Alexithymic and autistic traits : relevance for comorbid depression and social phobia in adults with and without autism spectrum disorder

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Max Planck Society via a grant for an Independent Max Planck Research Group awarded to L.S. L.A. was funded via the Else-Kröner-Fresenius-Stiftung (EKFS) as part of a joint residency/PhD program in translational psychiatry at the LMU Munich and the Max Planck Institute of Psychiatry.Peer reviewedPublisher PD

Intercellular Transport of Oct4 in Mammalian Cells: A Basic Principle to Expand a Stem Cell Niche?

Background: The octamer-binding transcription factor 4 (Oct4) was originally described as a marker of embryonic stem cells. Recently, the role of Oct4 as a key regulator in pluripotency was shown by its ability to reprogram somatic cells in vitro, either alone or in concert with other factors. While artificial induction of pluripotency using transcription factors is possible in mammalian cell culture, it remains unknown whether a potential natural transfer mechanism might be of functional relevance in vivo. The stem cell based regeneration of deer antlers is a unique model for rapid and complete tissue regeneration in mammals and therefore most suitable to study such mechanisms. Here, the transfer of pluripotency factors from resident stem cell niche cells to differentiated cells could recruit more stem cells and start rapid tissue regeneration. Methodology/Principal Findings: We report on the ability of STRO-1 + deer antlerogenic mesenchymal stem cells (DaMSCs) to transport Oct4 via direct cell-to-cell connections. Upon cultivation in stem cell expansion medium, we observed nuclear Oct4 expression in nearly all cells. A number of these cells exhibit Oct4 expression not only in the nucleus, but also with perinuclear localisation and within far-ranging intercellular connections. Furthermore, many cells showed intercellular connections containing both F-actin and a-tubulin and through which transport could be observed. To proof that intercellular Oct4-transfer has functional consequences in recipient cells we used a co-culture approach with STRO-1 + DaMSCs and a murine embryonic fibroblast indicator cell line (Oct4-GFP MEF). In this cell line a reporter gene (GFP) unde

Subclinically Anxious Adolescents Do Not Display Attention Biases When Processing Emotional Faces – An Eye-Tracking Study

Recent research suggests that early difficulties with emotion regulation go along with an increased risk for developing psychiatric disorders, such as anxiety disorders for example. Adolescent anxiety is often referred to as a gateway disorder, due to its high predictability for lifelong persistent mental health problems. It has been shown that clinically anxious adolescents exhibit attention biases toward negative stimuli, yet whether these biases can also be found in the subclinical range of subclinically anxious adolescents is currently unclear. In this study, we set out to investigate this question by combining an emotional Go-Nogo task with eye-tracking techniques to assess attention biases for emotional faces in a subclinical sample of 23 subclinically anxious adolescent girls. This combined approach allowed us to look at both, behavioral and covert attention biases. Using both traditional and Bayesian hypothesis testing, we found no evidence for a bias toward negative, threat-relevant stimuli in the behavioral level or eye-tracking data. We believe that the results can help close a gap in the current literature by showing that like low-anxious adolescents, subclinically anxious adolescents do not exhibit attention biases when viewing de-contextualized emotional stimuli in the Overlap task. Together with previous research findings in clinically anxious participants which have reported high levels of attention biases, our results seem to suggest that attention biases do no increase linearly as a function of individual anxiety level. Future research is now needed to explore the contribution of additional factors, such as depression for example

Positive and negative prediction error signals to violated expectations of face and place stimuli distinctively activate FFA and PPA

Surprising scenarios can have different behavioural and neuronal consequences depending on the violation of the expectation. On the one hand, previous research has shown that the omission of a visual stimulus results in a robust cortical response representing that missing stimulus, a so-called negative prediction error. On the other hand, a large amount of studies revealed positive prediction error signals, entailing an increased neural response that can be attributed to the experience of a surprising, unexpected stimulus. However, there has been no evidence, so far, regarding how and when these prediction error signals co-occur. Here, we argue that the omission of an expected stimulus can and often does coincide with the appearance of an unexpected one. Therefore, we investigated whether positive and negative prediction error signals evoked by unpredicted cross-category stimulus transitions would temporally coincide during a speeded forced-choice fMRI paradigm. Foremost, our findings provide evidence of a behavioural effect regarding the facilitation of responses linked to expected stimuli. In addition, we obtained evidence for negative prediction error signals as seen in differential activation of FFA and PPA during unexpected place and face trials, respectively. Lastly, a psychophysiological interaction analysis revealed evidence for positive prediction error signals represented by context-dependent functional coupling between the right IFG and FFA or PPA, respectively, implicating a network that updates the internal representation after the appearance of an unexpected stimulus through involvement of this frontal area. The current results are consistent with a predictive coding account of cognition and underline the importance of considering the potential dual nature of expectation violations. Furthermore, our results put forward that positive and negative prediction error signalling can be directly linked to regions associated with the processing of different stimulus categories

Subclinically Anxious Adolescents Do Not Display Attention Biases When Processing Emotional Faces – An Eye-Tracking Study

