Model-based analysis of dynamics in vergence adaptation.

We previously proposed a model to study the dynamics of disparity vergence responses. This model was based on known physiology and consisted of pulse and step neural control processes feeding a linear second-order oculomotor plant. Here, we apply a slightly modified version of that model to analyze the influence of short-term adaptation on vergence dynamics. This analysis showed that, unlike normal vergence responses, adapted responses could not be accurately simulated without a delay between the step and pulse components. Through simulations of normal vergence and adapted vergence responses, we found a strong correlation between delay of the step signal and the size of the movement overshoot. This correlation suggests a strong interaction between neural process generating the pulse and step motor control signals.

The influence of repetitive eye movements on vergence performance.

We measured the peak velocity of convergence eye movement responses in four normal subjects before and after a large number of either repetitive vergence or repetitive saccadic eye movements. A 20% decrease in the mean value of peak velocity was observed in vergence responses after 100 repetitive step vergence eye movements. However, 100 cycles of slow sinusoidal vergence tracking did not induce any notable change in vergence dynamics. Five hundred repetitive saccadic eye movements also caused an approximately 20% decrease in peak velocity. The reduction in peak velocity was related to the number of repetitions for both vergence and saccadic fatiguing stimuli. The frequency of occurrence of double-vergences was also used as an index to monitor the influence of repetitive eye movements on convergence performance. Results showed that repetitive step convergence movements could double, or even triple, the frequency of the occurrence of double-vergence responses, while slow sinusoidal vergence tracking or repetitive saccades had no influence on the frequency of response doubles.

Effects of prediction on timing and dynamics of vergence eye movements.

Periodic square waves were used to generate predictable vergence eye movement responses. The timing and dynamic characteristics of vergence eye movement responses to predictable and non-predictable stimuli were compared. Results showed significant changes in timing characteristics along with a highly characteristic anticipatory movement in the early part of predictable vergence responses. This phenomenon is similar to that seen in saccadic eye movements and appears to influence the timing and dynamics of the subsequent vergence response. A model-based analysis of dynamics showed that the pulse width, pulse gain, and step gain of the motor command signal did not show major differences between predictable and non-predictable response. However, other model parameters related to the acceleration of the response showed a substantial decrease when the movements were predictive.

Disparity vergence double responses processed by internal error.

Disparity vergence eye movements occasionally exhibit two high-velocity components to a single step stimulus (Alvarez, T. L., Semmlow, J. L. & Yuan, W. (1998). Journal of Neurophysiology, 79, 37-44). This research investigates the neural strategy used to trigger the second component of double high-velocity vergence eye movements. Vergence doubles evoked by an experimental protocol that induces post-movement visual error were compared to doubles that occur normally. The second component of a visually evoked response double occurred later, and with slower dynamics, than that of a naturally occurring double. These differences in timing and dynamics indicate that natural double responses are mediated, at least in part, by a mechanism other than visual feedback. The faster dynamics and timing of natural doubles suggest that an internal monitoring process triggers these movements.

Dynamics of the disparity vergence step response: a model-based analysis.

A new method to analyze the dynamics of vergence eye movements was developed based on a reconstruction of the presumed motor command signal. A model was used to construct equivalent motor command signals and transform an associated vergence transient response into an equivalent set of motor commands. This model represented only the motor components of the vergence system and consisted of signal generators representing the neural burst and tonic cells and a plant representing the ocular musculature and dynamics of the orbit. Through highly accurate simulations, dynamic vergence responses could be reduced to a set of five model parameters, each relating to a specific feature of the internal motor command. This dynamic analysis tool was applied to the analysis of inter-movement variability in vergence step responses. Model parameters obtained from a large number of response simulations showed that the width of the command pulse was tightly controlled while its amplitude, rising slope, and falling slope were less tightly regulated. Variation in the latter three parameters accounted for the most of the movement-to-movement variability seen in vergence step responses. Unlike version movements, pulse width did not increase with increased stimulus amplitude, although the other command signal parameters were substantially influenced by stimulus amplitude.

Dynamic details of disparity convergence eye movements.

Classically, the primary tool for quantifying the dynamics of vergence and other eye movements has been the main sequence. The main sequence is a plot of peak velocity versus response amplitude and is particularly useful for comparing the dynamics of a large number of eye movements over a range of response amplitudes. However, the main sequence represents only the equivalent first-order behavior of a response and does not describe its dynamics in detail. Since the main sequence is based on only two points on the dynamic trajectory, it is sensitive to measurement artifacts and noise. A new methodology is presented which quantifies the equivalent second-order dynamics of eye movements using a larger region of the transient response. These new indexes were applied to vergence eye movements and were found to differentiate between subtle, but important differences in movement dynamics.

