Dr. Eng. - University of Trieste, Trieste, Italy
Ph.D. - University of Trieste, Trieste, Italy
Clin. Eng. - University of Trieste, Trieste, Italy
Alternate Senator for SO, UAB Senate
Director Computer Module, VSRC
Scientist, UAB Center for the Development of Functional Imaging
Associate Scientist, Vision Science Research Center
UAB Graduate School Faculty
UAB Graduate Biomedical Sciences (GBS) Faculty
UAB Medical Scientist Training Program (MSTP) Faculty
VS141/VS141L “Eye Movements and Principles of Binocular Vision”
This is a first-year professional optometry course on the different types of eye movements and their neural circuitry and the main concepts of binocular vision. The course has laboratory classes where the students can directly experience vestibular, optokinetic, saccadic, smooth pursuit, and vergence oculomotor tasks as subjects, as well as horopter measures and other classical binocularity measures. Course Master.
VIS744 "Ocular Anatomy, Physiology, and Biochemistry"
As part of this graduate course, this is a series of seminars (4hrs) on the anatomy and physiology of the extraocular muscles, which drive the movements of the eyes in the orbit (Course Master Dr. Srivastava).
VIS747 "Central Visual Pathways"
Using the material presented in VIS744 as a starting point, this is a series of seminars and laboratory sessions (10hrs) on the neural and functional aspects of the oculomotor systems (Course Master Dr. Gawne).
BaSCO Lecture with Dr. Rutstein on “Testing of ocular motility: Evaluation of the extraocular muscles” - As part of the BaSCO seminar series, this is a 2 hrs lecture to the first year professional optometry students where I present the extraocular muscles from a basic-scientist point of view, while Dr. Rutstein, as clinician, links the basic science observations to the clinical field and to typical pathologies of oculomotor function. (Course Masters Dr. Norton and Dr. Rutstein)
NEURAL ORGANIZATION OF EYE MOVEMENTS IN DEPTH
(NEI - NIH 1 R01 EY017283 and associated ARRA, and VSRC NEI/NIH Core Grant P30 EY-03039) - The horizontal position of the eyes in the head can be divided into two geometrically independent entities. The first is the version, or horizontal cyclopean angle, which is the average sum of the horizontal angles of the two eyes with respect to the head. The second is the vergence angle, which is the difference of these two angles, i.e., the angle between the two eyes. Any horizontal position of the eyes can be computed as the algebraic sum of those two contributions, with the vergence contribution adding to the cyclopean contribution in one eye and subtracting in the other eye. There is extensive neural and clinical evidence that the primate brain has developed separate mechanisms to control the cyclopean angle of the two eyes (conjugate systems) and the vergence angle (vergence system), preferring this solution to the independent control of the two eyes. In this view, known as Hering's law of equal innervation, both eyes receive the same conjugate and vergence commands, with the eyes always acting as a yoked pair. The outcome of this neural arrangement, from a geometrical point of view, is indistinguishable from each eye rotation being controlled independently. In fact, Hering’s view was recently challenged by the evidence of neural signals that are more consistent with at least partial monocular control of the two eyes.
The first goal of this project is to re-evaluate what "vergence" means in terms of oculomotor commands and develop more realistic models of the vergence system. How much of what we externally record as changes in the angle between the two eyes is actually driven by the vergence system? How much "vergence" is, instead, the result of monocular asymmetric commands independently driving each eye? Furthermore, conjugate and vergence systems, while usually modeled as separate neural systems, are not independent. Another goal of this project is to precisely quantify these crossed interactions and to locate their neural sites in non-human primates by using standard electrophysiological techniques.
