Background
Methods
Participants
Procedures
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Color Stroop (Color-Word Interference) test[40]. This task was used to elicit an ANS stress reaction[41, 42], and shown to elicit both psychological and physiological arousal responses in typically developing populations[43] as well as children with ASD[10]. Participants completed a computerized, single-trial version of the task which involved the presentation of words corresponding to color names, printed in differently colored letters. The participants were required to name the color of the letters while ignoring the printed word. The task consisted of 5, one-minute blocks in which stimulus presentation frequency varied from 2 to 1.25 seconds/word (blocks one and five: 2 seconds/word, blocks 2 and 4: 1.5 seconds/word, block 5: 1.25 seconds/word). During the first and last blocks, only congruent stimuli were presented, whereas the remaining blocks consisted of only incongruent stimuli. Prior to starting the task, participants were provided with ten practice stimuli to ensure understanding of the task. Performance on this task was measured as the percentage of correct responses.
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Public speaking. For this task, participants were given 2 minutes to prepare a 3-minute talk on a topic of their choice. The talk was then delivered to three strangers. Public speaking tasks have been successfully used in previous studies examining cardiac responses to anxiogenic stimuli in neurotypical individuals[44‐46] and in children with ASD[15, 47]. Performance on this task was measured as the percentage of the time that the participant did not speak or vocalize during the task.
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Rapid visual information processing (CANTAB,http://www.camcog.com/). In this test of sustained attention and working memory[48], participants were presented with random single-digit numbers (2 through 9) at a rate of 100 digits per minute and asked to identify a prespecified three-digit sequence (for example, 3-5-7) by pressing the space bar. The duration of this task was 4 minutes. Performance was measured as the percentage of correctly identified sequences.
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Stop signal task[49]. This was a test of response inhibition. Participants were presented with a series of X’s and O’s and asked to press the left and right buttons on a gamepad when X’s and O’s appeared, respectively. The stimuli were occasionally followed by an auditory tone (stop signal), requiring the participants to withhold their response. The task consisted of 5 blocks, with 24 trials per block. The first block was practice. Total length of task was approximately 10 minutes. Task performance was measured as the latency of the stop process (stop signal reaction time (SSRT)) in milliseconds[50].
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Reading the Mind in the Eyes - child version[51]. This was a test of social cognition (theory of mind) where participants were presented with a set of 28 photographs depicting the eye region of the face, and asked to choose the word that best described what the person was thinking or feeling from a set of four choices. Performance was measured as the number of correct responses.
Measures
Statistical analyses
Results
Participants
TD (n = 34) | ASD (n = 40) | P value (group effect) | |
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Age | 12.5 ± 2.9 | 12.0 ± 2.9 | 0.5 |
Full-scale IQ | 113.1 ± 13.9 | 92.9 ± 20.6 | < 0.0001 |
Sex (male:female) ∗ | 19:15 | 33:7 | 0.02 |
SCQ | 18.0 ± 8.1 | ||
RCADS-SAD | 61.9 ± 17.4 | ||
RCADS-GAD | 58.6 ± 16.3 | ||
RCADS-PD | 57.3 ± 17.5 | ||
RCADS-SP | 53.1 ± 11.3 | ||
RCADS-OCD | 54.1 ± 10.5 | ||
RCADS-total anxiety | 58.4 ± 14.8 |
Task performance
TD | ASD | |
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Stroop task (% correct) | 85.5 ± 17.9 | 67.6 ± 30.8 |
Public speaking (seconds silence) | 37.6 ± 40.6 | 65.2 ± 51.3 |
RVP (% correct) | 91.8 ± 11.2 | 81.2 ± 19.4 |
Stop task (SSRT (ms)) | 325.0 ± 110 | 214.5 ± 86 |
Reading the Mind in the Eyes (# correct) | 23.4 ± 3.1 | 20.1 ± 4.6 |
TD | ASD | P value (group effect) | |
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Stroop task (% correct) | 85.3 ±2.1 | 80.8 ± 2.6 | 0.18 |
Public speaking (log(seconds silence)) | 3.2 ± 0.2 | 3.6 ± 0.2 | 0.21 |
RVP (% correct) | 85.1 ± 2.4 | 84.5 ± 2.5 | 0.87 |
Stop task (SSRT (ms)) | 339.0 ± 18.1 | 306.8 ± 19.0 | 0.25 |
Reading the Mind in the Eyes (# correct) | 18.8 ± 0.5 | 18.6 ±0.5 | 0.73 |
HR
RSA
