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Stefano Ramat

Publications and source records attributed to Stefano Ramat.

15 recordsLinked to original sources
PubMed2006

What clinical disorders tell us about the neural control of saccadic eye movements.

Saccades are rapid eye movements that redirect the fovea from one object to another. A great deal has been learned about the anatomy and physiology of saccades, making them an ideal system for studying the neural control of movement. Basic research on normal eye movements has greatly increased our understanding of saccadic performance, anatomy and physiology, and led to a large number of control system models. These models simulate normal saccades well, but are challenged by clinical disorders because they often do not incorporate the specific anatomical and physiological substrates needed to model clinically important abnormalities. Historically, studies of saccadic abnormalities in patients have played a critical role in understanding the neural control of saccades because they provide information that complements basic research and thus restricts hypotheses to those that are biologically plausible. This review presents four examples of clinical disorders (slow saccades, interrupted saccades, high-frequency saccadic oscillations and macrosaccadic oscillations) that have provided insights into the neurobiology of saccades, have driven the development of new models, and have suggested an explanation or treatment for these disorders. We raise general questions for both scientists and clinicians that will assist in their efforts to understand the neural control of movement, improve diagnostic criteria and develop new treatments.

Brain↗
PubMed2006

Latency detection in motor responses: a model-based approach with genetic algorithm optimization.

The latency of a response is one of the most frequently reported parameters when describing the characteristics of a motor system. Such measurement provides important information both to the basic researcher investigating the neural circuitry of the underlying physiological system and to the clinician gathering information for diagnosing a patient. Our concern here is that when the latency of a response is determined on experimentally recorded data by using the most commonly referenced techniques to find the onset of a motor response, the resulting figure encompasses both the neural processing time and the dynamics of the system producing the response (e.g., the musculoskeletal apparatus). Therefore, the resulting latency measurement cumulates information relative to two substantially different sources and thus having different implications. The goal of our study is that of suggesting a technique allowing the separation of the relative contributions of neural transmission and processing time from that of the dynamics of the motor system. This is accomplished by using a technique based on fitting a model to the experimentally recorded response, thus allowing to exploit as much as is known with regards to the dynamics of the studied motor system (e.g., model order and constraints on the values of the model parameters). The optimization of the model parameters for fitting the experimental data is carried out using a real-valued genetic algorithm, allowing to avoid trapping in local, suboptimal minima. The use of this approach allows to estimate the pure delay in the response introduced by neural processing more accurately than the traditional latency detection techniques based on adaptive thresholds.

Algorithms↗
PubMed2005

Interaural translational VOR: suppression, enhancement, and cognitive control.

We investigated the influence of cognitive factors on the early response of the interaural translational vestibuloocular reflex (tVOR) in six normal subjects. Variables were prior knowledge of direction of head motion and the position of the fixation target relative to the head [head-fixed (HF) or space-fixed (SF)]. A manually driven device provided a step-like head translation (approximately 35 mm distance, peak acceleration, 0.6-1.3 g). Subjects looked at the SF or HF target located 15 cm in front of their heads in otherwise complete darkness. The testing paradigms were: random interleaving of SF and HF targets with unknown direction of head movement, known target location with random head direction (SFR or HFR), and known target location with known head direction (SFP or HFP). Timing was always unpredictable. A "gain" of the slow phase was calculated with respect to ideal performance (maintained fixation of the SF target, recorded/ideal eye velocity computed at time of peak head velocity). At such times, there were no significant differences in gain between HF and SF trials in the random condition; the average gain was approximately 36% of ideal. On the other hand, responses in the SFR and HFR conditions differed as early as 20 ms after the head began moving. Average gain was higher (0.43 +/- 0.11 vs. 0.34 +/- 0.14; means +/- SD, P < 0.05) for each subject in the SFR than the HFR condition. For SFP and HFP, the responses differed from the onset of head motion. Average slow-phase gain was higher (0.49 +/- 0.12 vs. 0.31 +/- 0.12, P < 0.02) for each subject in SFP than in HFP. The timing of corrective saccades during the tVOR was also influenced by cognitive factors. Visual error signals seemed to be more important for triggering saccades in HF trials, whereas preprogramming, probably based on labyrinthine information, seemed to be more important in SF trials. Simulations showed that the changes in slow-phase gain with cognition could be reproduced with simple parametric adjustments of the gain of activity from otolith afferents and suggest that higher-level cognitive control of the VOR could occur as early as the synapse of peripheral afferents on neurons in the vestibular nuclei, either directly from higher level centers or via the cerebellum. In sum, the tVOR-both in its slow-phase response and the saccadic corrections-is subject to "higher-level" cognitive influences including knowledge of where the line of sight must point during head motion and the impending direction of head motion.

