Project Area B

Approach-avoidance conflicts when approaching a threatening situation.

How do individuals approach what they fear? This research question is essential for an anxiety disorder patient asked to approach a phobia-related situation. The project assumes that active versus passive approach towards the very same threatening context requires increased prefrontal cortex (PFC) recruitment and triggers specific biopsychological responses. To examine this hypothesis, we will immerse participants in virtual reality (VR) environments consisting of a threat-associated room previously paired with aversive stimuli and a neutral room. Active versus passive approaches towards the threat-associated room are expected to differ regarding head movements (VR-tracker), psychophysiological (startle, SCL) and brain responses (fNIRS or fMRI) with strongest psychophysiological and freezing responses during passive approach, but strongest PFC activation during active approach. In a second step, we will examine the hypothesis that the expectation of receiving rewards in the threat-associated context causes a simultaneous approach motivation and thereby reduces the approach-avoidance conflict and PFC recruitment.

Applicants should have a background in Psychology, Affective/Cognitive/Computational (Neuro-)Science, or a related field and a strong interest in experimental and clinical psychology and neuroscience. Excellent statistical skills are required. Programming skills (e.g. Matlab, R, Python) as well as prior experience with MRI or virtual reality are an advantage, but not a pre-requisite, however, willingness to learn these is expected.

Approach-avoidance conflicts when avoiding a rewarding situation.

How do individuals avoid what they like? This research question is essential for an addicted patient asked to avoid drug-associated contexts. The project assumes that active versus passive avoidance of the very same rewarding context requires increased prefrontal cortex (PFC) recruitment and triggers specific biopsychological responses. To examine this hypothesis, we will immerse participants in virtual reality (VR) environments consisting of a reward-associated room previously paired with monetary gains and a neutral room. Active versus passive avoidances towards the reward-associated room are expected to differ regarding head movements (VR-tracker), psychophysiological (startle, SCL) and brain responses (fNIRS or fMRI) with strongest head-movements and psychophysiological responses when passively leaving the reward associated room, but strongest PFC activation when actively leaving the reward-associated room.  In a second step, we will examine the hypothesis that the expectation of receiving punishments in the reward-associated context causes a simultaneous avoidance motivation and thereby reduces the approach-avoidance conflict and PFC recruitment.

Applicants should have a background in Psychology, Affective/Cognitive/Computational (Neuro-)Science, or a related field and a strong interest in experimental and clinical psychology and neuroscience. Excellent statistical skills are required. Programming skills (e.g. Matlab, R, Python) as well as prior experience with MRI or virtual reality are an advantage, but not a pre-requisite, however, willingness to learn these is expected.

Role of individual characteristics on approach-avoidance conflicts.

How do characteristics such as impulsivity, anxiety, or arousal modulate approach-avoidance conflicts? This project hypothesizes that anxiety and increased arousal bias towards avoidance, while impulsivity biases towards approach. This project builds on the approach-avoidance conflict paradigm described above (Project B1a), i.e. approach to a threat-associated situation, and examines participants selected to be anxious or impulsive. In high compared to low anxious participants, we expect stronger psychophysiological responses and freezing and weaker PFC activation when passively approaching the threat-associated room, but stronger PFC activation when actively approaching. In high versus low impulsive participants, weaker psychophysiological responses and freezing when approaching the threat-associated room, but no difference in PFC activation are expected. The mediating role of bodily arousal will be examined by experimentally increasing (by means of physical activity) or decreasing arousal (by means of relaxation instruction).

Applicants should have a background in Psychology, Affective/Cognitive/Computational (Neuro-)Science, or a related field and a strong interest in experimental and clinical psychology and neuroscience. Excellent statistical skills are required. Programming skills (e.g. Matlab, R, Python) as well as prior experience with MRI or virtual reality are an advantage, but not a pre-requisite, however, willingness to learn these is expected.

Approach and avoidance behaviour across development

Impulsivity-like phenotype and brain connectivity in St3Gal3-deficient mice.

The PhD student will investigate the behaviour of St3gal3-deficient mice vs. wildtype controls. This will include well-established behavioural paradigms, such as the open field test, 5-choice serial reaction time task, Barnes maze test, and social interaction tests to assess exploratory activity, impulsive behaviour, cognitive flexibility, and sociability. Next, imaging by fMRI and diffusion tensor imaging will be performed to challenge the hypothesis that the behavioural phenotype of St3gal3-deficient mice is associated with altered neural functioning and white matter structure within frontostriatal circuits. In this project, the PhD student will uniquely integrate both classical behavioural animal tests with state-of-the-art neuroimaging approaches to get a deeper insight into the neurogenetic background of core developmental deficits underlying neuropsychiatric disorders.

Applicants should have a background in (Neuro)biology, Biomedical Sciences, or Biophysics and a strong interest in neurobiology and neuroimaging. Experience in animal work is of advantage, strong interest and willingness to work with animals is essential. Experience in data analysis or programming (e.g. MATLAB, R) is preferred.

Influence of dysmyelination on fronto-striatal network dynamics.

The PhD student will conduct immunocytochemical and electrophysiological investigations of ST3GAL3-deficient human induced pluripotent stem cells (hiPSCs) both in a 2-D model of glutamatergic- and GABAergic co-culture and in 3-D forebrain organoids to investigate the process of human oligodendrogenesis and myelination. These investigations in mouse tissue will be translationally complemented by comparison of the brain's myelination pattern of St3gal3-deficient vs. wildtype mice with immunohistochemical and electrophysiological approaches. The focus will be on the quantitation of myelination-related marker proteins, such as Mbp, Mog, and Olig2, and on St3gal3 interaction partners, such as Ncam1 and Syncam1, which are key players for myelination during neurodevelopment. In this project, the PhD student combines findings from state-of-the-art human genetically-modified cell and experimental animal models to better understand the molecular substrates for myelination during CNS development.

Applicants should have a background in (Neuro)biology, Biomedical Sciences, or Biophysics and a strong interest in experimental neuroscience. Experience in cell culture work is of advantage, strong interest in translational neuroscience and hiPSC-technology with willingness to learn and further establish new methods for neuronal and glial cell differentiation is essential.

Myelination-moderated fronto-striatal dynamics and optogenetic approach to remodel impulsive choice.

The integrity of white matter tracts in the frontostriatal network is associated with impulsivity as measured by delay discounting tasks. However, the neural underpinnings of this finding are unclear. Therefore, the PhD student will use a novel optogenetic approach to measure neuronal activity in reward-related brain regions during impulsive decision making with a 5-choice serial reaction time task (5-CSRTT) in St3gal3-deficient and wild-type mice. First, the activity of multiple neurons in the ventromedial prefrontal cortex (VMPFC) and the ventral striatum (VS) will be recorded in vivo. Activation and inhibition patterns within this circuit will then be associated with impulsive behaviour during the 5-CSRTT. Second, the vmPFC input to the VS will be optogenetically altered to challenge the hypothesis that genetically-determined alterations in frontostriatal network activity can be optogentically restored to improve increased impulsive behaviour.

Applicants should have a background in (Neuro)biology, Biomedical Sciences, or Biophysics and basic experimental experience in neurophysiology and behavioural neuroscience. Experience in animal work and optogenetics is of advantage, strong interest and willingness in learning and further establishing a demanding new technology is mandatory. Experience in data analysis or programming (e.g. MATLAB, R) is preferred.