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Cholinergic Potentiation Improves Perceptual-Cognitive Training of Healthy Cholinergic potentiation improves perceptual-cognitive training of healthy young adults in three dimensional multiple object tracking Mira Chamoun1, Huppé-Gourgues Frédéric1, Isabelle Legault2, Pedro Rosa-Neto3, Daniela Dumbrava4, Jocelyn Faubert2, Elvire Vaucher1* 1École d’optométrie, Université de Montréal, Canada, 2École d'optométrie, Université de Montréal, 3 4 Canada, McGill Centre for Studies in Aging, Canada, École d'optométrie, Université de Montréal, Canada Submitted to Journal: Frontiers in Human Neuroscience Article type: Original Research Article Manuscript ID: 230044 Received on: 22 Sep 2016 InRevised review on: 27 Feb 2017 Frontiers website link: www.frontiersin.org Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest Author contribution statement EV: Lab Director, contributed in elaborating the project, providing the material, analyzing the data and writing the paper MC: Contributed in elaborating the project, testing the participants, analyzing the data and writing the paper FHG: Contributed in analyzing the data and writing the paper IL: Contributed in elaborating the project and analyzing the data JF: Contributed in elaborating the project, providing the material, analyzing the data and writing the paper PRN: Contributed in elaborating the project, providing the donepezil pills, writing the paper DD: Contributed in the medical examination of the participants Keywords Acetylcholine, Attention, 3D-multiple object tracking, Acetylcholinesterase (AChE) inhibitor, donepezil (Aricept), sensory training, cognitive enhancement, Visual Perception Abstract Word count: 203 A large body of literature supports cognitive enhancement as an effect of cholinergic potentiation. However, it remains elusive whether pharmacological manipulations of cholinergic neurotransmission enhance complex visual processing in healthy individuals. To test this hypothesis, we randomly administered either the cholinergic transmission enhancer donepezil (5 mg P.O.) or placebo (lactose) toIn young adults (n = 17) 3 hoursreview before each session of the 3D multiple object tracking (3D-MOT) task. This multi-focal attention task evaluates perceptual-cognitive learning over five sessions conducted 7 days apart. A significant amount of learning was observed in the donepezil group but not the placebo group in the fourth session. In the fifth session, this learning effect was observed in both groups. Furthermore, preliminary results for a subgroup of participants (n = 9) 4–14 months later suggested the cholinergic enhancement effect was long lasting. On the other hand, donepezil had no effect on basic visual processing as measured by a motion and orientation discrimination task performed as an independent one-time, pre-post drug study without placebo control (n = 10). The results support the construct that cholinergic enhancement facilitates the encoding of a highly demanding perceptual-cognitive task although there were no significant drug effects on the performance levels compared to placebo. Funding statement This work was supported by: Canadian Institutes of Health Research (Grant number: MOP-111003, to EV) and Natural Sciences and Engineering Research Council of Canada (Grant number: 238835-2011, to EV). MC received financial support from the School of Optometry, Université de Montréal. We would like to thank the Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal for financial resources support Ethics statements (Authors are required to state the ethical considerations of their study in the manuscript, including for cases where the study was exempt from ethical approval procedures) Does the study presented in the manuscript involve human or animal subjects: Yes Please provide the complete ethics statement for your manuscript. Note that the statement will be directly added to the manuscript file for peer-review, and should include the following information: Full name of the ethics committee that approved the study Consent procedure used for human participants or for animal owners Any additional considerations of the study in cases where vulnerable populations were involved, for example minors, persons with disabilities or endangered animal species As per the Frontiers authors guidelines, you are required to use the following format for statements involving human subjects: This study was carried out in accordance with the recommendations of 'name of guidelines, name of committee' with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the 'name of committee'. For statements involving animal subjects, please use: This study was carried out in accordance with the recommendations of 'name of guidelines, name of committee'. The protocol was approved by the 'name of committee'. If the study was exempt from one or more of the above requirements, please provide a statement with the reason for the exemption(s). Ensure that your statement is phrased in a complete way, with