A Spatial Decision Eye-Tracking Task in Patients with Prodromal and Mild Alzheimer's Disease.

BACKGROUND/OBJECTIVE: Performances on spatial decision eye-tracking tasks are known to be impaired in patients with moderate Alzheimer's disease (AD), but the clinical relevance of this deficit during earlier stages of AD remains unclear. METHODS: This study recruited patients with amnestic mild cognitive impairment (aMCI, prodromal AD), patients with mild AD, and age-matched controls from three French memory clinics. Participants' ability to make spatial judgments and decisions was assessed with an eye-tracking system, and cognitive performance on conventional neuropsychological tests was evaluated. RESULTS: We enrolled 26 controls, 25 aMCI patients (median Mini-Mental State Exam [MMSE] 26), and 23 mild-AD patients (median MMSE 23). Patients with mild AD had higher error rates on the spatial decision task than aMCI patients and controls (32.4% versus 23.5%; p < 0.01 and 32.4% versus 22.2%; p < 0.05, respectively), but there were no differences among the groups in anticipation rate or the percentage of express saccades. Additionally, error rates on the spatial decision task were inversely correlated with performance on visual memory tests (immediate and delayed recall on the DMS- 48: r =-0.44, p = 0.0019 and r =-0.43, p = 0.0020, respectively), semantic fluency (r =-0.44, p = 0.0016), and global cognition (MMSE: r =-0.44, p = 0.0019). Performance on the spatial decision task was not correlated with anti-saccades, processing speed, or attentional performance. CONCLUSIONS: Patients with mild AD made more errors on a spatial decision task than aMCI patients and controls. We hypothesize that impaired visuospatial judgment may explain these results and distinguish aMCI patients from mild AD patients.

Conscious processing of auditory regularities induces a pupil dilation.

Pupil dilation has been reliably identified as a physiological marker of consciously reportable mental effort. This classical finding raises the question of whether or not pupil dilation could be a specific somatic signature of conscious processing. In order to explore this possibility, we engaged healthy volunteers in the 'local global' auditory paradigm we previously designed to disentangle conscious from non-conscious processing of novelty. We discovered that consciously reported violations of global (inter-trials) regularity were associated with a pupil dilation effect both in an active counting task and in a passive attentive task. This pupil dilation effect was detectable both at the group-level and at the individual level. In contrast, unreported violations of this global regularity, as well as unreported violations of local (intra-trial) regularity that do not require conscious access, were not associated with a pupil dilation effect. We replicated these findings in a phonemic version of the 'local global'. Taken together these results strongly suggest that pupil dilation is a somatic marker of conscious access in the auditory modality, and that it could therefore be used to easily probe conscious processing at the individual level without interfering with participant's stream of consciousness by questioning him/her.

Prodromal Alzheimer's Disease Demonstrates Increased Errors at a Simple and Automated Anti-Saccade Task.

Saccade alterations are potential early signs of Alzheimer's disease. However, uncertainty persists in how early and reliably automated saccade recording systems detect impairments. This multicenter pathophysiological case-control transversal study explored saccade execution in carefully diagnosed amnestic mild cognitive impairment patients fulfilling research criteria for prodromal Alzheimer's disease (n = 29), as compared to both aged-matched mild Alzheimer's disease patients (n = 23) and controls (n = 27). Auto-coded saccades from horizontal (gap) vertical (step) stimulus elicited pro-saccades, and anti-saccade (gap) tasks were compared across the 3 groups. Mild cognitive impairment patients committed significantly more anti-saccade errors compared to controls (46.9 versus 24.3%, p < 0.001). Conventional analyses of the auto-coded stimulus elicited saccades parameters did not distinguish the amnestic mild cognitive impairment from controls or the mild Alzheimer's disease group. However, an offline analysis of manually coded saccade latencies, using resampling statistics did reveal subtle differences among the groups. Analysis of the manually coded data revealed that the mild Alzheimer's disease group had a reliably larger self-corrected error-rate than in amnestic mild cognitive impairment and controls (p = 0.003). Analysis of the manually coded saccade latencies, using more sensitive lognormal bootstrap analysis revealed a continuum, from amnestic mild cognitive impairment to mild Alzheimer's disease, of an increased severity of impaired inhibition of stimulus elicited saccades and correct voluntary saccade initiation. Anti-saccade error rates and psychometric measures of executive and several other cognitive functions were moderately and negatively correlated. Overall, inhibitory impairments in stimulus elicited saccades, characteristic of Alzheimer's disease, may be detected early in presumed prodromal patients using a simple, automated anti-saccade task.

