Peripheral inflammation is associated with remote global gene expression changes in the brain

Background: Although the central nervous system (CNS) was once considered an immunologically privileged site, in recent years it has become increasingly evident that cross talk between the immune system and the CNS does occur. As a result, patients with chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease or psoriasis, are often further burdened with neuropsychiatric symptoms, such as depression, anxiety and fatigue. Despite the recent advances in our understanding of neuroimmune communication pathways, the precise effect of peripheral immune activation on neural circuitry remains unclear. Utilizing transcriptomics in a well-characterized murine model of systemic inflammation, we have started to investigate the molecular mechanisms by which inflammation originating in the periphery can induce transcriptional modulation in the brain.<p></p> Methods: Several different systemic and tissue-specific models of peripheral toll-like-receptor-(TLR)-driven (lipopolysaccharide (LPS), lipoteichoic acid and Imiquimod) and sterile (tumour necrosis factor (TNF) and 12-O-tetradecanoylphorbol-13-acetate (TPA)) inflammation were induced in C57BL/6 mice. Whole brain transcriptional profiles were assessed and compared 48 hours after intraperitoneal injection of lipopolysaccharide or vehicle, using Affymetrix GeneChip microarrays. Target gene induction, identified by microarray analysis, was validated independently using qPCR. Expression of the same panel of target genes was then investigated in a number of sterile and other TLR-dependent models of peripheral inflammation.<p></p> Results: Microarray analysis of whole brains collected 48 hr after LPS challenge revealed increased transcription of a range of interferon-stimulated genes (ISGs) in the brain. In addition to acute LPS challenge, ISGs were induced in the brain following both chronic LPS-induced systemic inflammation and Imiquimod-induced skin inflammation. Unique to the brain, this transcriptional response is indicative of peripherally triggered, interferon-mediated CNS inflammation. Similar models of sterile inflammation and lipoteichoic-acid-induced systemic inflammation did not share the capacity to trigger ISG induction in the brain.<p></p> Conclusions: These data highlight ISG induction in the brain as being a consequence of a TLR-induced type I interferon response. As considerable evidence links type I interferons to psychiatric disorders, we hypothesize that interferon production in the brain could represent an important mechanism, linking peripheral TLR-induced inflammation with behavioural changes.<p></p&gt

Time-Optimal Transfer of Coherence

We provide exact analytical solutions for the problem of time-optimal transfer of coherence from one spin polarization to a three-fold coherence in a trilinear Ising chain with a fixed energy available and subject to local controls with a non negligible time cost. The time of transfer is optimal and consistent with a previous numerical result obtained assuming instantaneous local controls.Comment: Published version (with typos in eqs. (25)-(27) corrected

An Unattended Mask makes an Attended Target Disappear

In pattern masking, the target and mask are presented at the same location and follow one another very closely in time. When the observer attends to the target, he or she must also attend to the mask, as the switching time for attention is quite slow. In a series of experiments, we present mask–target–mask sequences staggered in time and location (Cavanagh, Holcombe, & Chou, 2008) that allow participants to attentively track the target location without attending to the masks. The results show that the strength of masking is on average unaffected by the removal of attention from the masks. Moreover, after isolating the target location perceptually with moving attention, it is clear that the target, when at threshold, has not been degraded or integrated with a persisting mask but it has vanished. We also show that the strength of masking is unaffected by the lateral spacing between adjacent target and mask sequences until the spacing is so large that the apparent motion driving the attentive tracking breaks down. Finally, we compare the effect of the pre- and postmask and find that the premask is responsible for the larger part of the masking

Integrating online communities and social networks with computerised treatment for insomnia: a qualitative study of service user and primary health care professional perspectives

The problem: Insomnia is the most commonly reported psychological complaint in Britain. Although hypnotic drugs are widely used for treatment of insomnia, they are only licensed short term and adverse effects are common. Cognitive Behavioural Therapy for insomnia (CBT-I), which is effective and safe long term, is recommended first line but is not widely used nor available, in part because of the lack of trained providers. In response to this, Computerised Cognitive Behavioural Therapy (CCBT) has been advocated. Existing CCBT programmes can suffer from poor rates of uptake, adherence and completion. We aimed to investigate patients and practitioners’ views on how CCBT for insomnia (CCBT-I) could be improved by incorporating features of modern technology including social networking functions. The approach: We used a qualitative design and the theory of planned behaviour to underpin the study. Interviews and focus groups were held with adult service users and health professionals using a topic guide designed to elicit participants’ beliefs, intentions and controlling factors that might facilitate or create barriers to the uptake and adherence to CCBT-I. We explored the data using thematic analysis supported by Nvivo. Findings: We interviewed 23 health professionals and 28 patients. We identified multi-faceted issues focused on meta-themes of trust and functionality which were perceived to increase likelihood of successful uptake and adherence. Trust and confidence would be increased if CCBT-I was perceived to be evidence-based and accredited; when referral was from a trusted professional within a supervised package of care; and when online support and follow-up were provided. Interaction with other users, by integrating CCBT-I with social networking, was perceived to provide mutual support but concerns from people with sleep problems included apprehension about online ‘strangers’ and concerns from practitioners included information security. Asynchronous communication such as posting a note, commenting on a forum or adding to a thread was considered safer than engaging in real-time on-line communication. To improve functionality patients wanted mobile applications; access in short periods; self-assessment of insomnia and its causes; more personalised information on sleep; an interactive approach; and contact with other users to be moderated or overseen. Consequences: Although previous qualitative studies have looked at CCBT uptake and adherence, none have looked at insomnia exclusively or explored the feasibility, advantages and drawbacks of online communication between participants. Improving uptake and adherence to online programmes for insomnia requires attention to design features which are focused on trust and functionality. Although computerised therapies for insomnia would allow more people to access treatment, some would not be suitable for online therapies because of lack of online access or poor computer literacy. The results of the study are being used the development of a novel platform for CCBT for insomnia and other health conditions