Gaze Strategies During Obstacle Negotiation in the Presence of Distractors: a Virtual Reality Based Assessment

Vision actively influences the gait, and older adults show altered visual patterns compared to their younger counterpart when approaching challenges in the travel path. Attentional distractors influence the motor strategies during obstacle crossing. In rehabilitation, treadmill and virtual reality (VR) are commonly used to train gait. The VR technology allows for repeatable, safe and full variable control tasks and is well accepted by the patients. The gaze behavior when watching at videos of a first perspective walking is similar to that adopted in the real world and the training of the gaze is effective to improve the accuracy of the gait. Therefore, the integration of the gaze monitoring in existing VR-based gait rehabilitation protocols could both give insights in the visuo-motor strategy adopted in challenging conditions and could improve the gait rehabilitation effectiveness. The research presented in this thesis consisted in the assessment of the visuo-motor strategies of young and older adults during obstacles crossing in a projected VR environment with visual distractors. The first part of the project consisted in testing a set-up allowing for such an assessment with a remote eye-tracking system. The tested remote eye-tracker was demonstrated to be reliable for treadmill walking, with gaze measurements comparable to those got for the static conditions. The second part of the project aimed at studying the effect of distractors during obstacle avoidance, by making young and older adults walking on a treadmill while navigating a purposely depicted VR world. Young and older adults showed different visual scan patterns of the scene. This study highlights the visuo-motor strategy of young and older adults in a set-up similar to those recently used in gait rehabilitation and showed that the two populations are distinguishable by the adopted visual strategy. This and further investigations are important to address better the gait rehabilitation interventions

Use of a remote eye-tracker for the analysis of gaze during treadmill walking and visual stimuli exposition

The knowledge of the visual strategies adopted while walking in cognitively engaging environments is extremely valuable. Analyzing gaze when a treadmill and a virtual reality environment are used as motor rehabilitation tools is therefore critical. Being completely unobtrusive, remote eye-trackers are the most appropriate way to measure the point of gaze. Still, the point of gaze measurements are affected by experimental conditions such as head range of motion and visual stimuli. This study assesses the usability limits and measurement reliability of a remote eye-tracker during treadmill walking while visual stimuli are projected. During treadmill walking, the head remained within the remote eye-tracker workspace. Generally, the quality of the point of gaze measurements declined as the distance from the remote eye-tracker increased and data loss occurred for large gaze angles. The stimulus location (a dot-target) did not influence the point of gaze accuracy, precision, and trackability during both standing and walking. Similar results were obtained when the dot-target was replaced by a static or moving 2D target and "region of interest" analysis was applied. These findings foster the feasibility of the use of a remote eye-tracker for the analysis of gaze during treadmill walking in virtual reality environments

A Cross-Recurrence Analysis of the Pupil Size Fluctuations in Steady Scotopic Conditions

Pupil size fluctuations during stationary scotopic conditions may convey information about the cortical state activity at rest. An important link between neuronal network state modulation and pupil fluctuations is the cholinergic and noradrenergic neuromodulatory tone, which is active at cortical level and in the peripheral terminals of the autonomic nervous system (ANS). This work aimed at studying the low- and high-frequency coupled oscillators in the autonomic spectrum (0–0.45 Hz) which, reportedly, drive the spontaneous pupillary fluctuations. To assess the interaction between the oscillators, we focused on the patterns of their trajectories in the phase-space. Firstly, the frequency spectrum of the pupil signal was determined by empirical mode decomposition. Secondly, cross-recurrence quantification analysis was used to unfold the non-linear dynamics. The global and local patterns of recurrence of the trajectories were estimated by two parameters: determinism and entropy. An elliptic region in the entropy-determinism plane (95% prediction area) yielded health-related values of entropy and determinism. We hypothesize that the data points inside the ellipse would likely represent balanced activity in the ANS. Interestingly, the Epworth Sleepiness Scale scores scaled up along with the entropy and determinism parameters. Although other non-linear methods like Short Time Fourier Transform and wavelets are usually applied for analyzing the pupillary oscillations, they rely on strong assumptions like the stationarity of the signal or the a priori knowledge of the shape of the single basis wave. Instead, the cross-recurrence analysis of the non-linear dynamics of the pupil size oscillations is an adaptable diagnostic tool for identifying the different weight of the autonomic nervous system components in the modulation of pupil size changes at rest in non-luminance conditions

A prediction of bone remodeling thanks to a mechanical signal on cells - Predizione del rimodellamento osseo a partire da un segnale meccanico sulle cellule