Saccadic eye movements in adults with high-functioning autism spectrum disorder.

In this study, we examined the accuracy and dynamics of visually guided saccades in 20 adults with autism spectrum disorder, as compared to 20 typically developed adults using the Step/Overlap/Gap paradigms. Performances in participants with autistic spectrum disorder were characterized by preserved Gap/Overlap effect, but reduced gain and peak velocity, as well as a greater trial-to-trial variability in task performance, as compared to the control group. While visual orienting and attentional engagement were relatively preserved in individuals with autistic spectrum disorder, overall these findings provide evidence that abnormal oculomotor behavior in autistic spectrum disorder reflects an altered sensorimotor control due to cerebellar abnormalities, rather than a deficit in the volitional control of eye movements. This study contributes to a growing body of evidence implicating this structure in the physiopathology of autism.

Postural Control and Emotion in Children with Autism Spectrum Disorders.

Autism Spectrum Disorders subjects (ASD) are well known to have deficits in social interaction. We recorded simultaneously eye movements and postural sway during exploration of emotional faces in children with ASD and typically developing children (TD). We analyzed several postural and ocular parameters. The results showed that all postural parameters were significantly greater in children with ASD; ASD made significantly fewer saccades and had shorter fixation time than TD, particularly in the eyes, and especially for unpleasant emotions. These results suggest that poor postural control of ASD and their impaired visual strategies could be due to a lack of interest in social cognition, causing a delay in the development of the cortical areas, and thus could have an effect on their postural control.

Saccadic eye movements as markers of schizophrenia spectrum: Exploration in at-risk mental states.

Schizophrenia is a neurodevelopmental disease with cognitive and motor impairments. Motor dysfunctions, such as eye movements or Neurological Soft Signs (NSS), are proposed as endophenotypic markers. Antisaccade (AS) and memory-guided saccades (MGS), two markers of inhibitory control mechanism, are altered in both patients with schizophrenia and their relatives, although these tools may have different sensitivities. Recently, emphasis has been put on identifying markers predictive of psychosis transition in subjects with ultra-high-risk psychosis in order to develop targeted prevention. This study investigates AS and MGS in 46 patients with schizophrenia, 23 ultra-high-risk subjects, and 39 full siblings compared to 47 healthy volunteers. NSS were assessed as a marker of abnormal neurodevelopment. The results revealed more errors in MGS in patients, ultra-high-risk subjects and siblings, than in controls, and more specifically ultra-high-risk subjects with high NSS scores. By contrast, the error rate in AS was significantly higher only in patients with schizophrenia compared to controls. These findings suggest that MGS could be more accurate to detect deficient inhibitory processes as a marker of vulnerability before the onset of schizophrenia. The use of the different paradigms (AS, MGS) revealed distinct profiles depending on the stage of the disease, indicating that some alterations could be pure endophenotypic markers of vulnerability for schizophrenia, while others could be markers of the disease progression.

Reduced saccadic inhibition of return to moving eyes in autism spectrum disorders.

