Changes in Timing and kinematics of goal directed eye-hand movements in early-stage Parkinson's disease

Objective: Many daily activities involve intrinsic or extrinsic goal-directed eye and hand movements. An extensive visuomotor coordination network including nigro-striatal pathways is required for efficient timing and positioning of eyes and hands. The aim of this study was to investigate how Parkinson's disease (PD) affects eye-hand coordination in tasks with different cognitive complexity.Methods: We used a touch screen, an eye-tracking device and a motion capturing system to quantify changes in eye-hand coordination in early-stage PD patients (H&amp;Y &lt; 2.5) and age-matched controls. Timing and kinematics of eye and hand were quantified in four eye-hand coordination tasks (pro-tapping, dual planning, anti-tapping and spatial memory task).Results: In the pro-tapping task, saccade initiation towards extrinsic goals was not impaired. However, in the dual planning and anti-tapping task initiation of saccades towards intrinsic goals was faster in PD patients. Hand movements were differently affected: initiation of the hand movement was only delayed in the pro-tapping and dual planning task. Overall, hand movements in PD patients were slower executed compared to controls.Interpretation: Whereas initiation of saccades in an extrinsic goal-directed task (pro-tapping task) is not affected, early stage PD patients have difficulty in suppressing reflexive saccades towards extrinsic goals in tasks where the endpoint is an intrinsic goal (e.g. dual planning and anti-tapping task). This is specific for eye movements, as hand movements have delayed responses in the pro-tapping and dual planning task. This suggests that reported impairment of the dorsolateral prefrontal cortex in early-stage PD patients affects only inhibition of eye movements. We conclude that timing and kinematics of eye and hand movements in visuomotor tasks are affected in PD patients. This result may have clinical significance by providing a behavioral marker for the early diagnosis of PD.</p

Effect of ethnic diversity on the saccadic reaction time among healthy Indian and Dutch adults

Eye movement perimetry (EMP) expresses the decline in visual field (VF) responsiveness based on the deviation in saccadic reaction times (SRTs) from their expected age-similar responses (normative database). Since ethnic dissimilarities tend to affect saccade parameters, we evaluated the effect of such a factor on SRT and its interaction with age, stimulus eccentricity, and intensity. 149 healthy adults, spread into five age groups, drawn from Indian and Dutch ethnicities underwent a customized EMP protocol integrated with a saccade task from which the SRTs to ‘seen’ visual stimuli were computed. The EMP test had a total of 54 coordinates (five stimulus eccentricities) tested using Goldmann size III visual stimuli presented at four stimulus intensity (SI) levels against a constant background. Considering SRT as a dependent variable, a Generalized Linear Mixed Model analysis was conducted that revealed a statistically significant (p &lt; 0.001) influence of ethnicity and interaction between the tested factors (ethnicity × age × stimulus eccentricity × intensity). However, during the post hoc analysis, out of the 100 possible pair-wise comparisons, only 6% (minor proportion) of the estimates showed statistical significance. Hence, the ethnic-specific differences need not be accounted for while implementing EMP in a diverse set of populations instead a collective database might serve the purpose.</p

Effect of ethnic diversity on the saccadic reaction time among healthy Indian and Dutch adults

Eye movement perimetry (EMP) expresses the decline in visual field (VF) responsiveness based on the deviation in saccadic reaction times (SRTs) from their expected age-similar responses (normative database). Since ethnic dissimilarities tend to affect saccade parameters, we evaluated the effect of such a factor on SRT and its interaction with age, stimulus eccentricity, and intensity. 149 healthy adults, spread into five age groups, drawn from Indian and Dutch ethnicities underwent a customized EMP protocol integrated with a saccade task from which the SRTs to ‘seen’ visual stimuli were computed. The EMP test had a total of 54 coordinates (five stimulus eccentricities) tested using Goldmann size III visual stimuli presented at four stimulus intensity (SI) levels against a constant background. Considering SRT as a dependent variable, a Generalized Linear Mixed Model analysis was conducted that revealed a statistically significant (p &lt; 0.001) influence of ethnicity and interaction between the tested factors (ethnicity × age × stimulus eccentricity × intensity). However, during the post hoc analysis, out of the 100 possible pair-wise comparisons, only 6% (minor proportion) of the estimates showed statistical significance. Hence, the ethnic-specific differences need not be accounted for while implementing EMP in a diverse set of populations instead a collective database might serve the purpose.</p

Eyes on CVI:Eye movements unveil distinct visual search patterns in Cerebral Visual Impairment compared to ADHD, dyslexia, and neurotypical children

