Papers by Giovanni Bertolini
Journal of Neurology
Concussed patients with chronic symptoms commonly report dizziness during exposure to environment... more Concussed patients with chronic symptoms commonly report dizziness during exposure to environments with complex visual stimuli (e.g. supermarket aisles, busy crossroads). Such visual induced dizziness is well-known in patients with vestibular deficits, in whom it indicates an overreliance on visual cues in sensory integration. Considering that optokinetic after-nystagmus (OKAN) reflects the response of the central network integrating visual and vestibular self-motion signals (velocity storage network), we investigated OKAN in 71 patients [17 (23.9%) females, 30.36 ± 9.05 years old] who suffered from persistent symptoms after a concussion and presented clinical signs suggesting visual dependence. Data were retrospectively compared with 21 healthy individuals [13 (61.9%) females, 26.29 ± 10.00 years old]. The median values of the slow cumulative eye position and of the time constant of OKAN were significantly higher in patients than in healthy individuals (slow cumulative eye position...
Frontiers in Neurology
Dizziness, slow visual tracking, or blurred vision following active head (or body) movements are ... more Dizziness, slow visual tracking, or blurred vision following active head (or body) movements are among the most common symptoms reported following sport-related concussion, often related to concurrent dysfunctions of the vestibular system. In some cases, symptoms persist even if bedside and auxiliary standard vestibular tests are unremarkable. New functional tests have been developed in recent years to objectify neurological alterations that are not captured by standard tests. The functional head impulse test (fHIT) requires the patient to recognize an optotype that is briefly flashed during head rotations with various angular accelerations (2,001-6,000 deg/s 2) and assesses the proportion if correct answers (pca). 268 active professional athletes (23.70 ± 5.32y) from six different sports were tested using fHIT. Pca were analyzed both pooling head acceleration in the range of 2,001-6,000 deg/s 2 and computing a single pca value for each 1,000 deg/s 2 bin in the range 2,001-8,000 deg/s 2. No significant difference (p = 0.159) was found between responses to head impulses in the plane of horizontal (pca: 0.977) and vertical semicircular canals (pca: 0.97). The sport practiced had a major effect on the outcome of the fHIT. Handball players achieved a better performance (p < 0.001) than the whole athlete group, irrespective of the direction of head impulses. The pca achieved by athletes practicing snowboard, bob and skeleton were instead significantly below those of the whole athlete group (p < 0.001) but only when vertical head impulses were tested. Overall, pca declined with increasing head acceleration. The decline was particularly evident in the range not included in the standard fHIT exam, i.e., 6,001-8,000 deg/s 2 for horizontal and 5,001-8,000 deg/s 2 for vertical head impulses. When vertical head impulses were tested, athletes practicing snowboard, bob and skeleton (non-ball sports) showed, beside the lower overall pca, also a steeper decline as a function of vertical head acceleration. The findings suggest that: (1) functional VOR testing can help understanding sport-specific VOR requirements; (2) the fHIT is able to detect and objectify subtle, sport-specific changes of functional VOR performance; (3) if sport-specific normative values are used, the fHIT test procedure needs to be optimized, starting from the highest acceleration to minimize the number of head impulses.
PLOS ONE
Objectives We propose a bottom-up, machine-learning approach, for the objective vestibular and ba... more Objectives We propose a bottom-up, machine-learning approach, for the objective vestibular and balance diagnostic data of concussion patients, to provide insight into the differences in patients' phenotypes, independent of existing diagnoses (unsupervised learning). Methods Diagnostic data from a battery of validated balance and vestibular assessments were extracted from the database of the Swiss Concussion Center. The desired number of clusters within the patient database was estimated using Calinski-Harabasz criteria. Complex (self-organizing map, SOM) and standard (k-means) clustering tools were used, and the formed clusters were compared. Results A total of 96 patients (81.3% male, age (median [IQR]): 25.0[10.8]) who were expected to suffer from sports-related concussion or post-concussive syndrome (52[140] days between diagnostic testing and the concussive episode) were included. The cluster evaluation indicated dividing the data into two groups. Only the SOM gave a stable clustering outcome, dividing the patients in group-1 (n = 38) and group-2 (n = 58). A large significant difference was found for the caloric summary score for the maximal speed of the slow phase, where group-1 scored 30.7% lower than group-2 (27.6[18.2] vs. 51.0[31.0]). Group-1 also scored significantly lower on the sensory organisation test composite score (69.0[22.3] vs. 79.0 [10.5]) and higher on the visual acuity (-0.03[0.33] vs.-0.14[0.12]) and dynamic visual acuity (0.38[0.84] vs. 0.20[0.20]) tests. The importance of caloric, SOT and DVA, was supported by the PCA outcomes. Group-1 tended to report headaches, blurred vision and balance problems more frequently than group-2 (>10% difference).