Preliminary studies funded by the EyeSight Foundation of Alabama and VSRC NEI/NIH Core Grant P30 EY-03039 on short-term conjugate and disconjugate saccadic adaptation in the macaque monkey have opened a second research path, which will be integrated into the main R01 project:
Human and non-human primates have frontal eyes with a large visual overlap between the images on the two retinae. The primate brain can recognize when images on the two retinae are from the same object and merges them into a single percept: binocular fusion. Double vision, i.e., the inability to fuse the images from the two retinae of the same object due to abnormal binocular eye alignment is perhaps the most common neurological complaint. More than 4% of the US population have abnormal binocular coordination, with the most common cause being strabismus. Binocular coordination is also disrupted in subjects required to wear spectacles with large differences in the magnification factor between the two eyes (anisometropic spectacles) or prisms.
The oculomotor systems, responsible for the movements of the eyes, are highly adaptable, i.e., they develop short-term and long-term changes in their responses when needed. Nonetheless, there are several cases where these compensatory mechanisms fail, strabismus being the most evident. In this 2-year pilot behavioral study in the macaque monkey, by comparing visually-driven vergence/saccadic interaction, conjugate short-term saccadic adaptation, and disconjugate (monocular and symmetric) short-term saccadic adaptation, we obtained key behavioral evidence that these three phenomena are driven by separate neural mechanisms. We plan to record in subcortical saccadic-related and vergence-related neurons in the macaque monkey during these tasks to directly verify these behavioral results and to localize the neural locations of these mechanisms.
The clinical importance of a better understanding of the neural mechanisms of binocular control and adaptation, and in particular the origin of their functional limits, is manifold, from a better understanding of the neurological source of a binocular abnormality to a better management of its treatment. Orthoptics is the clinical field where this knowledge would have the most direct impact, where the patients, mostly children, are asked to wear patches and optical devices to help the brain to adaptively correct for an abnormality in their binocular coordination. This approach is often tried as an initial alternative to a surgery at the level of the extraoculomotor muscles to mechanically obtain a better eye alignment, or during post-surgical rehabilitation.
Macaque monkeys have oculomotor systems which are almost identical to humans and are the preferred animal model for oculomotor studies. They can be trained to perform quite complex videogames reliably and, while functional magnetic resonance imaging is a non-invasive technique used also with humans, the precise quantification of the neuronal substrate can be achieved only with the direct recording with ultra-fine microelectrodes of the electrical activity at the level of the single neuron. This invasive technique can be used, with the exclusion of during human brain surgeries, only in animal models.
FUNCTIONAL MAGNETIC RESONANCE IMAGING OF SUBCORTICAL AND CORTICAL AREAS IN NON-HUMAN PRIMATES DURING SACCADES AND BLINKS
This is a new research area, still at its planning stages. While we were recording the behavior of brainstem saccadic omnipause neurons during saccadic eye movements and blinks as a timing control for the behavioral interpretation of the effects of blinks on ongoing vergence eye movements, we unexpectedly discovered that these neurons stop after the onset of blinks, not before. It was widely accepted that these neurons trigger blinks, and therefore they stop before the onset of the movement, as they do for saccades. This finding has major implications for the understanding of the organization of the blink circuitry and for normal and abnormal blink triggering like blepharospasm. Furthermore, while searching for the facial nucleus, where the orbicularis oculi motoneurons, which drive the upper eyelid downward during blinks, are located, we found a second area, never reported before, that was behaviorally indistinguishable from the facial nucleus. Its function is unknown. Our 4.7 Tesla non-human primate MRI/fMRI system is an ideal tool for the exploration of the organization of the blink circuitry during trigeminal and spontaneous/voluntary blinks, and its relationship to the saccadic oculomotor systems both at the cortical and subcortical level.