This text wants to explore the process of bone remodeling. The idea supported is that the signal, the cells acquire and which suggest them to change in their architectural conformation, is the potential difference on the free boundaries surfaces of collagen fibers. These ones represent the bone in the nanoscale. This work has as subject a multiscale model. Lots of studies have been made to try to discover the relationship between a macroscopic external bone load and the cellular scale. The tree first simulations have been a longitudinal, a flexion and a transversal compression force on a full longitudinal fiber 0-0 sample. The results showed first the great difference between a fully longitudinal stress and a flexion stress. Secondly a decrease in the potential difference has been observed in the transversal force configuration, suggesting that such a signal could be taken as the one, who leads the bone remodeling. To also exclude that the obtained results was not to attribute to a piezoelectric collagen effect and not to a mechanical load, different coupling analyses have been developed. Such analyses show this effect is really less important than the one the mechanical load is responsible of. At this point the work had to explore how bone remodeling could develop. The analyses involved different geometry and fibers percentage. Moreover at the beginning the model was to manually implement. The author, after an initial improvement of it, provided to implement a standalone version thanks to integration between Comsol Multiphysic, Matlab and Excel

Autosomal recessive cerebellar ataxias: a diagnostic classification approach according to ocular features

Autosomal recessive cerebellar ataxias (ARCAs) are a heterogeneous group of neurodegenerative disorders affecting primarily the cerebellum and/or its afferent tracts, often accompanied by damage of other neurological or extra-neurological systems. Due to the overlap of clinical presentation among ARCAs and the variety of hereditary, acquired, and reversible etiologies that can determine cerebellar dysfunction, the differential diagnosis is challenging, but also urgent considering the ongoing development of promising target therapies. The examination of afferent and efferent visual system may provide neurophysiological and structural information related to cerebellar dysfunction and neurodegeneration thus allowing a possible diagnostic classification approach according to ocular features. While optic coherence tomography (OCT) is applied for the parametrization of the optic nerve and macular area, the eye movements analysis relies on a wide range of eye-tracker devices and the application of machine-learning techniques. We discuss the results of clinical and eye-tracking oculomotor examination, the OCT findings and some advancing of computer science in ARCAs thus providing evidence sustaining the identification of robust eye parameters as possible markers of ARCAs. Copyright © 2024 Lopergolo, Rosini, Pretegiani, Bargagli, Serchi and Rufa

Anti-Saccades in Cerebellar Ataxias Reveal a Contribution of the Cerebellum in Executive Functions

Objective: Increasing evidence suggests a cerebellar contribution to modulate cognitive aspects of motor behavior and executive functions. Supporting findings come from studies on patients with neurodegenerative diseases, in which however, given the extent of the disease, the specific role of the cerebellum, could not be clearly isolated. Anti-saccades are considered a sensitive tool to test executive functions. The anti-saccade underlying neural network, consisting of different cortical areas and their downstream connections including the lateral cerebellum, has been largely clarified. To separate the role of the cerebellum with respect to other cortical structures in executive control, we compared the anti-saccade performances in two distinct cohorts of patients with cerebellar disorders (with and without cerebral cortical involvement). Methods: Eye movements during the execution of anti-saccades were recorded in 12 patients with spinocerebellar ataxia type 2 (a cortical-subcortical neurodegenerative disease), 10 patients with late onset cerebellar ataxia (an isolated cerebellar atrophy), and 34 matched controls. Results: In the anti-saccade task, besides dynamic changes already demonstrated in the pro-saccades of these patients, we found in both groups of cerebellar patients prolonged latency with larger variability than normal and increased directional error rate. Errors, however, were corrected by cerebellar patients as frequently as normal. No significant differences were found in patients with and without cortical involvement. Conclusion: Our results indicate, in a large cohort of cerebellar patients, that the cerebellum plays a critical role in the regulation of executive motor control not only, as well known, by controlling the end of a movement, but also modulating its initiation and reducing reflexive responses that would perturb voluntary actions

The role of dentate nuclei in human oculomotor control: Insights from cerebrotendinous xanthomatosis