Short term modification of disparity vergence eye movements.

Dynamics of disparity vergence eye movements can be modified by adaptive stimuli that generate large transient disparities. These modifications were observed for convergence as well as divergence eye movements. After modification, the peak velocities of the step responses for convergence and divergence were substantially higher than in normal baseline responses, a change observed in all four subjects studied. The change in peak velocity of a step response occurred very rapidly after presentation of the adaptive stimuli. Main sequence plots showed that first-order dynamic characteristics increased for post-adaptive responses with respect to normal step responses. Hence, response modification could be quantified as a change in gain accompanied with an increase in the effective response time constant. The adaptive responses to convergent and divergent 'disappearing' step stimuli revealed that the adaptation process modifies the high-velocity component of both disparity convergence and divergence eye movements. Moreover, a gain change in this component alone could account for both the gain and the time constant modifications seen in the overall response. A process of recovery or de-adaptation was also observed for both convergence and divergence eye movements. This observed short-term modification demonstrates a unique control mechanism for vergence eye movements that is effective in either direction.

Age-related changes in human ciliary muscle and lens: a magnetic resonance imaging study.

PURPOSE: To use high-resolution magnetic resonance (MR) images of the eye to directly measure the relationship between ciliary muscle contraction and lens response with advancing age. METHODS: A General Electric, 1.5-Tesla MR imager and a custom-designed eye imaging coil were used to collect high-resolution MR images from 25 subjects, 22 through 83 years of age. A nonmagnetic binocular stimulus apparatus was used to induce both relaxed accommodation (0.1 diopter [D]) and strong accommodative effort (8.0 D). Measurements of the ciliary muscle ring diameter (based on the inner apex), lens equatorial diameter, and lens thickness were derived from the MR images. RESULTS: Muscle contraction is present in all subjects and reduces only slightly with advancing age. A decrease in the diameter of the unaccommodated ciliary muscle ring was highly correlated with advancing age. Lens equatorial diameter does not correlate with age for either accommodative state. Although unaccommodated lens thickness (i.e., lens minor axis length) increases with age, the thickness of the lens under accommodative effort is only modestly age-dependent. CONCLUSIONS: Ciliary muscle contractile activity remains active in all subjects. A decrease in the unaccommodated ciliary muscle diameter, along with the previously noted increase in lens thickness (the "lens paradox"), demonstrates the greatest correlation with advancing age. These results support the theory that presbyopia is actually the loss in ability to disaccommodate due to increases in lens thickness, the inward movement of the ciliary ring, or both.

Dynamic asymmetries in disparity convergence eye movements.

Vergence eye movements have traditionally been considered the product of a single neural control center and are usually studied by combining the movements of each eye into a single 'vergence' response. In the present experiment, disparity-driven eye movements were produced by symmetrical step stimuli, and the dynamic properties of each eye movement were analyzed separately. Although the final positions of the two eyes were symmetrical, large dynamic asymmetries often occurred. The timing between the two eyes showed fair synchrony as they attained maximum velocity at approximately the same time. Since the final static positions were symmetrical, asymmetries occurring during the initial dynamic component must necessarily be compensated by offsetting asymmetries in the latter portion of the response.

Evidence for separate control of slow version and vergence eye movements: support for Hering's Law.

When a visual stimulus changes direction and distance simultaneously, Hering's Law argues that the resulting eye movements are the result of combined version and vergence control processes. Recently, it has been suggested that slow asymmetrical eye movements might be guided by monocular control processes wherein each eye is driven by its own retinal image. Experimental results presented here show behavioral differences between slow version and slow vergence eye movements, indicating that different control processes drive the two "pure" responses. Specifically, version tracking of constant velocity stimuli (i.e., smooth pursuit) is more precise, showing less variation in tracking velocity than movements of equal velocity produced by vergence stimuli. When the two stimuli are combined, the variability in tracking is consistent with the addition of the two components in proportion to their respective stimuli. These results provide support for Hering's Law, at least for low velocity, smooth tracking movements (i.e., slow version and slow vergence.

Initial component control in disparity vergence: a model-based study.

The dual-mode theory for the control of disparity-vergence eye movements states that two components control the response to a step change in disparity. The initial component uses a motor preprogram to drive the eyes to an approximate final position. This initial component is followed by activation of a late component operating under visual feedback control that reduces residual disparity to within fusional limits. A quantitative model based on a pulse-step controller, similar to that postulated for saccadic eye movements, has been developed to represent the initial component. This model, an adaptation of one developed by Zee et al. [1], provides accurate simulations of isolated initial component movements and is compatible with the known underlying neurophysiology and existing neurophysiological data. The model has been employed to investigate the difference in dynamics between convergent and divergent movements. Results indicate that the pulse-control component active in convergence is reduced or absent from the control signals of divergence movements. This suggests somewhat different control structures of convergence versus divergence, and is consistent with other directional asymmetries seen in horizontal vergence.

