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Responding to stress is adaptive for most complex organisms, aiding survival by temporarily mobilizing resources to let the organism better flee or defend itself in response to a perceived threat. Once the threat is ended, the response normally subsides, allowing the organism to pursue other key survival activities. But if the stress response never reverses, or is triggered inappropriately, as with extreme stressors such as trauma, it may lead to psychiatric disorders such as anxiety and PTSD. Some individuals, like Special Forces soldiers, are inherently resilient to most stressors. Such resilient individuals have higher levels of Neuropeptide Y (NPY) in their blood and CSF. Experimental injections of NPY into brain ventricles or into the amygdala of rodents can induce an acute resilience to stress and a prolonged (weeks to months) period of resilience with just a few repeated treatments. Conversely, the stress hormone, Corticotrophin Releasing Factor (CRF), respectively causes acute and prolonged vulnerability to stress when injected acutely or repeatedly into the same brain structures. Activity of projection neurons (PNs) in the basolateral amygdala (BLA) mediates fear and anxiety responses, and reducing PN activity reduces both. Earlier work from the Colmers and Urban laboratories demonstrated opposing actions of NPY and CRF on BLA PN excitability: NPY acutely hyperpolarized these cells, while CRF acutely depolarized them. The mechanism was unusual, in that NPY reduced a membrane ion current, the H-current (Ih), while CRF activated it. Because Ih is hyperpolarization-activated, it is active at the resting potential, so by closing Ih, NPY hyperpolarizes PNs, while CRF opening it depolarizes them. Repeated (5 x daily) injection of NPY causes stress resilience in rats (seen as increased social interaction) persisting longer than 4 weeks. BLA PNs from NPY-treated animals were hyperpolarized at 4W, exhibiting a relative marked loss of Ih and correlating with reductions in mRNA and protein levels for HCN1, the Ih channel subunit in these cells. shRNA knockdown of HCN1 in BLA caused long-term behavioral stress resilience, indicating HCN1’s role in behavior. Using a novel organotypic slice culture system of the BLA, we studied mechanisms underlying long-term changes, mimicking the repeated application of NPY and receptor-selective agonists. Briefly, NPY did reduce Ih in these cells,but more prominently reduced the extent of BLA PN dcendrites, while CRF increased them (as is known to happen in vivo both with CRF and stress). Studies in BLA from NPY-treated rats confirmed the reduction in dendritic trees in vivo. The NPY Y5 receptor mediates the long-term changes, and requires calcineurin and the autophagic pathway to do so, while the CRFR1 receptor is involved in the increase, and requires CaMKII. Because the work wasa all done in male rats, ongoing work is determining if the same actions of NPY and CRF occur in female BLA. [mehr]

Interacting with an individual brain in closed loop can open the door for detailed introspection into sensorimotor and cognitive processes. However, closed-loop paradigms require data analysis methods capable of decoding neural components of interest in single-trial, despite of low signal-to-noise ratio and non-stationarity. In my talk, I will report on two novel algorithmic developments of my lab. The methods allow for the robust supervised regression of informative oscillatory components of the EEG and the unsupervised classification of evoked potentials. Then I will show, how the derived components can be exploited in two brain state informed stroke therapy paradigms, which are designed to train up (1) hand motor performance and (2) the language network of chronic aphasic patients after stroke. [mehr]

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To optimally adapt to our ever-changing environments, our brain continuously integrates exteroceptive and interoceptive information, that is, signals received from external (e.g., through vision or touch) and internal sources (e.g., through viscerosensation or proprioception). Particularly the coupling between the heart and the brain or - more generally - between the autonomic and the central nervous system plays a major role for mental processes and behavior. I will present studies, in which we found (1) an association between resting heart rate variability (HRV) and resting-state functional connectivity, (2) task-related HRV changes in response to emotion or stress, and (3) that perception and behavior vary across the cardiac cycle. Showing the psychological relevance of both directions of the heart-brain axis suggests the "rest of the body’s" importance for the mind and contributes to a more comprehensive investigation of mind-brain-body interactions. [mehr]

