Neurobehavioral Level

A2

Conversion of implicitly acquired information into explicit knowledge

Witt, Karsten, Prof. Dr. med.

Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel
Schittenhelmstr. 10, 24105 Kiel

Telefon: +49-431-597-8509
E-Mail: k.witt@neurologie.uni-kiel.de

Verleger, Rolf, Prof. Dr. rer.soc.
Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck
Ratzeburger Allee 160, 23538 Lübeck

Telefon: +49-451-500-2916
E-Mail: rolf.verleger@neuro.uni-luebeck.de

Summary
The project aims at specifying how sleep supports the conversion of implicitly acquired information into explicit, conscious knowledge (implicit-explicit conversion). The overarching hypothesis is that, in addition to the hippocampal read-out that occurs during sleep, sleep promotes development of consciousness about knowledge that has so far remained non-conscious by establishing and intensifying connections between separate functional modules: between motor system and prefrontal control system, between left and righthemisphere visuo-motor systems, and between motor system and basal-ganglia motivational systems. Based on our results of the preceding funding period, in the next funding period we will focus on testing the pivotal role of the supplementary motor area (SMA) as an interface between implicit and explicit knowledge that is also involved in integrating divergent results of processing from the two hemispheres, in integrating motivational factors, and in being affected by increasing age. As before, the serial reaction-time task (SRTT) will serve as the model case for implicit-explicit conversion, performed in two sessions, before and after sleep. Changes of brain activity induced by learning and sleep will be recorded during tasks by fMRI or ERPs, and during sleep by EEG, and the causal role of the SMA will be tested through inhibiting its function by rTMS (repetitive transcranial magnetic stimulation).

A6

Brain stimulation and simulation to modulate sleep-dependent memory consolidation


Marshall, Lisa, Prof. Dr.

Institut für Neuroendokrinologie, Universität Lübeck
Ratzeburger Allee 160, D-23538 Lübeck

Telefon: +49-451-500-3644
E-Mail: marshall@uni-luebeck.de

Mölle, Matthias, Dr.
Institut für Medizinische Psychologie und Verhaltensneurobiologie, Universität Tübingen
Otfried-Müller-Str. 25, 72076 Tübingen

Telefon: +49-7071-29-88932
E-Mail: matthias.moelle@uni-tuebingen.de

Martinetz, Thomas, Prof. Dr.
Institut für Neuro- und Bioinformatik, Universität Lübeck
Ratzeburger Allee 160, D-23538 Lübeck

Telefon: +49-451-500-5500
E-Mail: martinetz@inb.uni-luebeck.de

Summary
During previous funding periods our research aimed at characterizing neuronal processing modes of sleepdependent memory consolidation with a focus on specific rhythms of oscillatory brain electric activity, both experimental and employing computer simulations. We showed that modulation of these rhythms with external stimulation (electric, magnetic, acoustic) can be of functional relevance for memory formation. Main conclusions from our previous work are that the effects of external stimulation are strongly brain statedependent and that external stimulation can be used to probe the phase-dependent responsiveness of the slow oscillation (SO) and its functional impact on memory. The main goals for the new funding period are twofold: (i) to develop brain stimulation protocols for optimized enhancement of memory consolidation during sleep, and (ii) to determine neurophysiological mechanisms contributing to these effects of brain stimulation on memory consolidation. These aims are to be achieved (i) by measuring the endogenous (up/down) statedependent responsiveness (EEG and behavioral) to brain stimulation during memory consolidation in sleep, (ii) by measuring the impact of stimulation on neurochemistry, and (iii) by computer simulations of models of the underlying processes. Based on differential neurophysiological effects of different stimulation types, the neural mass models to be developed are to aid in optimizing brain stimulation protocols.

A9

Consolidation of emotionally charged and behaviorally relevant memory during sleep of patients with psychiatric disorders


Junghanns, Klaus, Prof. Dr.
Klinik für Psychiatrie und Psychotherapie, Universität zu Lübeck,
Ratzeburger Allee 160, 23538 Lübeck

Telefon: +49-451-500-2920
E-Mail: klaus.junghanns@uksh.de

Göder, Robert, Privatdozent Dr.
Klinik für Psychiatrie und Psychotherapie, Universität Kiel,
Niemannsweg 147, 24105 Kiel

