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In regions of the visual cortex, the interactions between neurons have a particular spatial and temporal structure. This structure is dependent on the distance between neurons, the response properties of the neurons, the cortical layer in which they reside, and the behavioral state of the animal. Smith seeks to characterize the functional connectivity among neurons and understand how changes in that pattern are related to visual perception and cognition. Smith has primarily focused this work on the primary visual cortex (V1) and visual area V4, using implanted 100-electrode "Utah" arrays to record neural activity.

The Smith lab uses neurophysiological and computational approaches to study the primate visual system, with the aim of understanding how our visual perception of the world is constructed from the activity of populations of neurons. Smith’s research has revealed that measurement of the local circuitry in the visual cortex is critical for an understanding of the building blocks of visual processing, both within and across brain regions. Smith is currently exploring a number of questions, including: how interactions between cortical regions influence neural populations, such as feedback from prefrontal areas to the visual cortex; how functional connections among neurons are modulated by the animal's task, such as planning a saccade to different regions of the visual field; how information flow among neurons is altered within and between cortical lamina based on cognitive demands; how cortical circuitry is altered with abnormal visual experience (such as in amblyopia or glaucoma); and how a better understanding of cortical circuitry might lay the foundation for cortical visual prosthetic devices.