Re-Imagining “Spaces” for Relating Within and Between France and Germany in the Long Nineteenth Century

The “modern world” as we now know it is quite different from that which was emerging in Western Europe and began to accelerate in its development under the impetus of revolution and wars at the turn of the nineteenth century. Not only were material conditions in the process of shifting from those grounded in more traditional, rural and agrarian ways of life to those developing into more urban and industrialized ones, but the “social ontology” and cultural forms of “mapping” and communicating about reality were also changing. This study employs a “macro-historical” framework which incorporates complexity and complex system principles to investigate some of the patterns of these highly transformative systemic changes as they impacted Germany and France in particular in the long nineteenth century. These societies are employed in this investigation for two reasons: 1) because they were among that handful of communities that directly participated in the emergence of modernization as a rather explosive and rapidly developing phenomena in that historical moment (whose consequences also included the emergence of new social movements and forms of social structuration as expressed in nationalism and the modern nation-state), and 2) because, as directly neighboring communities, these two illustrate in a microcosm some of the dynamic operations of closely co-existing complex systems themselves. Consideration of the lives and selected literary works of pairs of German and French writers at three different time points in the century grounds the discussion, because these artists are themselves viewed as important innovators who both embodied and expressed signs of the new forms of society and culture that were then emerging. These particular writers (Heinrich von Kleist and Germaine de Staêl; Heinrich Heine and Honoré de Balzac; and Heinrich Mann and Stéphane Mallarmé) are particularly suitable for this study because of their notably protean capacities for vision as well as their positions “on the margins” of their communities which not only afforded them insightful perspectives on the shifting sociocultural landscape but also challenged them to employ their talents to give the latter some novel narrative shape. After an Introduction which outlines much of the theoretical framework for the discussion, chapter one considers Staël and Kleist who expressed creative visions of (potentially) new kinds of social agents and their relationships to (those virtual) societies that were then appearing to be on the verge of emerging after the French Revolution and Napoleonic Wars. The second chapter discusses Heine and Balzac as artists trying to develop new aesthetics in a kind of (implicit) service to their respective German and French communities’ post-war efforts at recuperating and reconfiguring a new “social order” trending towards the “new modern.” And the third chapter considers Mann and Mallarmé, who are viewed as confronting some of the new adaptive challenges in the latter part of the century arising from continued progression of the powerful (and perceptibly impersonal) self-organizing forces of modernization and many Europeans’ disillusionment with (and withdrawal from) them, to which these writers responded with their own creative strategies for trying to actively address these challenges and provoke their contemporaries to do the same. The conclusion reflects upon the value of using a complex systems interpretive lens for understanding the roles and work of such writers, who are regarded via this lens as significant innovators who responded particularly meaningfully to the individual and communal challenges raised by the self-organizing forces operating in their historical moments in the nineteenth century. It also briefly considers the pros and cons of employing such a “holistic” perspective for appreciating such artistic work more generally

Quantification of indirect pathway inhibition by the adenosine A 2a antagonist SYN115 in Parkinson disease

Adenosine A(2a) receptor antagonists reduce symptom severity in Parkinson disease (PD) and animal models. Rodent studies support the hypothesis that A(2a) antagonists produce this benefit by reducing the inhibitory output of the basal ganglia indirect pathway. One way to test this hypothesis in humans is to quantify regional pharmacodynamic responses with cerebral blood flow (CBF) imaging. That approach has also been proposed as a tool to accelerate pharmaceutical dose-finding, but has not yet been applied in humans to drugs in development. We successfully addressed both these aims with a perfusion MRI study of the novel adenosine A(2a) antagonist SYN115. During a randomized, double-blind, placebo-controlled, crossover study in 21 PD patients on levodopa but no agonists, we acquired pulsed arterial spin labeling MRI at the end of each treatment period. SYN115 produced a highly significant decrease in thalamic CBF, consistent with reduced pallidothalamic inhibition via the indirect pathway. Similar decreases occurred in cortical regions whose activity decreases with increased alertness and externally-focused attention, consistent with decreased self-reported sleepiness on SYN115. Remarkably, we also derived quantitative pharmacodynamic parameters from the CBF responses to SYN115. These results suggested that the doses tested were on the low end of the effective dose range, consistent with clinical data reported separately. We conclude that (1) SYN115 enters the brain and exerts dose-dependent regional effects, (2) the most prominent of these effects is consistent with deactivation of the indirect pathway as predicted by preclinical studies; and (3) perfusion MRI can provide rapid, quantitative, clinically relevant dose-finding information for pharmaceutical development

The emotional modulation of cognitive processing: An fMRI study

The functional neuroanatomy of visual processing of surface features of emotionally valenced pictorial stimuli was examined in normal human subjects using functional magnetic resonance imaging (fMRI). Pictorial stimuli were of two types: emotionally negative and neutral pictures. Task performance was slower for the negatively valenced than for the neutral pictures. Significant blood oxygen level dependent (BOLD) increases occurred in the medial and dorsolateral prefrontal cortex, midbrain, substantia innominata, and/or amygdala, and in the posterior cortical visual areas for both stimulus types. Increases were greater for the negatively valenced stimuli. While there was a small but significant BOLD decrease in the subgenual prefrontal cortex, which was larger in response to the negatively valenced pictures, there was an almost complete absence of other decreases prominently seen during the performance of demanding cognitive tasks [Shulman, G. L., Fiez, J. A., Corbetta, M., Buckner, R. L., Miezin, F. M., Raichle, M. E., & Petersen, S. E. (1997). Common blood flow changes across visual tasks: II. Decreases in cerebral cortex. Journal of Cognitive Neuroscience, 9, 648--663]. These results provide evidence that the emotional valence and arousing nature of stimuli used during the performance of an attention-demanding cognitive task are reflected in discernable, quantitative changes in the functional anatomy associated with task performance