Pharmaceutical cognitive enhancement in Greek university students: differences between users and non-users in social cognitive variables, burnout and engagement

Pharmaceutical cognitive enhancement (PCE) represents the non-medical use of prescribed medication for the improvement of cognitive functioning and academic performance. Although there are some studies about PCE prevalence, it is less clear how users and non-users of PCE substances differ with respect to their positive and negative student experiences (e.g., academic burnout, engagement with studies) and in social cognitive variables that relate to decision-making and self-regulation of PCE use. The present study assessed whether students with different experiences of PCE substance use displayed differences in academic burnout, study engagement and social cognitive variables relevant to PCE use. Three hundred and forty seven University students (M age = 22.15, SD = 1.69; 54% females) completed a battery of anonymous questionnaires on academic burnout, engagement with studies, social cognitive variables relevant to PCE use, and self-reported use of PCE substances and non-prescribed nutritional supplements. Three user groups emerged, namely, non-users (51.9%, n = 180), single users of non-prescribed dietary supplements (25.4%, n = 88), and dual users of both non-prescribed dietary supplements and PCE (22.8%, n = 79). Multivariate analysis of variance indicated significant differences among the three user groups in intentions, attitudes, social norms, and anticipated regret towards PCE use. No significant differences were observed with respect to academic burnout and work engagement. The findings show that University students may engage in PCE use independently of their student experiences. Rather, a chemically-assisted performance enhancement mindset seems to differentiate users from non-users of PCE substances

Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model

Loss of basal forebrain cholinergic neurons is an early and key feature of Alzheimer's disease, and magnetic resonance imaging (MRI) volumetric measurement of the basal forebrain has recently gained attention as a potential diagnostic tool for this condition. The aim of this study was to determine whether loss of basal forebrain cholinergic neurons underpins changes which can be detected through diffusion MRI using diffusion tensor imaging (DTI) and probabilistic tractography in a mouse model. To cause selective basal forebrain cholinergic degeneration, the toxin saporin conjugated to a p75 neurotrophin receptor antibody (mu-p75-SAP) was used. This resulted in similar to 25% loss of the basal forebrain cholinergic neurons and significant loss of terminal cholinergic projections in the hippocampus, as determined by histology. To test whether lesion of cholinergic neurons caused basal forebrain, hippocampal, or whole brain atrophy, we performed manual segmentation analysis, which revealed no significant atrophy in lesioned animals compared to controls (Rb-IgG-SAP). However, analysis by DTI of the basal forebrain area revealed a significant increase in fractional anisotropy (FA; + 7.7%), mean diffusivity (MD; + 6.1%), axial diffusivity (AD; + 8.5%) and radial diffusivity (RD; +4.0%) in lesioned mice compared to control animals. These parameters strongly inversely correlated with the number of choline acetyl transferase-positive neurons, with FA showing the greatest association (r(2) = 0.72), followed by MD (r(2) = 0.64), AD (r(2) = 0.64) and RD (r(2) = 0.61). Moreover, probabilistic tractography analysis of the septo-hippocampal tracts originating from the basal forebrain revealed an increase in streamline MD (+5.1%) and RD (+4.3%) in lesioned mice. This study illustrates that moderate loss of basal forebrain cholinergic neurons (representing only a minor proportion of all septo-hippocampal axons) can be detected by measuring either DTI parameters of the basal forebrain nuclei or tractography parameters of the basal forebrain tracts. These findings provide increased support for using DTI and probabilistic tractography as non-invasive tools for diagnosing and/or monitoring the progression of conditions affecting the integrity of the basal forebrain cholinergic system in humans, including Alzheimer's disease. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved

The therapeutic potential of attentional bias modification training for insomnia: study protocol for a randomised controlled trial.

The efficacy of attentional bias modification (ABM) as a treatment for anxiety and depression has been extensively studied with promising results. Despite some evidence of sleep-related attentional biases in insomnia, only a small number of studies, yielding mixed results, have examined the application of ABM in insomnia. This study specifically aims to determine whether ABM can reduce (i) the presence of an attentional bias for sleep-related threatening words; (ii) insomnia symptom severity; (iii) sleep onset latency; and (iv) pre-sleep cognitive arousal amongst individuals with insomnia compared to a non-treatment control group of individuals with insomnia. We propose a randomised controlled trial of 90 individuals from the general population who meet the criteria for Insomnia Disorder. Following an initial examination for the presence of a sleep-related attentional bias using the dot-probe paradigm, participants will be randomised to an online attentional bias modification training condition, or to a standard attentional bias task (non-treatment) control condition. Both conditions will be delivered online by a web platform. All participants allocated to the non-treatment control group will be offered ABM training once the study is complete. The primary outcome will be the attentional bias indices of vigilance and disengagement and self-reported insomnia symptoms, sleep onset latency and pre-sleep cognitive arousal. Attentional bias and insomnia symptoms will be assessed at baseline (day 1) and post-treatment (2 days after the final training session: day 9). Insomnia symptoms will be again assessed at follow-up (day 16). Secondary outcomes include examining whether sleep associated monitoring and worry are related to a sleep-related attentional bias in insomnia, and whether such reports reduce following ABM. All main analyses will be carried out on completion of follow-up assessments. The trial is supported by the Department of Psychology, Sociology and Politics at Sheffield Hallam University. This study will extend the research base examining the efficacy of attentional bias modification for insomnia. ISRCTN ( ISRCTN11643569 , registered on 5 June 2018)

