Animal models of restricted repetitive behavior in autism

Restricted, repetitive behavior, along with deficits in social reciprocity and communication, is diagnostic of autism. Animal models relevant to this domain generally fall into three classes: repetitive behavior associated with targeted insults to the CNS; repetitive behavior induced by pharmacological agents; and repetitive behavior associated with restricted environments and experience. The extant literature provides potential models of the repetitive behavioral phenotype in autism rather than attempts to model the etiology or pathophysiology of restricted, repetitive behavior, as these are poorly understood. This review focuses on our work with deer mice which exhibit repetitive behaviors associated with environmental restriction. Repetitive behaviors are the most common category of abnormal behavior observed in confined animals and larger, more complex environments substantially reduce the development and expression of such behavior. Studies with this model, including environmental enrichment effects, suggest alterations in cortical-basal ganglia circuitry in the development and expression of repetitive behavior. Considerably more work needs to be done in this area, particularly in modeling the development of aberrant repetitive behavior. As mutant mouse models continue to proliferate, there should be a number of promising genetic models to pursue

Affective Responses by Adults with Autism Are Reduced to Social Images but Elevated to Images Related to Circumscribed Interests

Individuals with autism spectrum disorders (ASD) demonstrate increased visual attention and elevated brain reward circuitry responses to images related to circumscribed interests (CI), suggesting that a heightened affective response to CI may underlie their disproportionate salience and reward value in ASD. To determine if individuals with ASD differ from typically developing (TD) adults in their subjective emotional experience of CI object images, non-CI object images and social images, 213 TD adults and 56 adults with ASD provided arousal ratings (sensation of being energized varying along a dimension from calm to excited) and valence ratings (emotionality varying along dimension of approach to withdrawal) for a series of 114 images derived from previous research on CI. The groups did not differ on arousal ratings for any image type, but ASD adults provided higher valence ratings than TD adults for CI-related images, and lower valence ratings for social images. Even after co-varying the effects of sex, the ASD group, but not the TD group, gave higher valence ratings to CI images than social images. These findings provide additional evidence that ASD is characterized by a preference for certain categories of non-social objects and a reduced preference for social stimuli, and support the dissemination of this image set for examining aspects of the circumscribed interest phenotype in ASD

Age-Related Differences in Restricted Repetitive Behaviors in Autism Spectrum Disorders

Restricted repetitive behaviors (RRBs) were examined in a large group of children, adolescents and adults with ASD in order to describe age-related patterns of symptom change and association with specific contextual factors, and to examine if the patterns of change are different for the various types of RRBs. Over 700 individuals with ASD were rated on the Repetitive Behavior Scale – Revised. RRBs were less frequent and less severe among older than younger individuals, corroborating that autism symptoms abate with age. Our findings further suggest that repetitive behaviors are a heterogeneous group of behaviors, with the subtypes of RRBs having their own individual patterns across the lifespan, and in some cases, a differential association with age depending on intellectual functioning

Evidence of increased non-verbal behavioral signs of pain in adults with neurodevelopmental disorders and chronic self-injury

The role of pain in relation to self-injurious behavior (SIB) among individuals with intellectual disabilities is not well understood. Some models of SIB are based on altered endogenous opioid system activity which could result in elevated pain thresholds. In this study, non-verbal behavioral signs indicative of pain as measured by the Non-Communicating Children’s Pain Checklist (NCCPC) were compared between matched individuals with (N = 35) and without (N = 35) chronic self-injurious behavior (SIB) and neurodevelopmental disorders. Significant (p Control Group) were found for the NCCPC Total Score, and for the Vocal, Social/Personality, and Eating/Sleeping subscales of the NCCPC. These results are not consistent with models of SIB in which pain sensitivity is assumed to be attenuated because of opioid system activity and are suggestive of intact and possibly amplified pain expression

Evidence for Reciprocal Interaction Effects Among Adults with Self-Injury and Their Caregivers

Patterns of caregiver responses to client adaptive behavior were compared between adults with intellectual disabilities with and without self-injurious behavior. Participants with moderate to profound intellectual disability and self-injury (n = 89) and age/IQ matched control participants (n = 20) were selected from a large sample of adults living in a regional residential center. Approximately 45 minutes of direct observation data were collected for each participant during unstructured leisure time. Data were sequentially analyzed and Yule’s Q scores derived and compared among groups. Results indicated that caregivers were more responsive to prosocial initiations and adaptive engagement among individuals with severe self-injurious behavior than to those with mild or no self-injurious behavior and that these responses were more likely to be in the form of a demand

Evaluating a Sham-Controlled Sensory-Testing Protocol for Nonverbal Adults With Neurodevelopmental Disorders: Self-Injury and Gender Effects

