Francesca Rosini

Differences in saccade dynamics between spinocerebellar ataxia 2 and late-onset cerebellar ataxias.

The cerebellum is implicated in maintaining the saccadic subsystem efficient for vision by minimizing movement inaccuracy and by learning from endpoint errors. This ability is often disrupted in degenerative cerebellar diseases, as demonstrated by saccade kinetic abnormalities. The study of saccades in these patients may therefore provide insights into the neural substrate underlying saccadic motor control. We investigated the different extent of saccade dynamic abnormalities in spinocerebellar ataxia type 2 and late-onset cerebellar ataxias, genetically undefined and with prevalent cerebellar atrophy. Reflexive and voluntary saccades of different amplitude (10°-18°) were studied in seven patients with spinocerebellar ataxia 2, eight patients with late-onset cerebellar ataxia and 25 healthy controls. Quantitative analysis of saccade parameters and measures of saccade accuracy were performed. Detailed neurological, neurophysiological and magnetic resonance imaging assessment was obtained for each patient. Genetic and laboratory screening for spinocerebellar ataxias and other forms of late-onset cerebellar ataxias were also performed. A lower peak saccade velocity and longer duration was observed in patients with spinocerebellar ataxia 2 with respect to those with late-onset cerebellar ataxia and controls. Unlike subjects with spinocerebellar ataxia 2, patients with late-onset cerebellar ataxia showed main sequence relationships to similar saccades made by normal subjects. Saccades were significantly more inaccurate, namely hypometric, in late-onset cerebellar ataxia than in spinocerebellar ataxia 2 and inaccuracy increased with saccade amplitude. The percentage of hypometric primary saccades and of larger secondary corrective saccades were consistently higher in late-onset cerebellar ataxia than in spinocerebellar ataxia 2 and controls. No other significant differences were found between groups. Two different mechanisms were adopted to redirect the fovea as fast and/or accurately as possible to peripheral targets by the two groups of cerebellar patients. Patients with spinocerebellar ataxia 2 maintained accuracy using slow saccades with longer duration. This reflects prevalent degenerative processes affecting the pontine burst generator and leading to saccade velocity failure. On the other hand, patients with late-onset cerebellar ataxia reached the target with a number of fast inaccurate, mostly hypometric saccades. Different degrees of cerebellar oculomotor vermis involvement may account for differences in optimizing the trade-off between velocity and accuracy in the two groups. In addition, as suggested by spinocerebellar patients having slow saccades that are no longer ballistic, visual feedback might be continuously available during the movement execution to guide the eye to its target.

Two novel HTRA1 mutations in a European CARASIL patient

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary, nonhypertensive cause of recurrent lacunar stroke and cognitive decline associated with alopecia, spondylosis deformans, and lumbago.1 The disease has been linked to mutations in the HTRA1 gene, encoding for serine protease HTRA1, loss of which causes dysregulation of transforming growth factor-β signaling.2

Wernicke Encephalopathy After Gastrointestinal Surgery for Cancer: Causes of Diagnostic Failure or Delay

ABSTRACT Wernicke encephalopathy (WE) is a neurological emergency due to thiamine deficiency. We aimed to identify clinical course and causes of diagnostic delay or failure of WE in a group of patients who underwent surgery for gastrointestinal tumors. A retrospective review of clinical, laboratory, neuroimaging, and therapeutic features of 10 patients with WE following abdominal surgery for cancer was carried out. Four patients died; in these subjects, diagnosis was delayed and supplementation of vitamin was absent or likely inadequate. Diagnostic delay or failure was also related to the coexistence of several medical complications at presentation masking typical symptoms of WE. In the surviving patients, outcome was influenced by promptness and type of therapy. Postoperative abdominal bleeding and number of subsequent operations may also had an effect. Postsurgical patients with gastrointestinal tumors may develop a subtle WE. The number of subsequent operations and the severity of postoperative complications may increase the risk of unrecognized WE. The disease should be suspected in postsurgical patients who have unexpected mental status changes, even under prophylactic treatment with vitamins. We suggest that prophylaxis with high doses of thiamine should be undertaken in patients with gastrointestinal tumors before surgery.

Influences of data filtering on human-computer interaction by gaze-contingent display and eye-tracking applications

We describe an interactive gaze-contingent display (GCD) applied to clinical applications; the system uses a simple texture hole to inhibit peripheral vision, to test and stress overt mechanisms of visual searching in normal subjects. The correct use of GCD in vision research is affected by tremor of the hole, due to system noise, nystagmus, eye blinking, calibration and subject reactivity. These issues compromise the execution of task. In order to obtain a stable GCD hole, we implemented a predictive gaze-contingent display (PGCD), fitting through dispersion of fixations and modulating a filter. The paper describes the PGCD and compare it with the common technique, providing evidence that humans fit exploration based on the characteristics of the computer system; in particular we found significant difference applying PGCD or a simple finite impulse response filter. We suggest that a correct human-computer interaction applied to neuropsychological context must be developed taking in consideration both technical point of view and human behavior.

