Social and non-social gaze cueing in autism spectrum disorder, attention-deficit/hyperactivity disorder and a comorbid group.

Recent trends in literature, along with the changes to the Diagnostic and Statistical Manual (DSM), make it imperative to study Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) together, in order to better understand potential aetiological commonalities between these highly comorbid disorders. The present study examines social cueing, a highly studied construct in ASD, and intra-subject variability (ISV), a potential endophenotype of ADHD, in four groups of typically developing (TD), ADHD, ASD- (ASD without ADHD), ASD+ (ASD with ADHD) participants (N = 85) aged 10-13 years. Results showed that social cueing is intact in the 'pure' ASD group when task expectations are clear. The ADHD group showed faster saccadic reaction times, no increased ISV and a pattern of viewing comparable to the TD group. However, the ASD + group showed a differences in processing style and ISV. A secondary analysis gives evidence of non-additive effects of the ASD and ADHD factors.

Visual search in ADHD, ASD and ASD + ADHD: overlapping or dissociating disorders?

Recent debates in the literature discuss commonalities between Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) at multiple levels of putative causal networks. This debate requires systematic comparisons between these disorders that have been studied in isolation in the past, employing potential markers of each disorder to be investigated in tandem. The present study, choose superior local processing, typical to ASD, and increased Intra-Subject Variability (ISV), typical to ADHD, for a head-to-head comparison of the two disorders, while also considering the comorbid cases. It directly examined groups of participants aged 10-13 years with ADHD, ASD with (ASD+) or without (ASD-) comorbid ADHD and a typically developing (TD) group (total N = 85). A visual search task consisting of an array of paired words was designed. The participants needed to find the specific pair of words, where the first word in the pair was the cue word. This visual search task was selected to compare these groups on overall search performance and trial-to-trial variability of search performance (i.e., ISV). Additionally, scanpath analysis was also carried out using Recurrence Quantification Analysis (RQA) and the Multi-Match Model. Results show that only the ASD- group exhibited superior search performance; whereas, only the groups with ADHD symptoms showed increased ISV. These findings point towards a double dissociation between ASD and ADHD, and argue against an overlap between ASD and ADHD.

Examining the Overlap Between ADHD and Autism Spectrum Disorder (ASD) Using Candidate Endophenotypes of ADHD.

Objective: Recent discussions of aetiological overlap between ADHD and Autism Spectrum Disorder (ASD) require comparative studying of these disorders. METHOD: We examined performance of ASD patients with (ASD+) and without (ASD-) comorbid ADHD, ADHD patients, and controls for selected putative endophenotypes of ADHD: Intrasubject Variability (ISV) of reaction times, working memory (WM), inhibition, and temporal processing. RESULTS: We found that patients with ADHD or ASD+, but not ASD-, had elevated ISV across the entire task battery and temporal processing deficits, and that none of the groups were impaired in WM or inhibition. High levels of ISV and generally poor performance in ASD+ patients were only partially due to additive effects of the pure disorders. CONCLUSION: Overall, we conclude that, within our limited but heterogeneous task battery, ISV and temporal processing deficits are most sensitive to ADHD symptomatology and that controlling for ADHD comorbidity is mandatory when assessing ISV in autism.

Studying global processing in autism and attention-deficit/hyperactivity disorder with gaze movements: The example of a copying task.

Recent discussions in the literature, along with the revision of the Diagnostic and Statistical Manual (DSM) (American Psychiatric Association 2013), suggest aetiological commonalities between the highly comorbid Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). Addressing this discussion requires studying these disorders together by comparing constructs typical to each of them. In the present study, we investigate global processing, known to be difficult for participants with ASD, and Intra-Subject Variability (ISV), known to be consistently increased in participants with ADHD, in groups, aged 10-13 years, with ADHD (n = 25), ASD without comorbid ADHD (ASD-) (n = 13) and ASD with ADHD (ASD+) (n = 18) in comparison with a typically developing group (n = 22). A Copying task, typically requiring global processing and in this case particularly designed using equally complex stimuli to also measure ISV across trials, was selected. Oculomotor measures in this task proved to be particularly sensitive to group differences. While increased ISV was not observed in the present task in participants with ADHD, both ASD groups looked longer on the figure to be drawn, indicating that global processing takes longer in ASD. However, the ASD+ group fixated on the figure only between drawing movements, whereas the ASD- group did this throughout the drawing process. The present study provides evidence towards ASD and ADHD being separate, not-overlapping, disorders. Since the pure ASD- group was affected more by central coherence problems than the ASD+ group, it may suggest that neuropsychological constructs interact differently in different clinical groups and sub-groups.