Brain and cognition, 2018
Line bisection studies generally find a left-to-right shift in bisection bias with increasing dis... more Line bisection studies generally find a left-to-right shift in bisection bias with increasing distance between the observer and the target line, which may be explained by hemispheric differences in the processing of proximo-distal information. In the present study, the segregation between near and far space was further characterized across the motor system and contextual cues. To this aim, 20 right-handed participants were required to perform a manual bisection task of simple lines presented at three different distances (60, 90, 120 cm). Importantly, the horizontal spatial location of the line was manipulated along with the viewing distance to investigate more deeply the hemispheric engagement in the transition from near to far space. As the motoric component of the manual task producing activations of left premotor and motor areas may be partially responsible for the observed transition, participants were also involved in an ocular bisection task. Further, participants were require...
Frontiers in neurology, 2017
Faster trains require tilting of the cars to counterbalance the centrifugal forces during curves.... more Faster trains require tilting of the cars to counterbalance the centrifugal forces during curves. Motion sensitive passengers, however, complain of discomfort and overt motion sickness. A recent study comparing different control systems in a tilting train, suggested that the delay of car tilts relative to the curve of the track contributes to motion sickness. Other aspects of the motion stimuli, like the lateral accelerations and the car jitters, differed between the tested conditions and prevented a final conclusion on the role of tilt delay. Nineteen subjects were tested on a motorized 3D turntable that simulated the roll tilts during yaw rotations experienced on a tilting train, isolating them from other motion components. Each session was composed of two consecutive series of 12 ideal curves that were defined on the bases of recordings during an actual train ride. The simulated car tilts started either at the beginning of the curve acceleration phase (no-delay condition) or with...
Journal of neurology, Jan 28, 2017
Motion sickness is associated with a variety of autonomic symptoms, presumably due to proximity o... more Motion sickness is associated with a variety of autonomic symptoms, presumably due to proximity or functional interconnectivity between the autonomic centers in the brainstem and the vestibular system. A direct influence of the vestibular system on cardiovascular variables, defined as the vestibulo-sympathetic reflex, has been reported previously. Our aim was to investigate the sudomotor components of the autonomic responses associated with motion sickness during passive cross-coupling stimulation ("roll while rotating"). Healthy subjects (n = 17) were rotated at 40°/s around an earth-vertical yaw axis alone and in combination with sinusoidal roll oscillations (0.2 Hz). Motion sickness was assessed verbally every minute using a 1-10 scale, while recording DC and AC skin conductance levels (SCL) from the forehead. Yaw rotation alone provoked neither motion sickness nor variations of forehead sweating. Yet during cross-coupling stimulation all subjects reported motion sickne...
Journal of neurophysiology, 2017
Accurate and precise estimates of direction of gravity are essential for spatial orientation. Acc... more Accurate and precise estimates of direction of gravity are essential for spatial orientation. According to Bayesian theory, multisensory vestibular, visual and proprioceptive input is centrally integrated in a weighted fashion based on the reliability of the component sensory signals. For otolithic input, a decreasing signal-to-noise ratio was demonstrated with increasing roll-angle. We hypothesized that the weights of vestibular (otolithic) and extra-vestibular (visual/proprioceptive) sensors are roll-angle dependent and predicted an increased weight of extra-vestibular cues with increasing roll-angle, potentially following the Bayesian hypothesis. To probe this concept, the subjective visual vertical (SVV) was assessed in different roll-positions (≤±120°, steps=30°, n=10) with/without presenting an optokinetic stimulus (velocity=±60°/s). The optokinetic stimulus biased the SVV towards the direction of stimulus-rotation for roll-angles ≥±30° (p<0.005). Offsets grew from 3.9±1.8°...
The Journal of Physiology, 2016
Key points The cerebellum is the core structure controlling gaze stability. Chronic cerebellar ... more Key points The cerebellum is the core structure controlling gaze stability. Chronic cerebellar diseases and acute alcohol intoxication affect cerebellar function, inducing, among others, gaze instability as Gaze-evoked nystagmus. Gaze-evoked nystagmus is characterized by increased centripetal eye-drift. It is used as an important diagnostic sign for patients with cerebellar degeneration and to assess the "driving while intoxicated" condition. We quantified the effect of alcohol on gaze-holding using an approach allowing, for the first time, the comparison of deficits induced by alcohol intoxication and cerebellar degeneration. Our results showed that alcohol intoxication induces a twofold increase of centripetal eye-drift. We establish analysis techniques for using controlled alcohol-intake as a model to help the study of cerebellar deficits. The observed similarity between the effect of alcohol and the clinical signs observed in cerebellar patients suggest a possible pathomechanism for gazeholding deficits.
