A01 A02 A03 A04 A05 A06 A07 A08 A09 A10 A11 A12 A13 A14 A15 A16 A18 F01 F02

The subprojects

In our project we investigate the fundamental processes of the brain that take place during relearning. For this we look at how pigeons learn. The animals learn a task for which they get drops if they complete it successfully. Then we change the task and the stimulus, which previously promised a reward, gives no food anymore (extinction). What makes our project special is the fourth dimension, the possibility to observe neural events over the entire period of the experiment, from the first acquisition over the fading of learned behaviour to the reinvigoration of the response to a stimulus. While our pigeons practice the tasks in which they learn (acquisition) as well as relearn (extinction), we record signals from single cells in the brain or measure brain activity with functional imaging in a high resolution MRI scanner. Additionally we can specifically activate or deactivate certain cells by the presentation of light in order to investigate key events and interactions between brain areas in the extinction network. When then comparing this to the neurobiologically well established behaviour we can show variant and invariant principles of extinction learning. As we can establish the systematic relationship between the animals behaviour and activation patterns in the brain, we can form a bridge between the behavioural and neurobiological level.

Find out more on the project page >>

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

Usually, context is disregarded during learning. The context is simply generalised, i.e. an inconspicuous context is saved as a replaceable canvas. Therefore, the learned information can be memorised exactly and recalled in very different situations, as in front of different canvases. In the extinction process however, the context plays an important role: the old information can not easily be overwritten by something new, as the context of the learned information is anchored deep inside the memory. We want to  know how the networks of learning control context perception, to understand what makes surrounding stimuli important or arbitrary for extinction learning.

We therefore compare stimulus specific context representations of healthy subjects (simultaneous EEG/fMRI recording) with those of epilepsy patients (intracranial EEG and single cell recordings). Our project offers one of the rare opportunities for the comparison of studies with animals and humans, as we will directly measure change in neural representations of specific contexts during acquisition and extinction in humans for the first time.

Find out more on the project page >>

Every learning process is consolidated as a memory trace, a so called engram in the brain. Here new events can give a new meaning to old experiences. But how is this progress represented in neural networks? Can differences in learning between individuals be fundamentally explained through structural or functional differences in these networks? These are the questions we pursue by looking at the progress of learning on an electrophysiological level. Activity in different areas of the extinction network can be observed through simultaneous fMRI and EEG recordings. Here we want to investigate how the electrophysiology and interactions within the extinction network change in different phases of learning.

Additionally we will look at what impact specific brain structures, such as the different amygdala nuclei, have on the extinction network with high resolution imaging techniques.

Find out more on the project page >>

We analyse how learned information is electrophysiologically coded in cells and what happens between cells of certain neuron populations that we look at. For this we combine different methods: on the one hand we analyse signal sources with single unit and multi unit recordings, meaning the excitation of single firing neurons as well as the entire system. These techniques are complemented by molecular biological methods such as fluorescence-in-situ-hybridization to mark DNA sequences and optogenetics to activate specific cell regions. To conclude we look at the acquisition, extinction and reactivation in rodents on a neurophysiological basis via electrophysiological and imaging methods. At the same time we investigate interactions between the hippocampus and other brain structures of the extinction network, such as the frontal lobe of the brain.

Find out more on the project page >>

Great fear can become entrenched deep in the brain. Where fear takes over control, rationality and behaviour become reflexive. Casting off involuntary fear behaviour, once acquired, is a complex task for the brain, as extinction has to reach many different areas of the brain. The function of the developmentally old cerebellum was long seen as purely motoric control. This assumption has to be revised in light of recent research. We want to know if and how the cerebellum is involved in the extinction process. Therefore we identify mechanisms underlying extincting in the cerebellum with the help of behavioural and imaging studies. With high resolution imaging we will investigate the processes within the cerebellum and the interactions with other brain structures such as the amydala, the hippocampus and the prefrontal cortex.

Find out more on the project page >>

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

The renewal effect describes the return of a previously unlearned reaction. This reinstatement occurs when a situation or a context is different from that in which extinction happened. Renewal occurs in very different learning situations, in fear conditioned behaviour as well as in learning through reward or punishment. In our studies without fear components only about half to two thirds of participant exhibit a renewal effect and related activation pattern in the hippocampus and the ventromedial prefrontal cortex. Additionally subjects with renewal show hippocampal activation already during the initial learning, not only during extinction. Here we want to gain a deeper understanding of which internal and external factors influence the occurrence of renewal. We manipulate context parameters such as serotonin levels or with the help of noninvasive brain stimulation, and look at how subjects perform a predictive learning task in an MRI scanner to analyse the resulting manifestation of the renewal effect.