The impact of the COMT genotype and cognitive demands on facets of intra-subject variability.

Intra-Subject Variability (ISV), a potential index of catecholaminergic regulation, is elevated in several disorders linked with altered dopamine function. ISV has typically been defined as reaction time standard deviation. However, the ex-Gaussian and spectral measures capture different aspects and may delineate different underlying sources of ISV; thus reflecting different facets of the construct. We examined the impact of factors associated with dopamine metabolism, namely, Catechol-O-Methyltransferase Val158Met (COMT) genotype and Working Memory (WM) and response-switching on ISV facets in young healthy adults. The Met allele was associated with overall increased variability. The rather exclusive sensitivity of ex-Gaussian tau to frequencies below 0.025 Hz and the quasi-periodic structure of particularly slow responses support the interpretation of tau as low frequency fluctuations of neuronal networks. Sigma, by contrast, may reflect neural noise. Regarding cognitive demands, a WM load-related increase in variability was present for all genotypes and all ISV facets. Contrastingly, ISV facets reacted differently to variations in response-switching as, across genotypes, sigma was elevated for rare target trials whereas tau was elevated for frequent standard trials, particularly for Met homozygotes. Our findings support the significant role of COMT in regulating behavioural ISV with its facetted structure and presumed underlying neural processes.

Electro-cortical correlates of multisensory integration using ecologically valid emotional stimuli: Differential effects for fear and disgust.

Multisensory integration (MSI) is crucial for human communication and social interaction and has been investigated in healthy populations and neurodevelopmental disorders. However, the use of stimuli with high ecological validity is sparse, especially in event-related potential (ERP) studies. The present study examined the ERP correlates of MSI in healthy adults using short (500 ms) ecologically valid professional actor-produced emotions of fear or disgust as vocal exclamation or facial expression (unimodal conditions) or both (bimodal condition). Behaviourally, our results show a general visual dominance effect (similarly fast responses following bimodal and visual stimuli) and an MSI-related speedup of responses only for fear. Electrophysiologically, both P100 and N170 showed MSI-related amplitude increases only following fear, but not disgust stimuli. Our results show for the first time that the known differential neural processing of fear and disgust also holds for the integration of dynamic auditory and visual information.

Cognitive endophenotypes of attention deficit/hyperactivity disorder and intra-subject variability in patients with autism spectrum disorder.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have previously been studied mainly in isolation from each other. However the two conditions may be aetiologically related and thus show overlap in aetiologically relevant functions. In order to address this question of potential aetiological overlap between ADHD and ASD, the present study set out to investigate putative endophenotypes of ADHD in N=33 typically developing (TD) children and N=28 patients with ASD that were (ASD+) or were not (ASD-) co-morbid for ADHD. With regard to both the cognitive endophenotype candidates (working memory, inhibition, temporal processing) and intra-subject variability (ISV) the pattern of abnormalities was inconsistent. Furthermore, the overall profile of ASD-TD differences was extremely similar to the pattern of differences between the ASD+ and ASD- sub-groups, suggesting that any abnormalities found were due to the comorbid ASD subgroup. This held in particular for ISV, which did not show in patients with ASD the task-general increase that is common in ADHD samples. Altogether, the present results do not support the hypothesis of aetiological overlap between ASD and ADHD.

Disturbed cingulate glutamate metabolism in adults with high-functioning autism spectrum disorder: evidence in support of the excitatory/inhibitory imbalance hypothesis.

Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N-acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas.

COMT Val158Met genotype is associated with fluctuations in working memory performance: converging evidence from behavioural and single-trial P3b measures.

Intra-subject variability in reaction times (ISV) is a promising endophenotype for several psychiatric conditions, but its neural underpinnings are not yet established. Converging evidence from neuroimaging, molecular genetics, and psychopharmacology suggests that ISV could index catecholaminergically-mediated neural noise. The fine-grained temporal resolution of electroencephalography is ideal for investigating ISV, but only if potential neural correlates of ISV can be assessed in single trials. Based on evidence that ISV is associated with dopaminergic functioning, we apply a recently developed method of single-trial P3b analysis to investigate the association of COMT Val(158)Met genotype with measures of ISV on the behavioural and neural levels at different working memory loads. Greater number of Met alleles was associated with poorer and more intra-individually variable performance on the tasks, and greater latency jitter in single-trial P3bs. These converging results at the behavioural and neurophysiological levels confirm previous observations that prefrontal dopamine availability is associated with stability and accuracy of cognitive performance. Together with previous studies, these data imply pleiotropic cognitive effects of COMT genotype.

[High-functioning autism spectrum disorders in adulthood]. / Autismusspektrumstörungen mit hohem Funktionsniveau im Erwachsenenalter.

The prevalence of autism spectrum disorders in the general population is approximately 1 %. Some individuals with high-functioning autism graduate from regular schools without autism having been diagnosed and problems only occur when the demands for social competence increase. Then patients often present with secondary psychiatric symptoms, such as depression, anxiety or interpersonal problems. At this time, typical autistic features, such as social interaction deficits, restricted interests and stereotypic behavior can be camouflaged by high compensatory skills, particularly in highly intelligent patients. Therefore, missed or wrong diagnoses are frequent. Interviews, questionnaires and neuropsychological tests might be used to support the diagnosis. In cases where there is evidence for a secondary cause of autistic symptoms, somatic disorders should be excluded. Pharmacological treatment should be symptom-oriented. Individualized psychotherapeutic approaches are becoming increasingly more available; however, pragmatic solutions often need to be deployed.

The initiation of smooth pursuit eye movements and saccades in normal subjects and in "express-saccade makers".

A vast knowledge exists about saccadic reaction times (RT) and their bi- or multimodal distributions with very fast (express) and regular RT. Recently, there has been some evidence that the smooth pursuit system may show a similar RT behavior. Since moving targets usually evoke a combined pursuit/saccade response, we asked which processes influence the initiation of pursuit and saccadic eye movements. Furthermore, we investigated whether and how the pursuit and saccadic system interact during the initiation of eye movements to moving targets. We measured the RT of the initial smooth pursuit (iSP) response and of the first corrective saccade and compared the RT behavior of both. Furthermore we compared the behavior of the corrective saccades to moving targets to that of saccades to stationary targets, known from the literature. The stimulus consisted of a target that moved suddenly at constant velocity (ramp). In addition, prior to the movement, a temporal gap, a position step or a combination of both could occur (gap-ramp, step-ramp, gap-step-ramp, respectively). Differently from most previous studies, we chose step and ramp with the same direction to provoke competition between the pursuit and saccade system. For the first time we investigated pursuit initiation in "express-saccade makers" (ES makers), a subject group known to produce an abnormally high percentage of short-latency saccades in saccade tasks. We compared their results with subject groups who were either naive or trained with respect to saccade tasks. The iSP started at approximately 100 ms, which corresponds to express saccade latencies. These short iSP-RT occurred reflex-like and almost independent of the experimental task. A bimodal frequency distribution of RT with a second peak of longer iSP-RT occurred exclusively in the ramp paradigm. The RT of the first corrective saccades in a pursuit task were comparable with that in a saccade task and depended on the stimulus. The ability of ES makers to produce a high number of express saccades was transferred to corrective saccades in the pursuit task, but not to pursuit initiation. In summary, short-latency pursuit responses differ from express saccades with respect to their independence of experiment and subject group. Therefore, a simple analogy to express saccades cannot be drawn, although some mechanisms seem to act similarly on both the pursuit and the saccade system (such as disengagement of attention with the gap effect). Furthermore, we found evidence that the initial pursuit response and the first corrective saccade are processed independently of each other. The first corrective saccades to moving targets behave like saccades to stationary targets. Normal pursuit but abnormal saccade RT of ES makers can be explained by recent theories of superior colliculus (SC) function in terms of retinal error handling.

