Project Area A
Circuit Switches for Approach and Avoidance
Approach and avoidance behaviours have been studied extensively, yet we are just beginning to understand where and how the neuronal circuits for these opposing behaviours interact to allow for rapid switching from one to the other. An influential concept postulates the existence of "brain systems" mediating either approach or avoidance behaviour. Their concomitant activation in conflicting situations triggers risk assessment that precedes action selection. Whereas approach behaviour has classically been investigated with its relation to reward, and thus, the reward system of the basal forebrain, research on avoidance behaviour has focused on fear- and anxiety- related forebrain regions such as the amygdala and the septo-hippocampal system. Reciprocal connections of these regions with prefrontal cortex influence the choice of approach or avoidance. Information flow mediating avoidance, risk assessment and approach may ultimately converge onto a common output pathway that involves circuits for defensive behaviour in the brainstem periaqueductal grey (PAG) region.
This project area focuses on three main hypotheses:
- Risk assessment determines the switch between approach and avoidance behaviour in conflict situations.
- A main circuit component of this switch consists of reciprocal prefrontal-brainstem connections.
- Inhibition of the circuit elements mediating avoidance will release approach behaviour in conflicting contexts.
Five PhD projects are currently available in this project area:
- A1a
- A1b
- A1d
- A2b
- A3b
A1: Characterization of prefrontal-amygdala-brainstem circuits in learned and innate approach-avoidance behaviour in mice
PI: Prof. Dr. Philip Tovote (tovote_p@ukw.de)
PhD Student: César Redondo
Prefrontal-amygdala-midbrain circuits in risk assessment and avoidance/approach switches.
This project will use neuroanatomical tracing strategies, cell-type and projection-specific imaging of calcium transients, EEG/ECG recordings and optogenetics during behavioural assays of defensive behaviour to understand the correlation of neuronal activity within prefrontal and CEA as well as PAG circuit elements.
Applicants should have a background in or experience with Systems Neurobiology and rodent behavioral/surgical methods.
Targeted manipulation of identified circuit elements to perturb risk assessment and avoidance behaviour.
This project will use optogenetics to interfere with normal activity within identified circuit elements in medial prefrontal cortex, central amygdala and periaqueductal grey to understand their function in risk assessment and switching from avoidance to approach. Addressing the expected complexity of the neuronal activation patterns, closed-loop stimulations of specific cell types and their terminals will be performed based on defined behavioural/autonomic and EEG states.
Applicants should have a background in (Neuro)biology, Biomedical Sciences, Psychology, or Biophysics.
Development of neurofeedback training for identified "switch" circuit elements to inhibit avoidance behaviour.
This project will focus on the development of a novel animal-neurofeedback paradigm, which uses neural activity linked to reduced avoidance to promote approach behaviour. Photometry-based calcium activity of identified circuit elements will be transformed into a neurofeedback signal. This will allow for targeted entrainment of desired network activity to attenuate avoidance or promote approach behaviour.
Applicants should have a background in (Neuro)biology, Biomedical Sciences, Psychology, or Biophysics.
High-dimensional analyses of neural, behavioral and autonomic data and defensive state modelling
This project will use multidimensional analyses and computational approaches to model defensive state dynamics. Data will be provided by previous and ongoing projects, which record multiple output parameters in freely moving mice during threat exposure. Large data sets need to be curated and standardized before applying analyses that take into account both, neuroarchitecture and information transfer between identified circuit elements.
Applicants should have a background in Computational Neuroscience, Mathematics, or (Bio)physics.
A2: Modulating oscillatory activity to reduce avoidance and increase approach behaviour in humans
PI: Prof. Dr. Andrea Kübler (andrea.kuebler@uni-wuerzburg.de)
PhD Students: Maria Pfeiffer, Eva Masson
Developing internally and externally valid paradigms to reliably elicit conflict situations between avoidance and approach.
To test the effects of altering oscillatory activity of the EEG (via neurofeedback) on risk assessment and the transition from avoidance to approach, we require experimental paradigms that reliably elicit such behaviour both under laboratory and field conditions. The project will start with an existing stop-signal task, which elicits goal-conflict specific EEG rhythmicity and corresponding behaviour. The core of the project will be to implement and newly establish approach and avoidance tasks and to describe the related EEG activity in different phases of the tasks. The result will be well characterised tasks to elicit approach and avoidance behaviour and specifically, to monitor the transition between approach and avoidance and vice versa.
Applicants should have a background in Psychology (cognitive, biopsychology, clinical) or Neuroscience (cognitive, clinical) and experience in experimental psychology and biopsychology/neuroscience. Basic experience in EEG data collection and analysis is a plus.
Neurofeedback of EEG correlates of approach-avoidance conflict and resolution.
This project relies on the application of neurofeedback, i.e. feedback of the neuronal activity of the brain in real-time to allow for validating the link between a specific neuronal measure and behaviour. In detail, we will train humans to down-regulate prefrontal theta synchrony to diminish reactions to fear-related stimuli and to increase alpha asymmetry in favour of left frontal alpha power to induce behavioural activation instead of conflict-induced inhibition. The respective brain activity will be recorded, filtered, and translated into a comprehensive feedback signal in real-time. Participants will be required to complete 10 neurofeedback sessions because self-regulation of brain activity involves learning by trial and error albeit strategies may be provided (e.g., imagination of action). Successful self-regulation and its effects on behaviour will be tested in respective approach-avoidance tasks in which participants will be required to apply the same mental strategy as learned during neurofeedback sessions while performing the probe task.
Applicants should have a background in Psychology (cognitive, biopsychology, clinical) or Neuroscience (cognitive, clinical) and experience in experimental psychology and biopsychology/neuroscience. Basic experience in EEG data collection and analysis is a plus.
A3: Approach and avoidance behaviour in pain management
PI: Prof. Dr. Claudia Sommer (Sommer@uni-wuerzburg.de)
Associated researcher: Dr. Daniel Zeller (zeller_d@ukw.de)
PhD Students: Morgane Paternoster, Sebastian Evers
Associated PhD Students: Salomea Löffl, Eleni Kakavela, Fiona Dewender
Oscillatory brain activity underlying approach and avoidance behavior in migraine.
Migraine is a potentially debilitating disease with a high prevalence in the general population, and it can be regarded as a disorder of functional brain connectivity. While there is a genetic predisposition for migraine in general, many patients can identify triggers that evoke the individual attacks. Increased avoidance of these triggers may lead to sensitization and to thus to increased headache frequency. The aim of this project is to establish a conflict paradigm for approach/avoidance behaviour for the most frequently encountered migraine triggers, and to identify their EEG correlates. The obtained data will build the basis for neurofeedback training directed at the approach/avoidance behavior toward migraine triggers.
Applicants should have good German and English communication skills. Experience in neurophysiology, specifically with high-density EEG, is of advantage.
Changes in response to preventive treatment in migraine trigger avoidance and CGRP blood levels.
The frequency of migraine attacks can be reduced, in most patients, by preventive treatment. We have identified correlates in EEG recordings and evoked potentials that characterize the migraine brain. Furthermore, we have established measurements of the levels of the neuropeptide CGRP in different bodyfluids as biomarkers of migraine. In this project, these parameters will be used in a prospectively recruited cohort of participants under novel preventive migraine treatment, whether pharmacological or non-pharmacological. We will test whether any of these findings is related to treatment response, and how this corresponds to trigger avoidance behavior.