Telefon: + 49-431-597-2589
E-Mail: robert.goeder@uksh.de

Summary
In this project we investigate sleep-dependent memory consolidation in clinical psychiatric samples. By showing that specific disturbances of sleep structure are associated with particular memory disturbances in relevant diagnostic groups, we want to strengthen the hypothesis that specific characteristics of sleep are critical for the consolidation of memory. In addition we want to apply strategies to improve sleep, and to study the effects of this improvement on memory consolidation and the investigated psychiatric disturbances. This research will thus extend our previous work on sleep and memory in schizophrenic, alcohol-dependent and insomniac patients. The emphasis in this funding period will be on the investigation of rapid eye movement (REM) sleep and cortisol, and their roles in the consolidation of emotional memories including memories of future relevance. As emotions and emotional memory play a major role in posttraumatic stress disorder (PTSD), we will additionally focus on this patient group. With the help of psychotherapeutical interventions, we will improve emotional functioning and examine the resulting changes in sleep patterns, emotional memory consolidation and neuroendocrine function. Finally, using transcranial direct current stimulation (tDCS) during sleep, we want to improve sleep-dependent memory consolidation in schizophrenic patients and we will test its effect on important treatment aspects like compliance and daily functioning. Ultimately, the project shall help to establish the modification of sleep as an important therapeutic goal in the treatment of major psychiatric diseases.

A12

The role of sleep in the consolidation of fear extinction memory


Prof. Dr. Büchel, Christian
Institut für systemische Neurowissenschaften Universitätsklinikum Hamburg-Eppendorf,
Martinistr. 52, 20246 Hamburg

Telefon: +49-40-7410-54726
E-Mail: buechel@uke.de

Dr. Ehrlich, Ingrid
Hertie Institut für klinische Hirnforschung und Zentrum für Integrative
Neurowissenschaften, Universität Tübingen,
Otfried-Müller-Str. 25, 72076 Tübingen

Telefon: +49-7071-29-89189
E-Mail: ingrid.ehrlich@uni-tuebingen.de

Summary
Classical fear conditioning and extinction of conditioned fear are forms of emotional learning highly relevant to understanding neuropsychiatric disorders such as anxiety and posttraumatic stress disorder (PTSD). Importantly, behavioral therapy using exposure is based on extinction learning. It is therefore of high clinical interest to identify mechanisms that influence the consolidation of extinction memories. In this combined human-rodent project, we focus on the hypothesis that sleep supports the consolidation of extinction memory. In human experiments, we will assess the role of sleep in the consolidation of extinction behaviorally and will then identify systems mechanisms by measuring activation of the amygdala, hippocampus and ventromedial prefrontal cortex (vmPFC) using fMRI. To address the underlying cellular mechanisms, we turn to rodent experiments. In a closely matched approach, we focus on the mechanisms of consolidation of extinction memory. After establishing the behavioral effect of sleep manipulations in mice, we assess how sleep affects plasticity at sensory and vmPFC inputs to the amygdala and test the hypothesis that sleep-dependent consolidation of extinction memories is associated with strengthening of prefrontal-amygdala synaptic connectivity.

A13

Prefrontal control in sleep-dependent selection of relevant memories in healthy and deviant development


Prehn-Kristensen, Alexander, Dipl.-Psych. Dr.
Klinik für Kinder- und Jugendpsychiatrie und –psychotherapie, Zentrum für Integrative
Psychiatrie Kiel, Niemannsweg 147, 24105 Kiel

Telefon: +49-431-9900-2531
E-Mail: a.prehn@zip-kiel.de

Baving, Lioba, Prof. Dr. Dr.
Klinik für Kinder- und Jugendpsychiatrie und –psychotherapie, Zentrum für Integrative
Psychiatrie Kiel, Niemannsweg 147, 24105 Kiel

Telefon: +49-431-9900-2669
E-Mail: l.baving@zip-kiel.de

Summary
Our experiments during the previous funding period indicated that not all encoded memories are equally well consolidated during sleep; rather sleep selectively strengthens those memories that are relevant for the future. We found that this selection in memory consolidation during sleep is even more pronounced in healthy children than in healthy adults, but absent in children suffering from attention-deficit/ hyperactivity disorder (ADHD). The major aim of this project for the next funding period is to elucidate the mechanisms underlying the age-dependent difference in the selectivity of sleep-dependent memory consolidation. It has been proposed that the prefrontal cortex (PFC) is involved in tagging relevant memories during and/or after their acquisition, which results in increased slow wave sleep (SWS)-dependent reactivation of these memories during subsequent sleep. In the first set of experiments, we therefore plan to investigate the interplay between the PFC and the selection of memories during sleep in healthy children, children suffering from ADHD, and adults. In a second set of experiments, we aim to modulate the selectivity of sleep-dependent memory consolidation by experimentally manipulating PFC functions and SWS in children with and without ADHD.

