Stefano Ramat | University of Pavia (original) (raw)

Papers by Stefano Ramat

We developed the head impulse testing device (HITD) based on an inertial sensing system allowing ... more We developed the head impulse testing device (HITD) based on an inertial sensing system allowing to investigate the functional performance of the rotational vestibulo-ocular reflex (VOR) by testing its gaze stabilization ability, independently from the subject's visual acuity, in response to head impulses at different head angular accelerations ranging from 2000 to 7000 deg/s 2 . HITD was initially tested on 22 normal subjects, and a method to compare the results from a single subject (patient) with those from controls was set up. As a pilot study, we tested the HITD in 39 dizzy patients suffering, non-acutely, from different kinds of vestibular disorders. The results obtained with the HITD were comparable with those from the clinical head impulse test (HIT), but an higher number of abnormalities was detectable by HITD in the central vestibular disorders group. The HITD appears to be a promising tool for detecting abnormal VOR performance while providing information on the functional performance of the rotational VOR, and can provide a valuable assistance to the clinical evaluation of patients with vestibular disorders.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2008

The rotational vestibulo-ocular reflex (rVOR) contributes to gaze stabilitization by compensating... more The rotational vestibulo-ocular reflex (rVOR) contributes to gaze stabilitization by compensating head rotational movements sensed by the semicircular canals (SCC). The CNS improves the performance of the horizontal rVOR through the so called velocity storage mechanism (VSM). However the properties of the VSM in response to pitch rotations are less well known. We recorded eye movements evoked by whole-body constant-velocity pitch rotations about an earth-horizontal, interaural axis in four healthy human subjects. Subjects were tumbled forward, and backward, at 60 deg/s for over one minute using a 3D turntable. In these conditions also the otoliths contribute to the perception of head rotation because they sense the changes in direction of the gravity vector. The vertical slow phase velocity (SPV) responses show the typical exponential decay of the rVOR and a residual, otolith-driven sinusoidal modulation with a bias. Here the estimates of the contributions coming from the otoliths a...

Experimental Brain Research, 2005

The human saccadic system is potentially unstable and may oscillate if the burst neurons, which g... more 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 saccadevergence, normal subjects and the cerebellar patient developed small-amplitude (0.1-0.5°), 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 (~0.7°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 postinhibitory 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.

Annals of the New York Academy of Sciences, 2002

The study of human cerebellar patients and monkeys with experimental cerebellar lesions has taugh... more 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.

Journal of Neurophysiology, 2006

Brief smooth eye-velocity responses to target position steps have been reported during smooth pur... more Brief smooth eye-velocity responses to target position steps have been reported during smooth pursuit. We investigated position-error responses in eight healthy human subjects, comparing the effects of a step-ramp change in target position when imposed on steady-state smooth pursuit, vestibuloocular reflex (VOR) slow phases, or fixation. During steadystate pursuit or VOR, the target performed a step-ramp movement in the same or in the opposite direction relative to ongoing eye movements. When the step was directed backward relative to steady-state smooth pursuit, eye velocity transiently decreased (1.3 Ϯ 0.4°/s; average peak change in amplitude Ϯ SD), beginning about 100 ms after the step. The amplitude of position-error responses varied inversely with the step size. In contrast, there was little or no response in trials with forward steps during steady-state smooth pursuit, when step-ramps were imposed on VOR or when smooth pursuit began from fixation. We hypothesize that during ongoing smooth tracking when a sudden shift in target position is detected the pursuit system compares the direction of ongoing eye velocity with the relative positional error on the retina. In the case of different relative directions between ongoing tracking and a new target eccentricity, a position-error response toward the new target is initiated. Such a mechanism might help the smooth pursuit system to respond better to changes in target direction. These experimental findings were simulated by a mathematical model of smooth pursuit by implementing direction-dependent behavior with a position-error gating mechanism.