Acceleration↗
PubMed2005

Ocular oscillations generated by coupling of brainstem excitatory and inhibitory saccadic burst neurons.

The human saccadic system is potentially unstable and may oscillate if the burst neurons, which generate saccades, are not inhibited by omnipause neurons. A previous study showed that combined saccade vergence movements can evoke oscillations in normal subjects. We set out to determine: 1) whether similar oscillations can be recorded during other paradigms associated with inhibition of omnipause neurons; 2) whether lesions of the fastigial nuclei disrupt such oscillations; and 3) whether such oscillations can be reproduced using a model based on the coupling of excitatory and inhibitory burst neurons. We recorded saccadic oscillations during vergence movements, combined saccade-vergence movements, vertical saccades, pure vergence and blinks in three normal subjects, and in a patient with saccadic hypermetria due to a surgical lesion affecting both fastigial nuclei. During combined saccade-vergence, normal subjects and the cerebellar patient developed small-amplitude (0.1 - 0.5 degrees), high-frequency (27-35 Hz), conjugate horizontal saccadic oscillations. Oscillations of a similar amplitude and frequency occurred during blinks, pure vergence and vertical saccades. One normal subject could generate saccadic oscillations voluntarily (approximately 0.7 degrees amplitude, 25 Hz) during sustained convergence. Previous models proposed that high-frequency eye oscillations produced by the saccadic system (saccadic oscillations), occur because of a delay in a negative feedback loop around high-gain, excitatory burst neurons in the brainstem. The feedback included the cerebellar fastigial nuclei. We propose another model that accounts for saccadic oscillations based on 1) coupling of excitatory and inhibitory burst neurons in the brainstem and 2) the hypothesis that burst neurons show post-inhibitory rebound discharge. When omnipause neurons are inhibited (as during saccades, saccade-vergence movements and blinks), this new model simulates oscillations with amplitudes and frequencies comparable to those in normal human subjects. The finding of saccadic oscillations in the cerebellar patient is compatible with the new model but not with the recent models including the fastigial nuclei in the classic negative-feedback loop model. Our model proposes a novel mechanism for generating oscillations in the oculomotor system and perhaps in other motor systems too.

Adult↗
PubMed2005

Binocular coordination in fore/aft motion.

Stabilization of images on the fovea during either fore/aft translation of a subject or fore/aft movement of a visual target in front of a stationary observer imposes complex geometrical requirements that depend upon the eccentricity of the object of interest with respect to the eyes. Each eye needs to be rotated independently with varying proportions of conjugate (version) and disconjugate (vergence) eye movements to maintain fixation of the target. Here, we describe binocular coordination in the early response to translational movements of normal subjects along their naso-occipital axis. We recorded the responses evoked by small (about 4 cm), abrupt (about 0.7 g), fore/aft translations in four normal subjects while they viewed a near target. In the forward and backward starting positions the target was 15 or 10.5 cm away, respectively. Each subject was tested with the target centered between the eyes, aligned on the right eye, and placed to the right of the right eye by approximately 3 cm. The three conditions differed only in the lateral eccentricity of the target, yet the geometrical requirements for image stabilization are very different: pure vergence, one eye still, or mostly version. We found that the eye-movement responses closely matched what was needed for visual stabilization of the target, though responses to stimuli calling for divergence were less accurate than those for convergence. The latency of these responses ranged from 40 to 65 ms and achieved about 80% of the ideal response by 90 to 100 ms after the onset of the stimulus. Next, we asked whether these eye movements were generated by the vestibular system or by high-level strategies for image stabilization, such as pursuit. Thus, in a second set of experiments we used the mean profile of fore\aft body motion computed for each subject to drive a small visual target across the same distances and in the same eccentricities used during body translations. We found that visually driven responses had longer latencies (by at least 80 ms, ranging from 144 to 155 ms) and slower dynamics (with significantly lower peak eye velocities), highlighting the different subsystems producing the two types of responses. Saccades were also an important component of the response to both visual and vestibular stimuli, less frequent during the centered-target configuration and more frequent during viewing of eccentric targets. Visual stimuli evoked saccadic corrections more often and at shorter latencies than did vestibular stimuli. Both smooth and saccadic eye movements were appropriately disconjugate and their pattern depended on whether the eyes were converging or diverging.