A14

The role of the hippocampal CA1 network in the hippocampal-neocortical dialogue during sleep


Bartsch, Thorsten, PD Dr. med. habil.
Klinik für Neurologie des Universitätsklinikums Schleswig Holstein UKSH – Campus Kiel,
Schittenhelmstr. 10, 24105 Kiel

Telefon: +49-431-597-8550
E-Mail: t.bartsch@neurologie.uni-kiel.de

Sirota, Anton, Dr.
Forschergruppe ‘Physiology of Cortico-Hippocampal Interaction’
Werner Reichardt Centrum für Integrative Neurowissenschaften
Otfried-Müller-Str. 25, 72076 Tübingen

Telefon: +49-07071-2989160
E-Mail: anton.sirota@cin.uni-tuebingen.de

Summary
During the last funding period, we have studied the role of hippocampal dysfunction and degeneration in patients with transient global amnesia (TGA) and Alzheimer’s disease (AD) in sleep-dependent mnemonic processes. In particular, the role of CA1 networks and of local lesions to this network in the human hippocampus has been studied with regard to the consolidation of spatial memory, autobiographical episodic memory and interaction with non-declarative memory systems. Based on these findings, during the next funding period, we aim at an in-depth analysis of the role of the hippocampal CA1 network in the hippocampalneocortical interaction during learning and sleep-dependent memory consolidation, using a translational approach combining experimentation in rodents and patients. We will use a local perturbational approach to investigate the causal role of the CA1 network in the mechanisms of memory consolidation during sleep. In rodents we will use multichannel recordings and optogenetic methods to modulate network dynamics. In patients with transient local lesions to CA1, we will use a combination of learning paradigms, functional imaging and sleep studies to dissect the network role of the CA1 network in memory consolidation.

A16

The role of reward- and novelty-related dopaminergic signals in sleep-mediated memory consolidation


Münte, Thomas F., Prof. Dr. med.
Klinik für Neurologie, Universität Lübeck,
Ratzeburger Allee 160, 23538 Lübeck

Telefon: +49-451-500-2925
E-Mail: thomas.muente@neuro.uni-luebeck.de

Heldmann, Marcus, Dr. rer. nat.
Klinik für Neurologie, Universität Lübeck,
Ratzeburger Allee 160, 23538 Lübeck

Telefon: +49-451-500-2925
E-Mail: marcus.heldmann@neuro.uni-luebeck.de


Summary
Children not only display a much higher learning capacity than adults but also a different sleep architecture. As in adults, sleep in children improves declarative memory consolidation but, surprisingly, does not lead to gains in procedural memory. We hypothesize that in healthy children a paramount consolidation of explicit aspects of procedural memories during sleep impairs implicit memory consolidation. In contrast, we expect that children with ADHD (Attention-Deficit/Hyperactivity Disorder) who are characterized by severe declarative memory deficits, show improved procedural memory consolidation, due to reduced competitive interaction between explicit and implicit aspects of procedural memory consolidation. With respect to emotional memory, in healthy children the benefit from sleep should be comparable or even stronger than in adults whereas in ADHD children deficits in dopaminergic neurotransmission is expected to impair sleep-associated emotional memory consolidation.

A17

Remembering the past to anticipate the future: The functional role of sleep in predictive coding and prospective memory


Rauss, Dr. Karsten

Institut für Medizinische Psychologie und Verhaltensneurobiologie, Universität Tübingen,
Otfried-Müller-Str. 25, 72076 Tübingen

Telefon: +49-7071-29-88921
E-Mail: karsten.rauss@uni-tuebingen.de

Diekelmann, Dr. Susanne
Institut für Medizinische Psychologie und Verhaltensneurobiologie, Universität Tübingen,
Otfried-Müller-Str. 25, 72076 Tübingen

Telefon: +49-7071-29-88917
E-Mail: susanne.diekelmann@uni-tuebingen.de

Summary
Recent research suggests that a central function of memory is to use stored information of the past to generate predictions for the future. Sleep is known to facilitate the consolidation and qualitative transformation of newly encoded information. In this project, we will examine whether consolidation processes during sleep selectively support the prospective aspect of memory. We aim to test on different levels of information processing whether sleep serves to process memories in such a way as to predict future events and to adapt future behavior optimally. In particular, we will address the question whether on the perceptual level sleep supports the transformation of perceptual memories into a format that allows for active predictions of upcoming sensations. We will further test whether similar mechanisms act on the behavioral level, with sleepdependent consolidation processes promoting the successful execution of intended actions in the future.