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Many eating-related psychological constructs have been proposed to explain obesity and over-eating. However, these constructs, including food addiction, disinhibition, hedonic hunger, emotional eating, binge eating, and the like all have similar definitions, emphasising loss of control over intake. As questionnaires measuring the constructs correlate strongly (r>0.5) with each other, we propose that these constructs should be reconsidered to be part of a single broad phenotype: Uncontrolled Eating (UE). Such an approach enables reviewing and meta-analysing evidence obtained with each individual questionnaire. Here, we describe robust associations between UE, body mass index (BMI), food intake, psychological traits, and brain systems. Reviewing cross-sectional and longitudinal data, we show that UE is phenotypically and genetically intertwined with BMI and food intake. We also review evidence on how three independent psychological constructs may contribute to UE: heightened food reward sensitivity, lower self-control, and higher negative affect. UE mediates all three constructs’ associations with BMI and food intake. Finally, we review and meta-analyse brain systems subserving UE: namely, (i) the dopamine mesolimbic circuit associated with reward sensitivity, (ii) frontal cognitive networks sustaining dietary self-control, and (iii) the hypothalamus-pituitary-adrenal axis, amygdala and hippocampus supporting stress reactivity. While there are limits to the explanatory and predictive power of the UE phenotype, we conclude that treating different eating-related constructs as a single concept, UE, enables drawing robust conclusions on the relationship between food intake and BMI, psychological variables, and brain structure and function. [mehr]

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Aus unserer Umwelt nehmen wir ständig Informationen auf, die eingeordnet und bewertet werden müssen, damit in unserem Bewusstsein ein individuell kohärentes Bild erschaffen werden kann. Eine Reihe empirischer Befunde in den letzten Jahren hat Hinweise erbracht, die darauf hindeuten, dass der funktionelle Zustand des Gehirns diese Informationsverarbeitung beeinflusst. So konnte beispielsweise gezeigt werden, dass die Amplitude und Phase kortikaler Aktivität, sowie die Kommunikation zwischen kortikalen Arealen relevant sind für die Verarbeitung unisensorischer und multisensorischer Reize. In diesem Vortrag werde ich die aktuelle Literatur zu den neuronalen Mechanismen multisensorischer Verarbeitung zusammenfassen und dabei vor Allem auf neuronale Oszillationen eingehen. Dabei schlage ich vor, dass unterschiedliche Frequenzbänder ergänzende Mechanismen multisensorischer Verarbeitung abbilden. Im Anschluss werde ich offene Fragen in diesem Forschungsfeld diskutieren, mit einem besonderen Augenmerk auf der Rolle kognitiver Prozesse, Aufmerksamkeit, Erwartungen und Emotionen. [mehr]

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Compared to the spatial synchronization, temporal dynamics of neuronal activity only recently gained a widespread attention in neuroscience. A particularly interesting discovery was a demonstration of Long-Range Temporal Correlations (LRTC) in the amplitude dynamics of neuronal oscillations. Neuronal LRTC might indicate a presence of a critical state in neuronal dynamics which was previously shown to be beneficial for the optimal processing of information in the brain. In my talk I will review studies showing relevance of LRTC for cognitive and motor tasks. Moreover, I will show that LRTC can serve as clinical biomarkers sensitive to pathological neuronal activations in Schizophrenia, Depression and Parkinson’s Disease. [mehr]

The identification of biomarkers. which can help predict disease outcome. remains one of the most promising research areas across a variety of diseases. Particularly. studying the spatial distribution of underlying disease burden may provide important insights into pathological patterns. Stroke is one of the leading causes of death and disability worldwide. however. it remains largely understudied in the acute setting due to time restrictions during data acquisition and the resulting low resolution magnetic resonance images. This has made outcome prediction particularly difficult. as it leads to heterogeneity in the data and/or methodologies between studies. One of the key phenotypes of stroke research is a patient's white matter hyperintensity (WMH) burden. most commonly assessed using FLAIR images. which has been linked to stroke outcome. Studies often rely on measuring the total burden and summarize it as a single number: it’s volume. based on manual outlines on a patient’s scan. The lack of an automated segmentation methodology for clinical data has so far hindered large-scale. reproducible investigations. In the first part of this talk. we present an automated pipeline for monomodal automatic WMH segmentation. which can alleviate some of these challenges. Specifically. we demonstrate it's efficacy for volume estimation in a cohort of 2.533 patients. showing the association between higher WMH burden and poorer outcome after stroke (p<0.001). In the second half of this talk. we demonstrate the use of WMH segmentations for investigating spatial WMH disease burden and how other clinical variables can modify these patterns. In particular. we demonstrate effects for hypertension and smoking status. and show that these clinical variables lead to a shift of disease burden from posterior to anterior vascular regions (p<0.05 and p<0.01. respectively). This illustrates the potential of uncovering spatial variations of disease patterns by using large-scale cohorts. [mehr]

