Control mechanisms in the human binocular oculomotor system

A study of human eye movements was made in order to elucidate the nature of the control mechanism in the binocular oculomotor system.

We first examined spontaneous eye movements during monocular and binocular fixation in order to determine the corrective roles of flicks and drifts. It was found that both types of motion correct fixational errors, although flicks are somewhat more active in this respect. Vergence error is a stimulus for correction by drifts but not by flicks, while binocular vertical discrepancy of the visual axes does not trigger corrective movements.

Second, we investigated the non-linearities of the oculomotor system by examining the eye movement responses to point targets moving in two dimensions in a subjectively unpredictable manner. Such motions consisted of hand-limited Gaussian random motion and also of the sum of several non-integrally related sinusoids. We found that there is no direct relationship between the phase and the gain of the oculomotor system. Delay of eye movements relative to target motion is determined by the necessity of generating a minimum afferent (input) signal at the retina in order to trigger corrective eye movements. The amplitude of the response is a function of the biological constraints of the efferent (output) portion of the system: for target motions of narrow bandwidth, the system responds preferentially to the highest frequency; for large bandwidth motions, the system distributes the available energy equally over all frequencies. Third, the power spectra of spontaneous eye movements were compared with the spectra of tracking eye movements for Gaussian random target motions of varying bandwidths. It was found that there is essentially no difference among the various curves. The oculomotor system tracks a target, not by increasing the mean rate of impulses along the motoneurons of the extra-ocular muscles, but rather by coordinating those spontaneous impulses which propagate along the motoneurons during stationary fixation. Thus, the system operates at full output at all times.

Fourth, we examined the relative magnitude and phase of motions of the left and the right visual axes during monocular and binocular viewing. We found that the two visual axes move vertically in perfect synchronization at all frequencies for any viewing condition. This is not true for horizontal motions: the amount of vergence noise is highest for stationary fixation and diminishes for tracking tasks as the bandwidth of the target motion increases. Furthermore, movements of the occluded eye are larger than those of the seeing eye in monocular viewing. This effect is more pronounced for horizontal motions, for stationary fixation, and for lower frequencies.

Finally, we have related our findings to previously known facts about the pertinent nerve pathways in order to postulate a model for the neurological binocular control of the visual axes.

Analog VLSI-based, neuromorphic sensorimotor systems: modeling the primate oculomotor system

Using neuromorphic analog VLSI techniques for modeling large neural systems has several advantages over software techniques. By designing massively-parallel analog circuit arrays which are ubiquitous in neural systems, analog VLSI models are extremely fast, particularly when local interactions are important in the computation. While analog VLSI circuits are not as flexible as software methods, the constraints posed by this approach are often very similar to the constraints faced by biological systems. As a result, these constraints can offer many insights into the solutions found by evolution. This dissertation describes a hardware modeling effort to mimic the primate oculomotor system which requires both fast sensory processing and fast motor control. A one-dimensional hardware model of the primate eye has been built which simulates the physical dynamics of the biological system. It is driven by analog VLSI circuits mimicking brainstem and cortical circuits that control eye movements. In this framework, a visually-triggered saccadic system is demonstrated which generates averaging saccades. In addition, an auditory localization system, based on the neural circuits of the barn owl, is used to trigger saccades to acoustic targets in parallel with visual targets. Two different types of learning are also demonstrated on the saccadic system using floating-gate technology allowing the non-volatile storage of analog parameters directly on the chip. Finally, a model of visual attention is used to select and track moving targets against textured backgrounds, driving both saccadic and smooth pursuit eye movements to maintain the image of the target in the center of the field of view. This system represents one of the few efforts in this field to integrate both neuromorphic sensory processing and motor control in a closed-loop fashion.

Macaque lateral intraparietal area and oculomotor behaviors

Neurons in the primate lateral intraparietal area (area LIP) carry visual, saccade-related and eye position activities. The visual and saccade activities are anchored in a retinotopic framework and the overall response magnitude is modulated by eye position. It was proposed that the modulation by eye position might be the basis of a distributed coding of target locations in a head-centered space. Other recording studies demonstrated that area LIP is involved in oculomotor planning. These results overall suggest that area LIP transforms sensory information for motor functions. In this thesis I further explore the role of area LIP in processing saccadic eye movements by observing the effects of reversible inactivation of this area. Macaque monkeys were trained to do visually guided and memory saccades and a double saccade task to examine the use of eye position signal. Finally, by intermixing visual saccades with trials in which two targets were presented at opposite sides of the fixation point, I examined the behavior of visual extinction.

In chapter 2, I will show that lesion of area LIP results in increased latency of contralesional visual and memory saccades. Contralesional memory saccades are also hypometric and slower in velocity. Moreover, the impairment of memory saccades does not vary with the duration of the delay period. This suggests that the oculomotor deficits observed after inactivation of area LIP is not due to the disruption of spatial memory.

In chapter 3, I will show that lesion of area LIP does not severely affect the processing of spontaneous eye movement. However, the monkeys made fewer contralesional saccades and tended to confine their gaze to the ipsilesional field after inactivation of area LIP. On the other hand, lesion of area LIP results in extinction of the contralesional stimulus. When the initial fixation position was varied so that the retinal and spatial locations of the targets could be dissociated, it was found that the extinction behavior could best be described in a head-centered coordinate.

In chapter 4, I will show that inactivation of area LIP disrupts the use of eye position signal to compute the second movement correctly in the double saccade task. If the first saccade steps into the contralesional field, the error rate and latency of the second saccade are both increased. Furthermore, the direction of the first eye movement largely does not have any effect on the impairment of the second saccade. I will argue that this study provides important evidence that the extraretinal signal used for saccadic localization is eye position rather than a displacement vector.

