(unchanged from the original version). Reward value integration and selective attention are deeply intersecting processes that interact to inform decisions. However, because of the historical divide between studies on the two processes, the neurobiological mechanisms through which these processes are unclear. This is a significant omission because deficits in decision-making are often accompanied by deficits in attention in humans, suggesting some disturbance in the neural mechanisms common to both processes. Here, we propose a series of experiments that will elucidate those mechanisms. We introduce a behavioral paradigm that can simultaneously measure attention and value during choice. We will determine how value and attention contribute to single-neuron activity in a prefrontal region that has been implicated in attention and decision-making: the frontal eye fields (FEF). Within the FEF, distinct, well-characterized classes of neurons work together to choose visual targets. These classes of neurons reflect different stages in choice formation: they include visual (input) cells, motor (output) cells, and visuomotor cells, which reflect intermediary computations. These cells are distributed across cortical layers, which have known cortical and subcortical connectivity: the various cortical layers themselves reflect input, output, and intermediate, local connections. It is unclear what role value and attention play in these distinct neural classes, layers, and their associated processing stages. Therefore, we will first use high- yield multi-electrode recordings from identified cortical layers to determine which neural classes signal value and attention. Next, we will evaluate and manipulate potential sources of value information for the FEF. First, we will look at a prefrontal executive control and action-value region with strong anatomical connections to the FEF: the dorsal anterior cingulate cortex (dACC). Using simultaneous multi-electrode recordings in both areas, we will examine the temporal relationship between value signals in the two regions. We will also describe the functional connectivity between the regions through examining trial-by-trial signal and noise correlations. We will then determine whether dACC sends value information to the FEF through inactivating dACC and observing its effects on choice formation in the FEF. Finally, we will ask how dopamine (DA) affects value signals in the FEF. We will manipulate dopamine (DA) through local delivery of selective agonists and antagonists while we record from single neurons in the FEF. We will observe the resulting effects on neural activity and on the independent behavioral measures of attention and value. The proposed experiments will elucidate how the prefrontal cortex directs attention towards choice options, weighs the value of potential outcomes, and then integrates those ongoing and overlapping processes into a choice.
/Public Heath Relevance (unchanged from the original version): The proposed research will elucidate the neural mechanisms involved in attentional control and the integration of reward value and enhance our understanding of human mental disorders that involve deficits in both processes, such as attention-deficit hyperactivity disorder (ADHD) and substance abuse. ADHD afflicts about 2-8 percent of people in the U.S., and is one of the most common mental disorders to affect children. Substance abuse affects over 20 million people each year and is a massive public health concern: it has substantial adverse impacts on health, including increased risk for infectious diseases such as HIV and Hepatitis, and cost over $180 billion a year in costs associated with health care, lost productivity, and crime.
| Ebitz, R Becket; Albarran, Eddy; Moore, Tirin (2018) Exploration Disrupts Choice-Predictive Signals and Alters Dynamics in Prefrontal Cortex. Neuron 97:450-461.e9 |
| Ebitz, R Becket; Moore, Tirin (2017) Selective Modulation of the Pupil Light Reflex by Microstimulation of Prefrontal Cortex. J Neurosci 37:5008-5018 |
| Ebitz, R Becket; Hayden, Benjamin Yost (2016) Dorsal anterior cingulate: a Rorschach test for cognitive neuroscience. Nat Neurosci 19:1278-9 |
