Computational Techniques for Eye Movements Analysis towards Supporting Early Diagnosis of Alzheimer's Disease: A Review <s> Eye Movements Analysis in Controlled Scenarios. <s> Many high-prevalence neurological disorders involve dysfunctions of oculomotor control and attention, including attention deficit hyperactivity disorder (ADHD), fetal alcohol spectrum disorder (FASD), and Parkinson's disease (PD). Previous studies have examined these deficits with clinical neurological evaluation, structured behavioral tasks, and neuroimaging. Yet, time and monetary costs prevent deploying these evaluations to large at-risk populations, which is critically important for earlier detection and better treatment. We devised a high-throughput, low-cost method where participants simply watched television while we recorded their eye movements. We combined eye-tracking data from patients and controls with a computational model of visual attention to extract 224 quantitative features. Using machine learning in a workflow inspired by microarray analysis, we identified critical features that differentiate patients from control subjects. With eye movement traces recorded from only 15 min of videos, we classified PD versus age-matched controls with 89.6 % accuracy (chance 63.2 %), and ADHD versus FASD versus control children with 77.3 % accuracy (chance 40.4 %). Our technique provides new quantitative insights into which aspects of attention and gaze control are affected by specific disorders. There is considerable promise in using this approach as a potential screening tool that is easily deployed, low-cost, and high-throughput for clinical disorders, especially in young children and elderly populations who may be less compliant to traditional evaluation tests. <s> BIB001 </s> Computational Techniques for Eye Movements Analysis towards Supporting Early Diagnosis of Alzheimer's Disease: A Review <s> Eye Movements Analysis in Controlled Scenarios. <s> We investigated rapid object categorization and, more specifically, the ability to detect a target object within a natural scene in people with mild Alzheimer's disease (AD) using a saccadic choice task. It has been suggested that the anatomical pathway likely used to initiate rapid oculomotor responses in the saccadic choice task could involve the Frontal Eye Field, a structure that is part of the dorsal attentional network, in which connectivity is disrupted in AD. Seventeen patients with mild AD and 23 healthy age-matched controls took part in the study. A group of 24 young healthy observers was included as it has been reported that normal aging affects eye movements. Participants were presented with pairs of colored photographs of natural scenes, one containing an animal (the target) and one containing various objects (distracter), displayed for 1 s left and right of fixation. They were asked to saccade to the scene containing an animal. Neither pathology nor age affected temporal (saccade latencies and durations) and spatial (saccade amplitude) parameters of eye movements. Patients with AD were significantly less accurate than age-matched controls, and older participants were less accurate than young observers. The results are interpreted in terms of noisier sensory information and increased uncertainty in relation to deficits in the magnocellular pathway. The results suggest that, even at a mild stage of the pathology, people exhibit difficulties in selecting relevant objects. <s> BIB002 </s> Computational Techniques for Eye Movements Analysis towards Supporting Early Diagnosis of Alzheimer's Disease: A Review <s> Eye Movements Analysis in Controlled Scenarios. <s> Patients with Alzheimer's disease (AD) develop progressive language, visuoperceptual, attentional, and oculomotor changes that can have an impact on their reading comprehension. However, few studies have examined reading behavior in AD, and none have examined the contribution of predictive cueing in reading performance. For this purpose we analyzed the eye movement behavior of 35 healthy readers (Controls) and 35 patients with probable AD during reading of regular and high- predictable sentences. The cloze predictability of words N - 1, and N + 1 exerted an influence on the reader's gaze duration. The predictabilities of preceding words in high-predictable sentences served as task-appropriate cues that were used by Control readers. In contrast, these effects were not present in AD patients. In Controls, changes in predictability significantly affected fixation duration along the sentence; noteworthy, these changes did not affect fixation durations in AD patients. Hence, only in healthy readers did predictability of upcoming words influence fixation durations via memory retrieval. Our results suggest that Controls used stored information of familiar texts for enhancing their reading performance and imply that contextual-word predictability, whose processing is proposed to require memory retrieval, only affected reading behavior in healthy subjects. In AD patients, this loss reveals impairments in brain areas such as those corresponding to working memory and memory retrieval. These findings might be relevant for expanding the options for the early detection and monitoring in the early stages of AD. Furthermore, evaluation of eye movements during reading could provide a new tool for measuring drug impact on patients' behavior. <s> BIB003 </s> Computational Techniques for Eye Movements Analysis towards Supporting Early Diagnosis of Alzheimer's Disease: A Review <s> Eye Movements Analysis in Controlled Scenarios. <s> Visual exploration is an omnipresent activity in everyday life, and might represent an important determinant of visual attention deficits in patients with Alzheimer’s Disease (AD). The present study aimed at