Visual System Involvement in CADASIL

BACKGROUND AND OBJECTIVE Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriolar small-vessel disease caused by Notch3 mutations. A detailed definition of the neuro-ophthalmologic spectrum of CADASIL might provide new insights in the pathophysiology of small-vessel diseases. Therefore, this study aims to precisely delineate the features and the prevalence of the visual system impairment in CADASIL. METHODS A cohort of 34 genetically confirmed CADASIL patients was enrolled in an observational cross-sectional study. Subjects underwent a complete neuro-ophthalmological evaluation. Clinical features and common cardiovascular risk factors were also considered. Data were compared with those already reported in previous studies. RESULTS Both afferent and efferent visual structures were commonly impaired in CADASIL patients. Retinal microvascular changes such as arteriolar narrowing and arteriovenous nicking, described in most patients and detected also in asymptomatic carriers, reflect the typical hemodynamic changes of CADASIL. However, less frequent findings, like early macular and lens changes, would indicate a possible further role played by susceptibility to premature aging and degeneration. Cotton wool spots and vessel occlusions were not common. Finally, eye movement abnormalities suggest that the brainstem is particularly vulnerable to damage in CADASIL. CONCLUSIONS Although no specific or prominent neuro-ophthalmologic finding can be considered as hallmark of the disease, afferent and efferent visual system abnormalities could be accounted as complementary markers to study cerebral small-vessel diseases.

Eye fixations identification based on statistical analysis - Case study

Eye movement is the most simple and repetitive movement that enable humans to interact with the environment. The common daily activities, such as watching television or reading a book, involve this natural activity which consists of rapidly shifting our gaze from one region to another. The identification of the main components of eye movement during visual exploration such as fixations and saccades, is the objective of the analysis of eye movements in various contexts ranging from basic neuro sciences and visual sciences to virtual reality interactions and robotics. However, many of the algorithms that detect fixations present a number of problems. In this article, we present a new fixation identification algorithm based on the analysis of variance and F-test. We present the new algorithm and we compare it with the common fixations algorithm based on dispersion. To demonstrate the performance of our approach we tested the algorithm in a group of healthy subjects.

Ocular-Motor Profile and Effects of Memantine in a Familial Form of Adult Cerebellar Ataxia with Slow Saccades and Square Wave Saccadic Intrusions

Fixation instability due to saccadic intrusions is a feature of autosomal recessive spinocerebellar ataxias, and includes square wave intrusions (SWI) and macrosaccadic oscillations (MSO). A recent report suggested that the non-competitive antagonist of NMDA receptors, memantine, could decrease MSO and improve fixation in patients with spinocerebellar ataxia with saccadic intrusions (SCASI). We similarly tested two sisters, respectively of 58 and 60 years, with an unrecognized form of recessive, adult-onset cerebellar ataxia, peripheral neuropathy and slow saccades, who showed prominent SWI and also complained with difficulty in reading. We tested horizontal visually guided saccades (10°–18°) and three minutes of steady fixation in each patient and in thirty healthy controls. Both patients showed a significant reduction of peak and mean velocity compared with control subjects. Large SWI interrupting steady fixation were prominent during steady fixation and especially following visually guided saccades. Eye movements were recorded before and during the treatment with memantine, 20 mg/daily for 6 months. The treatment with memantine reduced both the magnitude and frequency of SWI (the former significantly), but did not modified neurological conditions or saccade parameters. Thus, our report suggests that memantine may have some general suppressive effect on saccadic intrusions, including both SWI and MSO, thereby restoring the capacity of reading and visual attention in these and in other recessive forms of ataxia, including Friedreich’s, in which saccadic intrusions are prominent.

Automatic eye fixations identification based on analysis of variance and covariance

Eye movement is the simplest and repetitive movement that enables humans to interact with the environment. The common daily activities, such as reading a book or watching television, involve this natural activity, which consists of rapidly shifting our gaze from one region to another. In clinical application, the identification of the main components of eye movement during visual exploration, such as fixations and saccades, is the objective of the analysis of eye movements: however, in patients affected by motor control disorder the identification of fixation is not banal. This work presents a new fixation identification algorithm based on the analysis of variance and covariance: the main idea was to use bivariate statistical analysis to compare variance over x and y to identify fixation. We describe the new algorithm, and we compare it with the common fixations algorithm based on dispersion. To demonstrate the performance of our approach, we tested the algorithm in a group of healthy subjects and patients affected by motor control disorder.

Spike removal through multiscale wavelet and entropy analysis of ocular motor noise: a case study in patients with cerebellar disease

Wavelet decomposition of ocular motor signals was investigated with a view to its use for noise analysis and filtering. Ocular motor noise may be physiological, depending on brain activities, or experimental, depending on the eye recording machine, head movements and blinks. Experimental noise, such as spikes, must be removed, preserving noise due to neuro-physiological activities. The proposed method uses wavelet multiscale decomposition to remove spikes and optimizes the procedure by means of the covariance of the eye signals. To measure the noise on eye motor control, we used the wavelet entropy. The method was tested on patients with cerebellar disorders and healthy subjects. A significant difference in wavelet entropy was observed, indicating this quantity as a valuable measure of physiological motor noise.

Evaluating gaze control on a multi-target sequencing task

Many high cognitive applications, such as vision processing and representation and understanding of images, often need to analyse in detail how an ongoing visual search was performed in a representative subset of the image, which may be arranged into sequences of loci, called regions of interest (ROIs). We used the Trial Making Test (TMT) in which subjects are asked to fixate a sequence of letters and numbers in a logical alphanumeric order. The main characteristic of TMT is to force the subject to perform a default and well-known path. The comparison of the expected scan-path with the observed scan-path provides a valuable method to investigate how a task force the subject to maintain a top-down internal representation of execution and how bottom-up influences the performance. We developed a mechanism that analyses the scan path using different algorithms, and we compared it with other methods: we found that fixations outside the ROI are direct influence of exploration strategy. The paper discusses the method in healthy subjects.