Our Scientists

A major challenge of studying the integrative functions of the nervous system is to understand how complex mental operations emerge from the interaction of distributed sensory and motor representations. To date, the level of detail at which neurobiologists can describe the chain of events giving rise to perceptions, thoughts, memories, and decisions is extremely rudimentary. Indeed, even defining those phenomena in physiological terms is difficult. Our understanding of the root causes of disorders and dysfunctions of the above is likewise limited.

Much of the intense interest in understanding brain function is motivated by the hope that it might be possible to understand complex mental operations at the level of neurons and neural circuits. Research in my laboratory is focused precisely on that problem. Our primary goal is to identify the neural circuits and neural computations that are necessary and sufficient to drive fundamental cognitive functions. One key problem that my laboratory has focused on in recent years is how the nervous system selectively processes sensory input, or how it "pays attention."

Attention is the fundamental cognitive function that allows us to filter out irrelevant sensory information in favor of the relevant. It is an ability that is critical for normal goal-directed behavior. For well over 100 years, philosophers, physicists, neurologists, and psychologists have recognized the broad significance of attention in human perception and behavior. Humans with impaired attention, such as the 4–5 percent of adults and children in the United States with attention-deficit hyperactivity disorder (ADHD), provide a compelling example of the importance attention plays in normal, adaptive behavior. ADHD, which is characterized by a difficulty in "staying focused" and increased distractibility, is an impairment that is particularly disruptive in school-age children. In addition, as a fundamental cognitive function, abnormal attention is often observed in a number of other neurological disorders, such as autism spectrum disorder and Parkinson's disease. Attention is also a key component of the age-related decline in cognitive function observed in human subjects.

Neurophysiological studies have established correlates of selective attention within sensory systems, particularly the visual system of monkeys. These studies demonstrate that the signals conveyed by neurons within visual cortex are not merely determined by the retinal stimulus, but can be modulated according to the deployment of selective attention to behaviorally relevant stimuli. However, these observations provide only a neural correlate of attention; they leave the question of causation completely open, and with little established means of addressing it.

For more than a century, psychologists and neurologists have speculated about a possible role of gaze control mechanisms in driving visual selective attention. The visual and eye movement (oculomotor) systems of the primate brain are in fact highly interconnected. These organized connections include pathways by which visual information can guide eye movements during visual scanning, as well as pathways by which oculomotor preparation can modify incoming visual signals. A key brain structure within the primate brain (both monkeys and humans) where visual and oculomotor signals intermingle is the frontal eye field (FEF), an area within prefrontal cortex. Neurons in the FEF are known to play a role in the programming and triggering of saccadic eye movements (saccades). (Saccades are the frequently occurring, jumpy movements of the eyes that one uses, for instance, to read this text.) Many neurons within the FEF are selective for the amplitude and direction of impending saccades, and throughout the FEF, saccade direction and amplitude is mapped topographically.

Electrical stimulation of sites within the FEF, using currents on the order of microamperes, can elicit saccades of a fixed direction and amplitude. Thus, from a particular fixation starting point, the experimenter can shift a monkey's gaze to another location, depending on the location of the electrode within the FEF. Thus far, work in my laboratory has provided evidence that neurons within the FEF are responsible for shifts in visual attention, in addition to shifts in gaze.

In one experiment, we electrically stimulated sites within the FEF, using currents just below the threshold needed to elicit saccades, to test its effects on a monkey's ability to pay attention to a peripheral visual stimulus. Thus we tested the effect of subthreshold FEF stimulation on the monkey's ability to covertly deploy attention, allowing us to dissociate attention from changes in gaze. Remarkably, we found that FEF stimulation improved the monkey's ability to detect visual events during sustained attention, but only those events occurring at the point in space represented by the stimulation site. This observation provided the first causal evidence of a role of gaze control signals in the filtering of visual information. However, it quickly became crucial to know the impact that electrical stimulation of the FEF has on the visual system. To understand how FEF stimulation influences visual representations, we simultaneously recorded the visual responses of neurons within area V4 of visual cortex during FEF stimulation in monkeys passively viewing visual stimuli (Figure 1). We wished to know whether FEF stimulation is sufficient to produce the modulations in visual responses that many labs have reported during voluntarily directed attention.

These experiments demonstrated that subthreshold stimulation of spatial representations within the FEF altered the gain of visually driven responses in area V4. Specifically, when the receptive fields (RFs) of V4 neurons overlapped with the location to which saccades could be evoked with suprathreshold FEF stimulation, we could increase V4 visual responses. When they did not overlap, we could suppress them. From this and subsequent experiments we found that the effects of FEF stimulation on V4 neuron responses are indistinguishable from the effects observed when an experimenter trains a monkey to pay attention to RF stimuli. The results suggest that the ability of an organism to direct attention to a location in visual space is directly related to that organism's ability to prepare eye movements to that location.

Novel Methods Toward a Neural Circuit Basis of Cognition
There is little doubt that the study of relatively simple nervous systems (i.e., that of invertebrates or rodents) has yielded tremendous insight into the molecular and cellular bases of some fundamental brain functions (e.g., learning and memory). However, it is unclear whether one can extrapolate the "behaviors" exhibited by such model systems to the high-level, cognitive functions, and dysfunctions, exhibited by the human brain. Many of the neurologic and psychiatric disorders that afflict humans (e.g., schizophrenia) are known to involve highly evolved circuits within the human brain (e.g., within the frontal lobes), yet there is a scarcity of sophisticated tools and approaches with which to study those circuits in a more appropriate model organism (e.g., nonhuman primates).

What is clearly needed is the development and deployment of novel tools within a model nervous system that exhibits human-like cognitive functions, and in which those functions can be quantified. A second major goal of my laboratory is to develop and deploy novel methods in nonhuman primates trained to perform high-level cognitive tasks. In particular, we plan to develop new methods to control experimentally the activity of functionally defined neurons within particular circuits or particular classes of neural activity to test their causal roles in cognition.

Grants from the National Institutes of Health provide additional support for this research.

As of May 30, 2012