Anatomy and computational modeling of networks underlying cognitive-emotional interaction

The classical dichotomy between cognition and emotion equated the first with rationality or logic and the second with irrational behaviors. The idea that cognition and emotion are separable, antagonistic forces competing for dominance of mind has been hard to displace despite abundant evidence to the contrary. For instance, it is now known that a pathological absence of emotion leads to profound impairment of decision making. Behavioral observations of this kind are corroborated at the mechanistic level: neuroanatomical studies reveal that brain areas typically described as underlying either cognitive or emotional processes are linked in ways that imply complex interactions that do not resemble a simple mutual antagonism. Instead, physiological studies and network simulations suggest that top-down signals from prefrontal cortex realize "cognitive control" in part by either suppressing or promoting emotional responses controlled by the amygdala, in a way that facilitates adaptation to changing task demands. Behavioral, anatomical, and physiological data suggest that emotion and cognition are equal partners in enabling a continuum or matrix of flexible behaviors that are subserved by multiple brain regions acting in concert. Here we focus on neuroanatomical data that highlight circuitry that structures cognitive-emotional interactions by directly or indirectly linking prefrontal areas with the amygdala. We also present an initial computational circuit model, based on anatomical, physiological, and behavioral data to explicitly frame the learning and performance mechanisms by which cognition and emotion interact to achieve flexible behavior.R01 MH057414 - NIMH NIH HHS; R01 NS024760 - NINDS NIH HH

Virtual Reality for Enhanced Ecological Validity and Experimental Control in the Clinical, Affective and Social Neurosciences

This article highlights the potential of virtual reality environments for enhanced ecological validity in the clinical, affective, and social neurosciences

Embodied Robot Models for Interdisciplinary Emotion Research

Due to their complex nature, emotions cannot be properly understood from the perspective of a single discipline. In this paper, I discuss how the use of robots as models is beneficial for interdisciplinary emotion research. Addressing this issue through the lens of my own research, I focus on a critical analysis of embodied robots models of different aspects of emotion, relate them to theories in psychology and neuroscience, and provide representative examples. I discuss concrete ways in which embodied robot models can be used to carry out interdisciplinary emotion research, assessing their contributions: as hypothetical models, and as operational models of specific emotional phenomena, of general emotion principles, and of specific emotion ``dimensions''. I conclude by discussing the advantages of using embodied robot models over other models.Peer reviewe

Pulvinar and Affective Significance: Responses Track Moment-to-Moment Stimulus Visibility

Research on emotion has considered the pulvinar to be an important component of a subcortical pathway conveying visual information to the amygdala in a largely “automatic” fashion. An older literature has focused on understanding the role of the pulvinar in visual attention. To address the inconsistency between these independent literatures, in the present study, we investigated how pulvinar responses are involved in the processing of affectively significant stimuli and how they are influenced by stimulus visibility during attentionally demanding conditions. Subjects performed an attentional blink task during fMRI scanning involving affectively significant (CS+) and neutral stimuli (CS−). Pulvinar responses were not influenced by affective significance (CS+ vs. CS−) per se. Instead, evoked responses were only modulated by affective significance during hit trials, but not during miss trials. Importantly, moment-to-moment fluctuations in response magnitude closely tracked trial-by-trial detection performance, and thereby visibility. This relationship was only reliably detected during the affective condition. Our results do not support a passive role of the pulvinar in affective processing, as invoked in the context of the subcortical-pathway hypothesis. Instead, the pulvinar appears to be involved in mechanisms that are closely linked to attention and awareness. As part of thalamocortical loops with diverse cortical territories, we argue that the medial pulvinar is well positioned to influence information processing in the brain according to a stimulus's biological significance. In particular, when weak and/or brief visual stimuli have affective significance, cortico-pulvino-cortical circuits may act to coordinate and amplify signals in a manner that enhances their behavioral impact

Beyond Machine Learning: An fMRI Domain Adaptation Model for Multi-study Integration

Traditional machine learning analyses are challenging with functional magneticresonance imaging (fMRI) data, not only because of the amount of data that needs to becollected, adding a particular challenge for human fMRI research, but also due to the change inhypothesis being addressed with various analytical techniques. Domain adaptation is a type oftransfer learning, a step beyond machine learning which allows for multiple related, but notidentical, data to contribute to a model, can be beneficial to overcome the limitation of dataneeded but may address different hypothesis questions than anticipated given the analysiscomputation. This dissertation assesses a novel domain adaptation package, PyKale, created forcognitive fMRI data to determine the benefit and use it can have within cognitive research

