Search

Social transmission of fear is not restricted to visual or auditory cues, but extends to the phylogenetically more ancient olfactory domain. Anxious individuals exhibit heightened sensitivity towards chemosensory stress signals in sweat; however, it is still unknown whether endogenous neuromodulators such as the peptide hormone oxytocin (OXT) influence the chemosensory communication of stress. Here, we investigated whether OXT selectively diminishes behavioral and neural responses to social chemosensory stress cues utilizing a randomized, double-blind, placebo (PLC)-controlled, within-subject functional MRI study design. Axillary sweat was obtained from 30 healthy male donors undergoing the Trier Social Stress Test (stress) and bicycle ergometer training (sport). Subsequently, 58 healthy participants (30 females) completed a forced-choice emotional face recognition task with stimuli of varying intensities (neutral to fearful) while they were exposed to both sweat stimuli and a non-social control odor following intranasal OXT or PLC administration, respectively. OXT diminished stress-induced recognition accuracy and response time biases towards fear. On the neural level, OXT reduced stress-evoked responses in the amygdala in both sexes, the anterior cingulate cortex (ACC) in females, and the hippocampus in males. Furthermore, OXT reinstated the functional connectivity between the ACC and the fusiform face area that was disrupted by stress odors under PLC. Our findings reveal a new role for OXT signaling in the modulation of chemosensory communication of stress in humans. Mechanistically, this effect appears to be rooted in a downregulation of stress-induced limbic activations and concomitant strengthening of top-down control descending from the ACC to the fusiform face area.

BACE1 is the rate-limiting protease in the production of synaptotoxic β-amyloid (Aβ) species and hence one of the prime drug targets for potential therapy of Alzheimer’s disease (AD). However, so far pharmacological BACE1 inhibition failed to rescue the cognitive decline in mild-to-moderate AD patients, which indicates that treatment at the symptomatic stage might be too late. In the current study, chronic in vivo two-photon microscopy was performed in a transgenic AD model to monitor the impact of pharmacological BACE1 inhibition on early β-amyloid pathology. The longitudinal approach allowed to assess the kinetics of individual plaques and associated presynaptic pathology, before and throughout treatment. BACE1 inhibition could not halt but slow down progressive β-amyloid deposition and associated synaptic pathology. Notably, the data revealed that the initial process of plaque formation, rather than the subsequent phase of gradual plaque growth, is most sensitive to BACE1 inhibition. This finding of particular susceptibility of plaque formation has profound implications to achieve optimal therapeutic efficacy for the prospective treatment of AD. Electronic supplementary material The online version of this article (10.1007/s00401-017-1804-9) contains supplementary material, which is available to authorized users.

Social communication through touch and mutual grooming can convey highly salient socio-emotional signals and has been shown to involve the neuropeptide oxytocin (OXT) in several species. Less is known about the modulatory influence of OXT on the neural and emotional responses to human interpersonal touch. The present randomized placebo (PLC)-controlled within-subject pharmaco-functional magnetic resonance imaging (fMRI) study was designed to test the hypothesis that a single intranasal dose of synthetic OXT (24 IU) would facilitate both neural and emotional responses to interpersonal touch in a context- (female vs male touch) and trait- (autistic trait load) specific manner. Specifically, the experimental rationale was to manipulate the reward value of interpersonal touch independent of the intensity and type of actual cutaneous stimulation administered. Thus, 40 heterosexual males believed that they were touched by either a man or a woman, although in fact an identical pattern of touch was always given by the same female experimenter blind to condition type. Our results show that OXT increased the perceived pleasantness of female, but not male touch, and associated neural responses in insula, precuneus, orbitofrontal, and pregenual anterior cingulate cortex. Moreover, the behavioral and neural effects of OXT were negatively correlated with autistic-like traits. Taken together, this is the first study to show that the perceived hedonic value of human heterosexual interpersonal touch is facilitated by OXT in men, but that its behavioral and neural effects in this context are blunted in individuals with autistic traits.

Cerebral β-amyloidosis is induced by inoculation of Aβ seeds into APP transgenic mice, but not into App(-/-) (APP null) mice. We found that brain extracts from APP null mice that had been inoculated with Aβ seeds up to 6 months previously still induced β-amyloidosis in APP transgenic hosts following secondary transmission. Thus, Aβ seeds can persist in the brain for months, and they regain propagative and pathogenic activity in the presence of host Aβ.

Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA.