Filtering and model-based analysis independently improve skin-conductance response measures in the fMRI environment: Validation in a sample of women with PTSD.

Numerous methods exist for the pre-processing and analysis of skin-conductance response (SCR) data, but there is incomplete consensus on suitability and implementation, particularly with regard to signal filtering in conventional peak score (PS) analysis. This is particularly relevant when SCRs are measured during fMRI, which introduces additional noise and signal variability. Using SCR-fMRI data (n = 65 women) from a fear conditioning experiment, we compare the impact of three nested data processing methods on analysis using conventional PS as well as psychophysiological modeling. To evaluate the different methods, we quantify effect size to recover a benchmark contrast of interest, namely, discriminating SCR magnitude to a conditioned stimulus (CS+) relative to a CS not followed by reinforcement (CS-). Findings suggest that low-pass filtering reduces PS sensitivity (Δd = -20%), while band-pass filtering improves PS sensitivity (Δd = +27%). We also replicate previous findings that a psychophysiological modeling approach yields superior sensitivity to detect contrasts of interest than even the most sensitive PS method (Δd = +110%). Furthermore, we present preliminary evidence that filtering differences may account for a portion of exclusions made on commonly applied metrics, such as below zero discrimination. Despite some limitations of our sample and experimental design, it appears that SCR processing pipelines that include band-pass filtering, ideally with model-based SCR quantification, may increase the validity of SCR response measures, maximize research productivity, and decrease sampling bias by reducing data exclusion.

Low-Dose Testosterone Augmentation for Antidepressant-Resistant Major Depressive Disorder in Women: An 8-Week Randomized Placebo-Controlled Study.

OBJECTIVE: Low-dose testosterone has been shown to improve depression symptom severity, fatigue, and sexual function in small studies in women not formally diagnosed with major depressive disorder. The authors sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with antidepressant-resistant major depression. A functional MRI (fMRI) substudy examined effects on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation. METHODS: The authors conducted an 8-week randomized double-blind placebo-controlled trial of adjunctive testosterone cream in 101 women, ages 21-70, with antidepressant-resistant major depression. The primary outcome measure was depression symptom severity as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. The primary outcome of the fMRI substudy (N=20) was change in ACC activity. RESULTS: The participants' mean age was 47 years (SD=14) and their mean baseline MADRS score was 26.6 (SD=5.9). Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS scores decreased in both study arms from baseline to week 8 (testosterone arm: from 26.8 [SD=6.3] to 15.3 [SD=9.6]; placebo arm: from 26.3 [SD=5.4] to 14.4 [SD=9.3]), with no significant difference between groups. Improvement in fatigue and sexual function did not differ between groups, nor did side effects. fMRI results showed a relationship between ACC activation and androgen levels before treatment but no difference in ACC activation with testosterone compared with placebo. CONCLUSIONS: Adjunctive transdermal testosterone, although well tolerated, was not more effective than placebo in improving symptoms of depression, fatigue, or sexual dysfunction. Imaging in a subset of participants demonstrated that testosterone did not result in greater activation of the ACC.