Inhibition of Return (IOR) refers to slower reaction time to a target presented at the same location as a preceding stimulus. Here, we examine reflexive attention orienting via the saccadic IOR using a shift in gaze direction (i.e. from averted to direct) in faces presented as a peripheral cue, in upright and inverted orientations, in adults with Autism Spectrum Disorder (ASD) and typically developed comparison participants. While both groups showed an IOR in the inverted face condition, this effect was reduced in participants with ASD in the upright face condition, as compared to comparison participants, suggesting that moving eyes do not trigger reflexive exogenous orienting in individuals with ASD. Impaired reflexive orienting to eye gaze might severely compromise the later development of social functions in ASD, such as joint attention, face emotion recognition and mindreading.

Differences between Dyslexic and Non-Dyslexic Children in the Performance of Phonological Visual-Auditory Recognition Tasks: An Eye-Tracking Study.

The object of this study was to explore further phonological visual-auditory recognition tasks in a group of fifty-six healthy children (mean age: 9.9 ± 0.3) and to compare these data to those recorded in twenty-six age-matched dyslexic children (mean age: 9.8 ± 0.2). Eye movements from both eyes were recorded using an infrared video-oculography system (MobileEBT® e(y)e BRAIN). The recognition task was performed under four conditions in which the target object was displayed either with phonologically unrelated objects (baseline condition), or with cohort or rhyme objects (cohort and rhyme conditions, respectively), or both together (rhyme + cohort condition). The percentage of the total time spent on the targets and the latency of the first saccade on the target were measured. Results in healthy children showed that the percentage of the total time spent in the baseline condition was significantly longer than in the other conditions, and that the latency of the first saccade in the cohort condition was significantly longer than in the other conditions; interestingly, the latency decreased significantly with the increasing age of the children. The developmental trend of phonological awareness was also observed in healthy children only. In contrast, we observed that for dyslexic children the total time spent on the target was similar in all four conditions tested, and also that they had similar latency values in both cohort and rhyme conditions. These findings suggest a different sensitivity to the phonological competitors between dyslexic and non-dyslexic children. Also, the eye-tracking technique provides online information about phonological awareness capabilities in children.

The effect of face exploration on postural control in healthy children.

The objective was to explore how face exploration affects postural control in healthy children. The novelty here is that eye movements and posture were simultaneously recorded. Three groups of children participated in the study: 12 children of 7.8±0.5 years old, 13 children of 10.4±0.5 years old and 12 children of 15.7±0.9 years old. Eye movements were recorded by video-oculography and postural stability was recorded by a platform. Children were invited to explore five emotional faces (neutral, happy, sad fear and angry). Analysis of eye movements was done on saccadic latency, percentage of exploration time spent and number of saccades for each specific region of interest (ROI): eyes, nose and mouth. Analysis of posture was made on surface area, sway length and mean velocity of the center of pressures (CoP). Results showed that visual strategies, exploration and postural control develop during childhood and adolescence. Indeed, after nine years-old, children started to look the eyes ROI firstly, then the nose ROI and finally the mouth ROI. The number of saccades decreased with the age of children. The percentage of exploration time spent in eyes ROI was longer than the others ROIs and greater for unpleasant faces (sad, fear and angry) with respect to pleasant emotional face (happy). We found that in front of sad and happy faces the surface area of the CoP was significantly larger compared to other faces (neutral and angry). These results suggest that visual strategies and postural control change during children's development and can be influenced by the emotional face.

Accelerated time course of saccadic inhibition of return in individuals with autism spectrum disorders.

The inhibition of return (IOR) refers the observer's slower response time when the target stimulus appears on the previously attended location. In the present study, we examined the time course of saccadic IOR by using five stimuli onset asynchronies (SOAs) in a group of adults with autism spectrum disorders (ASDs) and a comparison group. The results showed that the IOR effect occurred earlier (300 ms SOA) in participants with ASDs, relative to the comparison participants (500 and 700 ms SOAs). The ASD group also committed a greater number of anticipatory saccades, which positively correlated with scores on restricted and repetitive behaviors, as assessed by the Autism Diagnostic Interview-Revised (ADI-R; Lord et al. in J Autism Dev Disord 24:659-685, 1994). These findings reveal an accelerated time course for saccadic IOR along with diminished volitional oculomotor control in participants with ASDs. We discussed these results with reference to the atypical and the superior visual search abilities often reported in this population.

