Valeria Serchi | University of Siena / Università di Siena (original) (raw)

Papers by Valeria Serchi

Journal of the Neurological Sciences, Nov 1, 2017

Mutations in OPA1 are responsible of 32-89% cases of Autosomal Dominant Optic Atrophy (ADOA). OPA... more Mutations in OPA1 are responsible of 32-89% 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 southeastern 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.

BioMed Research International, 2016

The knowledge of the visual strategies adopted while walking in cognitively engaging environments... more 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.

This text wants to explore the process of bone remodeling. The idea supported is that the signal,... more 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 ...

Brain, 2022

Two clinical phenotypes characterize the onset of amyotrophic lateral sclerosis (ALS): the spinal... more Two clinical phenotypes characterize the onset of amyotrophic lateral sclerosis (ALS): the spinal variant, with symptoms beginning in the limbs, and the bulbar variant, affecting firstly speech and swallowing. The two variants show some distinct features in the histopathology, localization and prognosis, but to which extent they really differ clinically and pathologically remains to be clarified. Recent neuropathological and neuroimaging studies have suggested a broader spreading of the neurodegenerative process in ALS, extending beyond the motor areas, toward other cortical and deep grey matter regions, many of which are involved in visual processing and saccadic control. Indeed, a wide range of eye movement deficits have been reported in ALS, but they have never been used to distinguish the two ALS variants. Since quantifying eye movements is a very sensitive and specific method for the study of brain networks, we compared different saccadic and visual search behaviours across spi...

Neurological Sciences, 2021

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations i... more Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene SETX (OMIM #606002), causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, oculomotor apraxia, and elevated alpha-fetoprotein (AFP) serum level [1]. Oculomotor apraxia is the ocular hallmark of the disease; when the head is free to move, patients make conspicuous thrusting head movements that are usually assumed to compensate for their inability to make normal voluntary eye movements. Quick phases of vestibular nystagmus and optokinetic nystagmus were assumed to be preserved in these patients [2], while the horizontal gaze failure is due to deficit in voluntary eye movements. These deficits can manifest as increased latency and/or hypometria of saccades with a staircase pattern [3]. Two siblings, a 12-year-old boy (in the following indicated with P1) and a 10-year-old girl (in the following indicated with P2), were referred to our neurologic ambulatory because of mild gait disturbances and incoordination. Neurologic examination together with laboratory, neuroimaging, and genetic tests uncovered an AOA2 diagnosis. Clinical, MRI, and genetic findings of both patients are already reported [4]. On neuro-ophthalmological examination, the afferent visual system was normal, while the efferent visual system showed gaze evoked and rebound nystagmus. A moderate head trusting was also seen in each sibling. Eye movements were recorded using an ASL-504 eyetracker device (Applied Science Laboratories, Bedford, MA, USA). Each recording session was preceded by an interactive calibration procedure based on nine static points and the relative validation. A visually guided GAP paradigm was used, with 200 ms of GAP before the target appearing in one of the four possible eccentric positions. Within a post-processing analysis, for each saccadic movement, we determined the following descriptive parameters: amplitude, accuracy, gain, duration, peak and mean velocity, and latency [5]. For the antisaccade (AS) tasks, we defined as a correct antisaccade the correct saccadic eye movement toward the opposite direction in respect to the visual target, for which we determined the latency, the gain, and accuracy; an erroneous prosaccade was the unsuppressed reflexive saccade toward the target; and a corrective antisaccade was the antisaccade made after an initial erroneous prosaccade. Moreover, the latency of correct AS and the number of erroneous prosaccades and of successive corrections were considered (Table 1). We also evaluated fixation abnormalities in terms of saccadic intrusions and nystagmus using a fixation task. Saccadic parameters of the two AOA2 patients, P1 and P2, were compared with the parameters of control populations (CNTRL). The control consisted of 8 healthy agematched subjects (2 males, 8 females) of mean age of 16.5 years. Differences in the saccadic parameters * A. Rufa rufa@unisi.it

Journal of the Neurological Sciences, 2017

Mutations in OPA1 are responsible of 32-89% cases of Autosomal Dominant Optic Atrophy (ADOA). OPA... more Mutations in OPA1 are responsible of 32-89% 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 southeastern 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.