Subcortical (cerebellar, midbrain, and brainstem) anatomical and functional magnetic resonance imaging are much more challenging than cortical imaging. This is due 1) to motion artifacts caused by movements of the mouth, tongue, and temporal and neck muscles, even in animals with rigid head posts; 2) the significant pulsating micro-movements of these brain areas caused by the basilar artery and other deep large vessels; and 3) the effects of the large amount of pulsating blood flow in these large vessels on the blood oxygen dependent response (BOLD) itself in the nearby micro-vasculature, the physiological basis of functional MRI. The goal of this pilot study is to develop methodologies to reduce these artifacts in subcortical MRI/fMRI imaging in alert behaving non-human primates by: 1) designing customized saturation-based MRI sequences suppressing the MRI signals coming from the areas originating the motion artifacts; 2) evaluating the feasibility of the technique of cardiac gating, i.e., the acquisition of the MRI images in synchrony with the heart cycle; 3) evaluating the use of surface coils, alone or in association with a decoupled TEM head coil; 4) development of an optimized event-related data analysis to be able to separately analyze trigeminal (elicited with gentle air-puffs) from spontaneous/voluntary blinks. Some of these techniques, although far from optimized, were developed as a one-year pilot study funded by UAB as a Faculty Development Grant. This study will be performed in alert macaque monkeys during air-puff elicited and spontaneous/voluntary blinks and saccades while in the 4.7 Tesla non-human primate 60 cm vertical bore magnet of the UAB Center for the Development of Functional Imaging.
These techniques will also be major tools for future studies of the subcortical areas responsible for binocular coordination. The long-term goal is to apply the same optimized protocols in human oculomotor fMRI studies and then in clinical fMRI of strabismic patients as pre-surgery functional evaluation and in patients with blink disorders.
THE EFFECT OF MILD TO MODERATE SEDATION ON SACCADIC EYE MOVEMENTS IN HUMANS
(PI: Dr. Michael A Froelich NIH-NCRR K23 RR021874 and GCRC M01RR-00032)
The function of the saccadic eye movements is to redirect the eyes from one element in the visual scene to another as fast as possible. Part of the saccadic circuitry is located in the brainstem and sedation is known to suppress brainstem activity. Not surprisingly, there is preliminary evidence in the literature that the level of sedation, by changing the level of brainstem activity, affects the latency and dynamics of saccades in a dose-dependent relationship. This study, in normal human volunteers, is evaluating the effects of propofol, midazolam, and dexmedetomidine, on the saccadic system. The main goal of the project is to determine if there is a clinically relevant correlation between the level of sedation and saccadic responses and if this methodology can be used as an objective quantitative method to determine the level of sedation of the patient as an alternative to classical pain level measures. Our laboratory has developed an integrated mobile human oculomotor station for this project and is responsible for the development of the acquisition and analysis software, the recording of the oculomotor data, and the quantification of the results. Dr. Froelich, Associated Professor and Clinician Scientist of the Department of Anesthesiology of UAB is responsible for the clinical aspects of the study.
INFANT APHAKIA TREATMENT STUDY (IATS)
The Infant Aphakia Treatment Study (IATS) is a multi-center clinical trial supported by NEI. The PI for this study is Dr. Scott Lambert of Emory University. Dr. Hartmann, of the UAB School of Optometry, is responsible for development of the testing protocol and for acquisition of the primary outcome data for this project. The initial IATS was a randomized clinical trial for infants between the ages of 4 weeks and 7 months who were born with a cataract in one eye. Several ocular, visual, and behavioral tests continued to be performed on these children on a regular basis. Two treatments types are being studied: 1) Cataract removal with a contact lens correction on the aphakic eye; 2) Cataract removal with a replacement intra-ocular lens placed inside the eye for correction (pseudo-phakia). Both groups of patients were prescribed patching therapy for the prevention of amblyopia. The first children of the study are now around 4-5 years old, and the study received funds to study them for another 5 years. My part of the project is to analyze their oculomotor fixation capabilities at 4.5 years of age to see if and how their ability to fixate visual targets affects their visual and behavioral function. To do so, we developed a travelling oculomotor laboratory that can be fitted in two large suitcases and is acceptable for air travel to the recording sites. The eyes of the child are acquired by an IR camera at 400 frames/s for 7 seconds with a 1280x1024 pixel resolution while the child is looking monocularly at one of 6 possible targets with the operated or the non-operated eye. The patch we use is an infrared filter, and therefore transparent for the camera, allowing also the recording of the position of the patched eye. For more information on the IATS project click here.