Filament condition-specific response elements control the expression of NRG1 and UME6, key transcriptional regulators of morphology and virulence in Candida albicans

Funding: D.S.C. was supported by a COSTAR fellowship (National Institute of Dental and Craniofacial Research Grant T32DE014318) in addition to a Ruth L. Kirschstein National Research Service Award for Individual Predoctoral Fellows (National Institute of Dental and Craniofacial Research Grant F31DE021930). D.K. was supported by Grant 5RO1AI083344 from the National Institute of Allergy and Infectious Diseases as well as a Voelcker Young Investigator Award from the Max and Minnie Tomerlin Voelcker Fund. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases, the National Institute of Dental and Craniofacial Research or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

When change is the only constant:The promise of longitudinal neuroimaging in understanding social anxiety disorder

Longitudinal studies offer a unique window into developmental change. Yet, most of what we know about the pathophysiology of psychiatric disorders is based on cross-sectional work. Here, we highlight the importance of adopting a longitudinal approach in order to make progress into the identification of neurobiological mechanisms of social anxiety disorder (SAD). Using examples, we illustrate how longitudinal data can uniquely inform SAD etiology and timing of interventions. The brain’s inherently adaptive quality requires that we model risk correlates of disorders as dynamic in their expression. Developmental theories regarding timing of environmental events, cascading effects and (mal)adaptations of the developing brain will be crucial components of comprehensive, integrative models of SAD. We close by discussing analytical considerations in working with longitudinal, developmental data

Candida albicans colonization and dissemination from the murine gastrointestinal tract : the influence of morphology and Th17 immunity

This article is protected by copyright. All rights reserved. This work was supported by the Wellcome Trust (086558, 080088, 102705), a Wellcome Trust Strategic Award (097377) and a studentship from the University of Aberdeen. D.K. was supported by grant 5R01AI083344 from the National Institute of Allergy and Infectious Diseases and by a Voelcker Young Investigator Award from the Max and Minnie Tomerlin Voelcker Fund.Peer reviewedPublisher PD

Psychotic experiences, working memory, and the developing brain: a multimodal neuroimaging study

Psychotic experiences (PEs) occur in the general population, especially in children and adolescents, and are associated with poor psychosocial outcomes, impaired cognition, and increased risk of transition to psychosis. It is unknown how the presence and persistence of PEs during early adulthood affects cognition and brain function. The current study assessed working memory as well as brain function and structure in 149 individuals, with and without PEs, drawn from a population cohort. Observer-rated PEs were classified as persistent or transient on the basis of longitudinal assessments. Working memory was assessed using the n-back task during fMRI. Dynamic causal modeling (DCM) was used to characterize frontoparietal network configuration and voxel-based morphometry was utilized to examine gray matter. Those with persistent, but not transient, PEs performed worse on the n-back task, compared with controls, yet showed no significant differences in regional brain activation or brain structure. DCM analyses revealed greater emphasis on frontal connectivity within a frontoparietal network in those with PEs compared with controls. We propose that these findings portray an altered configuration of working memory function in the brain, potentially indicative of an adaptive response to atypical development associated with the manifestation of PEs

Using real-time fMRI to influence effective connectivity in the developing emotion regulation network

For most people, adolescence is synonymous with emotional turmoil and it has been shown that early difficulties with emotion regulation can lead to persistent problems for some people. This suggests that intervention during development might reduce long-term negative consequences for those individuals. Recent research has highlighted the suitability of real-time fMRI-based neurofeedback (NF) in training emotion regulation (ER) networks in adults. However, its usefulness in directly influencing plasticity in the maturing ER networks remains unclear. Here, we used NF to teach a group of 17 7–16 year-olds to up-regulate the bilateral insula, a key ER region. We found that all participants learned to increase activation during the up-regulation trials in comparison to the down-regulation trials. Importantly, a subsequent Granger causality analysis of Granger information flow within the wider ER network found that during up-regulation trials, bottom-up driven Granger information flow increased from the amygdala to the bilateral insula and from the left insula to the mid-cingulate cortex, supplementary motor area and the inferior parietal lobe. This was reversed during the down-regulation trials, where we observed an increase in top-down driven Granger information flow to the bilateral insula from mid-cingulate cortex, pre-central gyrus and inferior parietal lobule. This suggests that: 1) NF training had a differential effect on up-regulation vs down-regulation network connections, and that 2) our training was not only superficially concentrated on surface effects but also relevant with regards to the underlying neurocognitive bases. Together these findings highlight the feasibility of using NF in children and adolescents and its possible use for shaping key social cognitive networks during development