Transcriptional network orchestrating regional patterning of cortical progenitors

We uncovered a transcription factor (TF) network that regulates cortical regional patterning in radial glial stem cells. Screening the expression of hundreds of TFs in the developing mouse cortex identified 38 TFs that are expressed in gradients in the ventricular zone (VZ). We tested whether their cortical expression was altered in mutant mice with known patterning defects (Emx2, Nr2f1, and Pax6), which enabled us to define a cortical regionalization TF network (CRTFN). To identify genomic programming underlying this network, we performed TF ChIP-seq and chromatin-looping conformation to identify enhancer–gene interactions. To map enhancers involved in regional patterning of cortical progenitors, we performed assays for epigenomic marks and DNA accessibility in VZ cells purified from wild-type and patterning mutant mice. This integrated approach has identified a CRTFN and VZ enhancers involved in cortical regional patterning in the mouse

Robo1 modulates proliferation and neurogenesis in the developing neocortex.

The elaborate cytoarchitecture of the mammalian neocortex requires the timely production of its constituent pyramidal neurons and interneurons and their disposition in appropriate layers. Numerous chemotropic factors present in the forebrain throughout cortical development play important roles in the orchestration of these events. The Roundabout (Robo) family of receptors and their ligands, the Slit proteins, are expressed in the developing forebrain, and are known to play important roles in the generation and migration of cortical interneurons. However, few studies have investigated their function(s) in the development of pyramidal cells. Here, we observed expression of Robo1 and Slit genes (Slit1, Slit2) in cells lining the telencephalic ventricles, and found significant increases in progenitor cells (basal and apical) at embryonic day (E)12.5 and E14.5 in the developing cortex of Robo1(-/-), Slit1(-/-), and Slit1(-/-)/Slit2(-/-), but not in mice lacking the other Robo or Slit genes. Using layer-specific markers, we found that both early- and late-born pyramidal neuron populations were significantly increased in the cortices of Robo1(-/-) mice at the end of corticogenesis (E18.5). The excess number of cortical pyramidal neurons generated prenatally appears to die in early postnatal life. The observed increase in pyramidal neurons was due to prolonged proliferative activity of their progenitors and not due to changes in cell cycle events. This finding, confirmed by in utero electroporation with Robo1 short hairpin RNA (shRNA) or control constructs into progenitors along the ventricular zone as well as in dissociated cortical cell cultures, points to a novel role for Robo1 in regulating the proliferation and generation of pyramidal neurons

Robo1 modulates proliferation and neurogenesis in the developing neocortex.

International audienceThe elaborate cytoarchitecture of the mammalian neocortex requires the timely production of its constituent pyramidal neurons and interneurons and their disposition in appropriate layers. Numerous chemotropic factors present in the forebrain throughout cortical development play important roles in the orchestration of these events. The Roundabout (Robo) family of receptors and their ligands, the Slit proteins, are expressed in the developing forebrain, and are known to play important roles in the generation and migration of cortical interneurons. However, few studies have investigated their function(s) in the development of pyramidal cells. Here, we observed expression of Robo1 and Slit genes (Slit1, Slit2) in cells lining the telencephalic ventricles, and found significant increases in progenitor cells (basal and apical) at embryonic day (E)12.5 and E14.5 in the developing cortex of Robo1(-/-), Slit1(-/-), and Slit1(-/-)/Slit2(-/-), but not in mice lacking the other Robo or Slit genes. Using layer-specific markers, we found that both early- and late-born pyramidal neuron populations were significantly increased in the cortices of Robo1(-/-) mice at the end of corticogenesis (E18.5). The excess number of cortical pyramidal neurons generated prenatally appears to die in early postnatal life. The observed increase in pyramidal neurons was due to prolonged proliferative activity of their progenitors and not due to changes in cell cycle events. This finding, confirmed by in utero electroporation with Robo1 short hairpin RNA (shRNA) or control constructs into progenitors along the ventricular zone as well as in dissociated cortical cell cultures, points to a novel role for Robo1 in regulating the proliferation and generation of pyramidal neurons