Despite the thorough mapping of brain pathways involved in eating behavior, no treatment aimed at modulating eating dysregulation has been established yet. Aiming for a feasible brain-modulation tool, we evaluated N.I.R. H.E.G. (Near Infra-Red Hemoencephalography) neurofeedback training on appetite control, weight and food-related brain activity. Following the intervention, we observed trends of increased self-control related to food, weight reduction and increased activation of sOFC during a response-inhibition fMRI task. N.I.R. H.E.G. holds a promising potential as a feasible neurofeedback platform for modulation of cortical brain circuits involved in self-control and eating behavior. This is an invitation for further evaluation and development of N.I.R. H.E.G. as a brain modifying device for the treatment and prevention of obesity. Based on: A pilot study of a novel therapeutic approach to obesity: CNS modification by N.I.R. H.E.G. neurofeedback Clin Nutr. 2018 Feb 7. pii: S0261-5614(18)30043-8. Percik R, Cina J, Even B, Gitler A, Geva D, Seluk L, Livny A [mehr]

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Stroke is a leading cause of life-long disability. The improvement of acute treatment has increased stroke survival, leaving more people in rehabilitative care than ever. Here, the recovery of function typically reaches a plateau after initial progress. Transcranial direct current stimulation (tDCS) has been suggested to facilitate recovery beyond this plateau, even in the chronic stage. However, no clear pattern of tDCS-induced effects could be established in patients yet, likely due to inconsistent experimental designs in previous studies. In this talk I will present data from two studies I performed during my PhD here at the MPI CBS. The first (pilot) study covers differential effects of tDCS on proprioception in healthy ageing and introduces and applies an individualised current modelling approach to explain differences between age groups. In the second study, we have investigated a large array of sensorimotor functions in chronic stroke patients and the impact of two different tDCS protocols on the kinematics of those functions. [mehr]

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The dopaminergic circuits lie at the core of learning and motivational processes through which we are able to form predictions about the future and take action accordingly. Studies in animals have shown that midbrain dopaminergic neurons projecting to the striatum signal events in the environment that deviate from what we expect. A prevalent model of the dopaminergic function suggests that these so-called prediction errors –propagated by the D1 dopamine receptors to cortical areas – modulate synaptic plasticity and thereby facilitate learning and initiation of action. While D2 dopamine receptors in the striatum as well as prefrontal striatal projection regulate and modulate this signal propagation. How this neurobiological model of dopaminergic activity relates to behaviour has been difficult to address. In my talk I will present several pharmacogenetic studies that map manipulations of the dopaminergic system on to various computational phenotypes. First of all, we are interested in the role of dopamine in updating beliefs in a social as well as a non-social context. And second, we explored dopamine’s involvement in model-based decision making. Specifically, how does blocking D2 transmission affect our ability to keep the regularities and knowledge about the world online as we make decisions and learn about the states of the world that are not directly observed? [mehr]

What drives us to trust someone we just met? Did we eat spaghetti for lunch because we saw our colleague eat spaghetti? Can we become happier when we are nicer to our neighbors? How does the content of our breakfast have anything to do with our social interactions throughout the day? Research from different disciplines such as economics, psychology and neuroscience have attempted to investigate the motives and modulators of human decision making. Our decisions can be flexibly modulated by the different experiences we have in our daily lives. These modulations can occur through our social networks, through the impact of our own behavior on the social environment, but also simply by the food we have eaten. Here, I will present a series of recent studies from my lab in which we shed light on the psychological, neural and metabolic motives and modulators of human decision making. [mehr]

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Recent studies have questioned the reliability of many functional neuroimaging findings reported in the literature over the past decades. In my talk I will illustrate how novel analytic workflows (Dukart et al., 2018, Scientific Reports; Holiga et al. 2019, Science Translational Medicine) may overcome some of the critical limitations of functional neuroimaging analyses improving the reliability of the methods as well as providing an improved interpretation of potential signals with respect to underlying biology and for identification of biomarkers for neurological and psychiatric diseases. [mehr]