Antidepressant-Like Effects of Ketamine on Fear Conditioning and Extinction

The experience of chronic stress plays an important role in the pathogenesis of major depressive disorder. Prolonged stress induces a state of chronically elevated glucocorticoid exposure in the brain, which is neurotoxic and can lead to the dysfunction of glutamatergic signaling. Since memory is highly dependent upon glutamatergic neurotransmission, patients with depression commonly display alterations in memory processing that bias the recollection of past events towards negative emotional information. Negative cognitive biases are believed to support the development and maintenance of depression, emphasizing the need for antidepressant treatments that can effectively combat these insidious symptoms. Memory for negative emotional events can be studied in animals using fear conditioning and extinction paradigms. Fear conditioning trains an animal to associate a neutral cue with an emotionally aversive experience, while extinction learning challenges this association by forming a new memory that identifies the cue as harmless. The aim of this dissertation was to investigate the antidepressant-like effects of ketamine on auditory fear conditioning and extinction in both healthy rats and those with chronic glucocorticoid exposure. The first experiment sought to dissociate the effects of ketamine on distinct stages of auditory fear conditioning and extinction by administering a subanesthetic dose of ketamine at one of three unique time points: before fear conditioning training, immediately after fear conditioning training, or before fear extinction training. Post-conditioning and pre- extinction ketamine attenuated the long-term expression of cue-elicited freezing, suggesting that the consolidation and recall of conditioned fear were impaired, respectively. Pre-conditioning ketamine did not disrupt the acquisition of fear conditioning, and none of the treatments examined affected the long-term expression of fear extinction. The second experiment aimed to build upon these findings by examining the effect of pre-extinction ketamine on conditioned fear and extinction behavior in a repeated exogenous corticosterone (CORT) animal model of depression. Repeated CORT treatment provoked a spontaneous recovery of conditioned freezing between extinction sessions and induced a reinstatement of freezing following a sub- conditioning retraining procedure. Ketamine prevented CORT-induced failures in long-term extinction expression, and also greatly reduced freezing during early phase extinction training. Collectively, the findings of this dissertation help establish ketamine as a powerful modulator of negatively-valenced memory and emotionally-driven behavior, and contribute to our understanding of its antidepressant-like qualities