Voluntary saccadic control in dyslexia.

The role of eye-movement control in dyslexia is still unclear. Recent studies, however, confirmed that dyslexics show poor saccadic control in single and sequential target tasks. In the present study we investigated whether dyslexic subjects are impaired on an antisaccade task requiring saccades against the direction of a stimulus. Altogether, 620 subjects between the ages of 7 and 17 years were classified as dyslexics (N = 506) or control subjects (N = 114) on the grounds of the discrepancy between their intellectual abilities and reading/spelling achievements. All subjects performed an overlap prosaccade and a gap antisaccade task with 100 trials to each side of stimulation in random order. Variables analysed were the overall saccadic reaction time of both tasks; and from the antisaccade task the number of errors (prosaccades), the number of corrected errors, and the number of trials in which the subjects still failed to reach the side opposite the stimulus even after two saccades. An analysis of variance was carried out taking into account the development of saccadic behaviour with age and the differences between the groups. The results confirm development of saccade control with age, especially in the voluntary component (a frontal-lobe function) for both groups, but indicate that the antisaccade task performance, as measured by the error and the correction rate, is significantly worse in the dyslexic group at ages above 8 years. Up to 50% of the dyslexics performed the antisaccade task 1.5 standard deviations below the mean of the controls.

Poor saccadic control correlates with dyslexia.

A large group of subjects, either average readers or reading/spelling disabled subjects (n = 185; age between 8-25 years; M = 13 +/- 4 years), were tested in various standardized cognitive tasks including reading/spelling assessment and in non-cognitive saccadic eye movement tasks. Dyslexics were separated into a subgroup (D1) with deficits in the serial auditory short-term memory and a subgroup (D2) with an isolated low achievement in reading/writing. Control subjects had no relevant cognitive deficit of any type. Saccadic eye movements were measured in a single target and in a sequential-target task. A significant correlation was found between abnormal saccadic control and reading disability. The two dyslexic groups showed only slight differences. As compared to the control group, the mean values of the standard deviations of the saccadic reaction times (SRT) and the amount of late saccades (SRT > 700) were significantly increased in both dyslexic groups and especially in group D1 who also showed an increased amount of anticipatory saccades. The number of express saccades (SRT = 80-134 ms) was increased, but not significantly, in D2 dyslexics. Both dyslexic groups produced significantly more regressive saccades in the sequential-target task. The correlation between saccadic variables and "reading factor" was 0.4. Significant deviations from normal performance of the saccadic variables were found in an estimated 50% of the dyslexics as compared to 20% of the control subjects. In spite of their worse level in saccadic control, dyslexics also developed with age in the eye movement performance as the control subjects did. Yet, the development was slower in group D1. It is suggested that reading process and saccade system are both controlled by visuo spatial attention and fixation systems that maybe impaired or develop slowly in many dyslexic subjects.

On the development of voluntary and reflexive components in human saccade generation.

