RESUMO
BACKGROUND: To examine the antidepressant efficacy and response predictors of R-DLPFC-LF rTMS for antidepressant-nonresponding BD. METHODS: We conducted a single-blind randomized sham-controlled trial for 54 (28 sham, 26 active) patients with antidepressant-nonresponding BD (baseline MADRS ≥ 20). Patients received 15 daily sessions of active or sham neuronavigated rTMS (Figure-of-8 coil, five 1 Hz 60 s 110% RMT trains). Outcome measures included depressive response (≥ 50% MADRS reduction, CGI ≤ 2) and remission (MADRS < 7, CGI = 1) rates, treatment emergent hypo/mania (YMRS), depressive and anxiety symptoms (HAM-A). RESULTS: 48 patients (25 sham, 23 active) completed treatment, with 3 drop-outs each in active and sham groups. Active rTMS did not produce superior response or remission rates at endpoint or 6 or 12 weeks (ps > 0.05). There was no significant group * time interaction (ps > 0.05) in a multivariate ANOVA with MADRS, HAMA and YMRS as dependent variables. Exploratory analysis found MADRS improvement to be moderated by baseline anxiety (p = 0.02) and melancholia (p = 0.03) at week 3, and depressive onset at weeks 6 (p = 0.03) and 12 (p = 0.04). In subjects with below-mean anxiety (HAMA < 20.7, n = 24), MADRS improvement from active rTMS was superior to sham at week 3 (ITT, t = 2.49, p = 0.04, Cohen's d = 1.05). No seizures were observed. Groups did not differ in treatment-emergent hypomania (p = 0.1). LIMITATIONS: Larger sample size might be needed to power subgroup analyses. Moderation analyses were exploratory. Single-blind design. Unblinding before follow-up assessments due to ethical reasons. CONCLUSIONS: 1-Hz 110% RMT (5 × 60 s trains) R-DLPFC-LF rTMS was not effective for antidepressant non-responding BD but may be further investigated at increased dosage and/or in BD patients with low anxiety. Trial registration CCRB Clinical Trials Registry, CUHK, CUHK_CCT00440. Registered 04 December 2014, https://www2.ccrb.cuhk.edu.hk/registry/public/279.
RESUMO
Depth sensitivity has been shown to be modulated by object context (plausibility). It is possible that it is behavioural relevance rather than object plausibility per se which drives this effect. Here, we manipulated the biological relevance of objects (face or a non-face) and tested whether object relevance affects behavioural sensitivity and neural responses to depth-position. In a first experiment, we presented human observers with disparity-defined faces and non-faces, and observers were asked to judge the depth position of the target under signal-noise and clear (fine) task conditions. In the second experiment, we concurrently measured behavioural and fMRI responses to depth. We found that behavioural performance varied across stimulus conditions such that they were significantly worse for the upright face than the inverted face and the random shape in the SNR task, but worse for the random shape than the upright face in the feature task. Pattern analysis of fMRI responses revealed that activity of FFA was distinctly different during depth judgments of the upright face versus the other two stimuli, with its responses (and to a stronger extent, those of V3) appearing functionally-relevant to behavioural performance. We speculate that FFA is not only involved in object analysis, but exerts considerable influence on stereoscopic mechanisms as early as in V3 based on a broader appreciation of the stimulus' behavioural relevance.Significance StatementWe asked how disparity sensitivity is modulated by object (biological) relevance using behavioural and neuroimaging paradigms. We show that behavioural sensitivity to depth-position changes in biological (face) vs non-biological (random surface) contexts, and that these changes are task-dependent. Imaging results highlight a potentially key role of the fusiform region for governing the modulation of stereo encoding by object relevance. These findings highlight powerful interactions between object recognition mechanisms and stereoencoding, such that the utility of disparity information may be up/down weighed depending on the biological relevance of the object.