Showing papers by "Susan L. Santangelo published in 2016"

Brain and Cognition in the “Omics” Era

Abstract: The developments of phenomics, connectomics, and Research Domain Criteria (RDoC) set forth in the introductory chapter are given expanded review in this chapter. The strategy of phenomics is laid out with particular reference to the influences of genetic studies—both candidate gene and genome-wide association studies. How current developments in genomics are serving the alignment of gene networks with phenotypic elements is also described. Connectomics is laid out through its two main prongs—cellular-level or microscale connectomics carried out through automated electron microscopy, and macroscale connectomics or white matter tractography, via functional imaging. Circuit neurophenotypes, from the perspective of connectomics, are also delineated. The RDoC initiative and related developments are described in terms of their rationale and approach, and attention is given to RDoC’s emphasis on the neural circuit as the central level around which a brain-based nosology of mental disorders may be constructed. This chapter elaborates on each of these developments while also bringing forth some perspectives of neural circuitry, a topic that is the focus in the following chapters.

Conclusion: Implications for Psychiatry and Neuropsychology

Abstract: The theme of this volume that psychiatry and neuropsychology be systematically aligned with the neurophenotype approach in order to facilitate a systems-level understanding of brain–behavior relationships is reiterated across chapters. This chapter outlines a few conceptual and programmatic adjustments that these disciplines must undertake in order to promote that goal. Firstly, this chapter argues that the historically influential endophenotype concept must be constrained that it has been applied by default to cognitive and neural markers without adequate consideration of the host of variables that modulate neural systems tied to cognition. In this regard, it is also argued that the broader neurophenotype concept has greater utility. Secondly, the need for refinement of cognitive and behavioral constructs is stressed; how ontologies for cognitive and neural processes serve this end is discussed. Thirdly, the imperative that psychiatry and neuropsychology adopt data formats that facilitate data integration in genome–phenome mapping systems is emphasized. And to illustrate the point, a few pioneering examples of knowledge discovery and neuroinformatics platforms that relate to these disciplines are described.

Appraising Circuit-Centered Neurophenotypes

Abstract: This chapter provides a critical appraisal of the concept of a circuit-centered neurophenotype that is conceptualized within a genome-to-phenome framework. Representing many of the kinds of variables that complicate this model are a few select ones that are sampled in this chapter. They include the following: (a) The problem of minimal circuit definition—the many scales of neural circuitry and the difficulty of demarcating circuits within some forms of neural architecture; (b) the modulation of neural circuits and the alterations of circuit architecture through non-gene-regulated factors such as synaptic plasticity, extra-synaptic neuromodulation, and bioelectric dynamics; and (c) technical and methodological considerations in circuit delineation—as is coming to light in the field of microscale connectomics. Adding these complex variables from neuroscience into the fray make for great attenuation of the notion of a circuit neurophenotype in the behavioral neurosciences, and this is given some depth of coverage in this chapter. However, the chapter does not dismiss the utility of the concept of circuit neurophenotypes. It concludes with a discussion of the kinds of additional information that may be needed in order for the concept to be better validated.

Introduction and Structure of the Volume

Abstract: This introductory chapter provides a summary description of key developments in the neurosciences and biomedical sciences that have compelled the topic of the volume—neural and cognitive markers. The emergence of “omics” disciplines is described—where large or complex data sets are deciphered with bioinformatics methods in a systems biology framework. The developments of phenomics in the context of genome-to-phenome mapping, connectomics in neuroscience, and Research Domain Criteria in psychiatry are then staged, as is the current research-scientific environment, characterized by data repositories and knowledge discovery systems. The central point converged upon is that the impact of systems biology necessitates that the clinical and behavioral neurosciences delineate cognitive and neural systems in a manner that can be integrated with broader scientific frameworks. This chapter also explains the volume’s adoption of the umbrella term “neurophenotype” and provides an operating definition of the term. The two-part structure of the volume is then laid out with the topic of each chapter summarized.