The saccadic performance of a large number (n = 281) of subjects of different ages (8-70 years) was studied applying two saccade tasks: the prosaccade overlap (PO) task and the antisaccade gap (AG) task. From the PO task, the mean reaction times and the percentage of express saccades were determined for each subject. From the AG task, the mean reaction time of the correct antisaccades and of the erratic prosaccades were measured. In addition, we determined the error rate and the mean correction time, i.e. the time between the end of the first erratic prosaccade and the following corrective antisaccade. These variables were measured separately for stimuli presented (in random order) at the right or left side. While strong correlations were seen between variables for the right and left sides, considerable side asymmetries were obtained from many subjects. A factor analysis revealed that the seven variables (six eye movement variables plus age) were mainly determined by only two factors, V and F. The V factor was dominated by the variables from the AG task (reaction time, correction time, error rate) the F factor by variables from the PO task (reaction time, percentage express saccades) and the reaction time of the errors (prosaccades!) from the AG task. The relationship between the percentage number of express saccades and the percentage number of errors was completely asymmetric: high numbers of express saccades were accompanied by high numbers of errors but not vice versa. Only the variables in the V factor covaried with age. A fast decrease of the antisaccade reaction time (by 50 ms), of the correction times (by 70 ms) and of the error rate (from 60 to 22%) was observed between age 9 and 15 years, followed by a further period of slower decrease until age 25 years. The mean time a subject needed to reach the side opposite to the stimulus as required by the antisaccade task decreased from approximately 350 to 250 ms until age 15 years and decreased further by 20 ms before it increased again to approximately 280 ms. At higher ages, there was a slight indication for a return development. Subjects with high error rates had long antisaccade latencies and needed a long time to reach the opposite side on error trials. The variables obtained from the PO task varied also significantly with age but by smaller amounts. The results are discussed in relation to the subsystems controlling saccade generation: a voluntary and a reflex component the latter being suppressed by active fixation. Both systems seem to develop differentially. The data offer a detailed baseline for clinical studies using the pro- and antisaccade tasks as an indication of functional impairments, circumscribed brain lesions, neurological and psychiatric diseases and cognitive deficits.

Human express saccade makers are impaired at suppressing visually evoked saccades.

1. We report the oculomotor behavior of human subjects who produce unusually high numbers (> 30%) of express saccades (latency range 85-135 ms) in the overlap saccade task, where express saccades are usually absent or small in number (< 15%). We refer to these subjects as "express saccade makers" (ES makers). 2. We tested the hypothesis that ES makers have difficulties in maintaining fixation and in suppressing unwanted saccades to a suddenly appearing peripheral target by comparing the performances of 10 ES makers and 10 control subjects in gap and overlap antisaccade tasks and in a memory-guided saccade task. 3. The ES makers produced between 35% and 95% incorrect saccades toward the stimulus (prosaccades) in the antisaccade tasks, compared with control subjects, who produced < 20%. Their correct antisaccades appeared to be normal. 4. We further tested the ability of ES makers to maintain fixation and to avoid reflexive saccades to the onset of a target in the memory-guided saccade task. ES makers tended to glance to the briefly presented cue in many trials (4 of them in 50-80% of the trials) instead of delaying the saccade until fixation point offset. Most of the inappropriate saccades had latencies in the range of express saccades. 5. These results can be associated with the finding of fixation related neurons in different cortical and subcortical brain regions (e.g., inferior-parietal and frontal cortex, basal ganglia, superior colliculus). The unusual number of express saccades made by the ES makers in the standard overlap and gap tasks, and their unwanted short-latency reflexive saccades to the target in the memory-guided saccade task, are reminiscent of the performance in these tasks of monkeys whose collicular fixation neurons were chemically deactivated. The collicular fixation neurons are probably the final common pathway in the control of active fixation, and are in mutual inhibitory relationship with the saccade cells. 6. The decreased saccadic control observed in the ES makers suggests that saccade execution in humans is also gated by a fixation system. These ES makers may have reduced voluntarily control over saccade generation as a result of a defect or poor development of their fixation system.

Fixation and saccade control in an express-saccade maker.