Annals of the New York Academy of Sciences, Jun 1, 2009
Single-unit recordings of vestibular afferents from the semicircular canals of squirrel monkeys h... more Single-unit recordings of vestibular afferents from the semicircular canals of squirrel monkeys have shown that the cupular time constant (T c) is between 5 and 6 sec. Such recordings obviously cannot be performed in humans, and the corresponding values have thus been inferred to be somewhat longer based on their size and on the cupulaendolymph system. The ocular motor response of the rotational vestibulo-ocular reflex (rVOR) is characterized by longer time constants, typically between 15 and 20 sec, due to the so-called velocity storage mechanism (VSM), which prolongs the time constant of the afferents through central processing. Recent studies have attempted to determine the time constant of the cupula by fitting the slow phase velocity (SPV) of the response to postrotational stimuli using a mathematical model of the rVOR processing. To this goal they considered the processing of head velocity due to the peripheral vestibular organs and to the VSM. The resulting estimates of T c are lower than expected, averaging about 4 sec. These modeling approaches, though, neglect both the processing of the final common pathway and the adaptation shown by the discharge of primary vestibular afferents. Here we argue that such an approach may be bound to underestimate the duration of the rVOR time constants.
Investigative ophthalmology & visual science, 2016
Impairment of visual acuity (VA) can be seen early on in various diseases and has a major impact ... more Impairment of visual acuity (VA) can be seen early on in various diseases and has a major impact on patients' daily activities. Zebrafish is an important model for studying visual disorders. We developed a new method in zebrafish larva to easily and precisely measure the VA, which should allow for better estimation of affected vision such as after genetic manipulation or pharmacologic intervention. We used an optokinetic reflex (OKR) paradigm with a staircase technique to estimate VA of zebrafish larva. Consistent eye displacements were used as the indicator for OKR. We measured VA and determined the dependence of VA on clockwise and counterclockwise horizontal stimulus directions. Visual acuity in zebrafish larva was estimated to be 0.179 ± 0.013 cyc/deg binocularly and 0.129 ± 0.008 cyc/deg (left eye) and 0.128 ± 0.012 cyc/deg (right eye) monocularly. We found within single subjects spatial frequency thresholds that showed highly significant differences between the two horizon...
Frontiers in Neurology, 2016
Motion sickness is a common disturbance occurring in healthy people as a physiological response t... more Motion sickness is a common disturbance occurring in healthy people as a physiological response to exposure to motion stimuli that are unexpected on the basis of previous experience. The motion can be either real, and therefore perceived by the vestibular system, or illusory, as in the case of visual illusion. A multitude of studies has been performed in the last decades, substantiating different nauseogenic stimuli, studying their specific characteristics, proposing unifying theories, and testing possible countermeasures. Several reviews focused on one of these aspects; however, the link between specific nauseogenic stimuli and the unifying theories and models is often not clearly detailed. Readers unfamiliar with the topic, but studying a condition that may involve motion sickness, can therefore have difficulties to understand why a specific stimulus will induce motion sickness. So far, this general audience struggles to take advantage of the solid basis provided by existing theories and models. This review focuses on vestibular-only motion sickness, listing the relevant motion stimuli, clarifying the sensory signals involved, and framing them in the context of the current theories.
Journal of neurophysiology, Jan 13, 2016
Inferring object orientation in the surroundings heavily depends on our internal sense of directi... more Inferring object orientation in the surroundings heavily depends on our internal sense of direction of gravity. Previous research showed that this sense is based on the integration of multiple information sources, including visual, vestibular (otolithic) and somatosensory signals. The individual noise characteristics and contributions of these sensors can be studied using spatial orientation tasks, such as the subjective visual vertical (SVV) task. A recent study reported that patients with complete bilateral vestibular loss perform similar as healthy controls on these tasks, from which it was conjectured that the noise levels of both otoliths and body somatosensors are roll-tilt dependent. Here, we tested this hypothesis in ten healthy human subjects by roll-tilting the head relative to the body to dissociate tilt-angle dependencies of otolith and somatosensory noise. Using a psychometric approach, we measured bias and variability in perceived orientation of a briefly flashed line ...
Cortex, 2016
The following work is licensed under a Creative Commons: Attribution-NonCommercial-NoDerivatives ... more The following work is licensed under a Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.
