Explore the vast range of titles available.

Detecting and responding to threat engages several neural nodes including the amygdala, hippocampus, insular cortex, and medial prefrontal cortices. Recent propositions call for the integration of more distributed neural nodes that process sensory and cognitive facets related to threat. Integrative, sensitive, and reproducible distributed neural decoders for the detection and response to threat and safety have yet to be established. We combine functional MRI data across varying threat conditioning and negative affect paradigms from 1465 participants with multivariate pattern analysis to investigate distributed neural representations of threat and safety. The trained decoders sensitively and specifically distinguish between threat and safety cues across multiple datasets. We further show that many neural nodes dynamically shift representations between threat and safety. Our results establish reproducible decoders that integrate neural circuits, merging the well-characterized ‘threat circuit’ with sensory and cognitive nodes, discriminating threat from safety regardless of experimental designs or data acquisition parameters. Discriminating threat from safety is critical for humans to navigate their environment. Here, the authors show that neural representations of threat and safety are distributed across brain systems that are robustly decoded across threat paradigms.

Examining the neural circuits of fear/threat extinction advanced our mechanistic understanding of several psychiatric disorders, including anxiety disorders (AX) and posttraumatic stress disorder (PTSD). More is needed to understand the interplay of large-scale neural networks during fear extinction in these disorders. We used dynamic functional connectivity (FC) to study how FC might be perturbed during conditioned fear extinction in individuals with AX or PTSD. We analyzed neuroimaging data from 338 individuals that underwent a two-day fear conditioning and extinction paradigm. The sample included healthy controls (HC), trauma-exposed non-PTSD controls, and patients diagnosed with AX or PTSD. Dynamic FC during extinction learning gradually increased in the HC group but not in patient groups. The lack of FC change in patients was predominantly observed within and between the default mode, frontoparietal control, and somatomotor networks. The AX and PTSD groups showed impairments in different, yet partially overlapping connections especially involving the dorsolateral prefrontal cortex. Extinction-induced FC predicted ventromedial prefrontal cortex activation and FC during extinction memory recall only in the HC group. FC impairments during extinction learning correlated with fear- and anxiety-related clinical measures. These findings suggest that relative to controls, individuals with AX or PTSD exhibited widespread abnormal FC in higher-order cognitive and attention networks during extinction learning and failed to establish a link between neural signatures during extinction learning and memory retrieval. This failure might underlie abnormal processes related to the conscious awareness, attention allocation, and sensory processes during extinction learning and retrieval in fear- and anxiety-related disorders.

In the present paper, we compare the predictions of two well known mechanisms considered able to solve the cusp/core problem (a. supernova feedback; b. baryonic clumps-DM interaction) by comparing their theoretical predictions to recent observations of the inner slopes of galaxies with masses ranging from dSphs to normal spirals. We compare the α - V rot and the α - M ∗ relationships, predicted by the two models with high resolution data coming from Adams et al. (Astrophys. J. 789, 63, 2014 ), Simon et al. (Astrophys. J. 621, 757, 2005 ), LITTLE THINGS (Oh et al. in Astron. J. 149, 180, 2015 ), THINGS dwarves (Oh et al. in Astron. J. 141, 193, 2011a ; Oh et al. in Astron. J. 142, 224, 2011b ), THINGS spirals (Oh et al. in Astron. J. 149, 180, 2015 ), Sculptor, Fornax and the Milky Way. The comparison of the theoretical predictions with the complete set of data shows that the two models perform similarly, while when we restrict the analysis to a smaller subsample of higher quality, we show that the method presented in this paper (baryonic clumps-DM interaction) performs better than the one based on supernova feedback. We also show that, contrarily to the first model prediction, dSphs of small mass could have cored profiles. This means that observations of cored inner profiles in dSphs having a stellar mass < 10 6 M ⊙ not necessarily imply problems for the Λ CDM model.

Neural plasticity in subareas of the rodent amygdala is widely known to be essential for Pavlovian threat conditioning and safety learning. However, less consistent results have been observed in human neuroimaging studies. Here, we identify and test three important factors that may contribute to these discrepancies: the temporal profile of amygdala response in threat conditioning, the anatomical specificity of amygdala responses during threat conditioning and safety learning, and insufficient power to identify these responses. We combined data across multiple studies using a well-validated human threat conditioning paradigm to examine amygdala involvement during threat conditioning and safety learning. In 601 humans, we show that two amygdala subregions tracked the conditioned stimulus with aversive shock during early conditioning while only one demonstrated delayed responding to a stimulus not paired with shock. Our findings identify cross-species similarities in temporal- and anatomical-specific amygdala contributions to threat and safety learning, affirm human amygdala involvement in associative learning and highlight important factors for future associative learning research in humans.

