Modeling mothering: the development of an experimental system in neurobiology.

This article explores the development of a rat model of mother-infant relationships from its origins in the psychosomatic investigations of the mid-1960s to its elaboration into a theoretical system in neurobiology. I reconstruct the research trajectory of a group of neurobiologists in the United States, with a focus on the experimental practices they adopted while building this animal model. Providing a microhistory of this decade-long undertaking, I show that what drove the development of the model in practice was a serendipitous finding about infants' response to maternal separation. Detected inadvertently, the pup's separation response acquired an epistemic significance of its own and reoriented the experimental system towards unanticipated paths. To explain this intriguing phenomenon, the neurobiologists kept on refining their material manipulations and stabilizing their experimental outcomes. They thus established a series of causal relationships that connected dysregulations of the infant's physiological systems to disruptions in maternal care. As important as this interactive stabilization of technique and objects in the laboratory was how the researchers theorized the network of relationships derived from this technically constituted objectivity. Highlighting the practice-driven aspects of model-building, I demonstrate that what facilitated this theoretical process was an integrated design of complementary experiments. The outcome of each separate experiment of the research program came to bear upon the outcomes of other experiments, informing the development of future manipulations. It was this strategically driven integration process that allowed the experimenters to build expanding networks of causal relationships and consolidate them into a neurobiological theory.

[The psychopathology of the Wernicke-Kleist-Leonhard School and its relevance for present-day psychiatry]. / Die Psychopathologie der Wernicke-Kleist-Leonhard Schule und ihre Bedeutung für die aktuelle Psychiatrie.

Historically, the Wernicke-Kleist-Leonhard School represents a countermovement to psychopathology as described by Karl Jaspers and Kurt Schneider. The School aimed to interlink psychopathological and neurobiological aspects. Starting from the model of different functional neuronal systems, each of which can be disturbed in the sense of a hypofunction, hyperfunction, or parafunction, it developed a comprehensive phenomenology of psychopathological symptoms and syndromes that finally culminated in Karl Leonhard's course descriptions. This school of thought can provide important impulses even today. Thus, on the one hand, the neurobiological models can serve as the basis for additional research projects and on the other hand, the psychopathological descriptions of disorders can perhaps also be interpreted in the sense of typological constructs that can contribute to pragmatic clinical decisionmaking.

The neurobiology of psychopathy: recent developments and new directions in research and treatment.

Psychopathic individuals account for substantial predatory and impulsive violence. To the present, the principal intervention used to decrease the harm inflicted by psychopaths has been confinement. Nevertheless, most confined psychopathic persons return to the community. Recent advances in the understanding of the neurobiology of psychopathy hold promise for new research directions and more effective treatments. In this article, we will explore recent advances in genetics, electrophysiology, brain imaging, and psychopharmacology, as well as, in brief, their implications for new directions in research and treatment.

The neurobiology of thought: the groundbreaking discoveries of Patricia Goldman-Rakic 1937-2003.

Patricia S. Goldman-Rakic (1937-2003) transformed the study of the prefrontal cortex (PFC) and the neural basis of mental representation, the basic building block of abstract thought. Her pioneering research first identified the dorsolateral PFC (dlPFC) region essential for spatial working memory, and the extensive circuits of spatial cognition. She discovered the cellular basis of working memory, illuminating the dlPFC microcircuitry underlying spatially tuned, persistent firing, whereby precise information can be held "in mind": persistent firing arises from recurrent excitation within glutamatergic pyramidal cell circuits in deep layer III, while tuning arises from GABAergic lateral inhibition. She was the first to discover that dopamine is essential for dlPFC function, particularly through D1 receptor actions. She applied a host of technical approaches, providing a new paradigm for scientific inquiry. Goldman-Rakic's work has allowed the perplexing complexities of mental illness to begun to be understood at the cellular level, including atrophy of the dlPFC microcircuits subserving mental representation. She correctly predicted that impairments in dlPFC working memory activity would contribute to thought disorder, a cardinal symptom of schizophrenia. Ten years following her death, we look back to see how she inspired an entire field, fundamentally changing our view of cognition and cognitive disorders.

