Neuroethological studies of fear, anxiety, and risky decision-making in rodents and humans

Prey are relentlessly faced with a series of survival problems to solve. One enduring problem is predation, where the prey's answers rely on the complex interaction between actions cultivated during its life course and defense reactions passed down by descendants. To understand the proximate neural responses to analogous threats, affective neuroscientists have favored well-controlled associative learning paradigms, yet researchers are now creating semi-realistic environments that examine the dynamic flow of decision-making and escape calculations that mimic the prey's real world choices. In the context of research from the field of ethology and behavioral ecology, we review some of the recent literature in rodent and human neuroscience and discuss how these studies have the potential to provide new insights into the behavioral expression, computations, and the neural circuits that underlie healthy and pathological fear and anxiety

An in vitro model to study immune activation, epithelial disruption and stromal remodelling in inflammatory bowel disease and fistulising Crohn’s disease

At present, preclinical models of inflammatory bowel disease (IBD) are insufficient, limiting translation between research and new therapeutics. This is especially true for fistulising Crohn’s disease (CD), as the severe lack of relevant models hinders research progression. To address this, we present in vitro human IBD mucosal models that recapitulate multiple pathological hallmarks of IBD simultaneously in one model system - immune cell infiltration, stromal remodelling and epithelial disruption. Stimulation of models induces epithelial aberrations common in IBD tissue including altered morphology, microvilli abnormalities, claudin gene expression changes and increased permeability. Inflammatory biomarkers are also significantly increased including cytokines and chemokines integral to IBD pathogenesis. Evidence of extracellular matrix remodelling, including upregulated matrix-metalloproteinases and altered basement membrane components, suggests the models simulate pathological stromal remodelling events that closely resemble fistulising CD. Importantly, MMP-9 is the most abundant MMP and mimics the unique localisation observed in IBD tissue. The inflamed models were subsequently used to elucidate the involvement of TNF-α and IFN- γ in intestinal stromal remodelling, in which TNF-α but not IFN- γ induced MMP upregulation, specifically of MMP-3 and MMP-9. Collectively, our results demonstrate the potential of the IBD models for use in preclinical research in IBD, particularly for fistulising CD

Insula and Striatum Mediate the Default Bias

Humans are creatures of routine and habit. When faced with situations in which a default option is available, people show a consistent tendency to stick with the default. Why this occurs is unclear. To elucidate its neural basis, we used a novel gambling task in conjunction with functional magnetic resonance imaging. Behavioral results revealed that participants were more likely to choose the default card and felt enhanced emotional responses to outcomes after making the decision to switch. We show that increased tendency to switch away from the default during the decision phase was associated with decreased activity in the anterior insula; activation in this same area in reaction to “switching away from the default and losing” was positively related with experienced frustration. In contrast, decisions to choose the default engaged the ventral striatum, the same reward area as seen in winning. Our findings highlight aversive processes in the insula as underlying the default bias and suggest that choosing the default may be rewarding in itself

Neuroethological studies of fear, anxiety, and risky decision-making in rodents and humans

Prey are relentlessly faced with a series of survival problems to solve. One enduring problem is predation, where the prey's answers rely on the complex interaction between actions cultivated during its life course and defense reactions passed down by descendants. To understand the proximate neural responses to analogous threats, affective neuroscientists have favored well-controlled associative learning paradigms, yet researchers are now creating semi-realistic environments that examine the dynamic flow of decision-making and escape calculations that mimic the prey's real world choices. In the context of research from the field of ethology and behavioral ecology, we review some of the recent literature in rodent and human neuroscience and discuss how these studies have the potential to provide new insights into the behavioral expression, computations, and the neural circuits that underlie healthy and pathological fear and anxiety

Long-Term Objective Physical Activity Measurements using a Wireless Accelerometer Following Minimally Invasive Transforaminal Interbody Fusion Surgery

We report on a case of a patient who underwent minimally invasive transforaminal lumbar interbody fusion (mi-TLIF) with objective physical activity measurements performed preoperatively and postoperatively at up to 12-months using wireless accelerometer technology. In the first postoperative month following surgery, the patient had reduced mobility, taking 2,397 steps over a distance of 1.8 km per day. However, the number of steps taken and distance travelled per day had returned to baseline levels by the second postoperative month. At one-year follow-up, the patient averaged 5,095 steps per day in the month over a distance of 3.8 km; this was a 60% improvement in both steps taken and distance travelled compared to the preoperative status. The use of wireless accelerometers is feasible in obtaining objective physical activity measurements before and after lumbar interbody fusion and may be applicable to other related spinal surgeries as well

