Epistemological challenges for neural correlates of consciousness: A defense of medical research on consciousness.

Recent work in the field of consciousness science has predominantly focused on the search for neural correlates of consciousness (NCC). However, despite significant technological advances in recent decades, defining NCC remains an ambitious goal in consciousness research. The main difficulty stems from an epistemological challenge known as the "Problem of coordination", which hinders or at least slows down the experimental process inherent to the study of consciousness. Fundamental research has mainly focused on a content-based conception of consciousness, often referred to as a "local" conception of consciousness. This approach suffers from the Problem of coordination and its consequences. However, an alternative, more reliable approach could be considered, namely, the global or "state-based" approach, which is grounded in clinical research on consciousness disorders.

[Multidimensional and computational theory of mood]. / Théorie multidimensionnelle et computationnelle de l'humeur.

What is mood? Despite its crucial place in psychiatric nosography and cognitive science, it is still difficult to delimit its conceptual ground. The distinction between emotion and mood is ambiguous: mood is often presented as an affective state that is more prolonged and less intense than emotion, or as an affective polarity distinguishing high and low mood swinging around a baseline. However, these definitions do not match the clinical reality of mood disorders such as unipolar depression and bipolar disorder, and do not allow us to understand the effect of mood on behaviour, perception and cognition. In this paper, we propose a multidimensional and computational theory of mood inspired by contemporary hypotheses in theoretical neuroscience and philosophy of emotion. After suggesting an operational distinction between emotion and mood, we show how a succession of emotions can cumulatively generate congruent mood over time, making mood an emerging state from emotion. We then present how mood determines mental and behavioral states when interacting with the environment, constituting a dispositional state of emotion, perception, belief, and action. Using this theoretical framework, we propose a computational representation of the emerging and dispositional dimensions of mood by formalizing mood as a layer of third-order Bayesian beliefs encoding the precision of emotion, and regulated by prediction errors associated with interoceptive predictions. Finally, we show how this theoretical framework sheds light on the processes involved in mood disorders, the emergence of mood congruent beliefs, or the mechanisms of antidepressant treatments in clinical psychiatry.

A Proposal to Make Biomedical Research into Alzheimer's Disease More Democratic Following an International Survey with Researchers.

BACKGROUND: Therapeutic research into Alzheimer's disease (AD) has been dominated by the amyloid cascade hypothesis (ACH) since the 1990s. However, targeting amyloid in AD patients has not yet resulted in highly significant disease-modifying effects. Furthermore, other promising theories of AD etiology exist. OBJECTIVE: We sought to directly investigate whether the ACH still dominates the opinions of researchers working on AD and explore the implications of this question for future directions of research. METHODS: During 2019, we undertook an international survey promoted with the help of the Alzheimer's Association with questions on theories and treatments of AD. Further efforts to promote a similar study in 2021 did not recruit a significant number of participants. RESULTS: 173 researchers took part in the 2019 survey, 22% of which held "pro-ACH" opinions, tended to have more publications, were more likely to be male, and over 60. Thus, pro-ACH may now be a minority opinion in the field but is nevertheless the hypothesis on which the most clinical trials are based, suggestive of a representation bias. Popular vote of all 173 participants suggested that lifestyle treatments and anti-tau drugs were a source of more therapeutic optimism than anti-amyloid treatments. CONCLUSION: We propose a more democratic research structure which increases the likelihood that promising theories are published and funded fairly, promotes a broader scientific view of AD, and reduces the larger community's dependence on a fragile economic model.

Amyloid-ß in Alzheimer's Disease: A Study of Citation Practices of the Amyloid Cascade Hypothesis Between 1992 and 2019.