Adult↗
PubMed2005

Evaluating large saccades in patients with brain-stem or cerebellar disorders.

Clinicians conventionally test saccades at the bedside by noting the accuracy, initiation time, and speed of large movements, with the patient's head stationary. Partly for methodological reasons, laboratory analysis of saccades has mainly focused on movements of 20 degrees or less. By measuring the velocity waveform of large saccades, it is possible to examine more closely the way in which brain stem and cerebellum guide the eye to the target. Large saccades made by healthy humans show a positively skewed velocity profile. Slow saccades made by patients with brain-stem disorders show a prolonged plateau of low velocity. Some patients with cerebellar disorders may show increased acceleration and deceleration of saccades. Each of these velocity waveforms can be modeled by changing the parameters that describe medium-lead burst neuron firing. In certain other brain-stem and cerebellar disorders, transient decelerations or premature terminations of saccades occur; such velocity waveforms cannot be modeled solely by changing the parameters that describe burst neuron firing. Instead, it is necessary to postulate dysfunction of the mechanism that normally inhibits pontine omnipause neurons, thereby permitting burst neurons to discharge until the saccade is completed. Analysis of large, abnormal saccades calls for application of novel techniques to identify the beginning and end of the saccadic pulse command.

Adult↗
PubMed2005

About the effects of velocity saturation on smooth pursuit.

By means of simple simulations and based on experimental results from the literature, it is argued that correct consideration of the well known velocity saturation of the smooth pursuit eye movement system may suggest new insight into some intriguing aspects of this system's behavior.

Feedback↗
PubMed2004

Influence of orientation of exiting wire of search coil annulus on torsion after saccades.

PURPOSE: Research has shown that the orientation of the exiting wire from a scleral search coil (nasal in the original coil, inferior in the modified coil) influences the pattern of torsion associated with blinks, presumably due to the upper eyelid touching the wire. The present study was conducted to investigate whether coil wire orientation also influences the pattern of torsion during fixation after saccades and consequently influences parameters that determine Listing's plane and Donders' law. METHODS: Three-axis, binocular eye rotations were recorded in three healthy human subjects looking at an array of small light-emitting diodes at a 124-cm distance. They made predominantly vertical or predominantly horizontal saccades (5-40 degrees, amplitude) at three (0 +/- 20 degrees) azimuths, or elevations. RESULTS: With the modified coil, the horizontal component of Listing's primary position was similar for horizontal (mean temporal deviation, 2.9 degrees) and vertical (3.3 degrees) saccades. With the original coil, the horizontal component of primary position was more temporal after horizontal (12.3 degrees) than vertical (6.1 degrees) saccades. The vertical component of primary position was similar with both coils after horizontal and vertical saccades. Listing's plane was thinner with the modified coil after horizontal (standard deviation of torsion from a plane of 0.71 degrees vs. 1.31 degrees) and vertical (0.84 degrees vs.1.67 degrees) saccades. The standard deviation of torsion at a given eye position (Donders' law) was smaller with the modified coil. CONCLUSIONS: Measures of torsion after horizontal or vertical saccades depend on whether the coil wire exits nasally or inferiorly and, with the original coil, whether the saccades are horizontal or vertical. Lid contact may account for these potential artifacts. They must be appreciated in the interpretation of three-dimensional search coil recordings, using the scleral annulus.

