Keep your eyes on the target
How can I choose to write these words at this moment and make my fingers strike the correct keys in the right sequence? How do my eyes simultaneously scan for errors? How do your eyes move across the page? Did you just glance at the clock? How did you know exactly where to look? How did you coordinate exactly the right movement of the eyes and the right movement of the head to accurately see that there is time to read on? I’m asking these questions to remind us of the amazing capabilities that we have and to point out that my field – neuroscience – still doesn’t have all the answers for even everyday (I won’t say “simple”) behaviors. What we do have is an enormous amount of working knowledge, which Whitman students and I are using to complete the picture of how this neural system works and also approach the next driving question – how do we fix it?
The question of how the brain works was enough to make me leave coral reef fish research in the Caribbean to study the neurobiology of eye movements with Dr. Albert Fuchs, a foremost oculomotor (i.e., eye movement) neurophysiologist at the University of Washington. The premise for studying this model system is straightforward: not only will revelations improve our knowledge of one of our most important behaviors (moving the eyes is critical since much of our behavior is visually guided), but, if we can understand how the brain controls eye movements like those used during reading (i.e., saccades), we can build an understanding of how the more complex movements of piano playing and soccer bicycle kicks might be controlled.
It’s a solid premise that has paid off. Most of what we know about how neurons, circuits and regions of the brain that control movement has come from leading labs like the Fuchs lab. One type of primate eye movement, saccades – rapid, accurate, high-velocity eye movements that shift one’s focus from point to point – involves neurons across all major regions of the brain and functional hierarchy (e.g., can be voluntary and involve higher cortical functions, e.g., for saccades made to remembered locations).
Because the control of saccades has been nearly completely characterized by several labs across the 45-year span of Albert’s research, I was able to extend this knowledge by examining eye saccades combined with rapid head shifts while recording the electrical activity of individual neurons. This was the next obvious step, because – like eye movements – head movements are much more amenable to study than multi-joint, multi-muscle, load-bearing limb or finger movements.
The EyeSeeCam records where the eyes look as they dart back and forth to focus on various points. Two cameras monitor the eyes’ locations, one camera records the scene in front of the subject and the GazeCam (the white camera at left in photo) moves with the eyes to record exactly what the eyes are seeing.
At Whitman, I extended our results with extensive characterization of how these neurons behave when an eye saccade is combined with a rapid head movement (e.g., that quick combined eye-head gaze shift across the room at the clock). I’ve published these results – including the first description of how individual cortical (think voluntary, cognitive control) neurons participate in coordinated movements of the eyes and head – in leading neuroscience journals and have recently started to look in a slightly different direction.
I have continued my research at Whitman and have offered our students approachable, yet unique, opportunities to explore coordinated movement behavior and its underlying neural circuitry. In 2008, my students and I started using functional neuroanatomical methods to demonstrate that mice have neural architecture underlying eye and head movements that is similar to primates. In 2011, I was able to complement this approach by adding the ability to examine human eye-head coordination using the EyeSeeCam, funded by my 2010 Murdock Charitable Trust Life Science Research Grant and generous matching funds from Whitman College. Our EyeSeeCam – one of three in the world (developed by my collaborators at the University of Munich) – is a new, portable “eye-tracker,” or videooculography device, which uses miniature video cameras to record the movement of a person’s eyes and accelerometers to measure head movement. The unique feature of our EyeSeeCam is the “gaze-cam” – a motorized miniature video camera that quickly moves in relation to the subject’s eye movements to film what the subject is viewing. Using the EyeSeeCam, my students, Peter Osseward ’12 and Whitney Griggs ’13, were able to quickly corroborate and extend results of a landmark study with a much greater number of subjects, volume of data and new results. (They presented their results at the 2011 Murdock College Science Research Program Conference.) This necessary first step paved the way for us to now use the EyeSeeCam for translational research – extending basic science to application for the improvement of patients.
How do we fix it?
Recent research applying basic oculomotor knowledge has shown that people with neurodegenerative diseases (e.g., Parkinson’s, PD) or mild-head injuries (MHI, e.g., concussions) exhibit impairment of saccades even though conventional neurological, neuropsychological and diagnostic imaging (e.g., MRI) examinations suggest an absence of disease. The same factors that make saccades a model system for research — that they can be quantified with great precision and that their programming involves multiple circuits across the brain — make them an excellent “early warning” indicator of compromised brain function. That is, years before a PD patient may show full onset of hallmark manifestations (e.g., difficulty walking), her saccades begin to slow, reaction times lengthen, and accuracy declines.
The EyeSeeCam records each eye’s position in real time by tracking the pupil (indicated by the ellipse inside the white square) and corneal (the surface of the eye) reflection in the high-speed video recording of each eye.
To better enable early intervention, I plan to use measurements of combined eye-head gaze shifts to provide early detection of movement and cognitive impairments. Because the coordination of voluntary, combined eye-head gaze shifts is more dependent upon frontal cortex function than saccades, examination of eye-head gaze shifts may be even better at revealing movement and early-stage cognitive dysfunction. Very few studies have begun investigating the effect of neural impairment on eye-head coordination, and this is where we hope to make a difference with our EyeSeeCam at Whitman.
Because detection depends on being able to compare eye-head coordination strategies of compromised subjects to those of healthy adult subjects, we have been working to solve the challenge of determining universal rules of human eye-head gaze shift coordination. To date, no one has found universals, because individuals have varying strategies, ranging from those who are predominantly “eye movers” to those who are “head movers.” For his 2012 Perry Summer Research Scholarship and thesis, Whitney began this work by manipulating a parameter thought to be critical to the mechanism of coordination of eye-head gaze shifts. He has found that this noninvasive manipulation has eliminated variability between subjects, perhaps giving us a universal rule. This has important implications for basic research, but we are even more excited that we now have a standardized way to identify dysfunctional strategies of coordination in patients.
In Fall 2012, I submitted a second Murdock grant proposal to fund two more years of investigation of eye-head gaze shifts in those at risk for mild head injury and neurodegenerative movement disorders. Whitney and I (supported by an Abshire Research Scholar Award), and with guidance from Walla Walla neurologist, Dr. Ken Isaacs, MD, have begun our preparations for this exciting new work. It dovetails wonderfully with an experimental mouse model of PD that Dr. Leena Knight and I are developing with collaborators at the University of Washington Department of Psychiatry and Behavioral Science and the Veterans Administration Puget Sound Health Care System. These two approaches, conducted in collaboration with Whitman students, will be mutually reinforcing and help us gain ground on PD mechanisms and detection.
Across my first sabbatical, I began learning more about the risk and effects of MHI in athletes (consider recent reports of brain damage in NFL players), and I believe that work with the EyeSeeCam will help to improve recovery from MHI-caused impairment. In collaboration with John Eckel, Whitman’s head athletic trainer, we will begin testing Whitman varsity athletes at risk for MHI in summer 2013. The objective of this work will be to determine whether subtle changes in eye-head gaze shifts occur when student athletes have suffered an MHI. More importantly, since subsequent exposure before full recovery can complicate outcomes, we intend to develop an approach for determining when an athlete has recovered sufficiently to return to sport. This would be the first diagnostic of its kind and may provide a systematic means of preventing permanent damage.
The most fascinating lesson I experienced when I started in research was how small, detailed observations, collected to test modest hypotheses, can be assembled to solve major challenges and result in a surprisingly large impact . I am very excited about the direction my research is taking and am hopeful that it will help our students experience for themselves how they, through small, careful steps, might contribute to major shifts in understanding. Keep your eyes on our progress.