investigating visual search performance in AD patients, in particular target detection in the far periphery, in daily living scenes. Eighteen AD patients and twenty healthy controls participated in the study. They were asked to freely explore a hemispherical screen, covering ± 90°, and to respond to targets presented at 10°, 30°, and 50° eccentricity, while their eye movements were recorded. Compared to healthy controls, AD patients recognized less targets appearing in the center. No difference was found in target detection in the periphery. This pattern was confirmed by the fixation distribution analysis. These results show a neglect for the central part of the visual field for AD patients and provide new insights by mean of a search task involving a larger field of view. <s> BIB004 </s> Computational Techniques for Eye Movements Analysis towards Supporting Early Diagnosis of Alzheimer's Disease: A Review <s> Eye Movements Analysis in Controlled Scenarios. <s> Eye movement patterns are found to reveal human cognitive and mental states that can not be easily measured by other biological signals. With the rapid development of eye tracking technologies, there are growing interests in analysing gaze data to infer information about people’ cognitive states, tasks and activities performed in naturalistic environments. In this paper, we investigate the link between eye movements and cognitive function. We conducted experiments to record subject’s eye movements during video watching. By using computational methods, we identified eye movement features that are correlated to people’s cognitive health measures obtained through the standard cognitive tests. Our results show that it is possible to infer people’s cognitive function by analysing natural gaze behaviour. This work contributes an initial understanding of monitoring cognitive deterioration and dementia with automatic eye movement analysis. <s> BIB005 </s> Computational Techniques for Eye Movements Analysis towards Supporting Early Diagnosis of Alzheimer's Disease: A Review <s> Eye Movements Analysis in Controlled Scenarios. <s> As a part of the automatic study of visual attention of affected populations with neurodegenerative diseases and to predict whether new gaze records a complaint of these diseases, we should design an automatic model that predicts salient areas in video. Past research showed, that people suffering form dementia are not reactive with regard to degradations on still images. In this paper we study the reaction of healthy normal control subjects on degraded area in videos. Furthermore, in the goal to build an automatic prediction model for salient areas in intentionally degraded videos, we design a deep learning architecture and measure its performances when predicting salient regions on completely unseen data. The obtained results are interesting regarding the reaction of normal control subjects against a degraded area in video. <s> BIB006 </s> Computational Techniques for Eye Movements Analysis towards Supporting Early Diagnosis of Alzheimer's Disease: A Review <s> Eye Movements Analysis in Controlled Scenarios. <s> BACKGROUND ::: Alzheimer's disease (AD) is associated with selective attention impairments, which could contribute to cognitive and functional deficits. Using visual scanning parameters, selective attention toward novel stimuli, or novelty preference, can be measured by a non-verbal, non-invasive method that may be of value in predicting disease progression. ::: ::: ::: OBJECTIVE ::: In this longitudinal study, we explored whether novelty preference can predict cognitive decline in AD patients. ::: ::: ::: METHODS ::: Mild to moderate AD patients viewed slides containing both novel and repeat images. The number of fixations, the average fixation time, and the relative fixation time on the two types of images were measured by an eye-tracking system. Novelty preference was estimated by the differences between the visual scanning parameters on novel and repeat images. Cognition and attention were assessed using the Standardized Mini-Mental Status Examination (sMMSE) and the Conners' Continuous Performance Test (CPT), respectively. Cognition was re-assessed every 6 months for up to 2 years. ::: ::: ::: RESULTS ::: Multivariate linear regressions of 32 AD patients (14 females, age = 77.9±7.8, baseline sMMSE = 22.2±4.4) indicated that reduced time spent on novel images (t = 2.78, p = 0.010) was also associated with greater decline in sMMSE scores (R2 = 0.41, Adjusted R2 = 0.35, F3,28 = 6.51, p = 0.002), adjusting for attention and baseline sMMSE. ::: ::: ::: CONCLUSION ::: These results suggest that novelty preference, measured by visual attention scanning technology, may reflect pathophysiological processes that could predict disease progression in the cognitively-impaired. <s> BIB007 </s> Computational Techniques for Eye Movements Analysis towards Supporting Early Diagnosis of Alzheimer's Disease: A Review <s> Eye Movements Analysis in Controlled Scenarios. <s> Studies of visual attention of patients with Dementia such as Parkinson’s Disease Dementia and Alzheimer Disease is a promising way for non-invasive diagnostics. Past research showed, that people suffering from dementia are not reactive with regard to degradations on still images. Attempts are being made to study their visual attention relatively to the video content. Here the delays in their reactions on novelty and “unusual” novelty of the visual scene are expected. Nevertheless, large-scale screening of population is possible only if sufficiently robust automatic prediction models can be built. In the medical protocols the detection of Dementia behavior in visual content observation is always performed in comparison with healthy, “normal control” subjects. Hence, it is a