Find out more on the project page >>

We would like to know how stress during fear conditioning strengthens or weakens the processes of extinction learning. As a relevant brain structure we investigate the amygdala. It plays a central role for memory based emotional behaviour such as fear and anxiety as well as signal processing of stress. Our project investigates the roll of the signalling pathways of the ‘happy chemical’ serotonin in the amygdala in normal situations compared to under stress. With optogenetic methods we can directly control the excretion of serotonin in the amygdala and on the other hand control the serotonin receptors 5HT2A- and 5HT2C. Optogenetics is a very recent method in which light sensitive proteins are introduced into brain cells and from there on the manipulated cell becomes reactive to light. It works as a kind of molecular on/off switch for electrical neural activity.

Find out more on the project page >>

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

Our project investigates why a memory sometimes returns after extinction but sometimes does not. This renewal effect can be caused by external causes, as a reaction to the personal history or also by internal causes, rooted in the process itself. As we know brain activation patterns for two regions for successful renewal, we can systematically test for potential reasons for renewal. On the one hand we look at the structure of participating brain regions, we look at what the influence of impaired attention through stress or medication is and how the salience of the learning context impacts behaviour.

Through the combination of noninvasive brain stimulation and imaging we can look at influences and interactions between brain regions and structures relevant for extinction during the renewal process.

Find out more on the project page >>

We investigate how stress and particularly the stress hormone cortisol impacts the extinction network at different points in time. Herefore we look at different areas:

Through imaging we try to find whether the effects of cortisol generalise similar fear relevant stimuli and which brain structures are involved. At the same time we look at the generalisation of fear relevant stimuli, by combining cortisol with recondsolidation processes, which describe how a consolidated fear memory trace can become unstable. Also, we look at the impact of stress on contextdependent renewal of fear through reinstatement. Furthermore we investigate how stress at different time points influences behaviour which is coupled with reward or punishment.

Find out more on the project page >>

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

Changes in learning and memory processes are critical for the development, but also the therapy of chronic pain. We have made it our aim to investigate behavioural and neural mechanisms and the clinical relevance for extinction learning in interoceptive, visceral pain, meaning pain in the inner organs. We pursue the question of whether the extinction of conditioned pain related fear of visceral pain is changed in patients with irritable bowel syndrome, meaning chronic stomach pains. In healthy subjects we test whether the stress hormone cortisol strengthens the reappearance of pain related fear after extinction. Eventually we aim to develop a new conditioning paradigm in which internal pain announcing signals are used and the learning environment plays an important role.

Find out more on the project page >>

We explore how patients with chronic back pain show changed behavioural and neuronal extinction mechanisms. For these questions we confront our patients with heat and sounds that are experienced as painful. In light of the picture of chronic back pain we have decided on three core questions:

What are the pain specific mechanisms of fear conditioning?

How does the intake of a dose of a stress hormone affect the fading and reinstatement of a memory?

When the test stimuli are either pleasantly relieved or unpleasantly strengthens, what are the similarities or differences of these pain coniditionings?

Find out more on the project page >>

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

Systematic inflammation can impact learning and memory processes. We investigate in this project, if and how acute or chronic inflammation impairs extinction of pain related fear. This could mean that inflammation is relevant for the development of chronic pain. We test healthy subjects whether experimentally induced acute inflammation leads to a change in the establishment and extinction of conditioned fear-related fear. We investigate the effects of chronic inflammation on fear extinction in patients with chronically inflamed intestinal problems.

Find out more on the project page >>

You need to face your fears to overcome them. This saying may actually be quite close to the truth: exposure therapy is the most effective form of therapy to treat anxiety disorders. In this treatment, also known as confrontation therapy, the patient faces the situation that induces anxiety in controlled steps. However, not all patients profit equally from this therapy. It is our aim to identify ways to improve exposure therapy for everyone.

As an example for patients with anxiety we work with people with spider phobia. To gain a better understanding of the fears underlying behavioural and neural mechanisms, we investigate extinction behaviour in a conditioning task. We would like to understand how stress and e.g. the feeling of self-efficacy can influence the success of exposure therapy. The question of how generalisability of therapy effects, i.e. that therapy succeeds not only in the treatment room, but also the spider in the own house consistently induces less fear, is also critical.