Ambiguous or blunted responses to sensory and painful stimuli among individuals with severe intellectual disabilities and co-morbid communicative impairments put them at risk for having their experience of pain discounted and their expression of pain misinterpreted. Valid measurement procedures of behavioral expression are critical for this vulnerable group of individuals. We investigated a sham-controlled sensory testing protocol as an approach to guard against observer bias during non-verbal behavioral recording for individuals with intellectual disabilities. Participants were 44 (52% male) adults (mean age = 46, sd = 10) with moderate (14%) and severe to profound (86%) intellectual impairment. The facial behavior of the participants before, during, and after five sensory stimulation modalities (pin prick, light touch, deep pressure, cool, warm) was coded by three raters using the Facial Action Coding System (FACS). For each participant, their 5 active sensory trials were randomized with sham trials during which no stimulation was applied. Observers were blinded to active vs. sham stimulation status. FACS scores increased significantly during active sensory trials (p < 0.05) compared with sham trials. There were significant effects for gender with females more expressive than males (p < 0.05). There were also significant effects for the presence of self-injurious behavior (SIB) with individuals with SIB more expressive than individuals without SIB (p < 0.05). The results suggest that the procedure was valid (i.e., distinguished between active vs. sham sensory stimulation) and provides additional evidence that individuals with significant intellectual impairments are sensitive to tactile stimulation consistent with quantitative sensory testing protocols

Evidence of altered epidermal nerve fiber morphology in adults with self-injurious behavior and neurodevelopmental disorders

The purpose of this preliminary study was to examine the morphology and neuropeptide density of epidermal nerve fibers quantified through skin biopsy samples from three adults with neurodevelopmental disorders and chronic self-injurious behavior (SIB) secondary to mental retardation compared with non-SIB normal IQ controls. A cross-sectional design was used with 3 mm punch skin biopsies collected from each participant from non-self-injurious body sites and compared with site-matched existing normal control skin samples. The study was conducted at an outpatient clinic. The primary dependent measure for the morphology analyses was the coefficient of variation (CV) to quantify the mean gap length between epidermal nerve fibers for each subject. Visual microscopic examination and quantitative analysis of the microscopy images suggested there were morphological abnormalities (increased CV) in the epidermal nerve fibers among the chronic SIB cases. Substance P (SP) fiber density was increased with 2 to 3 times as many fibers in SIB subjects as control subjects. Additional empirical work is needed to clarify the relation between sensory innervation of the skin and self-injury to improve assessment and treatment outcomes

Age trends in visual exploration of social and nonsocial information in children with autism

Because previous studies of attention in autism spectrum disorders (ASD) have been restricted in age range examined, little is known about how these processes develop over the course of childhood. In this study we examined cross-sectional age effects on patterns of visual attention to social and nonsocial information in 43 typically developing children and 51 children with ASD ranging in age from 2 to 18. Results indicated a sharp increase in visual exploration with age and a decrease in perseverative and detail-focused attention for both groups of children. However, increased age was associated with greater increases in visual exploration for typically developing children than for those children with ASD. The developmental differences were most pronounced for attention to certain nonsocial stimuli as children with ASD demonstrated a disproportionate attentional bias for these stimuli from very early in life. Disproportionate visual attention to certain nonsocial objects relative to social stimuli in ASD spanned from early to late childhood, and thus may represent both an early and a persistent characteristic of the disorder

Functional Neuroimaging of Social and Nonsocial Cognitive Control in Autism

This study investigated cognitive control of social and nonsocial information in autism using functional magnetic resonance imaging. Individuals with autism spectrum disorders (ASDs) and a neurotypical control group completed an oddball target detection task where target stimuli were either faces or nonsocial objects previously shown to be related to circumscribed interests in autism. The ASD group demonstrated relatively increased activation to social targets in right insular cortex and in left superior frontal gyrus and relatively decreased activation to nonsocial targets related to circumscribed interests in multiple frontostriatal brain regions. Findings suggest that frontostriatal recruitment during cognitive control in ASD is contingent on stimulus type, with increased activation for social stimuli and decreased activation for nonsocial stimuli related to circumscribed interests

Children with autism demonstrate circumscribed attention during passive viewing of complex social and nonsocial picture arrays

Although circumscribed interests are a hallmark characteristic of autism spectrum disorders, providing a means for quantifying their functional impairment has proven difficult. We developed a passive viewing task to measure aspects of visual attention in children with autism spectrum disorders and typically developing controls. Task stimuli included picture arrays that were matched for social and nonsocial content. Nonsocial content was balanced to include items related to circumscribed interests (e.g., trains) as well as more commonplace items (e.g., furniture). Discrete aspects of gaze behavior were quantified using eye-tracking technology. Results indicate that visual attention in the autism group was more circumscribed (as indicated by the exploration of fewer images), more perseverative (as indicated by longer fixation times per image explored), and more detail oriented (as indicated by a greater number of discrete fixations on explored images). This pattern of results was similar for both social and object arrays. Within the autism group, overall severity of repetitive behavior symptoms correlated positively with exploration of object pictures and negatively with perseveration on social pictures. Results suggest that children with autism have a domain-general pattern of atypical visual attention that may represent an exaggeration of a typical attentional process and is related to a tendency to perseverate on images of interest and explore them in a more detail-oriented manner. Discrete measures of visual attention may therefore provide a reasonable means of quantifying aspects of the repetitive behavior phenotype in autism