Progress in Brain Research, 2008

To investigate the contribution of the vestibular velocity-storage mechanism (VSM) to the vertica... more To investigate the contribution of the vestibular velocity-storage mechanism (VSM) to the vertical rotational vestibulo-ocular reflex (rVOR) we recorded eye movements evoked by off-vertical axis rotation (OVAR) using whole-body constant-velocity pitch rotations about an earth-horizontal, interaural axis in four healthy human subjects. Subjects were tumbled forward, and backward, at 60 deg/s for over 1 min using a 3D turntable. Slow-phase velocity (SPV) responses were similar to the horizontal responses elicited by OVAR along the body longitudinal axis, ('barbecue' rotation), with exponentially decaying amplitudes and a residual, otolith-driven sinusoidal response with a bias. The time constants of the vertical SPV ranged from 6 to 9 s. These values are closer to those that reflect the dynamic properties of vestibular afferents than the typical 20 s produced by the VSM in the horizontal plane, confirming the relatively smaller contribution of the VSM to these vertical responses. Our preliminary results also agree with the idea that the VSM velocity response aligns with the direction of gravity. The horizontal and torsional eye velocity traces were also sinusoidally modulated by the change in gravity, but showed no exponential decay.

ABSTRACT IntroductionAdaptive NetworksNeural NetworksLearningStructural AdaptationNeuro-Fuzzy Net... more ABSTRACT IntroductionAdaptive NetworksNeural NetworksLearningStructural AdaptationNeuro-Fuzzy NetworksGenetic Algorithms

The question of how the central nervous system can distinguish tilt with respect to gravity from ... more The question of how the central nervous system can distinguish tilt with respect to gravity from inertial acceleration due to translation in a horizontal plane using vestibular information has long been debated by the scientific community over the past ten years. Recently, it was hypothesized that such discrimination may be based on the multisensory integration of information provided by the otolith organs and the semicircular canals. Some evidence of such processing was found in the neural activity of cells in the fastigial nuclei and vestibular nuclei. To investigate the ability of the central nervous system to build an internal model of self motion based on vestibular signals, we developed an artificial vestibular sensor composed of accelerometers and gyroscopes providing movement data of the same nature as that transduced by the otoliths and canals, respectively. Here we show that the processing of these signals based on the multisensory integration hypothesis can be successfully used to discriminate tilt from translation and that the internal model based on such processing can successfully track angular and linear displacements over short periods of time.

Annals of the New York Academy of Sciences, 2005

Stabilization of images on the fovea during either fore/aft translation of a subject or fore/aft ... more 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.

IEEE Transactions on Biomedical Engineering, 2006

The latency of a response is one of the most frequently reported parameters when describing the c... more 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.

This study investigates the way in which the saccadic components (quick phases) of vestibular nys... more This study investigates the way in which the saccadic components (quick phases) of vestibular nystagmus are generated. We propose a neural network model for the vestibule saccadic pathway, which shows dynamic adaptation of the quick phase parameters in order to faithfully reproduce the vestibular nystagmus

Progress in brain research, 2008

Saccadic oscillations are unwanted back-to-back saccades occurring one upon the other that produc... more Saccadic oscillations are unwanted back-to-back saccades occurring one upon the other that produce a high-frequency oscillation of the eyes (usually 15-30 Hz). These may occur transiently in normal subjects, for example, around the orthogonal axis of a purely horizontal or vertical saccade, during combined saccade-vergence gaze shifts or during blinks. Some subjects may produce saccadic oscillations at will, usually with convergence. Pathological, involuntary saccadic oscillations such as flutter and opsoclonus are prominent in certain diseases. Our recent mathematical model of the premotor circuit for generating saccades includes brainstem burst neurons in the paramedian pontine reticular formation (PPRF), which show the physiological phenomenon of post-inhibitory rebound (PIR). This model makes saccadic oscillations because of the positive feedback among excitatory and inhibitory burst neurons. Here we review our recent findings and hypotheses and show how they may be reproduced u...

Progress in brain research, 2008

Saccadic palsy is a reported complication of cardiac surgery. One case that came to autopsy showe... more Saccadic palsy is a reported complication of cardiac surgery. One case that came to autopsy showed midline pontine gliosis; however, in most cases, no lesions are evident on neuroimaging. Since the saccadic palsy may range from single large slow saccades to a "staircase" of very small saccades that are normal in speed, it seems plausible that more than one mechanism is possible. Here we postulate that, in those patients who make a staircase of small saccades, loss of cerebellar Purkinje cells could cause fastigial nucleus neurons to fire prematurely, thereby decelerating saccades via inhibitory burst neurons.