Adult↗
PubMed2003

Ocular motor responses to abrupt interaural head translation in normal humans.

We characterized the interaural translational vestibulo-ocular reflex (tVOR) in 6 normal humans to brief (approximately 200 ms), high-acceleration (0.4-1.4g) stimuli, while they fixed targets at 15 or 30 cm. The latency was 19 +/- 5 ms at 15-cm and 20 +/- 12 ms at 30-cm viewing. The gain was quantified using the ratio of actual to ideal behavior. The median position gain (at time of peak head velocity) was 0.38 and 0.37, and the median velocity gain, 0.52 and 0.62, at 15- and 30-cm viewing, respectively. These results suggest the tVOR scales proportionally at these viewing distances. Likewise, at both viewing distances, peak eye velocity scaled linearly with peak head velocity and gain was independent of peak head acceleration. A saccade commonly occurred in the compensatory direction, with a greater latency (165 vs. 145 ms) and lesser amplitude (1.8 vs. 3.2 deg) at 30- than 15-cm viewing. Even with saccades, the overall gain at the end of head movement was still considerably undercompensatory (medians 0.68 and 0.77 at 15- and 30-cm viewing). Monocular viewing was also assessed at 15-cm viewing. In 4 of 6 subjects, gains were the same as during binocular viewing and scaled closely with vergence angle. In sum the low tVOR gain and scaling of the response with viewing distance and head velocity extend previous results to higher acceleration stimuli. tVOR latency (approximately 20 ms) was lower than previously reported. Saccades are an integral part of the tVOR, and also scale with viewing distance.

Acceleration↗
PubMed2003

Design, methods, and evaluation directions of a multi-access service for the management of diabetes mellitus patients.

Recent advances in information and communication technology allow the design and testing of new models of diabetes management, which are able to provide assistance to patients regardless of their distance from the health care providers. The M2DM project, funded by the European Commission, has the specific aim to investigate the potential of novel telemedicine services in diabetes management. A multi-access system based on the integration of Web access, telephone access through interactive voice response systems, and the use of palmtops and smart modems for data downloading has been implemented. The system is based on a technological platform that allows a tight integration between the access modalities through a middle layer called the multi-access organizer. Particular attention has been devoted to the design of the evaluation scheme for the system: A randomized controlled study has been defined, with clinical, organizational, economic, usability, and users' satisfaction outcomes. The evaluation of the system started in January 2002. The system is currently used by 67 patients and seven health care providers in five medical centers across Europe. After 6 months of usage of the system no major technical problems have been encountered, and the majority of patients are using the Web and data downloading modalities with a satisfactory frequency. From a clinical viewpoint, the hemoglobin A1c (HbA1c) of both active patients and controls decreased, and the variance of HbA1c in active patients is significantly lower than the control ones. The M2DM system allows for the implementation of an easy-to-use, user-tailored telemedicine system for diabetes management. The first clinical results are encouraging and seem to substantiate the hypothesis of its clinical effectiveness.

Diabetes Mellitus↗
PubMed2003

Eye-head coordination in darkness: formulation and testing of a mathematical model.

Passive head rotation in darkness produces vestibular nystagmus, consisting of slow and quick phases. The vestibulo-ocular reflex produces the slow phases, in the compensatory direction, while the fast phases, in the same direction as head rotation, are of saccadic origin. We have investigated how the saccadic components of the ocular motor responses evoked by active head rotation in darkness are generated, assuming the only available sensory information is that provided by the vestibular system. We recorded the eye and head movements of nine normal subjects during active head rotation in darkness. Subjects were instructed to rotate their heads in a sinusoidal-like manner and to focus their attention on producing a smooth head rotation. We found that the desired eye position signal provided to the saccadic mechanism by the vestibular system may be modeled as a linear combination of head velocity and head displacement information. Here we present a mathematical model for the generation of both the slow and quick phases of vestibular nystagmus based on our findings. Simulations of this model accurately fit experimental data recorded from subjects.

