Eye tracking paradigm to identify disease-specific behavioral biomarkers in neurodegeneration

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) has been identified as the most specific and common prodromal stage of α-synucleinopathies (αSYN) such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and the sporadic disease multiple system atrophy (MSA). Within 10 to 20 years, patients with this dream-sleep disorder convert in up to 85 % of cases to a neurodegenerative disease of the type of αSYN. Hence, iRBD is an ideal group for testing a disease-modifying therapy to postpone or even prevent phenoconversion. The latency, however, from diagnosis to phenoconversion is prolonged, lasting years to decades. Therefore, identifying iRBD patients more likely to phenoconvert needs highly sensitive and specific prodromal biomarkers and progression markers. The goal of this study was to contribute to the identification of biomarkers in manifest and prodromal αSYNs for their future selection as participants in protection trials. Furthermore, comparing patients with αSYN and Tauopathy is the second objective of this dissertation, aimed at identifying the underlying differences between the two disorders. To date, most of the biomarkers and progression markers for manifest αSYN relate to the motor and cognitive dysfunctions and imaging of the central nervous system but less to sensory and autonomic dysfunction. For iRBD, a recent review paper has summarized the state-of-the-art that confirms the above statement that most of the works in the field of biomarkers are performed on motor and cognitive functions and imaging. Until 2022, little has been published on oculomotor and pupillomotor dysfunctions in manifest and prodromal αSYN, but rather on the Tauopathy; progressive supranuclear palsy (PSP). The methodologies for studying eye movements and pupillary responses are highly developed. They offer a high resolution and precision in time and space for measuring sensory, autonomic, motor, and cognitive functions. Therefore, we systematically investigated the saccade, pupil, and blink behaviors in the manifest αSYN PD and MSA and their prodrome iRBD compared to healthy age and gender-matched controls. As a ”disease control” and for comparison, we also studied patients suffering from Tauopathy PSP. PSP is well-known for its oculomotor abnormalities, particularly for its characteristic symptom of relative vertical gaze palsy. PSP is – like MSA – another atypical parkinsonian disorder with multiple brain tissue losses, for example, in the frontal cortex. Because the early diagnosis of PD and MSA from PSP is difficult, PSP patients have been recruited for this study. As methods, we employed a structured saccade task that is called the Interleaved Pro/ Anti Saccade Task (IPAST) and a free viewing task (FV) to investigate oculomotor and pupillomotor function along with blink behavior in SYN and PSP. The IPAST is a structured saccade task that requires strong cognitive control, alertness, and attention. Previous studies on the manifest SYN have shown that patients with PD have systemic abnormalities in oculomotor, pupillometric parameters, and blink behavior in the IPAST. In order to simplify our method and broaden our ability to collect a wide range of eye movement parameters, we additionally employed another task, the unstructured free viewing of video clips (FV). Therefore, the research question is whether oculomotor and pupillomotor abnormalities and blinking during the IPAST and FV in iRBD patients differ from healthy controls, PD, MSA, and PSP. This study represents the first use of FV for the investigation of eye movement and pupil responses in subjects suffering from prodromal and manifest SYN. It is also the first study comparing prodromal and manifest SYN (PD, MSA) with PSP in FV. This dissertation has been performed in the context of the evolving disease-modifying therapy trials for manifest SYN, which are currently ongoing in patients with Parkinson’s disease. The next challenge will be to test these therapies in people with iRBD to slow or even prevent the full manifestation of the SYN. It will be essential to enrich prodromal populations with biomarkers of short-term conversion and to be able to monitor disease progression with serial measurements. Developing neurodegenerative disease treatments is becoming increasingly important as the population ages and the burden on families and society increases. In summary, we identified potential prodromal biomarkers in iRBD and differences between αSYN and the Tauopathy PSP, suggesting that the IPAST and especially FV task may be a tool to identify prodromal SYN and help to distinguish early manifest αSYN from early PSP. The future goal is intra-individual follow-up studies in iRBD patients to determine whether the so far observed subtle changes in oculo/pupillo-motor measures will progressively increase over time and allow the prediction of the phenoconversion of iRBD into manifest αSYN. These longitudinal studies will show whether oculo/pupillo-motor parameters can reliably distinguish the different neurodegenerative movement disorders in the manifest stages, and even more challenging, during their prodromal progression towards phenoconversion

Prevalence of retained primitive reflexes in patients with anxiety disorders

Anxiety is not only one of the mental health disorders most commonly referred to clinicians, but is also a research interest, producing subsequent modification in treatment approaches. However, there are suggestions in the literature that the effectiveness of some psychological treatments have not been systematically evaluated (Department of Health, 2001), or that treatment studies have employed methods unrepresentative of everyday clinical practice (World Health Organization.2000). Furthermore, from analysis of outcome studies, psychological therapies have been reported as effective for only half of those treated (Fisher & Durham, 1999). These findings suggest that there are individuals with anxiety who fail to respond to available therapies, and that alternative approaches for this group are not well studied.One biologically-based explanation for variable responses to treatment cites the possibility of anxiety as resulting from failed development of primitive and postural reflexes, necessary for processing sensory information and maintaining gravitational security. This theory is central to the work of the Institute for Neuro-Physiological Psychology (I.N.P.P.), recently applied to research which identified infantile reflexes, and failed transformation to adult responses, in a population of adults with differing sub-types of anxiety (Blythe, 1999).This study aimed to apply I.N.N.P. reflex tests to the detection of the characteristics of reflexes in a group of adult patients with Generalized Anxiety Disorder, compared to a group of non-anxious adults. A significant difference was found between patient and control group reflex test mean scores, patients achieving higher scores on all of the six iii tests employed in the study. From analysis of all individual test scores, two of these, detecting involvement of labyrinthine processes, resulted in the highest scores. The findings from analysis of resulting data are discussed in relation to implications for future study and further use of the measures with differing populations