American Journal of Ophthalmology, 2007

Saccades are rapid eye movements that redirect the fovea from one object to another. A great deal... more 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. Abbreviations: cFN ¼ caudal FN; cMRF ¼ central mesencephalic reticular formation; EBN ¼ excitatory PBN; FN ¼ fastigial nucleus; FNN ¼ FN neuron; IBN ¼ inhibitory PBN; IN ¼ internuclear neuron; INC ¼ interstitial nucleus of Cajal; LLBN ¼ long-lead burst neuron; LR ¼ lateral rectus muscle; MedRF ¼ medullary reticular formation; MN ¼ motor neuron; MR ¼ medial rectus; MVN ¼ medial vestibular nucleus; NMDA ¼ n-methyl D-aspartate; NPH ¼ nucleus prepositus hypoglossi; NRTP ¼ nucleus reticularis tegmenti pontis; OPN ¼ omnipause neuron; PBN ¼ premotor burst neuron; PG ¼ pulse generator; PMT ¼ paramedian tract; PPRF ¼ paramedian pontine reticular formation; riMLF ¼ rostral interstitial nucleus of the medial longitudinal fasciculus; RIP ¼ raphe interpositus nucleus; SC ¼ superior colliculus; SCBN ¼ SC burst neurons; SCBUN ¼ SC build-up neurons; SO ¼ superior oblique; SR ¼ superior rectus; T-channel ¼ T-type Ca 2+ channel; VIn ¼ sixth nerve

Journal of Neurophysiology, 2003

We characterized the interaural translational vestibulo-ocular reflex (tVOR) in six normal humans... more We characterized the interaural translational vestibulo-ocular reflex (tVOR) in six normal humans to brief (~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 four of six subjects, gains were the same as during binocular viewing and scaled closely with vergence angle.

Journal of Translational Medicine, 2008

Background: Essential tremor (ET) is the most common movement disorder and its pathophysiology is... more Background: Essential tremor (ET) is the most common movement disorder and its pathophysiology is unknown. We hypothesize that increased membrane excitability in motor circuits has a key role in the pathogenesis of ET. Specifically, we propose that neural circuits controlling ballistic movements are inherently unstable due to their underlying reciprocal innervation. Such instability is enhanced by increased neural membrane excitability and the circuit begins to oscillate. These oscillations manifest as tremor.

We developed the head impulse testing device (HITD) based on an inertial sensing system allowing ... more We developed the head impulse testing device (HITD) based on an inertial sensing system allowing to investigate the functional performance of the rotational vestibulo-ocular reflex (VOR) by testing its gaze stabilization ability, independently from the subject's visual acuity, in response to head impulses at different head angular accelerations ranging from 2000 to 7000 deg/s 2 . HITD was initially tested on 22 normal subjects, and a method to compare the results from a single subject (patient) with those from controls was set up. As a pilot study, we tested the HITD in 39 dizzy patients suffering, non-acutely, from different kinds of vestibular disorders. The results obtained with the HITD were comparable with those from the clinical head impulse test (HIT), but an higher number of abnormalities was detectable by HITD in the central vestibular disorders group. The HITD appears to be a promising tool for detecting abnormal VOR performance while providing information on the functional performance of the rotational VOR, and can provide a valuable assistance to the clinical evaluation of patients with vestibular disorders.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2008

The rotational vestibulo-ocular reflex (rVOR) contributes to gaze stabilitization by compensating... more The rotational vestibulo-ocular reflex (rVOR) contributes to gaze stabilitization by compensating head rotational movements sensed by the semicircular canals (SCC). The CNS improves the performance of the horizontal rVOR through the so called velocity storage mechanism (VSM). However the properties of the VSM in response to pitch rotations are less well known. We recorded eye movements evoked by whole-body constant-velocity pitch rotations about an earth-horizontal, interaural axis in four healthy human subjects. Subjects were tumbled forward, and backward, at 60 deg/s for over one minute using a 3D turntable. In these conditions also the otoliths contribute to the perception of head rotation because they sense the changes in direction of the gravity vector. The vertical slow phase velocity (SPV) responses show the typical exponential decay of the rVOR and a residual, otolith-driven sinusoidal modulation with a bias. Here the estimates of the contributions coming from the otoliths a...

Experimental Brain Research, 2005

The human saccadic system is potentially unstable and may oscillate if the burst neurons, which g... more 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 saccadevergence, normal subjects and the cerebellar patient developed small-amplitude (0.1-0.5°), 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 (~0.7°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 postinhibitory 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.