The startle response as a measure in mouse models of mood disorders

Ein großer Teil der Fragestellungen in den Neurowissenschaften beschäftigt sich mit dem Thema, wie das Säugerhirn Verhalten auslöst und steuert. Die Schreckreaktion ist ein relativ einfaches Verhalten, welches bei Säugetieren ohne großen Aufwand ausgelöst werden kann und variabel auf eine Vielfalt von experimentellen Behandlungen reagiert. Das Ziel der vorliegenden Arbeit war es, Schreckreaktions-Messungen am Max-Planck- Institut für Psychiatrie in München (MPI-P) zu etablieren. Vor dem Hintergrund aktueller Fragestellungen sollten die Experimente zu einsatzbereiten Messmethoden und Verhaltensparadigmen führen. In der vorliegenden Arbeit gelang es nicht, das Paradigma der furchtpotenzierten Schreckreaktion (FPS) zuverlässig in einem häufig am MPI-P eingesetzten Mausstamm anzuwenden. Das FPS maskierende Phänomen, daß die Präsentation eines unkonditionierten Tons bereits zu einer deutlich verstärkten Schreckreaktion in diesen Mäusen führt ("tone enhanced startle", TES) wurde dann charakterisiert und im Folgenden als ergänzendes Paradigma zur Messung und Abschätzung des Hörvermögens, der Stimulus Adaptation und der Aufmerksamkeit in Mäusen vorgeschlagen. Eine Literaturrecherche ergab, daß im Paradigma der Furchtkonditionierung ("fear conditioning", FC) und deren aktives Verlernen ("extinction of FC", ExFC) verwendete Stimulus-Parameter eine hohe Varianz zwischen verschiedenen Laboratorien aufweisen. Der im Verhalten ausgelesene Lernerfolg während einer FC wie auch einem ExFC hingen in den vorliegenden Experimenten wesentlich von der verwendeten Stimulusqualität ab (d.h. sinus-Ton oder weißes Rauschen). Im Umkehrschluß empfiehlt die vorliegende Arbeit einen überlegteren Umgang mit den eingetzten Stimulus-Parametern. Es zeigte sich, daß eine erhöhte Schreckreaktion (Übererregbarkeit) ohne weiteres in einem Tiermodell der Posttraumatischen Belastungsstörung ("posttraumatic stress disorder",PTSD) gemessen werden kann. Im Weiteren konnte gezeigt werden, daß verändertes Hippocampus-Volumen in diesen Tieren, gemessen über ultramikroskopische Aufnahmen und analog zu Hippocampusveränderungen in Patienten, unabhängig von anderen PTSD-ähnlichen Symptomen dieser Mäuse ist. In einem weiteren Abschnitt widmet sich die vorliegende Arbeit der laufenden Charakterisierung der Rolle von Dopaminrezeptoren (DR) in der Präpulsinhibition (PPI) und -Faszilitierung (PPF) der Schreckreaktion. Durch lokale injektion von DR-Antagonisten konnte gezeigt werden, daß die Blockade von DR1 wiederholbar PPI verstärkt, während die Rolle von DR2, getestet mit zwei verschiedenen Antagonisten, als ambivalent gedeutet werden muß. Basierend auf diesen Experimenten wurden optogenetische Methoden in die Schreckreaktionsmessung eingeführt. Transgenen Mäusen, die lichtsensitive Ionenkanäle in ihren neuronalen Zellmembranen bestimmter Zellpopulationen tragen, wurden Lichtblitze ins Gehirn appliziert. Auf diese Weise konnten PPI und PPF unabhängig voneinander manipuliert werden. Daraus folgend, und im Unterschied zur populären Summationshypothese der PPF, schlägt die vorliegende Arbeit einen eigenständigen, von der PPI unabhängigen PPF-Schaltkreis vor, der Pyramidenneuronen der präfrontalen Kortexschicht V beinhaltet. Die vorliegende Arbeit konnte erfolgreich verschiedene Protokolle und Verhaltensparadigmen der Schreckreaktionsmessung am MPI-P etablieren und zur sofortigen Nutzung zur Verfügung stellen. Es wurden nicht nur neue Techniken wie z.B. optogenetische Methoden in die Schreckreaktionsmessung eingeführt, die vorliegenden Experiemente leisten auch ihren Beitrag zur aktiven Forschung, in dem sie z.B. die große Bedeutung der Stimulus-Parameter für den Lernerfolg von Versuchstieren nachweisen.In neuroscience major efforts are focused on the question of how the mammalian brain generates and controls behaviour. The startle response is a relatively simple behaviour that can be easily elicited in mammals and is sensitive to a variety of experimental treatments. The aim of the present work was to establish startle response measures at the Max-Planck-Institute of Psychiatry (MPI-P), Munich, providing a set of readily applicable methods and paradigms, and contributing to questions in behavioural neuroscience. While the present thesis failed to robustly elicit fear potentiated startle (FPS) in a commonly used mouse strain at the MPI-P, strong unconditioned startle enhancement by acoustic stimulus presentation in that mouse strain was capitalised to propose tone enhanced startle (TES) as an additional paradigm to assess hearing capability, stimulus adaptation and attention in mice. A literature survey revealed considerably varying parameters used in fear conditioning (FC) and extinction of conditioned fear (ExFC). In the present work, FC, ExFC as well as FPS/TES highly depended on the stimulus quality (i.e. sine wave or white noise), demanding a more careful handling of stimulus parameters. Hyper-arousal was readily tested in a mouse model of posttraumatic stress disorder (PTSD). Additionally it was shown that altered hippocampal volume in these animals, assessed by ultramicroscopic measures and mimicking patient data, was independent of other symptoms present in this model. The present thesis contributes to the ongoing characterisation of the role of dopamine receptors (DR) in prepulse inhibition (PPI) and prepulse facilitation (PPF) of startle, manipulating PPI/F by injections of DR-antagonists into the prefrontal cortex of mice. It was found that blockade of DR1 reliably increases PPI, while the effect of DR2 was inconsistent, using to different DR2-antagonists. Based on this work, optogenetic methods were established. Applying intracerebral light flashes to transgenic mice carrying light sensitive ion channels on their neuronal cell membrane, PPI and PPF were manipulated independently, proposing the existence of a discrete PPF mediating pathway including prefrontal layer V pyramidal neurons, contrasting the popular summation hypothesis of PPF. The present work established and developed successfully different startle paradigms that are ready to use for animal characterisation and testing. Apart from combining startle measures with new techniques such as optogenetic methods, the present thesis points out the stimulus parameter dependence of animal learning, suggesting a fundamental discussion about fear conditioning and extinction learning protocols

Imaginary relish and exquisite torture: The elaborated intrusion theory of desire

The authors argue that human desire involves conscious cognition that has strong affective connotation and is potentially involved in the determination of appetitive behavior rather than being epiphenomenal to it. Intrusive thoughts about appetitive targets are triggered automatically by external or physiological cues and by cognitive associates. When intrusions elicit significant pleasure or relief, cognitive elaboration usually ensues. Elaboration competes with concurrent cognitive tasks through retrieval of target-related information and its retention in working memory. Sensory images are especially important products of intrusion and elaboration because they simulate the sensory and emotional qualities of target acquisition. Desire images are momentarily rewarding but amplify awareness of somatic and emotional deficits. Effects of desires on behavior are moderated by competing incentives, target availability, and skills. The theory provides a coherent account of existing data and suggests new directions for research and treatment