This study of reflexive and volitional saccades was undertaken to investigate the conflicting hypotheses of the cerebellar and neocortical systems models regarding the neural origin and cognitive basis of behavioral abnormalities in autism. The findings of the current study provide rigorous laboratory evidence of intrinsic dysfunction in the neural circuity of the prefrontal cortex and possibly also its neural connections with the parietal cortex, and of related cognitive deficits in spatial working memory and the executive control over reflexive behavior. No evidence was found of dysfunction of cerebellar vermal lobules VI and VII. Furthermore, no deficits were detected in the automatic processes of disengaging, shifting, and reengaging visual attention in the task that had no competing response demands and was not dependent on voluntary/endogenous regulation of attentional processes.
These findings have significant negative implications for the cerebellar model of autism.11
This study demonstrated intact saccade metrics and dynamics in the autistic subjects (i.e., normal latency, duration, and peak velocity of saccades on all tasks and accuracy of visually guided saccades). These data, in particular the normal accuracy of visually guided saccades, do not support the model that proposes a significant functional disturbance in cerebellar vermal lobules VI and VII in autism. The argument underlying the cerebellar model that focal vermal pathology in lobules VI and VII causes a disturbance in the complex regulation of attention is itself questionable, because such processes are widely accepted as being subserved by cortical systems.22
The data provided by the current study, which explicitly demonstrate a deficit in the executive and not in the reflexive or automatic regulation of visual attention, both support the cortical systems model of autism and fail to identify any attentional deficit that could be attributed reasonably to vermal pathology.
On both the antisaccade and oculomotor delayed-response tasks, the autistic subjects exhibited an increase in response suppression errors, reflecting an impaired capacity of the prefrontal cortex for volitionally suppressing context-inappropriate reflexive responses. In the oculomotor delayed-response task, the autistic subject also demonstrated reduced accuracy of saccades to remembered locations. This abnormality indicates a reduced capacity of the prefrontal cortex, and perhaps also its functional connectivity with the parietal cortex, to sustain location information in spatial working memory over brief periods of time to guide behavior.23
The role of the prefrontal cortex and its neural connections in subserving the capacity to volitionally suppress behavioral responses to compelling stimuli when the responses are not context appropriate, and for holding spatial information on-line over time to subserve anticipated behaviors, has been well documented with a variety of methods, including unit-recording and lesion studies with nonhuman primates,23,24
human functional neuroimaging,17
and clinical studies of behavioral deficits after stroke.25
The intact, visually guided saccades of the autistic subjects indicate that impaired performance on the volitional saccade tasks is reflective of intrinsic dysfunction of neocortical circuitry and is not secondary to impairments in the pons, cerebellum, or superior colliculus that subserve basic saccade mechanisms. The nature of the autistic subjects' abnormalities in volitional saccades is also not consistent with the profile of increased saccade latencies and intact performance on antisaccade tasks seen in the earlier stages of Parkinson's disease-one example of subcortical pathology.26,27
It could be argued that deficits demonstrated in the autistic subjects with the volitional saccade tasks reflect greater task difficulty, and that the autistic subjects merely put forth less effort or failed to understand these tasks. However, such an explanation is not supported by the performance curves of the autistic subjects on these tasks. On the antisaccade task, the autistic subjects demonstrated the same declining relationship between response suppression failures and increasing target distance from central fixation as the control subjects, as well as the capacity for successfully suppressing a reflexive response on a substantial percentage of the trials. Similarly, on the oculomotor delayed-response task, the performance curve for saccade error as a function of delay interval in the autistic group was parallel to that of the control group, demonstrating less precision in identifying the target location but responses that were in the general proximity of correct locations. It also could be argued that the autistic and control groups exhibited intact performance on the visually guided saccade task because of a floor effect related to the low difficulty of this task. However, visually guided saccades subserved by the cerebellum and the brainstem are reflexive saccades, and thus are inherently less difficult than voluntary saccade tasks. It is the increase in difficulty of the volitional saccade tasks associated with demands on endogenous attentional processes that brings neocortical systems into play for assessment. Furthermore, visually guided saccades are readily perturbed by a range of disorders, drowsiness, and inattentiveness, and thus are not insensitive to subtle pathology.14
The pattern of abnormal volitional saccades with preserved reflexive saccades is consistent with the generally accepted neurophysiologic characterization of autism.4,28
Event-related potential studies of autism in the past decade have documented a profile characterized by abnormalities in endogenous cognitive potentials and by the integrity of early and middle latency sensorially elicited event-related potentials.4
The consistency of the electrophysiologic profile with the saccadic eye movement profile provides evidence of the same pattern of supratentorial dysfunction from studies of two separate systems: the motor system subserving saccadic eye movements and the sensory systems assessed with electrophysiologic methods.
The findings of the current study are also consistent with recent neuropsychological studies in autism. Three studies comparing executive function and attention-shifting abilities in the same autistic subjects have found no evidence of impairment in the capacity for reflexive shifting of attention in autism, but have shown consistent evidence of deficits in the higher order voluntary regulation of attentional focus.29–31
These neuropsychologic studies have provided consistent evidence with different experimental methods that the abnormality in regulating attentional focus in autism has a conceptual rather than a perceptual basis. Reexamination of the neuropsychologic paradigm used to document the shifting attention deficit in autism 11,32
in the study leading to the current cerebellar model of autism reveals substantial executive function and working memory demands in the paradigm used to cue subjects to the need to shift attention from one focus to another. These demands were not examined separately from the effects of the exogenous demand for an attention shift, nor were they considered in the interpretation of the cognitive basis of the impaired capacity for shifting attention. Several studies of autism 33
have since demonstrated that it is the information processing demands of the cue to shift attention that determine whether an abnormal voluntary or normal reflexive response is elicited, and thus whether deficits are observed.
The findings of the current eye movement study provide evidence of intrinsic dysfunction of neocortical systems in autism and deficits in executive and working memory abilities as important elements of the cognitive and neural basis of autism. The findings do not support the hypotheses of the cerebellar model that vermal lobules VI and VII are dysfunctional or responsible for functional deficits in the regulation of attention.
The current study was confined primarily to a consideration of disturbances in the neocortical circuitry of frontal systems in autism. However, recent evidence 7,9,30,34,35
suggests that the involvement of neocortical systems and the higher order cognitive abilities they subserve will likely be more widespread. Structural imaging studies in autism have reported evidence of delayed maturation of the frontal lobes 9
and increased gray and white matter volumes of the temporal, parietal, and occipital cortex,34
which have been consistent with reports of increased head circumference and brain weight in autism.7,35
Similarly, a recent neuropsychological study 30
examining the profile of cognitive function in autism has reported deficits in higher order cognitive abilities besides executive function, including motor praxis, complex memory, complex language, and concept formation abilities with preservation of simpler abilities in these domains and in sensory perception and attention. This cognitive profile suggests selective involvement of higher order cognitive abilities across domains and the likelihood of neocortical systems involvement beyond frontal systems.