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Various psychological disorders are characterized by pronounced cognitive biases, including biased orienting of attention to certain stimuli, distorted expectation of the likelihood to encounter specific objects, biased interpretation of ambiguous information and biased perception. Although these biases are common in psychopathology, most of the studies so far focused on one bias by employing traditional analysis methods. Therefore, little is known about the correlational and causal relations between different biases and about combined patterns that may characterize certain disorders. In this talk, I will discuss recent behavioral, fMRI and autonomic data showing links between biases, as well as modulation of biased emotional processing in different populations. Moreover, by employing machine-learning based analysis, we managed to specify specific behavioral patterns that characterize anxiety vs. depression, two disorders that share many characteristics and show high comorbidity. Finally, I will discuss recent evidence for abnormalities in the blood pressure reaction to aversive pictures among individuals with pre- hypertension, a population that is usually not studied in the context of psychological reactions. Taken together, these findings suggest new strategies to explore and treat maladaptive behaviors that have fundamental implications on the patients’ life. [mehr]

A considerable body of work over the last 10 years combining non-invasive electrophysiology (electroencephalography/magnetoencephalography) in patient populations with preclinical research has contributed to the conceptualization of schizophrenia as a disorder associated with aberrant neural dynamics and disturbances in excitation/inhibition (E/I) balance parameters. Specifically, I will propose that recent technological and analytic advances in MEG provide novel opportunities to address these fundamental questions as well as establish important links with translational research. We have carried out several studies which have tested the importance of neural oscillations in the pathophysiology of schizophrenia through a combination of MEG-measurements in ScZ-patients and pharmacological manipulations in healthy volunteers which target the NMDA-receptor. These results highlight a pronounced impairment in high-frequency activity in both chronic and unmedicated patients which could provide novel insights into basic circuit mechanisms underlying cognitive and perceptual dysfunctions. However, acute Ketamine only partly recreates abnormalities observed in both resting-state and task-related neural oscillations in ScZ, suggesting potentially shortcoming of this pharmacological model for capturing large-scale network dysfunctions. Our recent work has employed MEG to develop a biomarker for early detection and diagnosis of ScZ. We have obtained MEG- and MRS-data from 125 participants meeting clinical high-risk criteria (CHR), 90 controls and 30 FEP-patients. We found marked changes in the synchrony of gamma-band oscillations in visual and auditory cortices during sensory processing which predicted clinical outcomes. In addition, CHR-participants were characterized by elevated broad-band gamma-band activity at rest which correlated with increased glutamate levels. Together, these findings highlight the potential of MEG-based biomarkers for the early diagnosis of ScZ in at-risk populations. [mehr]

Exposure to childhood adversity is common and associated with a host of negative developmental outcomes as well as differences in neural structure and function. It is commonly posited that these social experiences “get under the skin” in early childhood, increasing long-term risk through disruptions to biology. In this talk I propose a novel approach to studying the link between adversity, brain development, and risk for psychopathology, the dimensional model of adversity and psychopathology (DMAP). In this model we propose that adversity exposure can be defined according to different dimensions which we expect to impact health and well-being through different neural substrates. Whereas we expect deprivation to primarily disrupt function and structure of lateral association cortex (e.g., dorsolateral prefrontal cortex and superior parietal cortex) and thus complex cognitive processing such as executive functioning. In contrast, we expect threat to alter structure and function of subcortical structures such as the hippocampus and amygdala and midline regions associated with emotion regulation such as the ventral medial prefrontal cortex and thus, associated emotion reactivity and automatic regulation processes. In a series of studies I test the basic tenants of the DMAP concluding that initial evidence, using both a priori hypothesis testing and data-driven approaches is consistent with the proposed model. I conclude by describing future work addressing multiple dimensions of adversity and potential adjustments to the model. [mehr]

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Cerebrovascular risk factors increase the likelihood of dementia. High cerebrovascular burden leads to vascular dementia, accounting for around 20% of dementia cases. Less well appreciated, is that up to 70% of patients with Alzheimer’s disease (AD) also have cerebrovascular disease at post-mortem. The impact of mixed pathologies is likely greatly underestimated. Clinical studies of neurodegenerative dementias rarely control cerebrovascular burden, beyond age and obvious magnetic resonance imaging (MRI) markers like white matter hyperintensities (WMHs). In this talk, I will show work investigating MRI markers of cerebrovascular burden in healthy ageing in 22 000 people from the UK Biobank. I will demonstrate new methods for the estimation of the spatial distribution of cerebrovascular risk-related WMHs and their impact on cognition. I will also present work looking at the importance of microstructural integrity of normal appearing white matter and integrity of grey matter in distributed brain networks for the preservation of cognitive function in healthy ageing and after ischaemic stroke. Together, I will build up a picture of the important MRI markers of cerebrovascular burden that may act as transdiagnostic markers of cognitive impairment. [mehr]

