Philosophical transactions of the Royal Society of London. Series B, Biological sciences
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · Jan 2013
ReviewImportance of the matriline for genomic imprinting, brain development and behaviour.
Mammalian brain development commences during foeto-placental development and is strongly influenced by the epigenetic regulation of imprinted genes. The foetal placenta exerts considerable influence over the functioning of the adult maternal hypothalamus, and this occurs at the same time as the foetus itself is developing a hypothalamus. Thus, the action and interaction of two genomes in one individual, the mother, has provided a template for co-adaptive functions across generations that are important for maternal care and resource transfer, while co-adaptively shaping the mothering capabilities of each subsequent generation. ⋯ The neocortex has evolved to be adaptable and sustain both short-term and long-term synaptic connections that underpin learning and memory. The adapted changes are not themselves inherited, but the predisposing mechanisms for such epigenetic changes are heritable. This provides each generation with the same ability to make new adaptations while constrained by a transgenerational knowledge-based predisposition to preserve others.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · Dec 2012
ReviewTargeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities.
Human tissues express cannabinoid CB(1) and CB(2) receptors that can be activated by endogenously released 'endocannabinoids' or exogenously administered compounds in a manner that reduces the symptoms or opposes the underlying causes of several disorders in need of effective therapy. Three medicines that activate cannabinoid CB(1)/CB(2) receptors are now in the clinic: Cesamet (nabilone), Marinol (dronabinol; Δ(9)-tetrahydrocannabinol (Δ(9)-THC)) and Sativex (Δ(9)-THC with cannabidiol). These can be prescribed for the amelioration of chemotherapy-induced nausea and vomiting (Cesamet and Marinol), stimulation of appetite (Marinol) and symptomatic relief of cancer pain and/or management of neuropathic pain and spasticity in adults with multiple sclerosis (Sativex). ⋯ These include other kinds of pain, epilepsy, anxiety, depression, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, stroke, cancer, drug dependence, glaucoma, autoimmune uveitis, osteoporosis, sepsis, and hepatic, renal, intestinal and cardiovascular disorders. It also describes potential strategies for improving the efficacy and/or benefit-to-risk ratio of these agonists in the clinic. These are strategies that involve (i) targeting cannabinoid receptors located outside the blood-brain barrier, (ii) targeting cannabinoid receptors expressed by a particular tissue, (iii) targeting upregulated cannabinoid receptors, (iv) selectively targeting cannabinoid CB(2) receptors, and/or (v) adjunctive 'multi-targeting'.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · May 2012
ReviewKinds of access: different methods for report reveal different kinds of metacognitive access.
In experimental investigations of consciousness, participants are asked to reflect upon their own experiences by issuing reports about them in different ways. For this reason, a participant needs some access to the content of her own conscious experience in order to report. ⋯ We argue that there is not only a theoretical, but also an empirical difference between different methods of reporting. We hypothesize that differences in the sensitivity of different scales may reveal that different types of access are used to issue direct reports about experiences and metacognitive reports about the classification process.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · May 2012
ReviewA computational framework for the study of confidence in humans and animals.
Confidence judgements, self-assessments about the quality of a subject's knowledge, are considered a central example of metacognition. Prima facie, introspection and self-report appear the only way to access the subjective sense of confidence or uncertainty. Contrary to this notion, overt behavioural measures can be used to study confidence judgements by animals trained in decision-making tasks with perceptual or mnemonic uncertainty. ⋯ We present a case study using such a computational approach to study the neural correlates of decision confidence in rats. This work shows that confidence assessments may be considered higher order, but can be generated using elementary neural computations that are available to a wide range of species. Finally, we discuss the relationship of confidence judgements to the wider behavioural uses of confidence and uncertainty.
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Philos. Trans. R. Soc. Lond., B, Biol. Sci. · May 2012
ReviewMetacognition in human decision-making: confidence and error monitoring.
People are capable of robust evaluations of their decisions: they are often aware of their mistakes even without explicit feedback, and report levels of confidence in their decisions that correlate with objective performance. These metacognitive abilities help people to avoid making the same mistakes twice, and to avoid overcommitting time or resources to decisions that are based on unreliable evidence. ⋯ This convergence suggests that common principles govern metacognitive judgements of confidence and accuracy; in particular, a shared reliance on post-decisional processing within the systems responsible for the initial decision. However, research in both fields has focused rather narrowly on simple, discrete decisions-reflecting the correspondingly restricted focus of current models of the decision process itself-raising doubts about the degree to which discovered principles will scale up to explain metacognitive evaluation of real-world decisions and actions that are fluid, temporally extended, and embedded in the broader context of evolving behavioural goals.