1. Introduction Individuals with ASD show inhibitory control deficits that may be associated with the disabling repetitive behaviors characterizing this disorder. Stop signal tests provide a well-validated approach for assessing inhibitory control but have not often been used to study ASD. Methods Subjects Sixty individuals with ASD and 54 age- and nonverbal IQ- matched healthy control participants (Table 1) completed manual motor and oculomotor stop signal tasks (Figure 1). They also performed assessments of baseline reaction times for both hand and eye movements. Diagnosis was confirmed using the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Inventory – Revised (ADI). Inhibitory Control Deficits in Autism Spectrum Disorders (ASD) Rachel K. Greene 1, Matthew W. Mosconi 1*, Michael E. Ragozzino 2, Lauren Schmitt 1, Edwin H. Cook 3, John A. Sweeney 1 1 Department of Psychiatry, UT Southwestern Medical Center, Dallas TX, USA 2 Department of Psychology, University of Illinois at Chicago, Chicago IL, USA 3 Institute for Juvenile Research, University of Illinois at Chicago, Chicago IL, USA *Correspondence: Matt.Mosconi@UTSouthwestern.edu Results Individuals with ASD showed deficits stopping both hand and eye movements (Figures 2-3). Healthy control subjects and subjects with ASD each strategically delayed their responses during Stop Signal task GO trials relative to baseline GO trials (Table 2). But, individuals with ASD showed a reduced ability to strategically slow RT (Figure 4). Importantly, the degree to which individuals slowed their RT was strongly predictive of their ability to cancel STOP trial responses (Figure 5). For manual performance only, reduced stopping accuracy and reduced ability to strategically delay RT each were associated with more severe repetitive behaviors in individuals with ASD, suggesting that a reduced ability to inhibit behaviors contributed to the problem of repetitive behaviors in ASD. (Figures 7). Abstract BACKGROUND: Individuals with ASD show deficits inhibiting context- inappropriate behaviors. Findings from laboratory studies of response inhibition have been inconsistent, but several have documented deficits that are associated with increased rates of repetitive behaviors. We examined inhibitory control of hand and eye movements to determine the task and neural system specificity of inhibitory control deficits in ASD. METHODS: Sixty individuals with ASD and 54 age- and nonverbal IQ-matched healthy controls completed manual motor and oculomotor stop signal tasks. Baseline reaction times also were assessed for both hand and eye movements. RESULTS: Subjects with ASD made more STOP trial errors than healthy controls on both manual motor and oculomotor stop signal tasks. STOP trial error rates were associated with the degree to which subjects slowed their reaction times from baseline to task GO trials, such that greater slowing was associated with fewer STOP trial errors. Subjects with ASD did not strategically slow their reaction times as much as controls. Stopping errors were associated with more severe repetitive behaviors in individuals with ASD. DISCUSSION: Individuals with ASD show inhibitory control deficits that appear to equally affect manual motor and oculomotor systems. These deficits suggest a diminished capacity to utilize adaptive preparatory strategies as a factor that contributes to the difficulty suppressing prepotent responses. Thus deficits in inhibitory control and in the ability to strategically prepare to slow and inhibit responses may contribute to the disabling repetitive behaviors associated with ASD. This study was supported by NIH Autism Center of Excellence award HD055751, NIMH MH092696, Autism Speaks and the Department of Defense. Disclosures: Dr. Sweeney consults to Pfizer, Takeda, Asubio, BMS & Lilly and has a grant from Janssen. Dr. Cook consults to Seaside Therapeutics and receives grant support from them. Table 1. DEMOGRAPHIC CHARACTERISTICS ASD (N=60) Controls (N=54)p Gender (% males)8374ns Age15.4 (8.0)17.1 (7.9)ns Full-Scale IQ101 (18)108 (12).03 Performance IQ103 (17)105 (13)ns Verbal IQ100 (18)109 (14).002 Mean (sd) Stop Signal Task Subjects were instructed to either press a button (manual version) or make a saccade (oculomotor version) when a peripheral target appeared (‘GO' trials), or inhibit these responses when a central stop signal appeared following the appearance of the peripheral cue (‘STOP' trials). The stop signal delay, or the amount of time between the GO target onset and STOP cue onset, ranged from 50-275 ms for the manual test, and between 50-200 ms for the eye movement test. Stop signal delays were sampled in 17 ms intervals to match the monitor refresh rate (60 Hz). For the manual test, 60% of randomly interspersed trials were ‘GO’ trials, and 40% had a STOP cue (ratio was 66:33 for oculomotor testing). To examine baseline reaction time (RT), stop signal tests were preceded by control tasks with 50 consecutive GO trials. We examined subjects' reaction times (RT) during both baseline and stop signal task GO trials, as well as the rate at which they failed STOP trials (i.e., they pressed a button or looked towards the peripheral target). GO TRIALS (60%) Fixation (750-1500 ms) + STOP TRIALS (40%) + Cue (650 ms) Feedback for No Response (2500 ms) +  FASTER ! Stop Signal (Delay 50-275 ms) Feedback for Response + + + + X Fixation (750-1500 ms) Cue (650 ms) ASDControlsp Manual Motor Baseline RT354 (48)329 (47).01 Stop Signal ‘GO’ RT433 (39)445 (35).10 ‘GO’ RT – Baseline RT81 (40)116 (46)<.01 % Correct STOP Trials56 (15)63 (16).01 Oculomotor Baseline RT229 (38)233 (36)ns Stop Signal ‘GO’ RT299 (39)341 (43)<.01 ‘GO’ RT – Baseline RT70 (44)104 (47)<.01 % Correct STOP Trials61 (16)68 (12).02 Conclusions Our results demonstrate an important problem of inhibitory control in ASD that is related to the prominence of repetitive behaviors. These deficits also appear to reflect a reduced ability to strategically slow reaction times to enhance the ability to suppress context-inappropriate responses. Hand and eye movement deficits were of similar magnitude; however, they were not associated with one another. The findings that deficits in manual stopping and slowing each are related to repetitive behaviors, one of two core deficits of this disorder, indicate that a general difficulty suppressing prepotent behaviors is an important contributing factor causing this core impairment in ASD. Table 2. STOP SIGNAL and BASELINE RT TASK PERFORMANCE Figure 3 Figure 2 Figure 4 Hand Eye Schematic representation of stop signal tasks Figure 1 Manual stopping accuracy is reduced in ASD Eye movement stopping accuracy is reduced in ASD Individuals with ASD show reduced reaction time slowing during Stop Signal Task ‘GO’ trials Figure 5 Reaction time slowing predicts stopping accuracy Figure 6 Manual stop signal impairments are related to repetitive behaviors