Homepage of Matthijs Vink

Netherlands Organisation for Scientific Research (NWO)

Title:  Controlling psychotic symptoms in schizophrenia: a new approach to an old problem
Role: PI
Background: In the early 1990’s, a new model of schizophrenia was put forth to unite the dopamine hypothesis (i.e. subcortical dopamine hyperactivity leading to psychosis) with the hypofrontality hypothesis (i.e. cortical dopamine hypoactivity leading to deficient social and cognitive functioning).  It was postulated that in schizophrenia cortical control over subcortical systems fails, and that this failure gives rise to psychosis and related symptoms. Data from animal research supports this hypothesis in that frontal regions regulate (dopamine) activity in the subcortical areas, especially the striatum. As of yet, this model has not been tested directly in humans. The aim of this project is therefore to validate this model in healthy subjects, siblings of schizophrenia patients, and schizophrenia patients. This approach requires both a read-out measure of striatal activity and a method to manipulate cortical activation. Brain responses in the striatum during various levels of activity will be measured using functional MRI. Next, frontal regions controlling the striatum are identified as those regions whose activity covaries with that of the striatum and which evidence direct connections with striatum as determined with Diffusion Tensor Imaging (DTI). Activity in these frontal regions will be disrupted using repetitive Transcranial Magnetic Stimulation (rTMS), so that reduced frontal control can be mimicked in healthy controls and in siblings of patients. The effects of disrupting frontal activity will be assessed in terms of (a) subclinical manifestation of psychotic symptoms, (b) performance on a task sensitive to striatal functioning, and (c) striatal activity during this task as measured with functional MRI directly after rTMS treatment. By including siblings of patients, we can determine whether abnormalities in the frontal-striatal network are already present prior to the manifestation of schizophrenia, or rather caused by the potential degenerative effects of psychoses or by effects of antipsychotic medication.

Neuroscience&Cognition Utrecht, Rudolf Magnus Institute of Neuroscience

Title: Structural and functional neural correlates of the experience of self-agency in health and schizophrenia
Role: Co-investigator
Background: The major goal of this application is to examine the neural substrates of self-agency and volition in health and schizophrenia using fMRI and DTI.

Neuroscience&Cognition Utrecht, Rudolf Magnus Institute of Neuroscience

Title: Biological grounding of the unconscious human will: The role of the ventral striatum in outcome priming effects on motivated action.
Role: PI
Background: The major goal of this application is to examine the neural substrates of unconscious processing of primes which drive motivated actions.