Visual search problems are often reported in children with Cerebral Visual Impairment (CVI). To tackle the clinical challenge of objectively differentiating CVI from other neurodevelopmental disorders, we developed a novel test battery. Visual search tasks were coupled with verbal and gaze-based measurements. Two search tasks were performed by children with CVI (n: 22; mean age (SD): 9.63 (.46) years) ADHD (n: 32; mean age (SD): 10.51 (.25) years), dyslexia (n: 28; mean age (SD): 10.29 (.20) years) and neurotypical development (n: 44; mean age (SD): 9.30 (.30) years). Children with CVI had more impaired search performance compared to all other groups, especially in crowded and unstructured displays and even when they had normal visual acuity. In-depth gaze-based analyses revealed that this group searched in overall larger areas and needed more time to recognize a target, particularly after their initial fixation on the target. Our gaze-based approach to visual search offers new insights into the distinct search patterns and behaviours of children with CVI. Their tendency to overlook targets whilst fixating on it, point towards higher-order visual function (HOVF) deficits. The novel method is feasible, valid, and promising for clinical differential-diagnostic evaluation between CVI, ADHD and dyslexia, and for informing individualized training.</p

Detection of visual field defects using Eye Movement Pediatric Perimetry in children with intracranial lesions:feasibility and applicability

The study aimed at evaluating the feasibility of Eye Movement Pediatric Perimetry (EMPP) among children in detecting Visual Field Defects (VFDs) associated with Intracranial Lesions (IL). Healthy controls (n = 35) and patients diagnosed with IL (n = 19) underwent a comprehensive clinical evaluation followed by a Goldmann Visual Field (GVF) and a customised EMPP protocol. During EMPP, all the participants were encouraged to fixate on a central target and initiate Saccadic Eye Movement (SEM) responses towards randomly appearing peripheral stimuli. The SEM responses were recorded using an eye-tracking device and further inspected to calculate Performance Scores (PS), Saccadic Reaction Times (SRTs), and an EMPP Index (EMPI). The mean age (years) of the controls and cases were 7.3 (SD: 1.5) and 9.4 (SD: 2.4) respectively. Among the controls, the older children (≥7 years) showed statistically significantly faster SRTs (p = 0.008) compared to the younger group. The binocular EMPP measurements compared between the controls and the cases revealed no statistically significant differences in PS (p = 0.34) and SRT (p = 0.51). EMPP failed in 4 children because of data loss or unacceptably poor PS whereas GVF failed in 7 children due to unreliable subjective responses. Of the 16 reports, with regard to the central 30-degree VF, 63% of the outputs obtained from both methods were comparable. EMPP is a reliable method to estimate and characterise the central 30-degree VF in greater detail in children with IL. EMPP can supplement the conventional methods, especially in those children who fail to complete a long duration GVF test

Eyes on CVI:Eye movements unveil distinct visual search patterns in Cerebral Visual Impairment compared to ADHD, dyslexia, and neurotypical children

Visual search problems are often reported in children with Cerebral Visual Impairment (CVI). To tackle the clinical challenge of objectively differentiating CVI from other neurodevelopmental disorders, we developed a novel test battery. Visual search tasks were coupled with verbal and gaze-based measurements. Two search tasks were performed by children with CVI (n: 22; mean age (SD): 9.63 (.46) years) ADHD (n: 32; mean age (SD): 10.51 (.25) years), dyslexia (n: 28; mean age (SD): 10.29 (.20) years) and neurotypical development (n: 44; mean age (SD): 9.30 (.30) years). Children with CVI had more impaired search performance compared to all other groups, especially in crowded and unstructured displays and even when they had normal visual acuity. In-depth gaze-based analyses revealed that this group searched in overall larger areas and needed more time to recognize a target, particularly after their initial fixation on the target. Our gaze-based approach to visual search offers new insights into the distinct search patterns and behaviours of children with CVI. Their tendency to overlook targets whilst fixating on it, point towards higher-order visual function (HOVF) deficits. The novel method is feasible, valid, and promising for clinical differential-diagnostic evaluation between CVI, ADHD and dyslexia, and for informing individualized training.</p

Brain Damage and Visuospatial Impairments: Exploring Early Structure-Function Associations in Children Born Very Preterm

BACKGROUND: To provide insight into early neurosensory development in children born very preterm, we assessed the association between early structural brain damage and functional visuospatial attention and motion processing from one to two years corrected age. METHODS: In 112 children born at less than 32 weeks gestational age, we assessed brain damage and growth with a standardized scoring system on magnetic resonance imaging (MRI; 1.5 Tesla) scans performed at 29 to 35 weeks gestational age. Of the children with an MRI scan, 82 participated in an eye tracking-based assessment of visuospatial attention and motion processing (Tobii T60XL) at one year corrected age and 59 at two years corrected age. RESULTS: MRI scoring showed good intra- and inter-rater reproducibility. At one year, 10% children had delayed attentional reaction times and 23% had delayed motion reaction times. Moderate to severe brain damage significantly correlated with slower visuospatial reaction times. At two years, despite attention and motion reaction times becoming significantly faster, 20% had delayed attentional reaction times and 35% had delayed motion reaction times, but no correlations with MRI scores were found. The presence of structural brain damage was associated with abnormal functional performance over age. CONCLUSIONS: The present study indicates an association between moderate to severe brain damage and visuospatial attention and motion processing dysfunction at one year corrected age. This provides a new perspective on comprehensive MRI scoring and quantitative functional visuospatial assessments and their applicability in children born very preterm in their first years of life