In express-saccade makers a large incidence of express saccades (latencies around 100 ms) is paralleled by a reduced ability to suppress saccade generation when required. Such a behavior occurs frequently in dyslexics. We studied the latencies and the metrical properties of saccades in the very rare case of an adult, nondyslexic express-saccade maker (male, age 29 years). The subject produced 65-95% express saccades in the gap (fixation point removed 200 ms before target onset) as well as in the overlap (fixation point not removed) paradigm, which qualified the subject as the most clear case of an express-saccade maker found so far. The number of express saccades increased rather than decreased when fixation foreperiod, gap duration, and target location were randomized from trial to trial as compared to when they remained constant. In the memory-guided saccade and in the antisaccade paradigms in which immediate saccade execution to a visual target had to be suppressed, the subject often reacted to the target with express saccades in an involuntary way. The amplitudes of express saccades were--in some conditions--found to progressively decrease with increasing latency, giving rise to amplitude transition functions. The present findings disprove the notion that express saccades are generated based on the prediction of the time and location of target appearance and support the notion that they are the result of an optomotor reflex. It is argued that the operation of the reflex is gated by a separate fixation system. Express-saccade makers are described as subjects with a dysfunction of the fixation system. Recent neurophysiological findings suggest that the subject studied in the present study has a selective dysfunction of the fixation system at the level of the superior colliculus.

Oculomotor activity and visual spatial attention.

Subjects made a horizontal or vertical saccade in response to a non-lateralized auditory stimulus. Simple manual reaction time (RT) for the detection of light targets at extrafoveal locations was modulated by the intention to make the saccade insofar as RT to targets presented at the saccadic goal location or in the hemifield containing that location was faster than RT to targets presented at the opposite, mirror-symmetric location. This RT difference was maximal prior to the beginning of the saccade and vanished after saccade termination, indicating that the effect was caused by the neural activity leading to the saccade rather than to the eye movement or the eye position per se. The results have implications for the understanding of the relations between visual spatial attention and oculomotor control, especially with regard to inhibitory phenomena arising from the non-correspondence between the line of sight and the focus of attention.

Intertrial effects of randomization on saccadic reaction times in human observers.

We investigated the effect of randomizing different spatial and temporal parameters on saccadic reaction times (SRTs) in five human subjects, to explore the relative occurrence of express and regular saccades. Parameters randomized in various test sessions were: target direction (right/left), intertrial interval, fixation foreperiod and gap duration (two or three 400 msec) in gap and overlap trials. For the sake of comparison the parameters under consideration were kept constant in non-random control sessions. We found that express saccades were still present in the random test sessions but their relative frequency (and the number of regular saccades) obtained in a given test session depends on the type of randomized parameters: randomizing the intertrial interval or the fixation foreperiod in the gap task yielded modest but significant changes in the SRT distributions, express and fast regular saccades being present in both the control and the random conditions. Randomization of the fixation foreperiod in the overlap task, on the other hand, caused a quite drastic increase in the SRTs. Randomization of gap and overlap trials did not cause considerable effects on express and fast regular saccades in the gap trials, and the SRTs in the overlap trials were significantly increased only in two subjects. When two or three gap durations were randomly interleaved, we found effects that ranged from "negligible" (usually for the longest gap in a given test session) to highly significant differences as compared with the corresponding control condition. The results suggest that express saccades--as fast regular saccades--are visually guided saccades which occur when a certain state of saccade preparation has been reached before target onset. This state depends on the amount of activation in the brain structures involved in the control of attention and fixation, and the decision processes involved in saccade preparation.

Saccadic eye movements of dyslexic and normal reading children.

Twenty-four children made saccades in five noncognitive tasks. Two standard tasks required saccades to a single target presented randomly 4 deg to the right or left of a fixation point. Three other tasks required sequential saccades from the left to the right. 75 parameters of the eye-movement data were collected for each child. On the basis of their reading, writing, and other cognitive performances, twelve children were considered dyslexic and were divided into two groups (D1 and D2). Group statistical comparisons revealed significant differences between control and dyslexic subjects. In general, in the standard tasks the dyslexic subjects had poorer fixation quality, failed more often to hit the target at once, had smaller primary saccades, and had shorter reaction times to the left as compared with the control group. The control group and group D1 dyslexics showed an asymmetrical distribution of reaction times, but in opposite directions. Group D2 dyslexics made more anticipatory and express saccades, they undershot the target more often in comparison with the control group, and almost never overshot it. In the sequential tasks group D1 subjects made fewer and larger saccades in a shorter time and group D2 subjects had shorter fixation durations than the subjects of the control group.