Closely spaced, fast dynamic movements in disparity vergence.

Conflicting theories exist describing how symmetrical vergence responses, the inward or outward turning of the eyes, are mediated. Classical theories describe vergence control as mediated by visual feedback. Extensive experimental evidence indicates that two distinct control components comprise the vergence response, and a recent theory supports the concept that one of these components is not visually guided. Occasionally, saccadic eye movements will respond to a single step stimulus with two closely spaced saccades, a behavior that is indicative of its switching control structure. If a portion of the vergence response is controlled in a manner analogous to saccades, then occasional double fast dynamic components might be expected. During this study, eye movements were recorded in response to symmetrical vergence stimuli of 2, 4, 6, 8, and 10 degrees steps. The left and right eye movements were subtracted to yield a net vergence response, and only convergent responses were investigated. Double fast dynamic components associated with high-velocity movements were observed in all four subjects studied. In double high-velocity component responses, the average peak velocity of both fast dynamic movements was always considerably less than the average peak velocity found when the response to the same stimulus was made with only a single component. Response amplitudes of single and double movements showed that if the primary component of a double response did not reach >/=80% of the stimulus amplitude, a secondary component would be generated to aid the movement. Plots of peak velocity as a function of response amplitude for both double and single movements followed the main sequence for vergence eye movements demonstrating that the first-order dynamic characteristics of all high-velocity components were the same. The time at which maximum velocity occurred (relative to stimulus onset) was also the same for both single component responses and the first component of double responses. The similarity in dynamics and timing implies that the high-velocity components were processed by the same controller mechanism. The existence of double high-velocity movements is indicative of an internal, switching mechanism similar to that found in saccades and is difficult to explain with theories that rely on visual feedback control alone.

Comparison of ischemic and reperfusion injury in canine bowel viability assessment.

The purpose of these experiments was to evaluate two methods of bowel viability assessment in two distinct models of intestinal ischemia. Bowel viability was assessed in 32 dogs by means of three methods: (1) a probe that quantified the intestinal electromyographic (EMG) measurements in millivolts (mV), (2) Doppler ultrasonography, and (3) perfusion fluorometry, which quantified serosal blood flow in indexed dye fluorescence units (dfi). Ischemia was created using one of two methods: (1) a chronic model in which the blood supply to 40 cm of ileum was ligated and viability assessed 24 hours later, or (2) an acute model in which the main superior mesenteric artery was occluded for 3 1/2 hours and then released. Viability parameters were assessed every 5 minutes for 30 minutes after release. After viability assessment was completed, the ischemic bowel was resected and anastomosed at the site where the EMG measurements approximated 50% of the values obtained in normal bowel. In the chronic group 3 of 20 dogs died of necrosis in contrast to none of 12 dogs in the acute reperfusion group. In the acute model EMG values steadily increased after reperfusion, stabilizing by 15 minutes after release. Mean EMG values at 15 through 30 minutes after release were significantly greater than the 5- and 10-minute postrelease and prerelease values, suggesting that the electromyogram is affected by reperfusion. Conversely, postrelease fluorometry measurements rapidly increased to levels that exceeded measurements obtained in normal bowel. There was a significant difference in the number of audible Doppler signals in the marginal artery of survivors of the acute vs. the chronic model. Fluorometry measurements in survivors of the acute model (99+/-9 dfi) were significantly greater than measurements in the chronic model (54+/-4 dfi, P

Evaluation of quantitative approaches to assessment of bowel viability.

Predicting the survivability of intestine that has been made ischemic by impairment of blood flow is a major unsolved problem in gastrointestinal surgery. Currently, the surgeon must rely on qualitative, often subjective assessments that are known to have marginal reliability. This review describes various approaches to quantitatively assess the survivability of intestine compromised by ischemic disease. Much of the review centers on work done in the authors' laboratory to evaluate various approaches to predicting long-term survival and to develop new assessment parameters. Towards that end the authors have designed and developed techniques based on intestinal contractility and myoelectric activity (the intestinal EMG). Their evaluations of these and other methods of viability assessment utilize a highly representative canine model of intestinal ischemia that closely follows the development and treatment of ischemic intestinal disease in humans. Results to date suggest that the myoelectric measurements are more reliable than parameters based on blood flow or visual evaluation in terms of predicting bowel survival. However, improvements in instrumentation and technique are needed before this approach is suitable for clinical use.

