Bussiere, T. | bioRxiv Science

bioRxiv2019

Kinetic fingerprint of antibody therapies predicts outcomes of Alzheimer clinical trials

The amyloid cascade hypothesis, according to which the self-assembly of amyloid-{beta} peptide (A{beta}) is a causative process in Alzheimers disease, has driven many therapeutic efforts for the past 20 years. Failures of clinical trials investigating A{beta}-targeted therapies have been interpreted as evidence against this hypothesis, irrespective of the characteristics and mechanisms of action of the therapeutic agents, which are highly challenging to assess. We bring together kinetic analysis with quantitative binding measurements to address the mechanisms of action of four clinical stage anti-A{beta} antibodies, aducanumab, gantenerumab, bapineuzumab and solanezumab. We reveal and quantify the striking differences of these antibodies on the aggregation kinetics and on the production of oligomeric aggregates, and link these effects to the affinity and stoichiometry of each antibody for monomeric and fibrillar forms of A{beta}. Our results uncover that, uniquely amongst these four antibodies, aducanumab dramatically reduces the flux of oligomeric forms of A{beta}.

biophysics↗

bioRxiv2019

An artistic approach to neurofeedback for emotion regulation

Neurofeedback has been shown to be a promising tool for learning to regulate ones own emotions in healthy populations and in neuropsychiatric disorders. While it has been suggested that neurofeedback performance improves when sensory feedback is related to the pathology under consideration, it is still difficult to represent in real time a proper feedback representative of our emotional state. Since emotion is a central part of peoples dealings with artworks, we have initiated a collaboration between neuroscientists and artists to develop a visual representation of emotions that can be used in neurofeedback experiences. As a result of this collaboration, emotions were represented as particles, moving in a white sphere according to valence and arousal levels. In this study, several possibilities for particle control were explored: direction of particles, their concentration in a specific place, or their gravity. 107 participants evaluated these performances, either in laboratory condition or at various scientific and artistic events. At the end of the experiment, questionnaires were distributed to participants who were asked to indicate on scales ranging from 0 to 5 how artistic the different representations were and could be used as a clinical activity, whether they thought they had successfully controlled the particles during the neurofeedback exercise, and whether they had appreciated the experience. We found that influing on the direction and concentration of particles was considered the most artistic with an average score around 3/5. 47% of the participants considered the concentration of particles as artistic. In addition, although this is not the purpose of this study, we found that participants could significantly control the direction of particles during this session. These encouraging results constitute a first step before evaluating the effectiveness of our emotional neurofeedback over several sessions in healthy, then pathological populations.

neuroscience↗