Two grants to support joint research with Profs Robbins and Sahakian

We are very delighted that the Lundbeck Foundation has decided to support both professor Trevor Robbins and professor Barbara Sahakian from University of Cambridge, UK, with a substantial international neuroscience programme grant that each will cover a joint research project with NRU. Professors Robbins and Sahakian will during a planned research sabbatical in Copenhagen be visiting NRU for an extended period from May to September 2018, and the two grants, that total more than 5.3 mio DKK, enable an optimal initiation and implementation of both projects. We look very much forward to welcoming both of them at NRU and are thrilled to be able to host the joint cutting edge research projects. More information about the two projects below.


Title: From habits to compulsions: the role of serotonin in Obsessive-Compulsive Disorder
PI: Professor Trevor Robbins
Grant: 2.857.100 DKK
Period: May 1^st, 2018 - April 30^th, 2021
Abstract:
This application aims to support an international collaboration between the Universities of Cambridge (TW Robbins) and Copenhagen (GM Knudsen), by which a new cognitive approach to compulsive behaviour can be related to state-of-the-art neuroimaging measures of GABA/glutamate function, based on 7 Tesla Magnetic Resonance Spectroscopy (MRS) in Cambridge, and serotonin function, based on Positron Emission Tomography (PET) in Copenhagen. Compulsions, a core symptom of Obsessive Compulsive Disorder (OCD), have been hypothesised to result from the aberrant formation of, and control over, habits. The main evidence for this hypothesis depended on deficits in goal-directed behaviour in OCD and hence a hypothetical bias towards habitual control. However, no direct test of an over-active habit system in OCD has been conducted so far. We will test the hypothetical transition between habit and compulsion by means of a newly developed task that assesses not only habit formation but also habit perseveration. The aim of this application is to combine our original paradigm with a novel PET radiotracer developed in Copenhagen to clarify the role of 5-HT in compulsion development. We will use a multimodal PET/fMRI method as well as a psychopharmacological manipulation to test 1) whether OCD can be characterized by an abnormally overactive cortico-striatal system mediating habits and 2) to investigate how serotonin modulates the control of this habit-related system. Specifically, we aim to disentangle the neural contributions of the goal-directed and the habit brain systems in habit perseveration and its association with central serotonin function. The focus on the serotonergic system here is crucial to complement our GABA/glutamate approach in Cambridge as it will enable us to elucidate how potential dynamic changes in these major neurotransmitters relate to abnormal cortico-striatal neural circuitry underlying OCD symptoms.


Title: Serotonergic modulation of cognition, emotion and brain activation in healthy volunteers
PI: Professor Barbara Sahakian
Grant: 2.474.192 DKK
Period: Sep 1^st, 2018 - Augl 31^st, 2021
Abstract:
Aims/Objectives: The aim of this project is to understand the role of serotonin on cognition, emotion and activation of the brain in healthy human volunteers.
Background: Serotonin is a neurotransmitter in the brain that contributes toward wellbeing and happiness as well as influencing cognitive performance. Previous studies have shown widespread cognitive and emotional impairments following loss of serotonin. In addition, drugs which increase the level of serotonin in the brain (called serotonin reuptake inhibitors; SSRIs), have shown to promote positive mood and wellbeing and are used in the treatment of mental health conditions, such as depression and anxiety. Therefore, this project aims to understand the role of chronic SSRI administration on 'cold' cognition, particularly learning, and 'hot' social and emotional cognition and the underlying brain activations.
Methods and materials: 32 healthy volunteers will receive 20 mg of escitalopram for three weeks, whereas 32 healthy human volunteers will receive placebo for three weeks. All participants will undergo measures of functional magnetic resonance imaging while resting, functional magnetic resonance imaging during a learning task, and standardised measures of cognition, such as memory, and social and emotional cognition, such as emotional facial recognition and the Ultimatum game.
Expected outcome and perspectives: This project will inform how serotonin affects the brain and related cognitive, social and emotional changes. This will be important toward furthering our understanding of the role of serotonin in the regulation of non-emotional cognition and also social and emotional cognition in healthy people. This study also has implications for the use of SSRIs in the treatment of mood and anxiety disorders.