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, T; Freeman, R D (2014) Selective stimulation of neurons in visual cortex enables segregation of slow and fast connections. Neuroscience 274:170-86
Moore 4th, Bartlett D; Rathbun, Daniel L; Usrey, W Martin et al. (2014) Spatiotemporal flow of information in the early visual pathway. Eur J Neurosci 39:593-601
Li, B; Freeman, R D (2013) Binocular activation elicits differences in neurometabolic coupling in visual cortex. Neuroscience 248C:529-540
Moore 4th, Bartlett D; Freeman, Ralph D (2012) Development of orientation tuning in simple cells of primary visual cortex. J Neurophysiol 107:2506-16
Li, B; Freeman, R D (2012) Spatial summation of neurometabolic coupling in the central visual pathway. Neuroscience 213:112-21
Duong, Thang; Moore 4th, Bartlett D; Freeman, Ralph D (2011) Adaptation changes stereoscopic depth selectivity in visual cortex. J Neurosci 31:12198-207
Li, Baowang; Freeman, Ralph D (2011) Neurometabolic coupling differs for suppression within and beyond the classical receptive field in visual cortex. J Physiol 589:3175-90
Li, Baowang; Freeman, Ralph D (2010) Neurometabolic coupling in the lateral geniculate nucleus changes with extended age. J Neurophysiol 104:414-25
Qian, Ning; Freeman, Ralph D (2009) Pulfrich phenomena are coded effectively by a joint motion-disparity process. J Vis 9:24.1-16
Pasley, Brian N; Allen, Elena A; Freeman, Ralph D (2009) State-dependent variability of neuronal responses to transcranial magnetic stimulation of the visual cortex. Neuron 62:291-303

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