Find out more on the project page >>

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

We investigate learning mechanisms and neural fundaments which lead to the development of the context dependency of extinction learning.

We can measure what a learning environment contributes and which defining parameters are important in computer models and small test robots. We would like to understand why extinction learning is more context dependent than primary acquisition, how the learned information can be distinguished from simple contextual information, and why the hippocampus is necessary for context dependency.

Find out more on the project page >>

When a person or an animal is surprised, i.e. confronted with an event that deviates from our expectations, learning happens: expectations are adjusted to reality. We want to figure out how organisms integrate the diverse information from the environment into a model of their surroundings and then adjust their experiences, so that prediction errors no longer occur, as the model was brought into accordance with the reality. In our experiments we use a widespread theory, that is based on error correction. We are especially interested in which way errors are processed in extinction learning.

A negative prediction error dictates that an anticipated event does not occur. A positive prediction error describes an event that occurs unexpectedly. In our project we investigate how positive and negative predictions errors affect extinction learning.

Find out more on the project page >>

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

We research the development of extinction learning over the entire lifespan: from infancy, childhood, adolescence into young adulthood (18-22 years). Our experimental setups are designed so that subjects learn either to gain a pleasant reward or avoid an unpleasant situation. We compare how learning systems develop differently or similarly. We will follow extinction developmental transitions during brain maturation qualitatively and quantitatively. Also using developmental neuropsychological methods our project will apply findings from animal research to human research and create an important basis for future clinical applications for the first time.

Find out more on the project page >>

A fascinating example of the interaction between the central nervous system (CNS) and the peripheral immune system is the phenomenon of classical conditioning in immunological reactions. From an evolutionary perspective a learned immune response is most likely a sort of adaptive strategy to protect an organism from a potential harmful immune response. For example, allergies would lead to avoiding the contact with allergens in future. Classical conditioning of immunological reactions is best described in the model of conditioned taste aversion in rats. An animal is offered a new flavour in its water (e.g. a sweetened solution as a conditioned stimulus, CS) which is coupled to an injection of a immunomodulating medication (unconditioned stimulus, US) immediately beforehand. If the CS is presented at a later point in time and without an injection of the medication, the animals will avoid drinking the sugary drink (conditioned taste aversion). At the same time, you can see conditioned changes in the immune system, which correspond to the immunopharmacological effects of the medication given as a US in a weakened form.

Given the frame work of extinction learning, there is the question of how the learned immune suppression can be protected from extinction or specifically reactivated after presenting the CS again. First observations indicate that the extinction of a learned immune response can be prevented through reconsolidation or ‘memory updating’. We investigate the extinction and reconsolidation processes of learned immune responses with substances of different profiles, like Rapamycin (RAPA, used for treating cancer) and Methotrexat (MTX, used for treatment of chronic inflammatory autoimmune diseases). In an additional step we would like to test the insights into extinction learning and reconsolidation for possible clinical relevance, by using the learned immune response with RAPA and MTX in a tumor model as well as a model for chronic inflammatory autoimmune diseases.

Find out more on the project page >>

Play Video

Even before the SFB 1280 started, the subprojects presented their research plans to a number of experts in a short video.

How behaviour is adjusted from one phase of learning to the next can give indicators about the mechanisms of learning. In general learning is measured by averaging many rounds of learning and comparing a block of sessions before learning with a block of sessions after learning. These analyses are blind towards learning dynamics. Often learning curves are produced by averaging different subjects. If however individuals exhibit systematic differences in learning, the averaged curve may be misleading. The Focus Group Learning Dynamics will train and support other subprojects in the application of dynamic analysis methods and export data if necessary. Additionally, the Focus Group will import data from other subprojects to follow the own scientific goal: comparing learning dynamics between different individuals, phases of learning, experimental paradigms and species.

Find out more on the project page >>

Our Focus Group will use the opportunity to analyse the mass of acquired MRI data sets in the SFB 1280 for higher analyses. Our analyses will be technically highly complex and will seek patterns in the overall data, which stay hidden in the individual projects. We will of course integrate our technical expertise and insights into all subprojects.

Our focus lies on connectivity analyses in the extinction network, investigating how brain regions interact with each other and how they affect each other. Our questions focus on the individual variability in extinction learning, potential differences between learning through reward and punishment, participation of the cerebellum in extinction learning and disease related changes.

Find out more on the project page >>