Inverse effects of oxytocin on attributing mental activity to others in depressed and healthy subjects: a double-blind placebo controlled FMRI study.

BACKGROUND: Oxytocin is a stress-attenuating and pro-social neuropeptide. To date, no study has looked at the effects of oxytocin in modulating brain activity in depressed individuals nor attempted to correlate this activity with attribution of mental activity in others. METHOD: We enrolled 10 unmedicated depressed adults and 10 matched healthy controls in a crossover, double blind placebo controlled fMRI 40 i.u. intra-nasal oxytocin study (20 i.u. per nostril). Each subject performed reading the mind in the eyes task (RMET) before and after inhalation of oxytocin or placebo control for a total of 80 scans. RESULTS: Before oxytocin administration, RMET engaged the medial and lateral prefrontal cortex, amygdala, insula and associative areas. Depressed subjects showed increased anterior ventral activation for the RMET minus gender identification contrast whereas matched controls showed increased dorsal and frontal activity. Compared to placebo, oxytocin in depressed subjects showed increased activity in the superior middle frontal gyrus and insula, while controls exhibited more activity in ventral regions. Oxytocin also led to inverse effects in reaction times on attribution task between groups, with controls getting faster and depressed individuals slower to respond. CONCLUSION: Depression is associated with increased paralimbic activity during emotional mental attribution of others, appearing to be distinctly modulated by oxytocin when compared to healthy controls. Further studies are needed to explore long-term exposure to pro-social neuropeptides on mood in depressed populations and assess their clinical relevance.

More lateral and anterior prefrontal coil location is associated with better repetitive transcranial magnetic stimulation antidepressant response.

BACKGROUND: The left dorsolateral prefrontal cortex (DLPFC) is the most commonly used target for transcranial magnetic stimulation (TMS) in the treatment of depression. The "5-cm rule" is an empiric method used for probabilistic targeting of the DLPFC in most clinical trials. This rule may be suboptimal, as it does not account for differences in skull size or variations in prefrontal anatomy relative to motor cortex location. This study is a post hoc analysis of data from a large repetitive TMS (rTMS) trial in which we examined the variability of coil placement and how it affects antidepressant efficacy. METHODS: Fifty-four depressed subjects enrolled in a randomized, single-site trial received either active rTMS or sham for 3 weeks. Prior to treatment initiation, investigators placed vitamin E capsules at the point of stimulation and used a high-resolution magnetic resonance imaging (MRI) scan to image these fiducials relative to anatomy. We employed a semiautomated imaging-processing algorithm to localize the cortical region stimulated. RESULTS: Active TMS significantly reduced Hamilton Depression Rating Scale (HDRS) scores. A linear model for this improvement involving the coordinates of the stimulated cortex location, age, and treatment condition was highly significant. Specifically, individuals with more anterior and lateral stimulation sites were more likely to respond. CONCLUSIONS: These results suggest that within the general anatomical area targeted by the 5-cm rule, placing the TMS coil more laterally and anteriorly is associated with improved response rates in TMS depression studies. Controlled studies testing this anatomical hypothesis are needed.

Motor threshold in transcranial magnetic stimulation: the impact of white matter fiber orientation and skull-to-cortex distance.

The electrophysiology of transcranial magnetic stimulation (TMS) of motor cortex is not well understood. In this study, we investigate several structural parameters of the corticospinal tract and their relation to the TMS motor threshold (MT) in 17 subjects, with and without schizophrenia. We obtained structural and diffusion tensor MRI scans and measured the fractional anisotropy and principal diffusion direction for regions of interest in the corticospinal tract. We also measured the skull-to-cortex distance over the left motor region. The anterior-posterior trajectory of principle diffusion direction of the corticospinal tract and skull-to-cortex distance were both found to be highly correlated with MT, while fractional anisotropy, age and schizophrenia status were not. Two parameters-skull-to-cortex distance and the anterior component of the principle diffusion direction of the corticospinal tract as it passes the internal capsule-are highly predictive of MT in a linear regression model, and account for 82% of the variance observed (R2 = 0.82, F = 20.27, P < 0.0001) in measurements of MT. The corticospinal tract's anterior-posterior direction alone contributes 13% of the variance explained.

Vagus nerve stimulation (VNS) for depression: what do we know now and what should be done next?

Vagus nerve stimulation (VNS) therapy is the first US Food and Drug Administration-approved somatic clinical intervention for treatment-resistant depression (TRD). Long-term open data suggest a sustainable antidepressant response over time. Here we review the clinical data that exist so far and their limitations. We also discuss guidelines that may inform the clinical utilization of this procedure. Further clinical studies, in addition to prospective cost utilization and health economic investigations, are needed to better understand VNS therapy and the impact it holds on TRD care.