We examined procedural learning with a predictive saccade task known to engage frontostriatal systems in a relatively large group of individuals with autism. We did not observe abnormalities in the overall rate of procedural learning in autism (i.e., the reduction in response latencies over trials). However, individuals with autism displayed a speeding of rightward predictive/anticipatory responses. Internal clocks, in the form of striatal temporal oscillators (25
), are the means by which precise interval timing is perceived and used to initiate planned motor sequences (26
). The specific speeding of rightward saccades exhibited by individuals with autism on the predictive saccade task suggests a lateralized acceleration of the striatal temporal coding system that is used to time internally generated motor response sequences by the contralateral (left) hemisphere.
) and animal studies (28
) have demonstrated the importance of the basal ganglia in tasks requiring precisely timed responses, including predictive saccades (20
), and in the implicit judgment of time intervals (29
). Patients with cerebellar lesions typically have a reduced ability to acquire learned motor sequences during predictive saccade tasks rather than specific deficits in response timing (30
). The integrity of visually guided saccades in this sample of individuals with autism also argues against a cerebellar explanation for our results. Alterations in response timing on our predictive saccade task are within the response interval range regulated by striatal chronometric systems. Thus, our findings suggest that a speeded chronometric system in the left striatum is responsible for the observed pattern of results.
The neurophysiology of the striatal clock is known to be plastic, with regulation mediated by neurochemical systems. In rodent studies, acceleration and deceleration of interval timing has been demonstrated with striatal administration of dopamine agonists and antagonists respectively (31
) and with systemic administration of haloperidol and clozapine (32
). Thus, our findings are both consistent with striatal abnormalities observed in functional and structural neuroimaging studies of autism (7
) and might be related to neurochemical as well as neurodevelopmental factors.
An alternative explanation for our findings is that they might represent an inability to withhold planned motor responses until they are appropriate to execute. Deficits in prefrontally mediated inhibitory control in autism have been suggested by neuropsychological (1
) and oculomotor studies using the antisaccade task (33
). However, deficits on antisaccade tasks reflect a reduced ability to suppress responses to external stimuli rather than internally generated responses, and lateralization of these inhibitory deficits has not been observed. Furthermore, behavioral responses in some cognitive paradigms, including some oculomotor tasks, are slowed rather than accelerated in autism (33
). Together, these findings suggest that reduced prefrontal inhibition of planned behavior is likely not the cause of speeded predictive saccades in autism.
It is, of course, noteworthy that speeding selectively affected rightward anticipatory saccades, indicating a lateralized neurobiological alteration in individuals with autism. Although autism clearly affects functions localized in both hemispheres, our observation of a left-lateralized alteration leading to speeded rightward saccades is consistent with findings of greater left hemisphere abnormalities in some studies of autism (35
). Also, language deficits are a core feature of autism, whereas spatial and musical abilities are often less impaired in higher-functioning patients (36
). Neuroimaging studies have found abnormal growth trajectories (38
) and increased disorder and density of white matter bundles in left frontal language regions and superior temporal gyrus in autism (39
). Electroencephalography studies of autism have reported left fronto-temporal abnormalities (41
) and altered connectivity of left frontal and temporal cortex (42
). Manual (43
) and pursuit eye-movement performance (44
) and some neuroimaging findings (45
) provide evidence for left-lateralized disturbances of sensorimotor systems in autism. Thus, our findings add to a growing body of literature suggesting that some left hemisphere brain systems and the cognitive abilities they support are more compromised in at least some individuals with autism.
) but not all (46
) studies of procedural learning provide evidence for deficits in autism. Laterality effects were not investigated in these studies, because all responses were made with one hand. Variations in task complexity might account for these differences. Mostofsky et al.
) used a much more difficult serial reaction time task and reported reduced procedural learning in autism. The simplicity of our oculomotor paradigm might place less demand on prefrontally mediated skills, such as maintaining a longer stimulus sequence in working memory during the learning process. Also, Mostofsky et al.
studied adolescents, whereas the present study used a wider age range, mostly adults. Future studies are needed to address the importance of task complexity and developmental trends in relation to response timing and motor learning deficits in autism, as well as whether lateralized speeding in autism is seen in other tasks requiring precisely timed responses. Nonetheless, our findings are notable for demonstrating that the rate of procedural learning, at least on simple tasks, might be a relatively intact cognitive domain in autism in the context of widespread deficits in cognitive function (1
Our results identify functional abnormalities in an important cognitive process, coding temporal information for anticipatory behavior. Our findings implicate left striatal chronometric systems and might have clinical and developmental implications for impaired higher-order functions such as praxis and imitation learning.