The combined acquisition of 3D ultrasonic tomography and radar scans is growing for cultural heritage diagnostics. Both methods proved to be efficient in the detection and location of fractures and weaknesses within the investigated artefacts. Although the two techniques are widely applied together, an integrated approach for data interpretation is still missing. We present the results of radar and ultrasonic prospections carried out on the statue of the young Ramses II, an absolute masterpiece of the Egyptian art preserved in the collection of the Museo Egizio of Torino (Italy). Geophysical results are incorporated within the 3D model of the statue retrieved from total station measurements, ground-based and handheld laser scanning. A data integration approach is then proposed for the joint interpretation of the geophysical results, exploiting the final ultrasonic velocity model and radar attribute analysis (i.e. local dissimilarity computation) to define a combined damage index. The proposed methodology is efficient in fracture detection and location and improves the readability of the final results also for non-expert geophysical interpreters, offering guidance to the museum for preservation and restoration of the masterpiece.

Key Points Over the past decade, technological advances in molecular biology and cellular neurophysiology have allowed us to construct a much more complete picture of the genetic events, cellular mechanisms and subcortical networks that underlie the neurobiology of sleep. An interlocking positive–negative feedback mechanism that controls gene transcription in individual cells of the suprachiasmatic nucleus (SCN) of the hypothalamus is the molecular basis of circadian rhythmicity in mammals. This endogenous periodicity can be entrained to the ambient photoperiod by photons impinging on the circadian photopigment melanopsin in retinal ganglion cells. These cells use the neurotransmitter glutamate to convey this information to the SCN monosynaptically through the retinohypothalamic tract (RHT). SCN cells output their intrinsic circadian rhythmicity by action potentials that impinge on adjacent nuclei of the anterior hypothalamus, including the paraventricular nucleus, the subparaventricular nucleus (SPZ), the dorsomedial nucleus (DMH) and the medial preoptic area, which, in turn, convey circadian rhythmicity to structures that control rhythmic physiological processes, such as sleep, temperature and endocrine output. Feedback to the SCN circadian oscillator can occur by melatonin from the pineal gland, which reliably secretes this sleep-related hormone in response to polysynaptically conveyed signals from the SCN. In addition, other neuromodulatory systems, including the neurotransmitter acetylcholine, modulate the SCN's responsiveness to photic input from the RHT. The sensitivity of the circadian pacemaker to such modulation also shows temporal specificity: the SCN is responsive to particular modulatory signals only at specific times during the circadian day. A key hypothalamic structure that receives circadian output from the SCN through the SPZ and the DMH is the GABA (γ-aminobutyric acid)-containing ventrolateral preoptic area (VLPO), which promotes non-REM (NREM) sleep. The VLPO might initiate sleep onset through its reciprocal inhibition of cholinergic, noradrenergic and serotonergic arousal systems in the brainstem, as well as histaminergic arousal systems of the posterior hypothalamus and cholinergic systems of the basal forebrain, all of which are modulated by the orexinergic arousal system of the lateral hypothalamus. All these arousal systems promote the activated brain states of waking, whereas the cholinergic system acts alone to promote the activated state of rapid eye movement (REM) sleep. The VLPO is triggered to initiate sleep onset by both circadian input from the anterior hypothalamus and sleep–wake homeostatic information from endogenous chemical signals, such as adenosine, which accumulate in proportion to time spent awake. Circadian and homeostatic signals are integrated in diencephalic structures so as to initiate sleep with an adaptive timing. Once sleep is initiated, an ultradian oscillator in the mesopontine junction controls the regular alternation of NREM and REM sleep. The executive control of this oscillator involves a reciprocal interaction between cholinergic REM-on and aminergic REM-off cell groups, whose influence on one another is mediated by interposed excitatory, inhibitory and autoregulatory circuits that involve GABA and glutamate, as well as serotonin, noradrenaline and acetylcholine. Both the sleep–wake and REM–NREM oscillators give rise to regularly recurring changes in neuromodulation of the forebrain structures that mediate behaviour, consciousness and cognitive processes such as memory consolidation. The burgeoning literature detailing molecular-biological, cellular and neuromodulatory mechanisms indicates that sleep research has entered a new era. To appreciate the neural underpinnings of sleep, it is important to view this universal mammalian behaviour at multiple levels of its biological organization. Molecularly, the circadian rhythm of sleep involves interlocking positive- and negative-feedback mechanisms of circadian genes and their protein products in cells of the suprachiasmatic nucleus that are entrained to ambient conditions by light. Circadian information is integrated with information on homeostatic sleep need in nuclei of the anterior hypothalamus. These nuclei interact with arousal systems in the posterior hypothalamus, basal forebrain and brainstem to control sleep onset. During sleep, an ultradian oscillator in the mesopontine junction controls the regular alternation of rapid eye movement (REM) and non-REM sleep. Sleep cycles are accompanied by neuromodulatory influences on forebrain structures that influence behaviour, consciousness and cognition.