In chapter 5, I will demonstrate that in parietal monkeys the eye drifts toward the lesion side at the end of the memory saccade in darkness. This result suggests that the eye position activity in the posterior parietal cortex is active in nature and subserves gaze holding.

Overall, these results further support the view that area LIP neurons encode spatial locations in a craniotopic framework and is involved in processing voluntary eye movements.

The oculomotor system: (1) Vertical-horizontal interaction and signal recognition, (2) Time delays and power spectra

In the first section of this thesis, two-dimensional properties of the human eye movement control system were studied. The vertical - horizontal interaction was investigated by using a two-dimensional target motion consisting of a sinusoid in one of the directions vertical or horizontal, and low-pass filtered Gaussian random motion of variable bandwidth (and hence information content) in the orthogonal direction. It was found that the random motion reduced the efficiency of the sinusoidal tracking. However, the sinusoidal tracking was only slightly dependent on the bandwidth of the random motion. Thus the system should be thought of as consisting of two independent channels with a small amount of mutual cross-talk.

These target motions were then rotated to discover whether or not the system is capable of recognizing the two-component nature of the target motion. That is, the sinusoid was presented along an oblique line (neither vertical nor horizontal) with the random motion orthogonal to it. The system did not simply track the vertical and horizontal components of motion, but rotated its frame of reference so that its two tracking channels coincided with the directions of the two target motion components. This recognition occurred even when the two orthogonal motions were both random, but with different bandwidths.

In the second section, time delays, prediction and power spectra were examined. Time delays were calculated in response to various periodic signals, various bandwidths of narrow-band Gaussian random motions and sinusoids. It was demonstrated that prediction occurred only when the target motion was periodic, and only if the harmonic content was such that the signal was sufficiently narrow-band. It appears as if general periodic motions are split into predictive and non-predictive components.

For unpredictable motions, the relationship between the time delay and the average speed of the retinal image was linear. Based on this I proposed a model explaining the time delays for both random and periodic motions. My experiments did not prove that the system is sampled data, or that it is continuous. However, the model can be interpreted as representative of a sample data system whose sample interval is a function of the target motion.

It was shown that increasing the bandwidth of the low-pass filtered Gaussian random motion resulted in an increase of the eye movement bandwidth. Some properties of the eyeball-muscle dynamics and the extraocular muscle "active state tension" were derived.

Responses to auditory stimuli in macaque lateral intraparietal area

The lateral intraparietal area (LIP) of macaque posterior parietal cortex participates in the sensorimotor transformations underlying visually guided eye movements. Area LIP has long been considered unresponsive to auditory stimulation. However, recent studies have shown that neurons in LIP respond to auditory stimuli during an auditory-saccade task, suggesting possible involvement of this area in auditory-to-oculomotor as well as visual-to-oculomotor processing. This dissertation describes investigations which clarify the role of area LIP in auditory-to-oculomotor processing.

Extracellular recordings were obtained from a total of 332 LIP neurons in two macaque monkeys, while the animals performed fixation and saccade tasks involving auditory and visual stimuli. No auditory activity was observed in area LIP before animals were trained to make saccades to auditory stimuli, but responses to auditory stimuli did emerge after auditory-saccade training. Auditory responses in area LIP after auditory-saccade training were significantly stronger in the context of an auditory-saccade task than in the context of a fixation task. Compared to visual responses, auditory responses were also significantly more predictive of movement-related activity in the saccade task. Moreover, while visual responses often had a fast transient component, responses to auditory stimuli in area LIP tended to be gradual in onset and relatively prolonged in duration.

Overall, the analyses demonstrate that responses to auditory stimuli in area LIP are dependent on auditory-saccade training, modulated by behavioral context, and characterized by slow-onset, sustained response profiles. These findings suggest that responses to auditory stimuli are best interpreted as supramodal (cognitive or motor) responses, rather than as modality-specific sensory responses. Auditory responses in area LIP seem to reflect the significance of auditory stimuli as potential targets for eye movements, and may differ from most visual responses in the extent to which they arc abstracted from the sensory parameters of the stimulus.

Establishing the C. elegans uterine seam cell (utse) as a novel model for studying cell behavior

The molecular inputs necessary for cell behavior are vital to our understanding of development and disease. Proper cell behavior is necessary for processes ranging from creating one’s face (neural crest migration) to spreading cancer from one tissue to another (invasive metastatic cancers). Identifying the genes and tissues involved in cell behavior not only increases our understanding of biology but also has the potential to create targeted therapies in diseases hallmarked by aberrant cell behavior.

A well-characterized model system is key to determining the molecular and spatial inputs necessary for cell behavior. In this work I present the C. elegans uterine seam cell (utse) as an ideal model for studying cell outgrowth and shape change. The utse is an H-shaped cell within the hermaphrodite uterus that functions in attaching the uterus to the body wall. Over L4 larval stage, the utse grows bidirectionally along the anterior-posterior axis, changing from an ellipsoidal shape to an elongated H-shape. Spatially, the utse requires the presence of the uterine toroid cells, sex muscles, and the anchor cell nucleus in order to properly grow outward. Several gene families are involved in utse development, including Trio, Nav, Rab GTPases, Arp2/3, as well as 54 other genes found from a candidate RNAi screen. The utse can be used as a model system for studying metastatic cancer. Meprin proteases are involved in promoting invasiveness of metastatic cancers and the meprin-likw genes nas-21, nas-22, and toh-1 act similarly within the utse. Studying nas-21 activity has also led to the discovery of novel upstream inhibitors and activators as well as targets of nas-21, some of which have been characterized to affect meprin activity. This illustrates that the utse can be used as an in vivo model for learning more about meprins, as well as various other proteins involved in metastasis.