Overview: Control of attention by subcortical neuronal circuits We previously demonstrated that the control of spatial attention is not limited to the cortex but also includes the Superior Colliculus (SC), a highly conserved midbrain structure. Last year, we made a major advance by showing that perturbing activity in the SC did not change the response properties of neurons in visual cortex, even though the animal showed major deficits in attention. This dissociation between behavioral deficits and response properties in visual cortex shows that the SC acts through circuits downstream from the well-known sites for attention in visual cortex. We are investigating several possible neuronal mechanisms that could explain how the SC plays a crucial role in attention and yet operates outside the neuronal circuits in visual cortex. Our central hypothesis is that activity in the SC acts to weight the priority of stimuli at different locations. This weighting would be achieved by altering neuronal activity in other brain regions for instance, by enhancing sensory processing of the corresponding visual signals or regulating how these signals are pooled during the formation of perceptual judgments. Our current efforts are aimed at identifying which other brain regions are involved, and how this weighting takes place. Identifying the role of activity in cortical salience maps An important unanswered question is whether the SC acts within the cortex, but at processing stages downstream of MT and MST. Among the candidate cortical areas, the frontal eye fields (FEF) is the most important area to investigate, because of its well-established roles as possible salience maps for the control of attention, its role in representing decision variables during decision-making, and its anatomical connections with the SC and sensory areas involved in motion processing. Dr. Bollimunta is studying this issue by recoding in the FEF of nonhuman primates as they perform an attention task. He has completed training of a nonhuman primate on the task, and collected single-neuron and local field potential data in the FEF. We found that, in addition to the expected sustained changes in activity found with spatial cues, FEF neurons also show transient changes related to shifts of spatial attention and the detection of behaviorally relevant events. These results will be presented at the Annual Society for Neuroscience meeting in November 2013. In the coming year, we will combine these recordings with reversible inactivation of the SC to determine if any of these signals are altered when SC activity is perturbed. Testing how the striatum contributes to attention Another possibility is that the SC acts downstream of the cortex entirely. Of the possible pathways, the strongest candidate is a connection through the thalamus to the striatum, the input stage of the basal ganglia. The basal ganglia have been implicated in a wide range of neuropsychiatric disorders, but have been largely ignored as a site of operation for attention control. Dr. Arcizet has led our effort to examine this possibility by recording from neurons in the caudate nucleus, the part of the striatum that receives a major input from the SC via the thalamus, as well as a large number of inputs from the cortex. After training a nonhuman primate on an attention task, he has recorded from neurons across the caudate and has found neuronal signals related to specific aspects of task performance (e.g., visual stimulation, joystick response). These recordings support the idea that the caudate plays a role in linking the identification of the sensory context with the selection of the appropriate behavioral response. In the coming year, we will complete these recordings in the first animal, and then perform pharmacological manipulations of caudate neurons to test for a causal role in the control of attention. Using fMRI to identify the complete network of areas involved in attention Surprisingly, despite the widespread use of fMRI in humans during attention tasks, there is no fMRI data in monkeys about the set of brain regions showing BOLD signal activation during attention tasks. Working with David Leopold, we will identify the complete network of cortical and subcortical areas involved in the allocation of attention during our attention task. During the past year, Dr. Bogadhi has made substantial progress toward this goal. He has programmed the fMRI control equipment for conducting the experiment, trained a nonhuman primate on an attention task, succeeded in having the NHP perform the task while in the bore of the fMRI magnet, and started to collect fMRI scans from this animal during the attention task. The preliminary results suggest that several subcortical areas may be activated during the attention task, but we are still in the process of refining the data analysis. In the coming year, we expect to obtain complete functional data during the attention task in this NHP, and collect data from a second animal. In addition, we plan to begin experiments combining fMRI with manipulations of activity in the SC, so that we can identify the functional connections that are changed when SC activity is altered. Investigating the role of the SC in attention to color Studies of attention have often used visual motion stimuli, but surprising, attention to color has been much less studied, despite the importance of color to primate vision. I particular, studies of the SC have used visual motion stimuli almost exclusively, leaving open the question of whether the role of the SC in attention generalizes across stimulus features, or might be specialized for moving stimuli. Dr. Herman has led our effort to address this issue. He has designed and conducted behavioral experiments in humans on a color-change attention task, using a novel color stimulus. This work was presented at this years Vision Sciences Society meeting, and is currently being prepared for publication. He has also begun single-neuron recordings in the SC during this attention task. Preliminary data show that the activity of SC neurons is indeed modulated during attention to color, and that they also show remarkably large responses to slight changes in the color of stimuli, especially when they are behaviorally relevant. In the upcoming year, we will complete these recordings in the first animal, and then conduct reversible inactivation of the SC to determine if the SC is necessary for allocation attention to color stimuli. Using mice to investigate the circuitry involved in attention Current studies of sensory-motor functions are most often conducted in non-human primates, in which it is relatively difficult to apply targeted genetic, cellular and molecular manipulations. Consequently, another major effort in the lab is to study sensory decision-making in normal and genetically altered mice, using a combination of psychophysical, physiological, molecular and computational approaches. Dr. Wang is spear heading my labs efforts at establishing the mouse as a model system for investigating the neural mechanisms of spatial attention. During the past year, we have built the apparatus for behavioral studies in mice, conducted physiological recordings in the midbrain of mice, successfully filled and identified individual neurons in mouse brain, and trained mice in behavioral paradigms that we aim to join with physiological and optogenetic studies. In the upcoming year, we aim to extend these approaches to target specific classes of neurons in the caudate nucleus, both for tracing neuronal circuits and for manipulating circuit elements during behavior.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000511-02
Application #
8737670
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2013
Total Cost
$1,418,351
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
Zip Code
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