Noninvasive neuroimaging has become a powerful investigative and diagnostic tool for the study of the brain. It enables simultaneous observation of neural activity in all brain areas. It can be applied to awake behaving human subjects who are engaged in specific tasks. It provides an examination of the brain in a natural condition, and it enables analysis of large-scale patterns. Examination can be made in two primary states, a resting one in which only spontaneous activity occurs and an active one in which neural activity patterns are based on specific behavior or sensory stimulation. Currently, a major limitation in this process is that neural function is not measured directly. It is inferred from hemodynamic measurements. A major improvement in neuroimaging is possible by the establishment of direct connections between hemodynamic measurements and neural function. To do this, it is necessary to establish the neural basis of hemodynamic functional connectivity. Investigations are proposed in the visual system that will contribute toward this goal. We will examine functional connectivity between the lateral geniculate nucleus (LGN) of the thalamus and the visual cortex. We will also measure neurovascular coupling in lamina of the LGN and among cortical layers. Finally, we will study effects of electrical interference on normal neurovascular coupling by the application of electrical stimulation in the form of transcranial magnetic stimulation (TMS). Our first goal is to study neural and hemodynamic functional connectivity in the LGN and visual cortex. To do this, we will utilize sensors positioned simultaneously in LGN and visual cortex or between two areas in visual cortex to study relationships between hemodynamic and neuronal connectivity. Measurements will be made in both a passive resting state and an active condition in which neural activity is stimulated. The second goal is to examine neurovascular coupling across layers within both the thalamus and the visual cortex. The third goal is to apply TMS and measure changes in neurovascular connectivity in the cortico-geniculate pathway. We will also monitor these changes in real time by use of simultaneous TMS and functional magnetic resonance imaging (fMRI) in human subjects. And finally we will examine how altered connectivity from TMS application can constitute a condition of neural plasticity. Together, these studies will have direct application to the use of noninvasive neuroimaging and electrical stimulation techniques for the treatment of clinical disorders.

Public Health Relevance

Studies are planned to examine the primary relationships of neural and hemodynamic systems in the central visual pathway. These investigations will elucidate significant connections between the neural processing of visual information and the associated hemodynamic functions. Results will have direct application to noninvasive neuroimaging and will be relevant to both basic and clinical applications.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Cognitive Neuroscience Study Section (COG)
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Steinmetz, Michael A
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University of California Berkeley
Schools of Optometry/Ophthalmol
United States
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Kim, Taekjun; Freeman, Ralph D (2017) Binocular function during unequal monocular input. Eur J Neurosci 45:601-609
Freeman, Ralph D (2017) 2015 Charles F. Prentice Medal Award Lecture: Neural Organization of Binocular Vision. Optom Vis Sci 94:931-938
Kim, Taekjun; Freeman, Ralph D (2016) Direction selectivity of neurons in the visual cortex is non-linear and lamina-dependent. Eur J Neurosci 43:1389-99
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Li, B; Freeman, R D (2012) Spatial summation of neurometabolic coupling in the central visual pathway. Neuroscience 213:112-21

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