Binocular saccade coordination in reading and visual search: a developmental study in typical reader and dyslexic children.

Studies dealing with developmental aspects of binocular eye movement behavior during reading are scarce. In this study we have explored binocular strategies during reading and visual search tasks in a large population of dyslexic and typical readers. Binocular eye movements were recorded using a video-oculography system in 43 dyslexic children (aged 8-13) and in a group of 42 age-matched typical readers. The main findings are: (i) ocular motor characteristics of dyslexic children are impaired in comparison to those reported in typical children in reading task; (ii) a developmental effect exists in reading in control children, in dyslexic children the effect of development was observed only on fixation durations; and (iii) ocular motor behavior in the visual search tasks is similar for dyslexic children and for typical readers, except for the disconjugacy during and after the saccade: dyslexic children are impaired in comparison to typical children. Data reported here confirms and expands previous studies on children's reading. Both reading skills and binocular saccades coordination improve with age in typical readers. The atypical eye movement's patterns observed in dyslexic children suggest a deficiency in the visual attentional processing as well as an impairment of the ocular motor saccade and vergence systems interaction.

Vertical saccades in dyslexic children.

Vertical saccades have never been studied in dyslexic children. We examined vertical visually guided saccades in fifty-six dyslexic children (mean age: 10.5±2.56 years old) and fifty-six age matched non dyslexic children (mean age: 10.3±1.74 years old). Binocular eye movements were recorded using an infrared video-oculography system (mobileEBT®, e(ye)BRAIN). Dyslexic children showed significantly longer latency than the non dyslexic group, also the occurrence of anticipatory and express saccades was more important in dyslexic than in non dyslexic children. The gain and the mean velocity values were significantly smaller in dyslexic than in non dyslexic children. Finally, the up-down asymmetry reported in normal population for the gain and the velocity of vertical saccades was observed in dyslexic children and interestingly, dyslexic children also reported an up-down asymmetry for the mean latency. Taken together all these findings suggested impairment in cortical areas responsible of vertical saccades performance and also at peripheral level of the extra-ocular oblique muscles; moreover, a visuo-attentionnal bias could explain the up-down asymmetry reported for the vertical saccade triggering.

Effect of visual attention on postural control in children with attention-deficit/hyperactivity disorder.

We compared the effect of oculomotor tasks on postural sway in two groups of ADHD children with and without methylphenidate (MPH) treatment against a group of control age-matched children. Fourteen MPH-untreated ADHD children, fourteen MPH-treated ADHD children and a group of control children participated to the study. Eye movements were recorded using a video-oculography system and postural sway measured with a force platform simultaneously. Children performed fixation, pursuits, pro- and anti-saccades. We analyzed the number of saccades during fixation, the number of catch-up saccades during pursuits, the latency of pro- and anti-saccades; the occurrence of errors in the anti-saccade task and the surface and mean velocity of the center of pressure (CoP). During the postural task, the quality of fixation was significantly worse in both groups of ADHD children with respect to control children; in contrast, the number of catch-up saccades during pursuits, the latency of pro-/anti-saccades and the rate of errors in the anti-saccade task did not differ in the three groups of children. The surface of the CoP in MPH-treated children was similar to that of control children, while MPH-untreated children showed larger postural sway. When performing any saccades, the surface of the CoP improved with respect to fixation or pursuits tasks. This study provides evidence of poor postural control in ADHD children, probably due to cerebellar deficiencies. Our study is also the first to show an improvement on postural sway in ADHD children performing saccadic eye movements.

Vertical saccades in children: a developmental study.

