Children with autism spectrum disorders show abnormal conditioned response timing on delay, but not trace, eyeblink conditioning

Abstract

Children with autism spectrum disorder (ASD) and age-matched typically-developing (TD) peers were tested on two forms of eyeblink conditioning (EBC), a Pavlovian associative learning paradigm where subjects learn to execute an appropriately-timed eyeblink in response to a previously neutral conditioning stimulus (CS). One version of the task, trace EBC, interposes a stimulus-free interval between the presentation of the CS and the unconditioned stimulus (US), a puff of air to the eye which causes the subjects to blink. In delay EBC, the CS overlaps in time with the delivery of the US, usually with both stimuli terminating simultaneously. ASD children performed normally during trace EBC, exhibiting no differences from TD subjects with regard to the learning rate or the timing of the conditioned response. However, when subsequently tested on delay EBC, subjects with ASD displayed abnormally-timed conditioned eye blinks that began earlier and peaked sooner than those of TD subjects, consistent with previous findings. The results suggest an impaired ability of children with ASD to properly time conditioned eye blinks which appears to be specific to delay EBC. We suggest that this deficit may reflect a dysfunction of the cerebellar cortex in which increases in the intensity or duration of sensory input can temporarily disrupt the accuracy of motor timing over short temporal intervals.

Keywords: ADI-R; ANOVA; ASD; Autism Diagnostic Interview; CR; CS; PDD-NOS; TD; UR; US; analysis of variance; autism; autism spectrum disorder; cerebellum; conditioned response; conditioning stimulus; eyeblink conditioning; pervasive developmental disorder-not otherwise specified; timing; typically-developing; unconditioned response; unconditioned stimulus.

Fig. 1

EBC protocols. Square wave plots depict stimulus timing during (a) trace EBC and (b) delay EBC. The CS-US interval (US onset - CS onset) was held constant at 700 ms in the two testing paradigms. The duration of the trace period (US onset-CS offset) was 500 ms. In delay EBC the tone CS and air puff US co-terminated. Subjects performed two sessions of trace EBC followed by one session of delay EBC. Sessions were conducted on separate days. (c) Schematic of the eyeblink CR as measured during testing. Upward deflection of the plot denotes closure of the eyelid. Eye blinks of sufficient amplitude (see Methods) occurring after the CS and prior to the US were classified as CRs and their onset and peak latencies recorded (arrows).

Fig. 2

Percent CRs. Values represent percent CRs for each block of 10 trials (9 blocks per session, n = 16 for TD group and n = 14 for ASD group). (a) Results from two sessions of trace EBC. (b) Results for the single session of delay EBC. Percent CRs increased across the trace EBC sessions for both groups and did not differ between groups. Most of the increase in percent CRs occurred at the beginning of the second trace EBC session. There was no significant difference in percent CRs in the delay EBC session. Data presented as the mean ± 1 SEM.

Fig. 3

CR onset and peak latencies. (a,c) Group means for onset and peak latency, respectively, for the two sessions of trace EBC. (b,d) Mean onset and peak latency, respectively, for the session of delay EBC. In general, latencies were at their lowest values for all groups at the beginning of each session and gradually migrated toward the time of US onset as the session progressed. Onset latencies in the first 3 blocks of trace EBC were not different between the groups. In contrast, ASD group onset latencies were significantly lower at the outset of the delay EBC session (asterisks indicate p < 0.05). By the end of the session, ASD onset latencies were statistically indistinguishable from those of the TD group. Peak latency values for the groups during delay EBC displayed a similar pattern, though the decrease for the ASD group at the beginning of the session was not quite significant by ANOVA. Data presented as the mean ± 1 SEM.