BioMed Research International, 2016

The knowledge of the visual strategies adopted while walking in cognitively engaging environments... more 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 trackabil...

ArXiv, 2018

In the last three decades, human visual attention has been a topic of great interest in various d... more In the last three decades, human visual attention has been a topic of great interest in various disciplines. In computer vision, many models have been proposed to predict the distribution of human fixations on a visual input. Recently, thanks to the creation of large collections of data, machine learning algorithms have obtained state-of-the-art performance on the task of saliency map estimation. On the other hand, computational models of scanpath are much less studied. Works are often only descriptive or task specific. Computational models of scanpath with general purpose are present in the literature, but are then evaluated in tasks of saliency prediction, losing therefore information about the dynamics and the behaviour. This is due to the fact that the scanpath is harder to model because it must include the description of a dynamic. In addition to the difficulty of the problem itself, two technical reasons have limited the research. The first reason is the lack of robust and uni...

Frontiers in Neuroscience, Apr 30, 2019

Pupil size fluctuations during stationary scotopic conditions may convey information about the co... more 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 entropydeterminism 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.

Vision actively influences the gait, and older adults show altered visual patterns compared to th... more 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 you...

The Journal of physiology, Jan 7, 2017

A cerebellar dentate nuclei (DN) contribution to volitional oculomotor control has recently been ... more 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 accu...

Progress in Brain Research

Frontiers in Neuroscience

Pupil size fluctuations during stationary scotopic conditions may convey information about the co... more 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 entropydeterminism 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.

Frontiers in neurology, 2018

Increasing evidence suggests a cerebellar contribution to modulate cognitive aspects of motor beh... more 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). Eye movements during the execution of anti-saccades were recorded in 12 patients with spinocerebellar ataxia type 2 (a cortical-subcortical neurodegenerative...

Frontiers in neurology, 2018

Increasing evidence suggests a cerebellar contribution to modulate cognitive aspects of motor beh... more 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). Eye movements during the execution of anti-saccades were recorded in 12 patients with spinocerebellar ataxia type 2 (a cortical-subcortical neurodegenerative...

The Journal of Physiology, 2017

A cerebellar dentate nuclei (DN) contribution to volitional oculomotor control has recently been ... more 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 of the Neurological Sciences, 2016

Journal of the Neurological Sciences, Nov 1, 2017

Mutations in OPA1 are responsible of 32-89% cases of Autosomal Dominant Optic Atrophy (ADOA). OPA... more Mutations in OPA1 are responsible of 32-89% 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 southeastern 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.

BioMed Research International, 2016

The knowledge of the visual strategies adopted while walking in cognitively engaging environments... more 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.

This text wants to explore the process of bone remodeling. The idea supported is that the signal,... more 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 ...

Brain, 2022

Two clinical phenotypes characterize the onset of amyotrophic lateral sclerosis (ALS): the spinal... more Two clinical phenotypes characterize the onset of amyotrophic lateral sclerosis (ALS): the spinal variant, with symptoms beginning in the limbs, and the bulbar variant, affecting firstly speech and swallowing. The two variants show some distinct features in the histopathology, localization and prognosis, but to which extent they really differ clinically and pathologically remains to be clarified. Recent neuropathological and neuroimaging studies have suggested a broader spreading of the neurodegenerative process in ALS, extending beyond the motor areas, toward other cortical and deep grey matter regions, many of which are involved in visual processing and saccadic control. Indeed, a wide range of eye movement deficits have been reported in ALS, but they have never been used to distinguish the two ALS variants. Since quantifying eye movements is a very sensitive and specific method for the study of brain networks, we compared different saccadic and visual search behaviours across spi...