There are no studies exploring the development of vertical saccades in large populations of children. In this study, we examined the development of vertical saccades in sixty-nine children. Binocular eye movements were recorded using an infrared video oculography system [Mobile EBT(®), e(ye)BRAIN], and movements from both eyes had been analyzed. The gain and the peak velocity of vertical saccades show an up-down asymmetry. Latency value decreases with the age of children, and it does not depend on the direction of the saccades; in contrast, the gain and the peak velocity values of vertical saccades are stable during childhood. We suggest that the up-down asymmetry is developed early, or is innate, in humans. Latencies of vertical saccades develop with the age of children, in relationship with the development of the cortical network responsible for the saccade preparation. In contrast, the precision and the peak velocity are not age-dependent as they are controlled by the cerebellum and brainstem structures.

Smooth pursuit eye movements in children with strabismus and in children with vergence deficits.

PURPOSE: The objective of our study was to examine horizontal smooth pursuit performance in strabismic children and in children with vergence deficits, and to compare these data with those recorded in a group of control age-matched children. METHODS: Binocular eye movements were recorded by video-oculography in ten strabismic children (mean age: 9.8±0.8) and seven children with vergence deficits (mean age: 10.8±0.6). Data were compared to that of age-matched control children (mean age: 9.8±0.8 years). RESULTS: Catch-up saccades amplitude in strabismic children and in children with vergence deficits were significantly higher than in control age-matched children. Moreover, in strabismic children the amplitude of catch-up saccades was significantly higher in rightward than in leftward direction. The number of catch-up saccades was also significantly higher in rightward than in leftward direction. The gain value of pursuits in rightward direction was significantly higher in the right eye than in the left one; for the right eye, the gain value was significantly higher in rightward than in leftward direction. Binocular coordination of pursuit was better in control age-matched children than in children with vergence deficits and than in strabismic children. CONCLUSIONS: Binocular coordination of pursuit is abnormal in children with vergence deficits and worse in strabismic children. Binocular vision plays an important role in improving binocular coordination of pursuit.

Reading and visual search: a developmental study in normal children.

Studies dealing with developmental aspects of binocular eye movement behaviour during reading are scarce. In this study we have explored binocular strategies during reading and during visual search tasks in a large population of normal young readers. Binocular eye movements were recorded using an infrared video-oculography system in sixty-nine children (aged 6 to 15) and in a group of 10 adults (aged 24 to 39). The main findings are (i) in both tasks the number of progressive saccades (to the right) and regressive saccades (to the left) decreases with age; (ii) the amplitude of progressive saccades increases with age in the reading task only; (iii) in both tasks, the duration of fixations as well as the total duration of the task decreases with age; (iv) in both tasks, the amplitude of disconjugacy recorded during and after the saccades decreases with age; (v) children are significantly more accurate in reading than in visual search after 10 years of age. Data reported here confirms and expands previous studies on children's reading. The new finding is that younger children show poorer coordination than adults, both while reading and while performing a visual search task. Both reading skills and binocular saccades coordination improve with age and children reach a similar level to adults after the age of 10. This finding is most likely related to the fact that learning mechanisms responsible for saccade yoking develop during childhood until adolescence.

Binocular coordination of saccades during reading in strabismic children.

PURPOSE: To our knowledge, studies comparing binocular eye movements during reading task in strabismic children are scarce. The goal of our study was to examine binocular coordination of saccades during reading in strabismic children. METHODS: Binocular eye movements were recorded by an infrared system (mobile EBT) in 18 strabismic children 6.8 to 16 years old (mean age 10.2 ± 3) who were asked to read a four-line text silently during binocular viewing. Data were compared to that of 18 age-matched non-strabismic control children. RESULTS: Saccade amplitude was similar in strabismic and control children. In contrast, binocular coordination during and after the saccades was significantly poorer in strabismic children as opposed to control children. The duration of fixation also was significantly longer in strabismic children compared to controls. Binocular coordination in strabismic children who have binocular vision was better than those without binocular vision, but it still was worse than in control subjects. CONCLUSIONS: In strabismic children binocular saccade coordination is deficient and could be responsible for impaired reading capabilities. Binocular vision has an important role in improving binocular saccade yoking.