The amyloid cascade hypothesis (ACH) has dominated contemporary biomedical research into Alzheimer's disease (AD) since the 1990 s but still lacks definitive confirmation by successful clinical trials of anti-amyloid medicines in human AD. In this uncertain period regarding the centrality of amyloid-ß (Aß) in AD pathophysiology, and with the community apparently divided about the ACH's validity, we used citation practices as a proxy for measuring how researchers have invested their belief in the hypothesis between 1992 and 2019. We sampled 445 articles citing Hardy & Higgins (1992, "HH92") and classified the polarity of their HH92 citation according to Greenberg (2009)'s citation taxonomy of positive, neutral, and negative citations, and then tested four hypotheses. We identified two major attitudes towards HH92: a majority (62%) of neutral attitudes with consistent properties across the time period, and a positive attitude (35%), tending to cite HH92 earlier on within the bibliography as time went by, tending to take HH92 as an established authority. Despite the majority of neutral HH92 citations, there was a positive majority of attitudes toward different versions of the ACH and anti-amyloid therapeutic strategies (65%), suggesting that the ACH has been dominant and has undergone significant refinement since 1992. Finally, of those 110 original articles within the sample also testing the ACH empirically, an overwhelming majority (89%) returned a pro-ACH test result, suggesting that the ACH's central claim is reproducible. Further studies will quantify the extent to which results from different methods within such original studies convergence to provide a robust conclusion vis-à-vis Aß's pathogenicity in AD.

The Many Faces of EpigeneticsOxford, December 2017.

The conference 'The Many Faces of Epigenetics: Multidisciplinary Perspectives "over" Genetics' was held in Oxford (6-8 December 2017) and offered a valuable window into the domain of Epigenetics and its promises. The workshop revealed that, among a wealth of discourses about Epigenetics, it is not so easy to decipher which discourses are to be trusted. Because Epigenetics is a rather old notion that has generated many debates and promises, defining precisely what has changed and where we are currently is a challenge in itself. Interestingly, the conference allowed debates beyond statements such as 'If you don't know the cause, you say it's epigenetic' (Deichmann 2016), pointing out that the lack of a precise definition of Epigenetics was no hindrance to the discussions. Finally, it highlighted the grounds of (dis)agreement among communities of natural and social scientists; but eventually the discussions showed that epigenetic tools open the path to new topics and challenges that are awaiting us.

Perspective: plasticity, the enemy of the good.

Plasticity is an important feature of modern cancer research. However, the level at which we should consider it remains an open question. Such debate is not new in the field of cancer and can be exemplified by the different models explaining carcinogenesis. Those models mostly explain cell transformation through the deregulation of the internal circuitry. In the last years, those models dramatically increased our knowledge and led to a series of short-term successes in terms of therapeutics. However, cancer drug resistance inevitably arises. Recently, studies on the so-called tumor microenvironment enriched the cell-centered perspective but it also enlarged the complexity of cancer etiology in particular for advanced diseases. Here, we suggest that the plastic and multi-sites specific nature of cancer combined with our incapacity to promise cure should push towards a new perspective where early clinical actions, instead of late ones, should be heralded as the priority of cancer research and care.

Empirical agreement in model validation.

Empirical agreement is often used as an important criterion when assessing the validity of scientific models. However, it is by no means a sufficient criterion as a model can be so adjusted as to fit available data even though it is based on hypotheses whose plausibility is known to be questionable. Our aim in this paper is to investigate into the uses of empirical agreement within the process of model validation.

Species from Darwin onward.

Controversy regarding the species problem has been going on for many decades and no consensus has ever been reached about what a "species" really is and how best to define the concept. De Queiroz (1998) introduced a distinction between two aspects of this problem: on the one hand, the definition proper, and on the other, the criteria allowing biologists to recognize species in practice. This distinction is a first step on the way toward a solution of the problem. In the present paper, we show that de Queiroz's distinction is made possible by the radical theoretical change introduced by Darwin. We emphasize that the species problem did not appear in the 20th century, but long before, and that Darwin addresses it indirectly in the Origin of Species. It might seem paradoxical to refer to Darwin's views about species, because they are usually considered as unclear. However, we propose that an analysis of these views in the context of Darwin's own theory of evolution might reveal how a definition of the concept of species is made possible by being anchored to the very theory of evolution. To this aim, we present a plausible reconstruction of Darwin's implicit conception of species and show how this conception fits with the debates on species that took place in the 18th and 19th centuries. We then turn to today's biology and show what changes Darwin's implicit conception of species has brought about relative to the species concept and species delimitation.