Eye Movement & Visual Selection

National Eye Institute

Investigators

Linked publications, trials & patents

Abstract

Introduction The selection of relevant sensory signals and generation of appropriate actions are fundamental functions of the primate brain. Disruptions of these functions are implicated in a variety of disorders, including attention deficit hyperactivity disorder (ADHD) and autism. Scientists in my section investigate the neuronal circuits involved in this visual function using a range of techniques, in both non-human primates and mice, in order to understand how these neuronal circuits operate under normal conditions and to identify how breakdowns in these mechanisms cause disorders of sensory-motor coordination. Standard models of visual attention emphasize the role of the cerebral cortex. In contrast, our results demonstrate that higher-order functions like selective attention are built on top of conserved subcortical circuits in the superior colliculus (SC), thalamus and basal ganglia, that play a central role in action selection. Our aims are to understand the operation of the subcortical structures and how they interact with the cortex, with the long-term goal of identifying the detailed neuronal circuit so that more specific therapeutic interventions can be developed. 1) Neuronal circuits for the control of selective attention in primates Most of our work is done using non-human primates, whose close homology with humans makes them the best animal model of human visual attention. 1a) Activity in the midbrain plays a crucial role in shaping high-level visual properties in the primate temporal cortex We recently identified an unexpected link between the evolutionarily conserved structure in the midbrain, the superior colliculus, and a specific region of the temporal cortex that had previously been relatively unexamined. By combing fMRI mapping with reversible in activation of the superior colliculus during tasks that probe visual attention, we identified a novel region in the superior temporal sulcus (STS) with attention-related modulation that is especially depending on activity from the superior colliculus. Now we have targeted this new cortical region for neuronal recordings, and tested how the signals process in this region depend on inputs from the midbrain. Our results, published earlier this year in Neuron, show that several high-level aspects of visual processing are significantly attenuated when activity in the superior colliculus is transiently suppressed. These aspects of visual processing include not only the traditional modulation of activity by attention, but also the ability to detect relevant events and, more surprisingly, the ability of these cortical neurons to process object-related information. Our results reveal an unexpected dependence of higher-order visual processing on inputs from deep brain structures and suggest that this circuit is important for prioritizing the cortical processing of visual events that are detected through subcortical activity. These results are relevant for understanding how higher-order vision, including the recognition of objects, develops and depends on more basic signals from the midbrain. 1b) Activity from the midbrain also is necessary for effects of spatial attention in the basal ganglia One of our main hypotheses is that signal processing through the basal ganglia plays a central role in the control of visual selection attention, and that it does so by regulating the level of commitment to use particular signals based on the current behavioral context. To test this idea, we recorded in the caudate nucleus of the basal ganglia during a visual attention task, both before and during reversible inactivation of the superior colliculus. We previously showed that reversible inactivation of the superior colliculus causes major spatially specific deficits in visual attention. Thus, this combination of reversible deficits and neuronal recordings allowed us to determine whether the loss of attention-related process also involved signals through the basal ganglia. Our results, published this past year in eLife, showed that the spatial preferences in the basal ganglia shifted in ways that matched the spatially specific deficits in attention task performance. These results expand our understanding of the neuronal mechanisms of visual attention by providing causal evidence that signals processed through the basal ganglia are implicated in the allocation of spatial attention. These results are of broad importance, because the basal ganglia are also a major site for experience-dependent learning and the utilization of dopamine signaling, and thus opens up novel avenues for addressing the very common deficits of attention experienced in humans. 2) Role of subcortical neuronal circuits in visual detection and attention in mice Mice provide opportunities to work out the details of neuronal circuits in ways that are not yet possible in nonhuman primates and will help us identify worthwhile genetic and molecular targets in primates. 2a) Optogenetic manipulation of basal ganglia pathways in mice Building on our results in monkeys, we were able to use the circuit-specific manipulations possible in mice to perform causal tests of how signal processing through the basal ganglia might contribute to visual attention. We predicted that manipulation of basal ganglia circuits should reveal effects related to the subjects allocation of spatial attention. Specifically, we used optogenetic activation of neurons in the striatum that are part of a circuit referred to the direct pathway, which are believed to increase the level of commitment to a particular outcome or proposition. Our hypothesis is that attending to one side of space is akin to accepting the proposition that that side of space is behaviorally relevant. Indeed, we found that targeted activation of the direct pathway systematically altered the animals ability to perform the task, and the effects were specific to the cases when attention was allocated to the visual signals targed by the optogenetic manipulation. These results were published in Current Biology and provide strong causal evidence that circuits through the basal ganglia play a major role in the brain mechanisms of visual attention. Moreover, these experiments establish how we can target specific neuron classes and identify functional links between particular neurons and circuit elements to attention performance in mice, using techniques that are not yet available in non-human primates.