There is general acknowledgement that both the anterior cingulate and orbitofrontal cortex are implicated in reinforcement-guided decision making, and emotion and social behaviour. Despite the interest that these areas generate in both the cognitive neuroscience laboratory and the psychiatric clinic, ideas about the distinctive contributions made by each have only recently begun to emerge. This reflects an increasing understanding of the component processes that underlie reinforcement- guided decision making, such as the representation of reinforcement expectations, the exploration, updating and representation (...) of action values, and the appreciation that choices are guided not just by the prospect of reward but also by the costs that action entails. Evidence is emerging to suggest that the anterior cingulate and orbitofrontal cortex make distinct contributions to each of these aspects of decision making. (shrink)

In our reflections upon the view of Leibniz on the many religions and their relations we elaborate three points. In the first place, Leibniz appears to be a faithful Christian, nominally a Lutheran, but not exactly bound to just one confession. He tried to be a real ecumenist. During all his career he made efforts to come to one, universal church , on a dogmatic as well as a practical level. For this aim he corresponded on these topics with many (...) influential catholics of his time, e.g. with Arnauld, Bossuet and Pellisson . Leibniz saw the other forms of monotheism as preliminary stages of Christianity. For him the remaining religions were paganism and therefore they should be suppressed. But Christianity would be enriched by an exchange with the three other forms of monotheism. In the second place, we may conclude that Leibniz understood toleration as a recognition of the other and as an expectation for exchange. But in the third place, we have to take into account his final religious perspective: natural religion . This is an almost philosophical religion with Christian features, usually called deism. With the help of his natural religion Leibniz wanted to combat what he called the atheism and materialism of the philosophy of his time, i.e. the ideas of Hobbes, Descartes and Spinoza. But his own position is rather close to them. (shrink)

The relevance of nonlinear dynamics to calcium metabolism led us to reevaluate the role of Ca-regulating hormones in Ca homeostasis. We suggest that, firstly, the main Ca metabolic functions in rat-bone and gut - are organized as dynamic entities able to generate various temporal expressions, including self-oscillating patterns and, secondly, Ca homeostasis results from interaction between both metabolic and hormonal oscillators. Following this schema, a major role for the hormonal system, with its circadian pattern, could be to act directly on (...) metabolic functions or indirectly through feeding behaviour, in order to optimize, coordinate and synchronize the Ca fluxes at ECF level. (shrink)

In this paper we focus on what is referred to as the ‘mineness’ of experience, that is, the intimate familiarity we have with our own thoughts, perceptions, and emotions. Most accounts characterize mineness in terms of an experiential dimension, the first-person givenness of experience, that is subsumed under the notion of minimal self-consciousness or a ‘minimal self’. We argue that this account faces problems and develop an alternative account of mineness in terms of the coherence of experiences with what we (...) label an ‘embodied biography’. Building on a near consensus among consciousness researchers over the function of consciousness as integrating infor- mation, we argue that the phenomenology of mineness consists in the absence of any further thought on top of the experience itself. Finally we argue that this non-phenomenological account of mineness fits well with existing data on pathologies of mineness such as delusions of thought insertion. (shrink)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

BackgroundIn the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.MethodsBetween 2013 and 2019, 8252 participants (...) (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported.ResultsSevere structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy.ConclusionThe management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/nct02220582. (shrink)

This paper discusses some engineering considerations that should be taken into account when building a knowledge based system, and recommends isomorphism, the well defined correspondence of the knowledge base to the source texts, as a basic principle of system construction in the legal domain. Isomorphism, as it has been used in the field of legal knowledge based systems, is characterised and the benefits which stem from its use are described. Some objections to and limitations of the approach are discussed. The (...) paper concludes with a case study giving a detailed example of the use of the isomorphic approach in a particular application. (shrink)

Deficits in social cognition and more specifically in communication have an important impact on the real-life functioning of people with schizophrenia. In particular, patients have severe problems in communicative-pragmatics, for example, in correctly inferring the speaker’s communicative intention in everyday conversational interactions. This limit is associated with morphological and functional alteration of the left middle temporal gyrus, a cerebral area involved in various communicative processes, in particular in the distinction of ironic communicative intention from sincere and deceitful ones. We performed (...) an fMRI study on 20 patients with SZ and 20 matched healthy controls while performing a pragmatic task testing the comprehension of sincere, deceitful, and ironic communicative intentions. We considered the L-MTG as the region of interest. SZ patients showed difficulties in the correct comprehension of all types of communicative intentions and, when correctly answering to the task, they exhibited a higher activation of the L-MTG, as compared to HC, under all experimental conditions. This greater involvement of the L-MTG in the group of patients could depend on different factors, such as the increasing inferential effort required in correctly understanding the speaker’s communicative intentions, and the higher integrative semantic processes involved in sentence processing. Future studies with a larger sample size and functional connectivity analysis are needed to study deeper the specific role of the L-MTG in pragmatic processes in SZ, also in relation to other brain areas. (shrink)