Recently, the use of resting-state functional MRI (rsfMRI) has been extended beyond the assessment of the brain’s functional organization to the monitoring of various aspects of cerebral hemodynamics. This has found practical applications in various disease states, particularly in cerebrovascular disorders, and has substantial methodological implications for the use of rsfMRI in clinical research. In this talk, I will: ● Discuss recent findings regarding the physiological sources and mechanisms of the components of the blood oxygenation level dependent (BOLD) signal that reflect the brain’s hemodynamic status ● Present recent methodological and practical developments to established rsfMRI-based methods for the assessment of blood flow within the brain ● Present some upcoming techniques for extracting hemodynamic parameters from rsfMRI data and their potential use in various diseases. [mehr]

Computational visual neuroscience has come a long way in the past 10 years. For the first time, we have fully explicit, image-computable models that can recognise objects with near-human accuracy, and predict brain activity in high-level visual regions. I will present evidence that diverse deep neural network architectures all predict brain representations well, and that task-training and subsequent reweighting of model features is critical to this high performance. However, vision is not yet explained. The most successful models are deep neural networks that have been supervised using ground-truth labels for millions of images. Brains have no such access to the ground truth, and must instead learn directly from sensory data. Unsupervised deep learning, in which networks learn statistical regularities in their data by compressing, extrapolating or predicting images and videos, is an ecologically feasible alternative. I will show that an unsupervised deep network trained on an environment of 3D rendered surfaces with varying shape, material and illumination, spontaneously comes to encode those factors in its internal representations. Most strikingly, the network makes patterns of errors in its perception of material which follow, on an image-by-image basis, the patterns of errors made by human observers. Unsupervised deep learning may provide a coherent framework for how our perceptual dimensions arise. [mehr]

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Interest in disorders of later life have grown in proportion with the increase of this population group in many societies. We are accustomed to see age as a confounder, so attempts to pinpoint group difference while adjusting for age effects often result in the removal of differences that may be crucial to understanding the aging process. In addition, age reflects between-subject variation (particularly in cross-sectional studies), as well as within-subject changes over time in repeat measures designs. Both are relevant clinically, as the importance of education or IQ for dementia diagnosis and the gradual development of vascular and cognitive risks in mid-life for accelerated ageing demonstrate. I will try to illustrate these issues with studies from UK Biobank and the EU Lifebrain Consortium, covering concepts such as brain-, cognitive age and -reserve, and the role of the natural history and life-time course of depression in its relation to biomarkers and putative aetiologies. [mehr]

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What motivates us to do what we do? And why is it so incredibly difficult to do the right thing, even when we (think we) set our minds to it? Successful behavioural change is still a major challenge for people, both in clinical and non-clinical settings. This lack of flexibility, which often results in maladaptive behaviour of some kind, is what fascinates me and what broadly has been driving my research interest in real-world habits. In this talk, I would like to give you a concise overview of some of the studies I worked on regarding people’s ability to adjust to changes in learnt responses and reward probabilities (reversal learning, two-step task, outcome devaluation) in different target populations (e.g., disordered gambling, diet-induced obesity). Dopamine will be a red thread throughout the talk. Finally, I will discuss the idea that adaptive flexibility requires sufficient stability, and that it may be worth reconsidering the traditional dichotomous thinking in behavioural control research. [mehr]

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The OMEGA Lab’s research goal is to investigate lifestyle factors on brain health. In this colloquium, we will report on findings from the GUT-BRAIN study, a MPI in-house conducted double-blind cross-over within-subject designed randomized controlled trial. The study investigates potential effects of a two-week high-fiber diet in overweight healthy adults. We will report on a series of four projects, spanning from cross-sectional to longitudinal analyses. Associations of dietary and serum tyrosine on white matter microstructure and executive function Neurocognitive predictors of food memory Effects of a high-fiber diet on hypothalamic and peripheral inflammation Effects of a high-fiber diet on neural and behavioural correlates of food wanting Further studies on meal choices and methodological advances from the OMEGA Lab will be touched upon briefly. [mehr]

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Compulsive behavior is a common feature of both OCD and pathological gambling, despite their differing motivational contexts. This talk will explore the role of control and agency in the onset and perpetuation of compulsions in these two conditions. Specifically, I will examine how a single belief disturbance, such as a lack of trust in one's avoidance actions or an illusion of control, can trigger and maintain compulsions. Using computational models of cognition in conjunction with empirical data, I will demonstrate the direct link between this disturbance and the severity of compulsions. Overall, this talk will shed light on the importance of control and agency in understanding and treating compulsive behaviors across different contexts. [mehr]

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