The long-term goal of the lab is to understand the neural mechanisms of visual processing early in the cortical pathway. To this end the lab records from rhesus macaque visual cortex using a combination of intrinsic-signal optical imaging and electrophysiology while the animals perform visual tasks. This project derives from earlier work showing that V1 (primary visual cortex) imaging signals in alert, task- engaged macaques have two components. One component is related to stimulation and V1 neuronal activity. The other component - of comparable strength - is a novel task-related signal independent of local spiking. Later work showed that when the animal performs stereotyped tasks, the task-related signal can be removed linearly from stimulus-evoked signals which can then be related with particularly high reliability (>90%) to local spiking. The task-related signal, on the other hand, is strongly modulated by factors such as reward size, task structure and performance, suggesting its role as a form of arousal or attention independent of local spiking. These results were obtained using the support of my last grant. The current proposal is a resubmission of my request for a competitive renewal of the same grant. This current project has two goals that derive from the above observations. The first goal is to generalize the observed link between stimulus-evoked imaging and spiking, as a broad principle for interpreting brain images. This would be valuable for the interpretation of fMRI, one of the most widely used neuroscience research tools. The second goal is to define the factors controlling the task-related signal and the effect of this signal on performance. This goal is expected to provide insights about a novel brain mechanism of attention or arousal, as well as the etiology of attentional disorders such as ADD and ADHD. The novel findings at the base of this proposal were obtained as a result of an imaging technique developed in our laboratory, continuous dual-wavelength intrinsic-signal optical imaging, combined with electrode recordings, in alert behaving macaques. For the imaging, one wavelength, absorbed preferentially in oxygenated hemoglobin, monitors blood oxygenation;the other wavelength, absorbed equally in oxygenated and deoxygenated hemoglobin, measures blood volume. The simultaneous electrode recordings give an electrophysiological measure of the underlying neuronal activity. The continuous recording makes it possible to distinguish between ongoing signals and stimulus-evoked responses. This technique will form the basis of the current project, giving a unique combination of tools to answer the questions at hand.

Public Health Relevance

This project has two implications for public health. We propose to characterize a novel mechanism of brain arousal, thus shedding new light on processes of attention or alertness and their disorders (attention deficit disorder etc.). Further, our work intends establishing a reliable link between neural activity in the brain, and the brain imaging signals recorded using fMRI. As fMRI is the most commonly used means of studying the human brain in clinical or scientific settings, our work has major implications for the correct interpretation of the signals obtained with this critically important medical tool.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Araj, Houmam H
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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Herman, Max Charles; Cardoso, Mariana M B; Lima, Bruss et al. (2017) Simultaneously estimating the task-related and stimulus-evoked components of hemodynamic imaging measurements. Neurophotonics 4:031223
Ma, Ying; Shaik, Mohammed A; Kim, Sharon H et al. (2016) Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches. Philos Trans R Soc Lond B Biol Sci 371:
Chen, Brenda R; Kozberg, Mariel G; Bouchard, Matthew B et al. (2014) A critical role for the vascular endothelium in functional neurovascular coupling in the brain. J Am Heart Assoc 3:e000787
Lima, Bruss; Cardoso, Mariana M B; Sirotin, Yevgeniy B et al. (2014) Stimulus-related neuroimaging in task-engaged subjects is best predicted by concurrent spiking. J Neurosci 34:13878-91
Kozberg, Mariel G; Chen, Brenda R; DeLeo, Sarah E et al. (2013) Resolving the transition from negative to positive blood oxygen level-dependent responses in the developing brain. Proc Natl Acad Sci U S A 110:4380-5
Sirotin, Yevgeniy B; Cardoso, Mariana; Lima, Bruss et al. (2012) Spatial homogeneity and task-synchrony of the trial-related hemodynamic signal. Neuroimage 59:2783-97
Cardoso, Mariana M B; Sirotin, Yevgeniy B; Lima, Bruss et al. (2012) The neuroimaging signal is a linear sum of neurally distinct stimulus- and task-related components. Nat Neurosci 15:1298-306
McCaslin, Addason F H; Chen, Brenda R; Radosevich, Andrew J et al. (2011) In vivo 3D morphology of astrocyte-vasculature interactions in the somatosensory cortex: implications for neurovascular coupling. J Cereb Blood Flow Metab 31:795-806
Das, Aniruddha; Sirotin, Yevgeniy B (2011) What could underlie the trial-related signal? A response to the commentaries by Drs. Kleinschmidt and Muller, and Drs. Handwerker and Bandettini. Neuroimage 55:1413-8; discussion 1419-22
Chen, Brenda R; Bouchard, Matthew B; McCaslin, Addason F H et al. (2011) High-speed vascular dynamics of the hemodynamic response. Neuroimage 54:1021-30

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