Common and dissociable effects of oxytocin and lorazepam on the neurocircuitry of fear.

Benzodiazepines (BZDs) represent the gold standard of anxiolytic pharmacotherapy; however, their clinical benefit is limited by side effects and addictive potential. Consequently, there is an urgent need to develop novel and safe anxiolytics. The peptide hormone oxytocin (OXT) exhibits anxiolytic-like properties in animals and humans, but whether OXT and BZDs share similar effects on the neural circuitry of fear is unclear. Therefore, the rationale of this ultra-high-field functional MRI (fMRI) study was to test OXT against the clinical comparator lorazepam (LZP) with regard to their neuromodulatory effects on local and network responses to fear-related stimuli. One hundred twenty-eight healthy male participants volunteered in this randomized double-blind, placebo-controlled, between-group study. Before scanning using an emotional face-matching paradigm, participants were randomly administered a single dose of OXT (24 IU), LZP (1 mg), or placebo. On the behavioral level, LZP, but not OXT, caused mild sedation, as evidenced by a 19% increase in reaction times. On the neural level, both OXT and LZP inhibited responses to fearful faces vs. neutral faces within the centromedial amygdala (cmA). In contrast, they had different effects on intra-amygdalar connectivity; OXT strengthened the coupling between the cmA and basolateral amygdala, whereas LZP increased the interplay between the cmA and superficial amygdala. Furthermore, OXT, but not LZP, enhanced the coupling between the cmA and the precuneus and dorsomedial prefrontal cortex. These data implicate inhibition of the cmA as a common denominator of anxiolytic action, with only OXT inducing large-scale connectivity changes of potential therapeutic relevance.

Comparison of SMS-EPI and 3D-EPI at 7T in an fMRI localizer study with matched spatiotemporal resolution and homogenized excitation profiles.

The simultaneous multi-slice EPI (SMS-EPI, a.k.a. MB-EPI) sequence has met immense popularity recently in functional neuroimaging. A still less common alternative is the use of 3D-EPI, which offers similar acceleration capabilities. The aim of this work was to compare the SMS-EPI and the 3D-EPI sequences in terms of sampling strategies for the detection of task-evoked activations at 7T using detection theory. To this end, the spatial and temporal resolutions of the sequences were matched (1.6 mm isotropic resolution, TR = 1200 ms) and their excitation profiles were homogenized by means of calibration-free parallel-transmission (Universal Pulses). We used a fast-event "localizer" paradigm of 5:20 min in order to probe sensorimotor functions (visual, auditory and motor tasks) as well as higher level functions (language comprehension, mental calculation), where results from a previous large-scale study at 3T (N = 81) served as ground-truth reference for the brain areas implicated in each cognitive function. In the current study, ten subjects were scanned while their activation maps were generated for each cognitive function with the GLM analysis. The SMS-EPI and 3D-EPI sequences were compared in terms of raw tSNR, t-score testing for the mean signal, activation strength and accuracy of the robust sensorimotor functions. To this end, the sensitivity and specificity of these contrasts were computed by comparing their activation maps to the reference brain areas obtained in the 3T study. Estimated flip angle distributions in the brain reported a normalized root mean square deviation from the target value below 10% for both sequences. The analysis of the t-score testing for the mean signal revealed temporal noise correlations, suggesting the use of this metric instead of the traditional tSNR for testing fMRI sequences. The SMS-EPI and 3D-EPI thereby yielded similar performance from a detection theory perspective.