Deep brain stimulation or DBS has shown to be effective in therapy-resistant cases of a number of neurological and psychiatric diseases. Despite extensive clinical and experimental research, our knowledge of the mechanisms of action of DBS still is limited.
The research program of this group focuses on two main questions. 1. How does DBS work? How does high frequency stimulation affect brain tissue? Does it change functional neurocircuitry or alter neurochemical transmission? 2. What are the best and safest brain targets for changing pathological behavior in obsessive-compulsive disorder, major depression, addiction and eating disorders? As these diseases are characterized by profound behavioral alterations due to disturbances of affect, motivation and cognition, our research is fuocused on neurobiological substrates of motivational behavior in general.
Or approach is translational and multidisciplinary; clinical findings from DBS studies in humans are translated in relevant animal models, in which we observe effects of DBS on behavior and its underpinning neurocircuitry. Our animal research tools include methods for intracerebral stimulation in freely moving rodents, in combination with tests for emotional and cognitive behavior, in set-ups such as elevated plus maze and Skinner boxes, with in vivo neurochemical measurements based on microdialysis or fast-scan cyclic voltammetry and with electrophysiological recordings of single-unit activity with simultaneous reverse dialysis.
1. The effect of neurostimulation in rodents in relation to obsessive compulsive disorder (Addy van Dijk).
This PhD project will focus on two different directions. First, we will study the effects of DBS on behaviour related to the disease OCD such as anxiety and compulsivity. Second, we will explore the effect of neurostimulation on neurochemical and neurocellular alterations in brain areas which are related to OCD.
2. Effects of neuromodulation in the cortico-striatal-thalamo-cortical circuits on striatal dopamine release and motivated behaviour (Marianne Klanker).
This PhD-project focuses on the effects of DBS in the CSTC circuit on motivated behaviour and DA release in the striatum. Specifically, DBS in cortical and subcortical areas will be combined with measurements of phasic dopamine release in the striatum using fast-scan cyclic voltammetry.
3. Effects of DBS in Nucleus Accumbens subareas on neuronal responses in the cortico-striato-thalamo-cortical circuits (Soon-Lim Shin).
In this project we stimulate the NAcc core or shell while measuring single cell responses and local field potentials in PFC and other stations of the CSTC under normal conditions and in the presence of transmitter (e.g. glutamate) antagonists using reverse-microdialysis in anaesthesized and freely moving animals.
4. Optogenetics: DBS, compulsivity and flexibility (Wieke van Leeuwen).
The present project aims to use optogenetic techniques to increase our understanding of compulsivity and to elucidate the mechanisms of deep brain stimulation. We will use the combination of optogenetics and behavioural testing as described in Stuber et al (2011), but using typical DBS stimulation settings.
5. DBS evoked modulation of global neural activity and reward-driven behaviour (Chris Klink).
The effects of deep brain stimulation are not limited to the local area where stimulation is applied. By combining microstimulation with fMRI and cognitive tasks that involve reward-based decisions and cognitive flexibility, we aim to identify functional neural networks involved in the DBS treatment of depression and OCD.
6. Effects of Deep Brain Stimulation and developmental drug treatment on functional connectivity in rat brain circuits (Maik Derksen). DBS in the CSTC circuit has proven to be an effective treatment in OCD. By conducting (rs-)fMRI studies in awake animals, changes in functional connectivity within the CSTC circuit resulting from DBS in various target areas will be assessed.