Annals of the New York Academy of Sciences, 2002

The study of human cerebellar patients and monkeys with experimental cerebellar lesions has taugh... more 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.

Journal of Neurophysiology, 2006

Brief smooth eye-velocity responses to target position steps have been reported during smooth pur... more Brief smooth eye-velocity responses to target position steps have been reported during smooth pursuit. We investigated position-error responses in eight healthy human subjects, comparing the effects of a step-ramp change in target position when imposed on steady-state smooth pursuit, vestibuloocular reflex (VOR) slow phases, or fixation. During steadystate pursuit or VOR, the target performed a step-ramp movement in the same or in the opposite direction relative to ongoing eye movements. When the step was directed backward relative to steady-state smooth pursuit, eye velocity transiently decreased (1.3 Ϯ 0.4°/s; average peak change in amplitude Ϯ SD), beginning about 100 ms after the step. The amplitude of position-error responses varied inversely with the step size. In contrast, there was little or no response in trials with forward steps during steady-state smooth pursuit, when step-ramps were imposed on VOR or when smooth pursuit began from fixation. We hypothesize that during ongoing smooth tracking when a sudden shift in target position is detected the pursuit system compares the direction of ongoing eye velocity with the relative positional error on the retina. In the case of different relative directions between ongoing tracking and a new target eccentricity, a position-error response toward the new target is initiated. Such a mechanism might help the smooth pursuit system to respond better to changes in target direction. These experimental findings were simulated by a mathematical model of smooth pursuit by implementing direction-dependent behavior with a position-error gating mechanism.

Progress in Brain Research, 2008

To investigate the contribution of the vestibular velocity-storage mechanism (VSM) to the vertica... more To investigate the contribution of the vestibular velocity-storage mechanism (VSM) to the vertical rotational vestibulo-ocular reflex (rVOR) we recorded eye movements evoked by off-vertical axis rotation (OVAR) using whole-body constant-velocity pitch rotations about an earth-horizontal, interaural axis in four healthy human subjects. Subjects were tumbled forward, and backward, at 60 deg/s for over 1 min using a 3D turntable. Slow-phase velocity (SPV) responses were similar to the horizontal responses elicited by OVAR along the body longitudinal axis, ('barbecue' rotation), with exponentially decaying amplitudes and a residual, otolith-driven sinusoidal response with a bias. The time constants of the vertical SPV ranged from 6 to 9 s. These values are closer to those that reflect the dynamic properties of vestibular afferents than the typical 20 s produced by the VSM in the horizontal plane, confirming the relatively smaller contribution of the VSM to these vertical responses. Our preliminary results also agree with the idea that the VSM velocity response aligns with the direction of gravity. The horizontal and torsional eye velocity traces were also sinusoidally modulated by the change in gravity, but showed no exponential decay.

ABSTRACT IntroductionAdaptive NetworksNeural NetworksLearningStructural AdaptationNeuro-Fuzzy Net... more ABSTRACT IntroductionAdaptive NetworksNeural NetworksLearningStructural AdaptationNeuro-Fuzzy NetworksGenetic Algorithms

The question of how the central nervous system can distinguish tilt with respect to gravity from ... more The question of how the central nervous system can distinguish tilt with respect to gravity from inertial acceleration due to translation in a horizontal plane using vestibular information has long been debated by the scientific community over the past ten years. Recently, it was hypothesized that such discrimination may be based on the multisensory integration of information provided by the otolith organs and the semicircular canals. Some evidence of such processing was found in the neural activity of cells in the fastigial nuclei and vestibular nuclei. To investigate the ability of the central nervous system to build an internal model of self motion based on vestibular signals, we developed an artificial vestibular sensor composed of accelerometers and gyroscopes providing movement data of the same nature as that transduced by the otoliths and canals, respectively. Here we show that the processing of these signals based on the multisensory integration hypothesis can be successfully used to discriminate tilt from translation and that the internal model based on such processing can successfully track angular and linear displacements over short periods of time.

Annals of the New York Academy of Sciences, 2005

Stabilization of images on the fovea during either fore/aft translation of a subject or fore/aft ... more 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.

IEEE Transactions on Biomedical Engineering, 2006

The latency of a response is one of the most frequently reported parameters when describing the c... more 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.