research question per see as to develop an automatic prediction models for specific visual content to use in psycho-visual experience involving Patients with Dementia (PwD). The difficulty of such a prediction resides in a very small amount of training data. In this paper the reaction of healthy normal control subjects on degraded areas in videos was studied. Furthermore, in order to build an automatic prediction model for salient areas in intentionally degraded videos for PwD studies, a deep learning architecture was designed. Optimal transfer learning strategy for training the model in case of very small amount of training data was deployed. The comparison with gaze fixation maps and classical visual attention prediction models was performed. Results are interesting regarding the reaction of normal control subjects against degraded areas in videos. <s> BIB008
Since the past years, research studies have moved forward to conduct other types of experiments aiming to identify eye movements abnormalities related to AD. For example, in BIB002 the participants performed a more complex task that only attend a target point that consisted in detecting and categorizing a specific object within a natural scene. The participants observed two visual stimuli in a monitor, one including an image with an animal and the other including a distractor image. The participants were asked to saccade to the image that contained the animal while their success to fixate to the animal and to the correct image was measured. The results from this study show that persons with AD, even in a mild stage of the disease, when compared with control groups have difficulties to select the relevant targets. Another example is given by the work in BIB003 that focuses on the analysis of reading behavior of PwAD. Reading is an ADL that involves the use of working memory and memory retrieval function. Thus, the experiments in BIB003 involve analysis of more complex task than usual SEM studies. The experiment consisted in a comparison of the eye gaze position of PwAD and control participants when reading sentences. The findings from BIB003 show that PwAD have a longer gaze duration than controls. Additionally, they found that a predictability degree on the sentences is accounted by control subjects but not by PwAD. This suggests that PwAD have impairments with their working memory and memory retrieval functions. Although the work in BIB003 is towards analysis of eye movements in ADL, the current experiments are under controlled scenarios in the sense that use screen based eye trackers and even use a chin rest to constrain head movements. Another research studies the attention to repeated and novel stimuli BIB007 that is related to cognition and attention. The experiments consist in presenting slides to mild-to-moderate PwAD that contain novel and repeated images. The researchers report that fixations on the images serve to evaluate attendance to repeated and novel content providing the potential to be used to measure disease progression. Another study analyzes the effects of AD on visual exploration BIB004 . The study focuses on visual search performance for target detection in the far periphery. The participants, AD patients, and control subjects explore a hemispherical screen and respond to presented targets. The results from this study show differences in AD patients and control subjects when identifying targets on different eccentricities from the screen. Researchers also report differences on target detection times and number of fixations. The work in BIB005 uses eye movements analysis during video watching to infer people's cognitive function. Researches defined 13 features from fixations and found correlations between the features and memory capability. Example of these features include mean fixation duration, fixation count, and mean saccade amplitude. Different from other specific laboratory tasks, in these experiments the participants freely watch videos from different scenarios while features from eye movements are extracted. A pilot study in France, LYLO BIB008 , focused on measuring the rigidity and lack of curiosity of PwAD. In this study, the patients were screened in laboratory settings with static images displayed. And statistical parameters computed from recordings of saccades and fixations were compared. A step forward measuring visual impairments in a naturalistic situation consists in using everyday visual content such as colour video content for patients screening. The lack of curiosity hence can be induced from gaze recordings of intentionally degraded natural video content. The baseline model of automatic prediction of attention for normal control subjects was developed in BIB008 BIB006 . Contrarily to BIB001 where the first step to make the observation "natural" was done by using video in free viewing conditions, in BIB006 BIB001 video was intentionally degraded. While studying visual deficits on laboratory tasks has been productive for AD assessment, its application requires cooperative scenarios. That is, subjects must cooperate consciously performing the oculomotor tasks to get their assessment. Thus, this type of assessment is adequate when there is already an evident manifestation of dementia that requires evaluation. In addition, the manifestation cannot be severe enough so the subject is not able to cooperate. To achieve early diagnosis, it is necessary to have techniques that allow the evaluation of eye movements abnormalities on scenarios that allow naturalistic assessment without the explicit cooperation from subjects, for example, to analyze how AD affects eye movements in ADL, such as cooking or gardening. In the following section we describe the work related to analysis of eye movements in naturalistic scenarios.