Transcranial direct current stimulation (tDCS) in the treatment of depression: Systematic review and meta-analysis of efficacy and tolerability

BACKGROUND Transcranial direct current stimulation (tDCS) is a potential alternative treatment option for major depressive episodes (MDE). OBJECTIVES We address the efficacy and safety of tDCS in MDE. METHODS The outcome measures were Hedges' g for continuous depression ratings, and categorical response and remission rates. RESULTS A random effects model indicated that tDCS was superior to sham tDCS (k=11, N=393, g=0.30, 95% CI=[0.04, 0.57], p=0.027). Adjunctive antidepressant medication and cognitive control training negatively impacted on the treatment effect. The pooled log odds ratios (LOR) for response and remission were positive, but statistically non-significant (response: k=9, LOR=0.36, 95% CI[-0.16, 0.88], p=0.176, remission: k=9, LOR=0.25, 95% CI [-0.42, 0.91], p=0.468). We estimated that for a study to detect the pooled continuous effect (g=0.30) at 80% power (alpha=0.05), a total N of at least 346 would be required (with the total N required to detect the upper and lower bound being 49 and 12,693, respectively). CONCLUSIONS tDCS may be efficacious for treatment of MDE. The data do not support the use of tDCS in treatment-resistant depression, or as an add-on augmentation treatment. Larger studies over longer treatment periods are needed

Current progress in real-time functional magnetic resonance-based neurofeedback: Methodological challenges and achievements

Neurofeedback (NF) is a research and clinical technique, characterized by live demonstration of brain activation to the subject. The technique has become increasingly popular as a tool for the training of brain self-regulation, fueled by the superiority in spatial resolution and fidelity brought along with real-time analysis of fMRI (functional magnetic resonance imaging) data, compared to the more traditional EEG (electroencephalography) approach. NF learning is a complex phenomenon and a controversial discussion on its feasibility and mechanisms has arisen in the literature. Critical aspects of the design of fMRI-NF studies include the localization of neural targets, cognitive and operant aspects of the training procedure, personalization of training, and the definition of training success, both through neural effects and (for studies with therapeutic aims) through clinical effects. In this paper, we argue that a developmental perspective should inform neural target selection particularly for pediatric populations, and different success metrics may allow in-depth analysis of NF learning. The relevance of the functional neuroanatomy of NF learning for brain target selection is discussed. Furthermore, we address controversial topics such as the role of strategy instructions, sometimes given to subjects in order to facilitate learning, and the timing of feedback. Discussion of these topics opens sight on problems that require further conceptual and empirical work, in order to improve the impact that fMRI-NF could have on basic and applied research in future

Process-based framework for precise neuromodulation

Functional MRI neurofeedback (NF) allows humans to self-modulate neural patterns in specific brain areas. This technique is regarded as a promising tool to translate neuroscientific knowledge into brain-guided psychiatric interventions. However, its clinical implementation is restricted by unstandardized methodological practices, by clinical definitions that are poorly grounded in neurobiology, and by lack of a unifying framework that dictates experimental choices. Here we put forward a new framework, termed ‘process-based NF’, which endorses a process-oriented characterization of mental dysfunctions to form precise and effective psychiatric treatments. This framework relies on targeting specific dysfunctional mental processes by modifying their underlying neural mechanisms and on applying process-specific contextual feedback interfaces. Finally, process-based NF offers designs and a control condition that address the methodological shortcomings of current approaches, thus paving the way for a precise and personalized neuromodulation

A placebo-controlled investigation of synaesthesia-like experiences under LSD

The induction of synaesthesia in non-synaesthetes has the potential to illuminate the mechanisms that contribute to the development of this condition and the shaping of its phenomenology. Previous research suggests that lysergic acid diethylamide (LSD) reliably induces synaesthesia-like experiences in non-synaesthetes. However, these studies suffer from a number of methodological limitations including lack of a placebo control and the absence of rigorous measures used to test established criteria for genuine synaesthesia. Here we report a pilot study that aimed to circumvent these limitations. We conducted a within-groups placebo-controlled investigation of the impact of LSD on colour experiences in response to standardized graphemes and sounds and the consistency and specificity of grapheme- and sound- colour associations. Participants reported more spontaneous synaesthesia-like experiences under LSD, relative to placebo, but did not differ across conditions in colour experiences in response to inducers, consistency of stimulus-colour associations, or in inducer specificity. Further analyses suggest that individual differences in a number of these effects were associated with the propensity to experience states of absorption in one’s daily life. Although preliminary, the present study suggests that LSD-induced synaesthesia-like experiences do not exhibit consistency or inducer-specificity and thus do not meet two widely established criteria for genuine synaesthesia