This study investigates the way in which the saccadic components (quick phases) of vestibular nys... more This study investigates the way in which the saccadic components (quick phases) of vestibular nystagmus are generated. We propose a neural network model for the vestibule saccadic pathway, which shows dynamic adaptation of the quick phase parameters in order to faithfully reproduce the vestibular nystagmus

Progress in brain research, 2008

Saccadic oscillations are unwanted back-to-back saccades occurring one upon the other that produc... more Saccadic oscillations are unwanted back-to-back saccades occurring one upon the other that produce a high-frequency oscillation of the eyes (usually 15-30 Hz). These may occur transiently in normal subjects, for example, around the orthogonal axis of a purely horizontal or vertical saccade, during combined saccade-vergence gaze shifts or during blinks. Some subjects may produce saccadic oscillations at will, usually with convergence. Pathological, involuntary saccadic oscillations such as flutter and opsoclonus are prominent in certain diseases. Our recent mathematical model of the premotor circuit for generating saccades includes brainstem burst neurons in the paramedian pontine reticular formation (PPRF), which show the physiological phenomenon of post-inhibitory rebound (PIR). This model makes saccadic oscillations because of the positive feedback among excitatory and inhibitory burst neurons. Here we review our recent findings and hypotheses and show how they may be reproduced u...

Progress in brain research, 2008

Saccadic palsy is a reported complication of cardiac surgery. One case that came to autopsy showe... more Saccadic palsy is a reported complication of cardiac surgery. One case that came to autopsy showed midline pontine gliosis; however, in most cases, no lesions are evident on neuroimaging. Since the saccadic palsy may range from single large slow saccades to a "staircase" of very small saccades that are normal in speed, it seems plausible that more than one mechanism is possible. Here we postulate that, in those patients who make a staircase of small saccades, loss of cerebellar Purkinje cells could cause fastigial nucleus neurons to fire prematurely, thereby decelerating saccades via inhibitory burst neurons.

American Journal of Ophthalmology, 2007

Saccades are rapid eye movements that redirect the fovea from one object to another. A great deal... more 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. Abbreviations: cFN ¼ caudal FN; cMRF ¼ central mesencephalic reticular formation; EBN ¼ excitatory PBN; FN ¼ fastigial nucleus; FNN ¼ FN neuron; IBN ¼ inhibitory PBN; IN ¼ internuclear neuron; INC ¼ interstitial nucleus of Cajal; LLBN ¼ long-lead burst neuron; LR ¼ lateral rectus muscle; MedRF ¼ medullary reticular formation; MN ¼ motor neuron; MR ¼ medial rectus; MVN ¼ medial vestibular nucleus; NMDA ¼ n-methyl D-aspartate; NPH ¼ nucleus prepositus hypoglossi; NRTP ¼ nucleus reticularis tegmenti pontis; OPN ¼ omnipause neuron; PBN ¼ premotor burst neuron; PG ¼ pulse generator; PMT ¼ paramedian tract; PPRF ¼ paramedian pontine reticular formation; riMLF ¼ rostral interstitial nucleus of the medial longitudinal fasciculus; RIP ¼ raphe interpositus nucleus; SC ¼ superior colliculus; SCBN ¼ SC burst neurons; SCBUN ¼ SC build-up neurons; SO ¼ superior oblique; SR ¼ superior rectus; T-channel ¼ T-type Ca 2+ channel; VIn ¼ sixth nerve

Journal of Neurophysiology, 2003

We characterized the interaural translational vestibulo-ocular reflex (tVOR) in six normal humans... more We characterized the interaural translational vestibulo-ocular reflex (tVOR) in six normal humans to brief (~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 four of six subjects, gains were the same as during binocular viewing and scaled closely with vergence angle.

Journal of Translational Medicine, 2008

Background: Essential tremor (ET) is the most common movement disorder and its pathophysiology is... more Background: Essential tremor (ET) is the most common movement disorder and its pathophysiology is unknown. We hypothesize that increased membrane excitability in motor circuits has a key role in the pathogenesis of ET. Specifically, we propose that neural circuits controlling ballistic movements are inherently unstable due to their underlying reciprocal innervation. Such instability is enhanced by increased neural membrane excitability and the circuit begins to oscillate. These oscillations manifest as tremor.