Journal of Neurology, 2015
The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem neural velocityt... more The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem neural velocityto-position integrator to provide stable gaze holding. In healthy humans small-amplitude centrifugal nystagmus is present at extreme gaze-angles, with a non-linear relationship between eye-drift velocity and eye eccentricity. In cerebellar degeneration this calibration is impaired, resulting in pathological gaze-evoked nystagmus (GEN). For cerebellar dysfunction, increased eye drift may be present at any gaze angle (reflecting pure scaling of eye drift found in controls) or restricted to far-lateral gaze (reflecting changes in shape of the non-linear relationship) and resulting eyed-drift patterns could be related to specific disorders. We recorded horizontal eye positions in 21 patients with cerebellar neurodegeneration (gaze-angle = ±40°) and clinically confirmed GEN. Eye-drift velocity, linearity and symmetry of drift were determined. MR-images were assessed for cerebellar atrophy. In our patients, the relation between eye-drift velocity and gaze eccentricity was non-linear, yielding (compared to controls) significant GEN at gaze-eccentricities 20°. Pure scaling was most frequently observed (n = 10/18), followed by pure shape-changing (n = 4/18) and a mixed pattern (n = 4/18). Pure shape-changing patients were significantly (p = 0.001) younger at disease-onset compared to pure scaling patients. Atrophy centered around the superior/dorsal vermis, flocculus/paraflocculus and dentate nucleus and did not correlate with the specific drift behaviors observed. Eye drift in cerebellar degeneration varies in magnitude; however, it retains its non-linear properties. With different drift patterns being linked to age at disease-onset, we propose that the gaze-holding pattern (scaling vs. shape-changing) may discriminate early-from late-onset cerebellar degeneration. Whether this allows a distinction among specific cerebellar disorders remains to be determined.
Cognition, Jan 8, 2015
The present study examined whether traveling through serially-ordered verbal memories exploits ov... more The present study examined whether traveling through serially-ordered verbal memories exploits overt visuospatial attentional resources. In a three-phase behavioral study, five single-digits were presented sequentially at one spatial location in phase 1, while recognition and verbal recall were tested in phases 2 and 3, respectively. Participants' spontaneous eye movements were registered along with the verbal responses. Results showed that the search and the retrieval of serially-ordered information were mediated by spontaneous ocular movements. Specifically, recognizing middle items of the memorized sequence required longer inspection times and, importantly, a greater involvement of overt attentional resources, than recognizing the serially first-presented item and, to a lesser extent, the last-presented item. Moreover, serial order was found to be spatially encoded from left-to-right, as eye position during vocal responses deviated the more to the right, the later the serial ...
PLOS ONE, 2015
INTRODUCTION: Impaired balance control is a hallmark symptom in Parkinson's disease (PD). Altered... more INTRODUCTION: Impaired balance control is a hallmark symptom in Parkinson's disease (PD). Altered sensory-motor integration contributes to the deficiency. We aimed to determine whether impaired vestibular signal processing added to the disorder. We exposed patients (N = 11; 68±6y) and age-matched healthy subjects (hS: N = 19; 65±11y) on a motion platform in complete darkness to two consecutive forward tilt movements (12 series; N = 24; overall 288 trials) and asked them to indicate which tilt was perceived larger. By combing tilt movements with translations we manipulated vestibular sensory input in order to investigate whether putative impairment resulted from a deficiency of the sensory organs (semicircular canals in 'single-SCC-cue-condition', otoliths in 'single-OT-cue-condition') themselves or to a sensory integration failure ('multi-cue-condition'). RESULTS: Tilt discrimination in the multi-cue-condition was inferior in patients compared to hS (p = 0.02). No significant differences between the two groups were found for both single-cue-conditions. Comparison of multi-cue-condition with a prediction resulting from the combination of both single-cue-conditions by optimal observer theory revealed that patients (p = 0.04), in contrast to hS, failed to efficiently combine SCC and OT information to improve tilt perception. CONCLUSION: We found that PD patients distinguished forward tilts less precise than hS, suggesting impaired vestibular perception. Tilt discrimination in patients, moreover, did not improve as much as in hS in conditions where both SCC and OT information was available compared to conditions where only SCC or OT cues were activated. The latter provides evidence that tilt misperception in PD most likely results from an integration failure of vestibular signals.
Journal of neurophysiology, 2014
The subjective visual vertical (SVV) indicates perceived direction of gravity. Even in healthy hu... more The subjective visual vertical (SVV) indicates perceived direction of gravity. Even in healthy human subjects, roll angle-dependent misestimations, roll overcompensation (A-effect, head-roll > 60° and <135°) and undercompensation (E-effect, head-roll < 60°), occur. Previously, we demonstrated that, after prolonged roll-tilt, SVV estimates when upright are biased toward the preceding roll position, which indicates that perceived vertical (PV) is shifted by the prior tilt (Tarnutzer AA, Bertolini G, Bockisch CJ, Straumann D, Marti S. PLoS One 8: e78079, 2013). Hypothetically, PV in any roll position could be biased toward the previous roll position. We asked whether such a "global" bias occurs or whether the bias is "local". The SVV of healthy human subjects (N = 9) was measured in nine roll positions (-120° to +120°, steps = 30°) after 5 min of roll-tilt in one of two adaptation positions (±90°) and compared with control trials without adaptation. After a...
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Papers by Giovanni Bertolini