Neural circuits can bridge systems and cognitive neuroscience

Abstract

There has been an emerging focus in neuroscience research on circuit-level interaction between multiple brain regions and behavior. This broad circuit-level approach creates a unique opportunity for convergence and collaboration between studies of humans and animal models of cognition. Measurement of broad-scale brain networks may be particularly important for understanding changes that occur in brain organization and function during development. Recent studies in humans have gained much leverage from trying to understand circuit-level interactions among brain regions over the course of development. Such studies use connectivity analyses of functional magnetic resonance imaging both during cognitive activity and during rest (fcMRI), and diffusion tensor imaging (DTI) to measure (respectively) the functional and structural connectivity between discrete brain regions (e.g. Rissman et al., 2004; Snook et al., 2005; Mori and Zhang, 2006; Fox and Raichle, 2007). Studies using these approaches have revealed that, over the course of development, functional connectivity increases between distant brain regions (in the rostro-caudal axis) while it decreases between local regions of the frontal, parietal, and cingulate cortex (Fair et al., 2008). Developmental trajectories may be altered in diseased brains (e.g., Church et al., 2009), and functional and structural differences in connectivity may reflect individual differences in cognitive abilities (e.g., Niogi and McCandliss, 2006; Seeley et al., 2007; also see reviews this issue). These findings emphasize the importance of understanding the development of associative neural circuits. Going forward, a key challenge will be to gain an understanding of what these circuits do during development at multiple levels of analysis, from cellular mechanism to cognitive function. Currently, the cellular and synaptic basis of changes in functional connectivity and DTI imaging remain unclear. Are these changes due to myelination, novel growth, elaboration or pruning of new connections? What happens when development is altered or connections are silenced? Understanding the mechanistic basis of connectivity changes in humans, and how these changes relate to changes in behavior, is challenging and may benefit greatly from animal models. We propose that an emerging focus on broad-scale neural circuits provides a unique opportunity for collaborative studies that bridge research in mice and humans. New research methods and technology targeting neural circuits in both human and mouse neuroscience labs have great potential for enhancing overlap and collaboration between these two scientific cultures. Furthermore, many of the cognitive paradigms in humans draw from, or have parallels in, the animal conditioning literature, such as reward prediction, reversal learning, relational memory, rule extraction, and set shifting. This overlap in behavioral paradigms and cognitive domains suggests the promise of integrating a circuit-level understanding of cognitive development across species. To facilitate such collaborations, there is a need for researchers to communicate across technical and cultural boundaries. Communication and education in the research possibilities available to each sub-field will also facilitate the opportunity for researchers on both sides to make explicit predictions that can be tested in the most appropriate species, advancing research progress on common questions.