Outcome measures in Angelman syndrome

Background: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children’s functioning with standard clinical tests. Feasible outcome measures are needed to measure current functioning and change over time, in clinical practice and clinical trials. Aim: Our first aim is to assess the feasibility of several functional tests. We target domains of neurocognitive functioning and physical growth using the following measurement methods: eye-tracking, functional Near-Infrared Spectroscopy (fNIRS), indirect calorimetry, bio-impedance analysis (BIA), and BOD POD (air-displacement plethysmography). Our second aim is to explore the results of the above measures, in order to better understand the AS phenotype. Methods: The study sample consisted of 28 children with AS aged 2–18 years. We defined an outcome measure as feasible when (1) at least 70% of participants successfully finished the measurement and (2) at least 60% of those participants had acceptable data quality. Adaptations to the test procedure and reasons for early termination were noted. Parents rated acceptability and importance and were invited to make recommendations to increase feasibility. The results of the measures were explored. Results: Outcome measures obtained with eye-tracking and BOD POD met the definition of feasibility, while fNIRS, indirect calorimetry, and BIA did not. The most important reasons for early termination of measurements were showing signs of protest, inability to sit still and poor/no calibration (eye-tracking specific). Post-calibration was often applied to obtain valid eye-tracking results. Parents rated the BOD POD als most acceptable and fNIRS as least acceptable for their child. All outcome measures were rated to be important. Exploratory results indicated longer reaction times to high salient visual stimuli (eye-tracking) as well as high body fat percentage (BOD POD). Conclusions: Eye-tracking and BOD POD are feasible measurement methods for children with AS. Eye-tracking was successfully used to assess visual orienting functions in the current study and (with some practical adaptations) can potentially be used to assess other outcomes as well. BOD POD was successfully used to examine body composition. Trial registration: Registered d.d. 23-04-2020 under number ‘NL8550’ in the Dutch Trial Register: https://onderzoekmetmensen.nl/en/trial/23075</p

Outcome measures in Angelman syndrome

Background: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe intellectual disability, little to no expressive speech, visual and motor problems, emotional/behavioral challenges, and a tendency towards hyperphagia and weight gain. The characteristics of AS make it difficult to measure these children’s functioning with standard clinical tests. Feasible outcome measures are needed to measure current functioning and change over time, in clinical practice and clinical trials. Aim: Our first aim is to assess the feasibility of several functional tests. We target domains of neurocognitive functioning and physical growth using the following measurement methods: eye-tracking, functional Near-Infrared Spectroscopy (fNIRS), indirect calorimetry, bio-impedance analysis (BIA), and BOD POD (air-displacement plethysmography). Our second aim is to explore the results of the above measures, in order to better understand the AS phenotype. Methods: The study sample consisted of 28 children with AS aged 2–18 years. We defined an outcome measure as feasible when (1) at least 70% of participants successfully finished the measurement and (2) at least 60% of those participants had acceptable data quality. Adaptations to the test procedure and reasons for early termination were noted. Parents rated acceptability and importance and were invited to make recommendations to increase feasibility. The results of the measures were explored. Results: Outcome measures obtained with eye-tracking and BOD POD met the definition of feasibility, while fNIRS, indirect calorimetry, and BIA did not. The most important reasons for early termination of measurements were showing signs of protest, inability to sit still and poor/no calibration (eye-tracking specific). Post-calibration was often applied to obtain valid eye-tracking results. Parents rated the BOD POD als most acceptable and fNIRS as least acceptable for their child. All outcome measures were rated to be important. Exploratory results indicated longer reaction times to high salient visual stimuli (eye-tracking) as well as high body fat percentage (BOD POD). Conclusions: Eye-tracking and BOD POD are feasible measurement methods for children with AS. Eye-tracking was successfully used to assess visual orienting functions in the current study and (with some practical adaptations) can potentially be used to assess other outcomes as well. BOD POD was successfully used to examine body composition. Trial registration: Registered d.d. 23-04-2020 under number ‘NL8550’ in the Dutch Trial Register: https://onderzoekmetmensen.nl/en/trial/23075</p

Identifying Behavioural Changes due to Parkinson's Disease Progression in Motor Performance Data

Parkinson's disease (PD) is a progressive nervous system disorder that affects movement. PD has a severely negative impact on the quality of life of patients and their caregivers. The timing of treatment depends, amongst others, on the quantification of patients' motor performance. To date, the resolution used in scaling motor performance is too low to detect subtle behavioral changes over time. This paper investigates if 'longitudinal' data-sets of motor performance data obtained from tracking tasks can detect behavioural changes in motor performance data representative for PD symptoms. Such longitudinal data were approximated using a combined data-set based on 50 trials of collected experiment data from 25 healthy participants (age range 55-75 years), augmented with 25 bootstrapped samples scaled to represent 'Mild' or 'Severe' motor performance degradation. An approach based on general linear regression models was tested for its capacity to detect the adverse trends in typical tracking task metrics (Kp, τ, ζnms, ωnms, RMSe, and RMSu). Overall, it was found that with this approach in at least 50% of all participants, a simulated change in motor behaviour was successfully detected, a number that may increase to 97% for the most sensitive metric (ζnms) and consistent participant data. This indicates that the developed approach is promising towards the development of more objective and detailed monitoring of disease progression and treatments in PD patients