Adult↗
PubMed2002

Context-specific adaptation of the gain of the oculomotor response to lateral translation using roll and pitch head tilts as contexts.

Previous studies established that vestibular and oculomotor behaviors can have two adapted states (e.g., gain) simultaneously, and that a context cue (e.g., vertical eye position) can switch between the two states. The present study examined this phenomenon of context-specific adaptation for the oculomotor response to interaural translation (which we term "linear vestibulo-ocular reflex" or LVOR even though it may have extravestibular components). Subjects sat upright on a linear sled and were translated at 0.7 Hz and 0.3 gpeak acceleration while a visual-vestibular mismatch paradigm was used to adaptively increase (x2) or decrease (x0) the gain of the LVOR. In each experimental session, gain increase was asked for in one context, and gain decrease in another context. Testing in darkness with steps and sines before and after adaptation, in each context, assessed the extent to which the context itself could recall the gain state that was imposed in that context during adaptation. Two different contexts were used: head pitch (26 degrees forward and backward) and head roll (26 degrees or 45 degrees, right and left). Head roll tilt worked well as a context cue: with the head rolled to the right the LVOR could be made to have a higher gain than with the head rolled to the left. Head pitch tilt was less effective as a context cue. This suggests that the more closely related a context cue is to the response being adapted, the more effective it is.

Adaptation, Psychological↗
PubMed2002

The cerebellar contribution to eye movements based upon lesions: binocular three-axis control and the translational vestibulo-ocular reflex.

The study of human cerebellar patients and monkeys with experimental cerebellar lesions has taught us much about the role of the cerebellum in normal ocular motor control. Here we emphasize recent findings that point to a role for the cerebellum in (1) the control of the three-dimensional axis about which the eye rotates in response to visual and vestibular stimuli, and (2) the generation of the translational VOR. Findings in cerebellar patients include abnormalities of eye torsion during attempted fixation that suggest a cerebellar role in the control of torsion so that Listing's law is obeyed. Abnormal torsion during vertical pursuit suggests that central processing of information for smooth pursuit may be based upon a phylogenetically old, semicircular canal coordinate scheme. Inappropriate and disconjugate vertical and torsional eye movements ("cross-coupling") occur during brief, high-acceleration rotations of the head. This suggests a role for the cerebellum in the binocular control of the rotation axis of the VOR. Finally, abnormalities of the modulation of the translational VOR with near viewing in cerebellar patients, but with sparing of the very initial 25-30 msec of response, suggests an important role for the cerebellum in the translational VOR.

Animals↗
PubMed2002

Vergence-mediated modulation of the human horizontal angular VOR provides evidence of pathway-specific changes in VOR dynamics.

The horizontal vestibulo-ocular reflex (VOR) evoked by passive, high-acceleration, head-on-body rotations (head thrusts) while viewing a far (124-cm) or near (15-cm) target was recorded (scleral search coil) in four subjects with normal vestibular function and in one subject with unilateral vestibular hypofunction. For responses in the subjects with normal vestibular function, the latency of responses relative to the onset of head movement was 7.5 +/- 1.5 ms for the VOR and 21.6 +/- 1.2 ms for the vergence-mediated increase in VOR gain. The gain of the VOR at the peak of the velocity response while viewing a far target was 1.01 +/- 0.06; while viewing a near target, it was 1.25 +/- 0.08 (p <0.003). The responses were modeled with two pathways based on the different latencies. The "far-viewing" pathway was represented by a constant gain term. The "near-viewing" pathway was represented by a first-order lead term, a gain that was dependent on viewing distance, and a delay. Analysis of the responses revealed that the lead term was greater for the adducting than the abducting eye. In the subject with unilateral vestibular hypofunction, ipsilesional responses showed no change in VOR gain with respect to viewing distance. Contralesional responses retained the vergence-dependent increase in gain. A bilateral model was developed based on the data from the subjects with normal vestibular function. Simulations of this model when inputs were eliminated from one side predict the changes observed in the subject with unilateral vestibular hypofunction. The response asymmetries arise because the near-viewing pathway is more susceptible to inhibitory cutoff than is the far-viewing pathway.

Adult↗