Bacterial translocation after mesenteric ligation in dogs.

These experiments were designed to determine the relationship between translocation of Escherichia coli and viability of ischemic small bowel. Twenty beagles were gavaged with 14C-labeled E. coli at two time intervals (3 and 24 h) prior to ligation of the blood supply to a 40-cm segment of ileum. Mesenteric lymph node (MLN) biopsies and bacterial cultures of the peritoneal fluid, peripheral arterial blood, and splanchnic venous blood were taken immediately prior to ligation and 24 h later both before and after the ischemic bowel was resected and anastomosed. Biopsies of each resection margin were taken to measure translocation of E. coli into the bowel wall. Several hemodynamic hemodynamic parameters were also measured before and 24 h after ligation. Seven of the 20 dogs died of further bowel necrosis. In survivors A-alpha DO2 was significantly decreased 24 h after mesenteric ligation vs. preligation, whereas in dogs that died DO2 was significantly increased after ligation vs. preligation. The incidence of mesenteric venous cultures positive for E. coli was significantly higher 24 h after ligation vs. preligation. However, there was no correlation between survival and the incidence of positive E. coli cultures in the blood or peritoneal fluid. Mean MLN counts were significantly higher in dogs gavaged at 3 h vs. those gavaged 24 h prior to laparotomy. However, there was no correlation between survival and translocation into either the bowel wall or MLN at either time interval. Viability of ischemic small bowel in this canine model was not affected by translocation of E. coli. Hemodynamic parameters that are altered during the course of sepsis also did not correlate with survival.

Comparison of blood flow and myoelectric measurements in two chronic models of mesenteric ligation.

OBJECTIVE: To determine whether the predictive accuracy of intestinal motility and blood flow measurements is altered by the magnitude of ischemic damage. DESIGN: Inception cohort study (dogs). Motility was measured using a probe that quantifies both the electromyographic (EMG) measurements and the magnitude of evoked contractile response (ECR). Intestinal blood flow was assessed using Doppler ultrasonography in the marginal artery and perfusion fluorometry, which quantifies fluorescein in the bowel wall in dye fluorescence units. SETTING: Vivarium animal research facilities at a medical school. INTERVENTIONS: The blood supply of a 40-cm length of ileum was ligated in 102 dogs: 52 in which the marginal artery was ligated at two points 8 cm apart (severe model), and 50 in which the marginal artery was ligated only once (moderate model). Twenty-four hours after ligation, the motility and blood flow parameters were measured in normal bowel and at 2-cm intervals within the 40-cm ischemic segment. Resection and anastomosis of ischemic bowel was then performed using either EMG, ECR, or fluorometry to determine the site of resection. OUTCOME MEASURE: Anastomotic leak from progressive ischemia. RESULTS: There were 26 fatal anastomotic leaks, all due to necrosis at the anastomosis. Perfusion fluorometry and ECR measurements did not correlate with survival in either model. An audible Doppler pulse in the marginal artery correlated with survival in the moderate (P < or = .02) but not the severe model (P = .59). The EMG measurements were significantly greater in survivors vs nonsurvivors in both models. CONCLUSIONS: The EMG measurements may be useful in bowel viability assessment. Correlation of Doppler ultrasonographic findings with survival in the moderate model suggests that blood flow measurements may be more reliable in predicting viability in less ischemic bowel.

Vergence eye movements under natural viewing conditions.

PURPOSE: To determine whether there are any fundamental differences in vergence dynamics under different viewing conditions, both in instrument space and free space. METHODS: Symmetric vergence responses were measured for a variety of conditions under the traditional instrument space as well as the more natural free space viewing environment. Vergence eye movements were recorded objectively in three subjects using the infrared reflection technique. Within each environment, four conditions were tested: aperiodic self-initiated voluntary gaze shifts between two simultaneously viewed targets; periodic (0.33 Hz) voluntary gaze shifts between the same two targets; gaze shifts in total darkness to the near target following initial far target fixation in the light; and gaze shifts in total darkness to the two remembered target positions. In addition, an experiment was performed in instrument space using randomized step changes of target disparity, in which the responses served as the standard for comparison. For all conditions, target disparities ranged from 0.5 degrees to 10 degrees. The peak velocity of each vergence response was calculated and plotted versus its amplitude. RESULTS: It was found that the data for all conditions tested fell within the standard "main sequence" cluster, indicating similarity in dynamics and thus similarity in the motoneuronal controller signal. Also, the data from investigators who claimed differences in dynamics were also typically found to fall within the normal cluster. CONCLUSIONS: This indicates that the vergence motoneuronal controller signal produced the same dynamics for a particular response amplitude, independent of both viewing environment and test condition.