Low-Froude-number stable flows past mountains

A new approximate analysis is presented for stably stratified flows at low Froude number F past mountains of heightH. In the “top” layer where the streamlines pass above the surface of themountain, there is a perturbation flow. This approximately matches the lower flow in the “middle” ‘horizontal’ layer [M] in which the streamlines pass round the mountain in nearly horizontal planes, as in Drazin’s (DRAZIN P. G., On the steady flow of a fluid of variable density past an obstacle, Tellus, 13 (1961) 239-251) model. The pressure associated with the diverging streamlines on the lee side of the summit layer flow drives the separated flow in the horizontal layer (which is not included in Drazin’s model). This explains the vortical wake flow in experiments and in the “inviscid” computations of Smolarkiewicz and Rotunno (SMOLARKIEWICZ P. K. and ROTUNNO R., Low Froude number flow past three-dimensional obstacles. Part I: Baroclinically generated lee vortices, J. Atmos. Sci., 46 (1989) 1154-1164). A method for estimating the height HT FH of the cut-off mountain is derived, as a function of upstream shear, mountain shape and other parameters. Recent laboratory experiments have confirmed how the curvature of the oncoming shear flow profile

Reflected glory and failure: the role of the medial prefrontal cortex and ventral striatum in self vs other relevance during advice-giving outcomes

Despite the risks, people enjoy giving advice. One explanation is that giving beneficial advice can result in reflected glory, ego boosts or reputation enhancement. However, giving poor advice can be socially harmful (being perceived as incompetent or untrustworthy). In both circumstances, we have a vested interest in the advice follower's success or failure, especially when it reflects specifically on us compared with when it is diffused between multiple advisors. We examined these dynamics using an Advisor-Advisee Game, where subjects acted as an Advisor to a confederate Advisee who selected one of the three options when trying to win money: accept the subject's advice, accept the advice of a second confederate Advisor or accept both Advisors' advice. Results showed that having one's advice accepted, compared with being rejected, resulted in activity in the ventral striatum--a core reward area. Furthermore, the ventral striatum was only active when the subject's advice led to the advisee winning, and not when the advisee won based on the confederate's advice. Finally, the medial prefrontal cortex (MPFC) was more active when the Advisee won or lost money based solely on the subject's advice compared with when the second Advisor's advice was accepted. One explanation for these findings is that the MPFC monitors self-relevant social information, while the ventral striatum is active when others accept advice and when their success leads to reflected glory

Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling

Increased transcriptional complex activity, or pharmacological mimics of increased complex activity, predict lifespan in mice and mediate the protective effects of dietary restriction during aging

Barriers to participation in a placebo-surgical trial for lumbar spinal stenosis

© 2019 Background: Placebo-controlled trials are an important tool when assessing the efficacy of spinal surgical procedures. The most common spinal surgical procedure in older adults is decompression for lumbar spinal stenosis. Before conducting a placebo-surgical trial on decompression surgery, an investigation of patients’ willingness to participate in a placebo-controlled trial of decompression surgery and barriers to participation were explored. Materials: An online survey. Methods: Descriptive analyses of demographic and clinical data, and participants' willingness to participate in a placebo-surgical trial. Logistic regression was used to examine potential predictors of willingness to participate. Two independent researchers performed a coded framework analysis of patients’ barriers to participation. Results: 68 patients were invited and 63 participants completed the survey (91.3% response, mean (SD) age 69.5 (10.9) years, 52% females), 71% suffered from moderate to very severe pain. Ten participants (15.9%) were willing to participate in a placebo-controlled trial. Being married was associated with decreased odds of participating (OR: 0.2; 95% CI, 0.05 to 0.8; P = 0.03), while the main barriers were a lack of information about the procedure, reassurance of a positive outcome with participation, and concerns about the risks and benefits of placebo surgery. Conclusions: A minority of patients with lumbar spinal stenosis were willing to participate in a placebo-controlled trial of surgery. The identified barriers indicate that educating eligible patients about: the need for placebo-surgical trials, the personal risks and benefits of participation, and the importance and potential benefits of placebo trials to others, may be crucial to ensure adequate recruitment into the placebo-controlled surgical trial. Conclusions should be read cautiously however, given the small sample size present in this study