Neurological Sciences, 2021

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations i... more Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene SETX (OMIM #606002), causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, oculomotor apraxia, and elevated alpha-fetoprotein (AFP) serum level [1]. Oculomotor apraxia is the ocular hallmark of the disease; when the head is free to move, patients make conspicuous thrusting head movements that are usually assumed to compensate for their inability to make normal voluntary eye movements. Quick phases of vestibular nystagmus and optokinetic nystagmus were assumed to be preserved in these patients [2], while the horizontal gaze failure is due to deficit in voluntary eye movements. These deficits can manifest as increased latency and/or hypometria of saccades with a staircase pattern [3]. Two siblings, a 12-year-old boy (in the following indicated with P1) and a 10-year-old girl (in the following indicated with P2), were referred to our neurologic ambulatory because of mild gait disturbances and incoordination. Neurologic examination together with laboratory, neuroimaging, and genetic tests uncovered an AOA2 diagnosis. Clinical, MRI, and genetic findings of both patients are already reported [4]. On neuro-ophthalmological examination, the afferent visual system was normal, while the efferent visual system showed gaze evoked and rebound nystagmus. A moderate head trusting was also seen in each sibling. Eye movements were recorded using an ASL-504 eyetracker device (Applied Science Laboratories, Bedford, MA, USA). Each recording session was preceded by an interactive calibration procedure based on nine static points and the relative validation. A visually guided GAP paradigm was used, with 200 ms of GAP before the target appearing in one of the four possible eccentric positions. Within a post-processing analysis, for each saccadic movement, we determined the following descriptive parameters: amplitude, accuracy, gain, duration, peak and mean velocity, and latency [5]. For the antisaccade (AS) tasks, we defined as a correct antisaccade the correct saccadic eye movement toward the opposite direction in respect to the visual target, for which we determined the latency, the gain, and accuracy; an erroneous prosaccade was the unsuppressed reflexive saccade toward the target; and a corrective antisaccade was the antisaccade made after an initial erroneous prosaccade. Moreover, the latency of correct AS and the number of erroneous prosaccades and of successive corrections were considered (Table 1). We also evaluated fixation abnormalities in terms of saccadic intrusions and nystagmus using a fixation task. Saccadic parameters of the two AOA2 patients, P1 and P2, were compared with the parameters of control populations (CNTRL). The control consisted of 8 healthy agematched subjects (2 males, 8 females) of mean age of 16.5 years. Differences in the saccadic parameters * A. Rufa rufa@unisi.it

Journal of the Neurological Sciences, 2017

Mutations in OPA1 are responsible of 32-89% cases of Autosomal Dominant Optic Atrophy (ADOA). OPA... more Mutations in OPA1 are responsible of 32-89% 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 southeastern 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.

BioMed Research International, 2016

The knowledge of the visual strategies adopted while walking in cognitively engaging environments... more 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 trackabil...

ArXiv, 2018

In the last three decades, human visual attention has been a topic of great interest in various d... more In the last three decades, human visual attention has been a topic of great interest in various disciplines. In computer vision, many models have been proposed to predict the distribution of human fixations on a visual input. Recently, thanks to the creation of large collections of data, machine learning algorithms have obtained state-of-the-art performance on the task of saliency map estimation. On the other hand, computational models of scanpath are much less studied. Works are often only descriptive or task specific. Computational models of scanpath with general purpose are present in the literature, but are then evaluated in tasks of saliency prediction, losing therefore information about the dynamics and the behaviour. This is due to the fact that the scanpath is harder to model because it must include the description of a dynamic. In addition to the difficulty of the problem itself, two technical reasons have limited the research. The first reason is the lack of robust and uni...

Frontiers in Neuroscience, Apr 30, 2019

Pupil size fluctuations during stationary scotopic conditions may convey information about the co... more 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 entropydeterminism 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.

Vision actively influences the gait, and older adults show altered visual patterns compared to th... more 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 you...

The Journal of physiology, Jan 7, 2017

A cerebellar dentate nuclei (DN) contribution to volitional oculomotor control has recently been ... more 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 accu...

Progress in Brain Research

Frontiers in Neuroscience

Pupil size fluctuations during stationary scotopic conditions may convey information about the co... more 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 entropydeterminism 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.

Frontiers in neurology, 2018

Increasing evidence suggests a cerebellar contribution to modulate cognitive aspects of motor beh... more 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). Eye movements during the execution of anti-saccades were recorded in 12 patients with spinocerebellar ataxia type 2 (a cortical-subcortical neurodegenerative...

Frontiers in neurology, 2018

Increasing evidence suggests a cerebellar contribution to modulate cognitive aspects of motor beh... more 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). Eye movements during the execution of anti-saccades were recorded in 12 patients with spinocerebellar ataxia type 2 (a cortical-subcortical neurodegenerative...

The Journal of Physiology, 2017

A cerebellar dentate nuclei (DN) contribution to volitional oculomotor control has recently been ... more 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 of the Neurological Sciences, 2016