clear and concise sentences. The procedures were in accordance with the Helsinki Declaration of 2013 and the ethical standards of the Comite d'ethique de la recherche en sante, Universite; de Montreal, approval #12-084-CERES-P Information and consent form Donepezil effect on visual attention and perceptual learning in healthy young adults Taking place at the school of Optometry of the University of Montreal Laboratory of psychophysics and visual perception 3744, rue jean Brillant Montreal, Quebec, H3T1P1 CANADA Mira Chamoun Ph.D student in Sciences de la vision [email protected] (514) 343-6162 RESEARCH COORDINATOR: Isabelle Legault, Ph.D [email protected] (514)-343-6111 #8764 RESEARCH DIRECTOR: Elvire Vaucher, Ph.D., doctor in neuroscience [email protected] (514) 343-7537In review RESEARCH CO-DIRECTOR: Jocelyn Faubert, Ph. D., doctor in psychophysics [email protected] (514) 343-728 NEUROLOGIST ASSOCIATED TO THE PROJECT: Dr Pedro Rosa Neto, M.D., Ph.D. Douglas hospital (514) 766-2010 You are invited to participate in our research project studying the effect of the medication Aricept, usually used to treat Alzheimer’s disease to improve memory and cognitive functions. In the present project, the medication Aricept is tested for its capacity to improve the perceptual learning during visual training. Aricept is only made by Pfizer, but the company is not involved in the project. Before accepting to participate to this research project, please read carefully this consent form. It explains the objective, the procedures, the risks, the benefits and the inconveniences of this study. It also provides coordinates of the key people to contact in case you have any question or concern. This form may contain words you may not understand. Please feel free to ask all the questions you might have and clarifications you might need. 1. Project description The purpose of this project is to study the effect of stimulation of a certain type of neurons (cholinergic) of the brain on the visual training and the perceptual learning. The cholinergic system stimulation is induced by administrating a medication, Aricept, 5mg. The long-term goal is to improve, for re-adaptation purposes, the visual performance of people having a visual or attentional deficit. The visual training and the perceptual learning will be tested in an attentional task consisting of visual tracking of moving spheres in a 3 dimensions (3D) environment (sitting position). This study will count 34 participants randomized into two equal groups: an Aricept administred group and a placebo-administred group - providing a control group. The placebo is a lactose pill having no effect on the body. This study thus involves taking medication. 2. Nature of participation and duration of study If you agree to participate in this study, you will have to be present at l’ecole d’optometrie de l’Universite; de Montreal, 3744, rue Jean-Brillant, Montreal (Quebec), H3T 1P1, room 210-10, once a week for 5 consecutive weeks (one 1h-session and four 4h-sessions). Each session is independent and there is a 5 to 7 days interval between each session, depending on your availability. To participate in the study, you must have had a complete eye exam within one year prior to the study. Moreover, we will ask you a written consent in order to have access to your visual examination medical file and this, only during the period of participation. Before the study, you must have a general medical examination, to know your health state and make sure you do not have cardiac or respiratory problems. This exam will be conducted by Dr Dumbrava. In addition, you will have to pass an electrocardiogram (placement of electrodes on the chest), in the premises of the university, which will be then analyzed by a cardiologist. Before and after each session your blood pressure and heartbeat will be monitored by a qualified person. Women should pass a urine pregnancy test before each session to make sure they are not pregnant. During the first session, you will have to answer a few questions and go through some visual tests to make sure you fit the participation criteria. Afterwards, you will perform an exercise of target tracking in immersive virtual reality environment, called C.A.V.E. This environment consists of four screens (one at the front, one on each side and one on the ground) on which images are projected. These screens form a cubic space of 8 feet in length, width and heights and are open at the rear. During this exercise, you will be seated on a chair and wear 3D glasses. The object tracking exercise, called 3D-M.O.T., consists in tracking four virtual spheres moving in a set of 8 identical spheres. This set of spheres is presented in a virtual cubic volume. Before the movement of the spheres, 4 of them are indexed via changing color for a five seconds period in order to be identified as the target. The 4 spheres return to their original color and the 8 spheres start moving within the restricted 3D virtual space.
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