Deficits in the initiation of eye movements in the absence of a visual target in adolescents with high functioning autism

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Abstract

Background: We used ocular motor paradigms to examine whether or not saccades are impaired in individuals with high functioning autism (HFA). Methods: We recorded eye movements in patients with HFA (n=11), and in normal adolescents (n=11) on anti-saccade, memory-guided saccade (MGS), predictive saccade and gap/overlap tasks. Results: Compared with the normal subjects, patients with HFA had (1) a significantly higher percentage of directional errors on the anti-saccade task (63.2% versus 26.6%), (2) a significantly higher percentage of response suppression errors on a MGS task (60.3% versus 29.5%) and (3) a significantly lower percentage of predictive eye movements on a predictive saccade task. They also showed longer latencies on a MGS task and for all conditions tested on a gap/null/overlap task (fixation target extinguished before, simultaneously, or after the new peripheral target appeared). When the latencies during the gap condition were subtracted from the latencies in the overlap condition, there was no difference between patients and normals. Conclusions: Abnormalities in ocular motor function in patients with HFA provide preliminary evidence for involvement of a number of brain regions in HFA including the dorsolateral prefrontal cortex (dlPFC) and the frontal eye fields (FEFs) and possibly the basal ganglia and parietal lobes.

Introduction

Autism is marked by abnormalities in three major domains of functioning: social interactions, reciprocal and non-verbal communication, and restricted repetitive and stereotyped patterns of behavior, interests, and activities [1]. A recent report suggests that this triad of behavioral symptoms affects approximately 17 per 10,000 children [9]. Autism is heterogeneous—both etiologically and symptomatically—with about one-third of patients having average intelligence (high functioning autism, HFA).

Ocular motor testing provides a means for learning about the ability to control motor responses and a way for understanding more about the neural basis of developmental disorders. While there have been several studies that have investigated ocular motor function in developmental disorders such as attention deficit-hyperactivity disorder [41], [43], dyslexia [4], [14], [18], and obsessive compulsive disorder [58] there have been only three quantitative studies that investigated saccadic eye movements in individuals with autism [34], [40], [59]. Only one of these studies, by Minshew et al. [40], involved individuals with HFA (mean full scale IQ=94.0±14.1); the other two studies included relatively lower functioning individuals with autism having full scale IQs in the 60–100 range [59] and with a mean full scale IQ of 71.6 and S.D. of 15.0 [34]. Kemner et al. [34] examined the frequency of eye movements during different stimulus presentations but not saccade dynamics (e.g. latency, velocity, duration). Rosenhall et al. [59] found visually-guided saccades abnormal in 6 of 11 children (age 9–16 years) with autism (having below normal to normal intelligence) compared with a group of healthy comparison children of normal intelligence. Six of the children with autism had hypometric saccades, with four of these six having reduced saccade velocities compared with the mean for the comparison group. Minshew et al. [40] found that teenagers and adults with HFA (mean age=20.2years±8.5 years) often looked towards the cued locations on an anti-saccade task even though they were instructed to make an eye movement of equal size to the opposite visual field. In addition, on a memory-guided saccade (MGS) task, the individuals with HFA had difficulty preventing a saccade towards the briefly flashed target in a peripheral location, before the cue to move their eyes. In contrast to Rosenhall et al., Minshew et al. [40] found that saccade latency, accuracy, duration, and peak velocity were normal in a visually guided saccade task in which subjects were instructed to immediately look at a light as soon it appeared in the periphery.

Minshew et al. concluded that their data did not support the cerebellar hypothesis of impairment to vermian lobules VI and VII in autism [11] because saccade metrics were not impaired in their patients with HFA. Moreover, the fact that saccade latency on the various paradigms was not impaired, led to their conclusion that teens and adults with autism were able to disengage, shift, and reengage visual attention normally. In addition, because of the large number of response suppression errors made on the anti-saccade task, and the increased response suppression errors on the memory guided task, they concluded that dysfunction in neural circuitry of the prefrontal cortex played a decisive roll in autistic behavior.