Saccadic eye movements in children: a developmental study.

To our knowledge, there are no studies exploring the development of voluntary and reflexive saccades in children using different types of paradigms to investigate horizontal saccades. In the present study, we examined the development of horizontal saccades in children aged 6-15 years. Binocular eye movements were recorded using an infrared video-oculography system (mobileEBT(®), e(ye)BRAIN) in seventy-two children (aged 6-15). Several paradigms were used to stimulate reflexive and voluntary horizontal saccades: gap, step and overlap paradigms. Horizontal anti-saccades were also examined. In all paradigms, the latency of saccades decreased with the age of children and it did not depend on the direction of the saccades (left/right); the error rate in the anti-saccade task decreased with age; the gain of horizontal saccades improved with age; the peak velocity of horizontal saccades was stable throughout childhood. We conclude that saccadic performances are influenced by age and cortical circuits responsible for the preparation of reflexive or voluntary saccades are completed at 12 years old. These data could be used as reference values for further studies dealing with pathologic development.

Immaturity of the oculomotor saccade and vergence interaction in dyslexic children: evidence from a reading and visual search study.

Studies comparing binocular eye movements during reading and visual search in dyslexic children are, at our knowledge, inexistent. In the present study we examined ocular motor characteristics in dyslexic children versus two groups of non dyslexic children with chronological/reading age-matched. Binocular eye movements were recorded by an infrared system (mobileEBT®, e(ye)BRAIN) in twelve dyslexic children (mean age 11 years old) and a group of chronological age-matched (N = 9) and reading age-matched (N = 10) non dyslexic children. Two visual tasks were used: text reading and visual search. Independently of the task, the ocular motor behavior in dyslexic children is similar to those reported in reading age-matched non dyslexic children: many and longer fixations as well as poor quality of binocular coordination during and after the saccades. In contrast, chronological age-matched non dyslexic children showed a small number of fixations and short duration of fixations in reading task with respect to visual search task; furthermore their saccades were well yoked in both tasks. The atypical eye movement's patterns observed in dyslexic children suggest a deficiency in the visual attentional processing as well as an immaturity of the ocular motor saccade and vergence systems interaction.

How cognitive performance-induced stress can influence right VLPFC activation: an fMRI study in healthy subjects and in patients with social phobia.

The neural bases of interactions between anxiety and cognitive control are not fully understood. We conducted an fMRI study in healthy participants and in patients with an anxiety disorder (social phobia) to determine the impact of stress on the brain network involved in cognitive control. Participants performed two working memory tasks that differed in their level of performance-induced stress. In both groups, the cognitive tasks activated a frontoparietal network, involved in working memory tasks. A supplementary activation was observed in the right ventrolateral prefrontal cortex (VLPFC) in patients during the more stressful cognitive task. Region of interest analyses showed that activation in the right VLPFC decreased in the more stressful condition as compared to the less stressful one in healthy subjects and remain at a similar level in the two cognitive tasks in patients. This pattern was specific to the right when compared to the left VLPFC activation. Anxiety was positively correlated with right VLPFC activation across groups. Finally, left dorsolateral prefrontal cortex (DLPFC) activation was higher in healthy subjects than in patients in the more stressful task. These findings demonstrate that in healthy subjects, stress induces an increased activation in left DLPFC, a critical region for cognitive control, and a decreased activation in the right VLPFC, an area associated with anxiety. In patients, the differential modulation between these dorsal and ventral PFC regions disappears. This absence of modulation may limit anxious patients' ability to adapt to demanding cognitive control tasks.