Recent research suggests that early difficulties with emotion regulation go along with an increased risk for developing psychiatric disorders, such as anxiety disorders for example. Adolescent anxiety is often referred to as a gateway disorder, due to its high predictability for lifelong persistent mental health problems. It has been shown that clinically anxious adolescents exhibit attention biases toward negative stimuli, yet whether these biases can also be found in the subclinical range of subclinically anxious adolescents is currently unclear. In this study, we set out to investigate this question by combining an emotional Go-Nogo task with eye-tracking techniques to assess attention biases for emotional faces in a subclinical sample of 23 subclinically anxious adolescent girls. This combined approach allowed us to look at both, behavioral and covert attention biases. Using both traditional and Bayesian hypothesis testing, we found no evidence for a bias toward negative, threat-relevant stimuli in the behavioral level or eye-tracking data. We believe that the results can help close a gap in the current literature by showing that like low-anxious adolescents, subclinically anxious adolescents do not exhibit attention biases when viewing de-contextualized emotional stimuli in the Overlap task. Together with previous research findings in clinically anxious participants which have reported high levels of attention biases, our results seem to suggest that attention biases do no increase linearly as a function of individual anxiety level. Future research is now needed to explore the contribution of additional factors, such as depression for example

Early alpha/beta oscillations reflect the formation of face-related expectations in the brain

Although statistical regularities in the environment often go explicitly unnoticed, traces of implicit learning are evident in our neural activity. Recent perspectives have offered evidence that both pre-stimulus oscillations and peri-stimulus event-related potentials are reliable biomarkers of implicit expectations arising from statistical learning. What remains ambiguous, however, is the origination and development of these implicit expectations. To address this lack of knowledge and determine the temporal constraints of expectation formation, pre-stimulus increases in alpha/beta power were investigated alongside a reduction in the N170 and a suppression in peri-/post-stimulus gamma power. Electroencephalography was acquired from naive participants who engaged in a gender classification task. Participants were uninformed, that eight face images were sorted into four reoccurring pairs which were pseudorandomly hidden amongst randomly occurring face images. We found a reduced N170 for statistically expected images at left parietal and temporo-parietal electrodes. Furthermore, enhanced gamma power following the presentation of random images emphasized the bottom-up processing of these arbitrary occurrences. In contrast, enhanced alpha/beta power was evident pre-stimulus for expected relative to random faces. A particularly interesting finding was the early onset of alpha/beta power enhancement which peaked immediately after the depiction of the predictive face. Hence, our findings propose an approximate timeframe throughout which consistent traces of enhanced alpha/beta power illustrate the early prioritisation of top-down processes to facilitate the development of implicitly cued face-related expectations

Transport of Oct4 fusion protein via cytoplasmic connections.

<p>(<b>a–d</b>) Time series pictures of a transfected STRO-1⁺ DaMSC. The GFP fluorescence of the Oct4 fusion protein is visible within the cytoplasm as well as inside the membrane tubes. Membrane dilatations (gondolas) filled with Oct4 fusion proteins are moving away from the cellular body. Starting points are marked with white dashed lines. Scale bar = 20 µm.</p

Mixed culture of Oct4-GFP MEF cells and STRO-1⁺ DaMSCs.

<p>(<b>a</b>) Colony of Oct4-GFP MEF cells without any GFP expression. (<b>b</b>) Individual Oct4-GFP MEF cell after 24 hours of pre-cultivation in stem cell expansion medium on the eve of co-cultivation. (<b>c</b>) The same Oct4-GFP MEF cell after 24 hours of co-cultivation with STRO-1⁺ DaMSCs (interacting DaMSCs are outside of the display window). GFP expression (pseudo-coloured green) is visible within the cytoplasm. (<b>d</b>) Mixed culture after 96 hours of co-cultivation. More GFP⁺ cells interacting with GFP⁻ cells are visible. (<b>e</b>) Cell with distinct GFP expression after 120 hours of co-cultivation. At that time GFP⁺ cells interact continuously with GFP⁻ cells and are well integrated into the forming multilayer. (<b>f</b>) After 144 hours of co-cultivation some cells exhibit widely distributed intracellular GFP expression. (a,b,c,f = phase contrast pictures; d,e = varel contrast pictures; a–e = pictures of living cultures, f = fixed cells).</p

Cytoskeletal elements of STRO-1⁺ DaMSCs and long-distance cell-to-cell connections (TNTs).

<p>(<b>a,b</b>) Different cell-to-cell connections between STRO-1⁺ cells. Intercellular connections are able to bridge long distances even across neighbouring cells (Phalloidin/Tubulin staining, merged images). (<b>b</b>) Thick tubes (diameter >0.4 µm, example is marked by red arrow) contain F-actin and α-tubulin, whereas thin tubes (diameter <0.4 µm, example is marked by green arrow) contain only F-actin. (<b>c</b>) Negative control, staining without Tubulin antibody. (<b>d–f</b>) Scanning electron microscope pictures (SEM) of a mixed culture of antlerogenic cells. Cells form long connections across neighbouring cells (<b>d,e</b>) and very high magnification (<b>f</b>) proves that the surface of TNTs exhibit small appendages; long-distance connections are also possible between morphologically distinguishable cell types (<b>d</b>). (<b>h–m</b>) Multichannel pictures of Phalloidin (<b>h,k</b>) and Tubulin (<b>i,l</b>) stained DaMSCs demonstrate that their intercellular connections continuously consist of F-actin but only partially of microtubules. The visible spindle apparatus (<b>i</b>, detail enlargement) point to an initiating cell division and provides evidence that the used α-tubulin antibody is also efficient in DaMSCs. (<b>j,m</b>). Merged Images.</p