Disrupted sleep is a major feature in numerous clinical disorders and is related to decrements in affective memory processing. The prevalence of sleep disruption in post-traumatic stress disorder (PTSD) is suggested to be a key feature that exacerbates the impaired ability to recall extinction memories during experimental fear conditioning. We hypothesized that an intervention employing blue-wavelength light therapy (BLT) to regulate sleep and stabilize circadian rhythms in patients with PTSD (i.e., via regulated morning exposure) would be associated with PTSD symptom improvement, decreased sleep-related complaints, as well as improved consolidation and retention of extinction memories relative to a fear conditioning/extinction paradigm. Eighty-two individuals with PTSD underwent a well-validated fear conditioning/extinction protocol with subsequent assignment to receive morning BLUE (BLT) or placebo AMBER (ALT) light therapy daily for 30-minutes over 6-weeks. Participants returned after the intervention for post-treatment extinction recall, comprised of exposure to the previously conditioned stimuli, with the difference in skin conductance response between the “extinguished” and the “never-extinguished” stimuli at follow-up. Participants also viewed previously conditioned stimuli in a novel context during a functional magnetic resonance imaging (fMRI) scan. BLUE light therapy was associated with improvements relative to correlated decreases between PTSD symptoms and sleep-related complaints. Participants receiving BLT also sustained retention of the extinction memory, while those in the placebo amber light treatment group showed impairment, characterized by the restoration of the extinguished fear response after 6-weeks. Participants in the ALT also demonstrated greater reactivity in the left insula when viewing the previously extinguished fear-conditioned stimuli in a novel context. Daily BLUE-wavelength morning light exposure was associated with greater retention of extinction learning in patients with PTSD when compared to ALT, as supported by both autonomic and neurobiological reactivity. We speculate that improved sleep facilitated by a stabilized circadian rhythm, after fear-learning, led to greater consolidation of the fear extinction memory, decreased PTSD symptom presentation, and associated decreases in sleep-related complaints. Prominent exposure treatments for PTSD incorporate principles of fear extinction, and our findings suggest that blue light treatment may facilitate treatment gains by promoting the consolidation of extinction memories via improved sleep.

Background Findings about sex differences in the field of fear conditioning and fear extinction have been mixed. At the psychophysiological level, sex differences emerge only when taking estradiol levels of women into consideration. This suggests that this hormone may also influence sex differences with regards to activations of brain regions involved in fear conditioning and its extinction. Importantly, the neurobiological correlates associated with the use of hormonal oral contraceptives in women have not been fully contrasted against men and against naturally cycling women with different levels of estradiol. In this study, we begin to fill these scientific gaps. Methods We recruited 37 healthy men and 48 healthy women. Of these women, 16 were using oral contraceptives (OC) and 32 were naturally cycling. For these naturally cycling women, a median split was performed on their serum estradiol levels to create a high estradiol (HE) group ( n  = 16) and a low estradiol (LE) group ( n  = 16). All participants underwent a 2-day fear conditioning and extinction paradigm in a 3 T MR scanner. Using the 4 groups (men, HE women, LE women, and OC users) and controlling for age and coil type, one-way ANCOVAs were performed to look at significant activations within the nodes of the fear circuit. Using post-hoc analyses, beta-weights were extracted in brain regions showing significant effects in order to unveil the differences based on hormonal status (men, HE, LE, OC). Results Significant main effect of hormonal status group was found across the different phases of the experiment and in different sub-regions of the insular and cingulate cortices, amygdala, hippocampus, and hypothalamus. During conditioning, extinction and recall, most of the observed differences suggested higher activations among HE women relative to men. During the unconditioned response, however, a different pattern was observed with men showing significantly higher brain activations. Conclusions Our data further support the important contribution of estradiol levels in the activation of brain regions underlying fear learning and extinction. The results highlight the need to document gonadal hormonal levels, menstrual cycle phase as well as oral contraceptive use in women in order to avoid overlooking sex differences when investigating the neurobiology of emotional regulation.

The RNA helicase p68 (DDX5) is an established co-activator of the p53 tumour suppressor that itself has a pivotal role in orchestrating the cellular response to DNA damage. Although several factors influence the biological outcome of p53 activation, the mechanisms governing the choice between cell-cycle arrest and apoptosis remain to be elucidated. In the present study, we show that, while p68 is critical for p53-mediated transactivation of the cell-cycle arrest gene p21 WAF1/CIP1 , it is dispensable for induction of several pro-apoptotic genes in response to DNA damage. Moreover, p68 depletion results in a striking inhibition of recruitment of p53 and RNA Pol II to the p21 promoter but not to the Bax or PUMA promoters, providing an explanation for the selective effect on p21 induction. Importantly, these findings are mirrored in a novel inducible p68 knockout mouse model in which p68 depletion results in a selective inhibition of p21 induction in several tissues. Moreover, in the bone marrow, p68 depletion results in an increased sensitivity to γ-irradiation, consistent with an increased level of apoptosis. These data highlight a novel function of p68 as a modulator of the decision between p53-mediated growth arrest and apoptosis in vitro and in vivo.