A18

Sleep-dependent reorganization of neocortical microcircuits


Dr. Sato, Takashi
Center for Integrative Neuroscience, Universität Tübingen
Otfried-Müller-Straße 25, 72076 Tübingen, Germany

Telefon: +49-7071-29-89133
E-Mail: takashi.sato@cin.uni-tuebingen.de

Prof. Dr. Born, Jan
Institut für Medizinische Psychologie und Verhaltensneurobiologie, und
Center for Integrative Neuroscience, Universität Tübingen
Otfried-Müller-Straße 25 ,72076 Tübingen, Germany

Telefon: +49-7071-29-88924
E-Mail: jan.born@uni-tuebingen.de

Summary
Sleep improves memory by facilitating consolidation of newly acquired knowledge and skills. The prevailing hypothesis is that consolidation is mediated by the reactivation of neural representations during sleep. The goal of the current proposal is to investigate how reactivation affects the neural circuits mediating the consolidation of memory representations during sleep. For this goal, we will perform in vivo two-photon calcium imaging in rodents while they learn a Go/NoGo task that requires motor and prefrontal cortices. Two-photon imaging combined with a genetically encoded calcium indicator will allow us to monitor the activity of neurons over several days. Thus, we can investigate the effect of learning and sleep on the activity pattern of populations of neurons across multiple sessions. Using this technique, at the behavioral level, we will examine whether reactivation during sleep will affect the animals’ performance on the following session. At the level of neural circuits, we will investigate whether reactivated neurons will show learning-induced changes in their response patterns, functional connectivity, and anatomical structures. Through these studies, combined with detailed investigations of the neural circuits that underlie reactivation, we aim to achieve a mechanistic description of the relationship between reactivation and sleep-dependent memory consolidation.

A19

Sleep-dependent consolidation of social perceptual skills in normal and pathological brain development


Wilke, Marko, PD Dr. med.

Universitätskinderklinik, Abteilung für Neuropädiatrie und Entwicklungsneurologie
Hoppe-Seyler-Straße 1, 72076 Tübingen

Telefon: +49-7071-29-83416
E-Mail: marko.wilke@med.uni-tuebingen.de

Anders, Silke, Prof. Dr. rer. nat.
Klinik für Neurologie, Universität zu Lübeck
Ratzeburger Allee 160, 23538 Lübeck

Telefon: +49-451-500-4520
E-Mail: silke.anders@neuro.uni-luebeck.de

Krägeloh-Mann, Ingeborg, Prof. Dr. med.
Universitätskinderklinik, Abteilung für Neuropädiatrie und Entwicklungsneurologie
Hoppe-Seyler-Straße 1, 72076 Tübingen

Telefon: +49-7071-29-84735
E-Mail: ingeborg.kraegeloh-mann@med.uni-tuebingen.de

Summary
The overall goal of this project is to investigate the neurophysiological mechanisms underlying sleepdependent consolidation of social perceptual skills in the context of normal and pathological brain development. Social perceptual learning is a type of learning that is of utmost importance to an individual’s social development, but that has so far been greatly neglected in the field of sleep and memory research. We will examine and compare sleep-dependent consolidation of social and non-social perceptual skills (discrimination of facial expressions versus trees at different seasons), motor skills (serial reaction time task) and declarative memories (picture–name pair learning task) in typically developing school-aged children, children with pathological brain development and adults, at the behavioral and the neural level (using fMRI). Children with benign epilepsy with centrotemporal spikes (BECTS, also known as Rolandic epilepsy) will be used as a model of impaired slow wave sleep (SWS) and spindle generation. Children born very preterm will be used as a model of delayed brain maturation. We expect that by examining two well-described models of pathological brain development and by including a type of procedural learning of special importance for social development, this project will significantly increase our understand of the interplay between brain maturation, development and sleep-dependent memory consolidation.

Last Update: 26.06.2013