Another paradigm that may be useful for understanding the contribution of frontal and prefrontal neural systems is the prediction task. In the predictive saccade task, subjects are required to look back and forth between two alternately illuminated lights such that the eye arrives to the position of the light just as it comes on. As a result, the saccade must begin at least 100 m (the time it takes to make the saccade) before the light appears. The ability to accurately time eye movements to match the alternating target is thought to depend upon the frontal eye fields (FEFs) [63], [56] though other brain regions may also be involved. Here, in addition to the prediction paradigm, we used the memory guided saccade task and the anti-saccade tasks to examine the contribution of frontal and pre-frontal regions including the ability to inhibit unwanted saccades and to hold a target location “in mind.” A gap/null/overlap task was also used to assess the contribution of the parietal systems in order to look indirectly at the ability to disengage attention [54], [55]. We hypothesized that if the FEF and dorsolateral prefrontal cortex (dlPFC) were impaired in individuals with autism, we would see deficits in prediction as well as increased response suppression errors for both the MGS and the anti-saccade tasks [19], [48], [49], [51], [52], [65].

Section snippets

High functioning autism group

Eleven adolescents with autism, age 12–18 years (eight boys and three girls; mean age=13.8 years, S.D.=1.5 years), were recruited through the Baltimore/Washington, DC chapters of the Autism Society of America and from the Center for Autism and Related Disorders at the Kennedy Krieger Institute. All individuals in the HFA group were diagnosed, by one of the authors (MG), with idiopathic autism (e.g. no history of Fragile X, encephalitis, tuberous sclerosis, or other known medical conditions

Apparatus and stimuli

The apparatus used for ocular motor testing consisted of a custom-made wooden framework mounted onto a desk. To record eye movements, we used infrared (IR) sensors with a sensitivity of 0.1° and a horizontal recording range of ±20° (Microguide Inc.) [35]. The infrared sensors were attached to the wooden framework and were connected to the signal processing unit. A black and white CCD video camera (Panasonic WV-B2200) located approximately 30 cm away from the IR sensors, presented an image of the

Predictive saccade task

Fig. 1 illustrates that the percentage of predictive saccades was greater for the comparison group compared with the HFA group for all three frequencies tested (Mann–Whitney U(0.375Hz)=27.5, P=0.03; 0.75Hz=27.0, P=0.028; 1.5Hz=21.0, P=0.017).

Table 2 shows the mean and S.D. for saccade latency, latency variance, amplitude, and peak velocity at each of the three target frequencies on the predictive saccade task. As shown in Table 2, individuals with HFA showed greater variability (latency

Overview

Anti-saccade, MGS, predictive saccade and gap/null/overlap paradigms were used to examine ocular motor behavior in high-functioning adolescents with autism compared with normal adolescents. As hypothesized, we found that patients with HFA made more errors on the anti-saccade task and had a higher percentage of response suppression errors on a MGS task (Fig. 2, Fig. 3). Unlike Minshew et al. [40], however, we found increased latencies in the memory guided saccade task but no differences between

Conclusion

We have found impairments in generating predictive saccade and in inhibiting saccades when they were not called for, in adolescents with HFA. We found no impairments in disengaging fixation. Table 5 summarizes these results by comparing the percentage of inappropriate saccades towards the target for the antisaccade task, the percent of response suppression errors produced during the memory guided saccade task, the percentage of predictive saccades produced during the 0.75 Hz predictive task and

Acknowledgements

The authors thank all of the participants and their parents for volunteering their time for this research. The authors also thank Dale Roberts, Darren Baker and Richard Leigh for their assistance in developing procedures for eye movement testing and measurement. We extend our gratitude to Dr. Martha Denckla and Dr. Mark Walker for sharing their knowledge as we interpreted the findings of this study. This work was supported by grants from the National Alliance for Autism Research (to RJL, DSZ,

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      Thus, the difference in saccadic reaction time during overlap trials compared to gap trials is called the disengagement cost, or the gap effect (Fischer, Koldewyn, Jiang, & Kanwisher, 2014; van der Geest et al., 2001). To date the evidence is mixed on the question of whether individuals with ASD have impairments in either disengaging or shifting attention to peripheral stimuli (Elsabbagh et al., 2009, 2013; Goldberg et al., 2002; Kawakubo et al., 2007; Landry & Bryson, 2004; for a review see Sacrey et al., 2014). Landry and Bryson (2004) used eye tracking during a gap-overlap paradigm with content-neutral stimuli (i.e., colored rectangles) and found that children with ASD took almost three times longer than controls to initiate an eye movement towards a peripheral stimulus on overlap trials, but no group differences emerged on gap trials.

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