Key points: A cerebellar dentate nuclei (DN) contribution to volitional oculomotor control has recently been hypothesized but not fully understood. Cerebrotendinous xanthomatosis (CTX) is a rare neurometabolic disease typically characterized by DN damage. In this study, we compared the ocular movement characteristics of two sets of CTX patients, with and without brain MRI evidence of DN involvement, with a set of healthy subjects. Our results suggest that DN participate in voluntary behaviour, such as the execution of antisaccades, and moreover are involved in controlling the precision of the ocular movement. The saccadic abnormalities related to DN involvement were independent of global and regional brain atrophy. Our study confirms the relevant role of DN in voluntary aspects of oculomotion and delineates specific saccadic abnormalities that could be used to detect the involvement of DN in other cerebellar disorders. It is well known that the medial cerebellum controls saccadic speed and accuracy. In contrast, the role of the lateral cerebellum (cerebellar hemispheres and dentate nuclei, DN) is less well understood. Cerebrotendinous xanthomatosis (CTX) is a lipid storage disorder due to mutations in CYP27A1, typically characterized by DN damage. CTX thus provides a unique opportunity to study DN in human oculomotor control. We analysed horizontal and vertical visually guided saccades and horizontal antisaccades of 19 CTX patients. Results were related to the presence/absence of DN involvement and compared with those of healthy subjects. To evaluate the contribution of other areas, abnormal saccadic parameters were compared with global and regional brain volumes. CTX patients executed normally accurate saccades with normal main sequence relationships, indicating that the brainstem and medial cerebellar structures were functionally spared. Patients with CTX executed more frequent multistep saccades and directional errors during the antisaccade task than controls. CTX patients with DN damage showed less precise saccades with longer latencies, and more frequent directional errors, usually not followed by corrections, than either controls or patients without DN involvement. These saccadic abnormalities related to DN involvement but were independent of global and regional brain atrophy. We hypothesize that two different cerebellar networks contribute to the metrics of a movement: the medial cerebellar structures determine accuracy, whereas the lateral cerebellar structures control precision. The lateral cerebellum (hemispheres and DN) also participates in modulating goal directed gaze behaviour, by prioritizing volitional over reflexive movements. Journal compilatio

Genotype-phenotype and OCT correlations in Autosomal Dominant Optic Atrophy related to OPA1 gene mutations: Report of 13 Italian families

Mutations in OPA1 are responsible of 32â\u80\u9389% cases of Autosomal Dominant Optic Atrophy (ADOA). OPA1 ADOA usually presents in childhood with bilateral, progressive visual loss due to retinal ganglion cells neurodegeneration, but environmental factors are supposed to influence onset and phenotype. Sixty Italian OPA1 mutations carriers (fifty-two symptomatic), belonging to thirteen families, underwent neuro-ophthalmologic evaluation. Visual acuity (n = 60) and Optical Coherence Tomography (OCT) (n = 12) were compared in missense mutations (OPA-M) versus haploinsufficiency-inducing mutations (OPA-H) and correlated with age. Presence of plus phenotypes was investigated. We found four known mutations, the most common being missense c.1034G > A, and a new missense mutation, c1193A > C, the latter in a 54-yrs old female with late-onset phenotype. Visual acuity, colour sensitivity, and optic disc atrophy were sensitive indicators of disease. OCT RNFL thickness was reduced in OPA1 compared to controls. OPA-M showed worst visual acuity than OPA-H, but not more frequent plus-phenotype, observed only in four OPA-H patients. In both groups, visual acuity worsened with age. Our data confirm worst vision in OPA-M, but not increased plus-phenotype. Since most patients belonged to nine families from south-eastern Sicily (a famous region for the cult of St. Lucy, patron of the blinds) local genetic and environmental factors might have accounted for the low occurrence of plus-phenotypes

Anti-Saccades in Cerebellar Ataxias Reveal a Contribution of the Cerebellum in Executive Functions

ObjectiveIncreasing evidence suggests a cerebellar contribution to modulate cognitive aspects of motor behavior and executive functions. Supporting findings come from studies on patients with neurodegenerative diseases, in which however, given the extent of the disease, the specific role of the cerebellum, could not be clearly isolated. Anti-saccades are considered a sensitive tool to test executive functions. The anti-saccade underlying neural network, consisting of different cortical areas and their downstream connections including the lateral cerebellum, has been largely clarified. To separate the role of the cerebellum with respect to other cortical structures in executive control, we compared the anti-saccade performances in two distinct cohorts of patients with cerebellar disorders (with and without cerebral cortical involvement).MethodsEye movements during the execution of anti-saccades were recorded in 12 patients with spinocerebellar ataxia type 2 (a cortical-subcortical neurodegenerative disease), 10 patients with late onset cerebellar ataxia (an isolated cerebellar atrophy), and 34 matched controls.ResultsIn the anti-saccade task, besides dynamic changes already demonstrated in the pro-saccades of these patients, we found in both groups of cerebellar patients prolonged latency with larger variability than normal and increased directional error rate. Errors, however, were corrected by cerebellar patients as frequently as normal. No significant differences were found in patients with and without cortical involvement.ConclusionOur results indicate, in a large cohort of cerebellar patients, that the cerebellum plays a critical role in the regulation of executive motor control not only, as well known, by controlling the end of a movement, but also modulating its initiation and reducing reflexive responses that would perturb voluntary actions