Historical postmortem studies on catatonia: Close reading and analysis of Kahlbaum's cases and scientific texts between 1800 and 1900.

In the 19th century, postmortem brain examination played a central role in the search for the neurobiological origin of psychiatric and neurological disorders. During that time, psychiatrists, neurologists, and neuropathologists examined autopsied brains from catatonic patients and postulated that catatonia is an organic brain disease. In line with this development, human postmortem studies of the 19th century became increasingly important in the conception of catatonia and might be seen as precursors of modern neuroscience. In this report, we closely examined autopsy reports of eleven catatonia patients of Karl Ludwig Kahlbaum. Further, we performed a close reading and analysis of previously (systematically) identified historical German and English texts between 1800 and 1900 for autopsy reports of catatonia patients. Two main findings emerged: (i) Kahlbaum's most important finding in catatonia patients was the opacity of the arachnoid; (ii) historical human postmortem studies of catatonia patients postulated a number of neuroanatomical abnormalities such as cerebral enlargement or atrophy, anemia, inflammation, suppuration, serous effusion, or dropsy as well as alterations of brain blood vessels such as rupture, distension or ossification in the pathogenesis of catatonia. However, the exact localization has often been missing or inaccurate, probably due to the lack of standardized subdivision/nomenclature of the respective brain areas. Nevertheless, Kahlbaum's 11 autopsy reports and the identified neuropathological studies between 1800 and 1900 made important discoveries, which still have the potential to inform and bolster modern neuroscientific research in catatonia.

Christfried Jakob's late views (1930-1949) on the psychogenetic function of the cerebral cortex and its localization: culmination of the neurophilosophical thought of a keen brain observer.

This article follows the culmination of the scientific thought of the neurobiologist Christfried Jakob (1866-1956) during the later part of his career, based on publications from 1930 to 1949, when he was between 64 and 83 years of age. Jakob emphasized the necessity of bridging philosophy to the biological sciences, neurobiology in particular. Thus, we consider him as one of the early protagonists in the emergence of neurophilosophy in the 20th century. The topics that occupied his mind were the foundations for a future philosophy of the brain, and the 'neurobiogenetic', 'neurodynamic', and 'neuropsychogenetic' problems in relation to how consciousness emerges. Jakob's views have many elements in common with great thinkers of philosophy and psychology, including Immanuel Kant, William James, Edmund Husserl, Henri Bergson, Jean Piaget and Willard Quine. A common denominator can also be discerned between Jakob's dynamic approach and certain aspects of cybernetics and neurophenomenology. Jakob propounded the interdisciplinarity of sciences as an indispensable tool for ultimately solving the enigma of consciousness.

MicroRNA in central nervous system trauma and degenerative disorders.

MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that negatively regulate gene expression at the posttranscriptional level by binding to the 3'-untranslated region of target mRNAs leading to their translational inhibition or sometimes degradation. MiRNAs are predicted to control the activity of at least 20-30% of human protein-coding genes. Recent studies have demonstrated that miRNAs are highly expressed in the central nervous system (CNS) including the brain and spinal cord. Although we are currently in the initial stages of understanding how this novel class of gene regulators is involved in neurological biological functions, a growing body of exciting evidence suggests that miRNAs are important regulators of diverse biological processes such as cell differentiation, growth, proliferation, and apoptosis. Moreover, miRNAs are key modulators of both CNS development and plasticity. Some miRNAs have been implicated in several neurological disorders such as traumatic CNS injuries and neurodegenerative diseases. Recently, several studies suggested the possibility of miRNA involvement in neurodegeneration. Identifying the roles of miRNAs and their target genes and signaling pathways in neurological disorders will be critical for future research. miRNAs may represent a new layer of regulators for neurobiology and a novel class of therapeutic targets for neurological diseases.