the right anterior insula and the left dorsolateral prefrontal cortex is associated with depression and may be a target for neuromodulation. In a five-center, parallel, double-blind, randomized controlled trial we personalized resting-state functional magnetic resonance imaging neuronavigated connectivity-guided intermittent theta burst stimulation (cgiTBS) at a site based on effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. We tested its efficacy in reducing the primary outcome depression symptoms measured by the GRID Hamilton Depression Rating Scale 17-item over 8, 16 and 26 weeks, compared with structural magnetic resonance imaging (MRI) neuronavigated repetitive transcranial magnetic stimulation (rTMS) delivered at the standard stimulation site (F3) in patients with 'treatment-resistant depression'. Participants were randomly assigned to 20 sessions over 4-6 weeks of either cgiTBS (n = 128) or rTMS (n = 127) with resting-state functional MRI at baseline and 16 weeks. Persistent decreases in depressive symptoms were seen over 26 weeks, with no differences between arms on the primary outcome GRID Hamilton Depression Rating Scale 17-item score (intention-to-treat adjusted mean, -0.31, 95% confidence interval (CI) -1.87, 1.24, P = 0.689). Two serious adverse events were possibly related to TMS (mania and psychosis). MRI-neuronavigated cgiTBS and rTMS were equally effective in patients with treatment-resistant depression over 26 weeks (trial registration no. ISRCTN19674644).

Effects of Prior Upper Body Exercise on the 3-min All-Out Cycling Test in Men.

INTRODUCTION: Prior upper body exercise reduces the curvature constant (W') of the hyperbolic power-duration relationship without affecting critical power. This study tested the hypothesis that prior upper body exercise reduces the work done over the end-test power (WEP; analog of W') during a 3-min all-out cycling test (3MT) without affecting the end-test power (EP; analog of critical power). METHODS: Ten endurance-trained men (V˙O2max = 62 ± 5 mL·kg·min) performed a 3MT without (CYC) and with (ARM-CYC) prior severe-intensity, intermittent upper body exercise. EP was calculated as the mean power output over the last 30 s of the 3MT, whereas WEP was calculated as the power-time integral above EP. RESULTS: At the start of the 3MT, plasma [La] (1.8 ± 0.4 vs 14.1 ± 3.4 mmol·L) and [H] (42.8 ± 3.1 vs 58.6 ± 5.5 nmol·L) were higher, whereas the strong ion difference (41.4 ± 2.2 vs 30.9 ± 4.6 mmol·L) and [HCO3] (27.0 ± 1.9 vs 16.9 ± 3.2 mmol·L) were lower during ARM-CYC than CYC (P < 0.010). EP was 12% lower during the 3MT of ARM-CYC (298 ± 52 W) than CYC (338 ± 60 W; P < 0.001), whereas WEP was not different (CYC: 12.8 ± 3.3 kJ vs ARM-CYC: 13.5 ± 4.1 kJ, P = 0.312). EP in CYC was positively correlated with the peak [H] (r = 0.78, P = 0008) and negatively correlated with the lowest [HCO3] (r = -0.74, P = 0.015). CONCLUSIONS: These results suggest that EP during a 3MT in endurance-trained men is sensitive to fatigue-related ionic perturbation.