Ocular manifestations of Parkinson disease

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder. We aimed to review both the disease and the drug-related ocular manifestations of PD. Methods: In this manuscript, we have reviewed and summarized existing literature on the ocular manifestations and drug-related complications of PD. We have also discussed the use of current noninvasive imaging techniques, such as optical coherence tomography (OCT), for the early diagnosis and monitoring of PD. Results: Impaired color vision, reduced stereopsis, reduced contrast sensitivity, pupillary abnormalities, eye movement disorders, convergence insufficiency, dry eye syndrome, glaucoma, visual dysfunctions, retinal abnormalities, and drug-related side effects were among the listed ocular manifestations of PD. There is a large knowledge gap regarding the type of glaucoma affecting PD patients—whether it is open-angle or other types. Further case studies and long-term follow-ups during PD progression are necessary to fill this gap. Patient compliance with follow-up visits for more visual field tests and OCT during PD progression may become problematic when dementia and cognitive impairment occur. Conclusions: There is a general need for clinicians to perform further tests and more visual examinations to rule out ocular manifestations. Furthermore, additional clinical trials are needed to further evaluate the use of different types of OCT findings as biomarkers of PD progression. This would aid in early diagnosis and in delaying disease progression, if treated promptly

Does Personalisation Promote Learners’ Attention? An Eye-Tracking Study

The personalisation principle is a design recommendation and states that multimedia presentations using personalised language promote learning better than those using formal language (e.g., using ‘your’ instead of ‘the’). It is often assumed that this design recommendation affects motivation and therefore allocation of attention. To gain further insight into the processes underlying personalisation effects we conducted an eye tracking experiment with 37 German university students who were presented with either personalised or formal learning materials. We examined group differences in attention allocation parameters (fixation count, fixation duration, transition count). The eye-tracking data was combined with self-reports concerning motivation, cognitive load, and learning outcomes. Eye-tracking data revealed a significantly higher reading depth for the main picture areas of interest in the personalised condition. Additionally, participants found the personalised version more appealing and inviting. For learning outcomes, there was a significant positive effect of personalisation for retention, not for transfer. We discuss additional explanatory variables as well as methodological and practical implications for instructional design

Eye tracking as an MT evaluation technique

Eye tracking has been used successfully as a technique for measuring cognitive load in reading, psycholinguistics, writing, language acquisition etc. for some time now. Its application as a technique for measuring the reading ease of MT output has not yet, to our knowledge, been tested. We report here on a preliminary study testing the use and validity of an eye tracking methodology as a means of semi-automatically evaluating machine translation output. 50 French machine translated sentences, 25 rated as excellent and 25 rated as poor in an earlier human evaluation, were selected. Ten native speakers of French were instructed to read the MT sentences for comprehensibility. Their eye gaze data were recorded non-invasively using a Tobii 1750 eye tracker. The average gaze time and fixation count were found to be higher for the “bad” sentences, while average fixation duration and pupil dilations were not found to be substantially different for output rated as good and output rated as bad. Comparisons between HTER scores and eye gaze data were also found to correlate well with gaze time and fixation count, but not with pupil dilation and fixation duration. We conclude that the eye tracking data, in particular gaze time and fixation count, correlate reasonably well with human evaluation of MT output but fixation duration and pupil dilation may be less reliable indicators of reading difficulty for MT output. We also conclude that eye tracking has promise as a semi-automatic MT evaluation technique, which does not require bi-lingual knowledge, and which can potentially tap into the end users’ experience of machine translation output

Inconsistencies between mental fatigue measures under compensatory control theories

Mental fatigue has traditionally been defined as a condition of reduced cognitive efficiency and performance, accompanied by a subjective feeling of fatigue. Even though we could expect to find associations between the three defining characteristic of mental fatigue (performance impairment, physiological deactivation and subjective fatigue), research has shown that the emergence of inconsistencies between measures is more frequent than one might expect: people proved capable of maintaining adequate performance levels even after having declared themselves fatigued. This could be explained under the compensatory control mechanism models, which state that humans are able to provide additional resources under demanding conditions, but only at the expense of psychophysiological cost and subjective fatigue. We tested this explanation by manipulating task complexity and time performing a simulated air-traffic control task. We collected psychophysiological, performance and subjective data. A decrease in pupil size was seen in the low-aircraft-density condition, while pupil size remained constant in the high-aircraft-density condition. Participants’ task performance was optimal in both conditions, though they showed an increase in subjective feelings of fatigue, especially in the high-complexity task condition. Thus, complexity seemed to trigger compensatory mechanisms, which reallocated extra resources that physiologically activated participants in order to deal with a higher complexity task, whereas subjective fatigue could be acting as a signal to the organism of impending resource depletion. Our findings support compensatory control theories and offer an explanation of inconsistencies between fatigue measures. Further research on compensatory mechanisms is needed to enable better management of fatigue effects to prevent work-related accidents.Spanish Ministry of Industry PI-1461/201

Functional Biomarkers to Assess Visual System Integrity: An eye tracking based approach:Functional Biomarkers to Assess Visual System Integrity

Functional Biomarkers to Assess Visual System Integrity: An eye tracking based approac

Functional Biomarkers to Assess Visual System Integrity: An eye tracking based approach:Functional Biomarkers to Assess Visual System Integrity

Functional Biomarkers to Assess Visual System Integrity: An eye tracking based approac