Association with demographic, anxiety, and performance measures
Age | IQ | RCADS GAD | Performance | |
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Baseline HR | -1.57 ± 0.70 ∗ | |||
HR speaking-pre baseline | 0.18 ± 0.05 ∗∗ | -0.15 ± 0.06 ∗ | ||
HR speaking-post baseline | 0.19 ± 0.06 ∗∗ | -0.18 ± 0.06 ∗ | 0.08 ± 0.04 ∗ | |
RSA Eyes-pre baseline | -0.02 ± 0.005 ∗∗ | |||
RSA Eyes-post baseline | -0.01 ± 0.005 ∗ |
Discussion
Task performance
Baseline differences
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Co-morbid anxiety in ASD: Anxiety disorders are one of the most prevalent co-morbidities in ASD[27] and may exacerbate or occasionally drive the core deficits of ASD[30]. While the nature of anxiety in ASD is still largely unknown[63], ASD has been associated with genetic[28, 29], neurobiological, and phenotypical overlap with anxiety disorders[30, 31]. From a neurobiological perspective, both ASD and anxiety disorders have been associated with differences in central structures involved in emotional processing (such as the amygdala, anterior cingulate cortex, prefrontal cortex, and the insular cortex)[64, 65]. In terms of phenotypic presentation, ASD and anxiety are thought to present with overlapping symptoms related to repetitive and restrictive interests (for example, perseverative behavior), social and emotional reciprocity, avoidance behaviors, and speech difficulties[31, 63, 66]. Interestingly, subclinical ASD traits have been reported in children with anxiety disorders[31].The clinical presentation of anxiety is conceptualized as having three interconnected dimensions: behavioral (such as crying, avoidance, or tantrums), subjective-cognitive (such as maladaptive or negative thoughts), and physiological (such as increased heart rate or perspiration)[67, 68]. The latter often manifests itself as a "fight or flight" response which is associated with excitation and inhibition of the sympathetic and parasympathetic branches of the ANS, respectively. Highlighting the role of the physiological dimension, chronically elevated HR has been reported in anxiety disorders[32‐34]. A similar pattern was found in the present study, suggesting physiological symptom overlap between ASD and anxiety disorders. As such, the hyperarousal found herein may reflect the cardiac signs of co-morbid anxiety.In this study, we did not find a significant correlation between baseline HR and trait anxiety measured by the RCADS. Previous literature findings on this association are mixed[45].
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Hyperarousal as a feature of ASD: ANS hyperarousal may also be related to neurobiological differences associated with ASD. Although the ANS response is modulated both at the central and peripheral levels, in the absence of any evidence indicating primary ANS dysfunction in ASD, we suggest that hyperarousal of the ANS system may be secondary to hyperarousal at the central level. At this level, hyperarousal may be associated with over-responsivity of networks involved in perception, processing, and responding to emotional stimuli[34]. Processes that may contribute to this over-responsivity include increased threat perception, increased and misinterpreted perception of bodily sensations[34], or decreased inhibition of the fear response. ASD has been associated with neurobiological differences in brain networks responsible for these functions (for example, the prefrontal cortex, the insular cortex, and the anterior cingulate cortices)[6], and aspects of these differences have been associated with anxiety symptom severity[69, 70]. For example, total and right amygdala volumes have been positively associated with scores on the anxiety subscale of the Child Behavior Checklist[69] in a sample of children with ASD. At the same time, ASD has been associated with enlargement of the amygdala[2‐4]. While these findings further support the role of the central nervous system in ANS hyperarousal, neuroimaging studies are needed to examine this hypothesis.
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Interaction of ASD and anxiety features: The observed hyperarousal in our sample may also be related to an interaction between anxiety and ASD features. For example, ASD features such as sensory sensitivities, insistence on sameness, or other affective and cognitive deficits may lead to increased stressors experienced by this population, which can ultimately lead to increased arousal[63, 71]. Moreover, neurological dyregulation (for example, in threat perception or in introception) may further increase the susceptibility to conditioning by negative experiences and hyperarousal.