Introduction to JINS Special Issue on Human Brain Connectivity in the Modern Era: Relevance to Understanding Health and Disease.

Last year (2015) commemorated the 50th anniversary of Norman Geschwind’s seminal papers in Brain on “Disconnexion syndromes in animals and man” (Geschwind, 1965a, 1965b). In the past 50 years, huge advances have occurred in the tools and technologies available for the in vivo assessment of both structural and functional connectivity in the human brain, including diffusion imaging for examining structural brain connectivity, and functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), and magneto-encephalogram (MEG) approaches to understanding functional brain connectivity. This has led to a dramatic increase in our understanding of the core principles of human brain connectivity and their relationship to cognitive, emotional, motor, and sensory function in health, and more recently, in clinical populations. Facilitated by the availability of novel imaging techniques, this enhanced understanding of brain–behavior relationships reflects a fundamental conceptual shift. Basic and translational research examining task-related brain activation has been remarkably informative in terms of our understanding of the neural substrates of particular cognitive and affective processes and how these may go awry in conditions associated with impaired brain function. However, over time, it has become clear that rarely does any particular cognitive or affective process require only a single brain region, and rarely is any particular form of cognitive or behavioral dysfunction associated with disruption of only a single brain region. Furthermore, basic neuroscience research has long made it clear that activity in any individual brain region (or any individual neuron!) is the result of inputs from and outputs to different areas of the brain. Such realizations have led to a shift in focus on neural circuits rather than on specific brain regions. More specifically, this shift has been to questions about the relationship between and among different brain regions in producing successful cognitive and affective function in health, and the ways in which abnormalities at the level of circuits contribute to the development and maintenance of specific neuropsychological impairments. The growing work on the role of brain oscillations in coordinating activity within and between neutral networks (Canavier, 2015; Ketz, Jensen, & O’Reilly, 2015; Pittman-Polletta, Kocsis, Vijayan,Whittington, &Kopell, 2015; Uhlhaas & Singer, 2015) is consistent with such hypotheses that localize neuropsychological impairments at the circuit level of function rather than within specific individual brain regions. Aimed at highlighting this conceptual shift, this special issue has three specific goals. The first is to provide a brief overview of the current methodological and analytic tools available for understanding both normative and dysfunctional human brain connectivity. As outlined in the article by Lowe and colleagues, and to some extent in the article by Hayes and colleagues, we have seen major advances in our ability to image white matter connections in the human brain, including state-of-the art techniques that now allow researchers to follow the path of white matter connections through areas where many different fiber tracts merge, dramatically improving our ability to understand the structural basis of both short and long range communication within brain circuits. Furthermore, as also described in the article by Lowe and colleagues, the last 30 years have also seen the emergence of methods for studying functional brain connectivity, or the covariance of spontaneous brain activity across brain regions. Originally, the concept of functional connectivity was applied to simultaneous recordings of neuronal spike trains (Gerstein & Perkel, 1969; Gerstein, Perkel, & Subramanian, 1978; Perkel, Gerstein, & Moore, 1967), which are thought to contribute to the functional connectivity observed in humans using non-invasive neuroimaging methods. A main inference of functional connectivity is that, if two regions have highly correlated neuronal activity (i.e., have high functional connectivity), then they are more likely to engage in a common set of processingmechanisms. As such, functional connectivity provides a tool for understanding what brain regions may be communicating while engaging in specific cognitive or affective processes, and therefore what brain circuits support performance and ability in different domains of cognition, emotion and/or social processing. A major breakthrough in the development and application of functional connectivity methods for humans came in 1995, when Biswal and colleagues reported that spontaneous activity