Relation between early motor delay and later communication delay in infants at risk for autism.

BACKGROUND: Motor delays have been reported in retrospective studies of young infants who later develop Autism Spectrum Disorders (ASDs). OBJECTIVE: In this study, we prospectively compared the gross motor development of a cohort at risk for ASDs; infant siblings of children with ASDs (AU sibs) to low risk typically developing (LR) infants. METHODS: 24 AU sibs and 24 LR infants were observed at 3 and 6 months using a standardized motor measure, the Alberta Infant Motor Scale (AIMS). In addition, as part of a larger study, the AU sibs also received a follow-up assessment to determine motor and communication performance at 18 months using the Mullen Scales of Early Learning. RESULTS: Significantly more AU sibs showed motor delays at 3 and 6 months than LR infants. The majority of the AU sibs showed both early motor delays and later communication delays. LIMITATIONS: Small sample size and limited follow-up. CONCLUSIONS: Early motor delays are more common in AU sibs than LR infants. Communication delays later emerged in 67-73% of the AU sibs who had presented with early motor delays. Overall, early motor delays may be predictive of future communication delays in children at risk for autism.

Social and non-social visual attention patterns and associative learning in infants at risk for autism.

BACKGROUND: Social inattention is common in children with autism whereas associative learning capabilities are considered a relative strength. Identifying early precursors of impairment associated with autism could lead to earlier identification of this disorder. The present study compared social and non-social visual attention patterns as well as associative learning in infant siblings of children with autism (AU sibs) and low-risk (LR) infants at 6 months of age. METHODS: Twenty-five AU sibs and 25 LR infants were observed in a novel social-object learning task, within which attention to social and non-social cues was contrasted. Video recorded data were coded for percent duration of gaze to objects or caregiver. Movement rates to activate the toy within the associative learning task were also quantified. RESULTS: Both groups learned the association between moving a switch and activating a cause-effect toy. AU sibs spent less time looking at caregivers and more time looking at the toy or joystick when their caregivers made no attempts to engage their attention. However, response to caregiver-initiated social bids was comparable for both groups. CONCLUSIONS: Infrequent self-initiated socially directed gaze may be an early marker of later social and communication delays.

Normal physiological emotions but differences in expression of conscious feelings in children with high-functioning autism.

To provide insight into what aspects of the emotional circuit might be affected in high-functioning autism, we measured indices of physiological emotions and of the expression of conscious feelings in 10 children with high-functioning autism or Asperger syndrome and 10 comparison participants. Pleasant, unpleasant, and neutral pictures were presented while skin conductance responses were measured. Self-report ratings of pleasantness and interestingness were taken between pictures. Skin conductance responses did not differ between the groups. Self report ratings were different, with the children with autism giving more similar answers to the two questions than the comparison children. Impairments in socio-emotional expression in autism may be related to deficits in perception and/or expression of conscious feelings; physiological emotions may be relatively preserved.

Subtle executive impairment in children with autism and children with ADHD.

BACKGROUND: The executive functions of inhibition, planning, flexible shifting of actions, and working memory are commonly reported to be impaired in neurodevelopmental disorders. METHOD: We compared these abilities in children (8-12 years) with high functioning autism (HFA, n = 17), attention deficit-hyperactivity disorder (ADHD, n = 21) and healthy controls (n = 32). Response inhibition was assessed using the Stroop Color and Word Test (Golden, 1978). Problem solving, set-shifting, and nonverbal memory were assessed using three tasks, respectively, from the CANTAB (Cambridge Cognition, 1996): the Stockings of Cambridge task; the Intra-Dimensional/Extra-Dimensional set-shifting task; and the Spatial Working Memory task (SWM) with tokens hidden behind 3, 4, 6, and 8 boxes. RESULTS: There were no group differences on the response inhibition, planning, or set-shifting tasks. On the SWM task, children with HFA made significantly more between-search errors compared with controls on both the most difficult problems (8-box) and on the mid-difficulty problems (6-box); however, children with ADHD made significantly more errors compared to controls on the most difficult (8-box) problems only. CONCLUSION: Our findings suggest that spatial working memory is impaired in both ADHD and HFA, and more severely in the latter. More detailed investigation is needed to examine the mechanisms that differentially impair spatial working memory, but on this set of tasks there appears to be sparing of other executive functions in these neuropsychiatric developmental disorders.

Deficits in the initiation of eye movements in the absence of a visual target in adolescents with high functioning autism.

BACKGROUND: We used ocular motor paradigms to examine whether or not saccades are impaired in individuals with high functioning autism (HFA). METHODS: We recorded eye movements in patients with HFA (n=11), and in normal adolescents (n=11) on anti-saccade, memory-guided saccade (MGS), predictive saccade and gap/overlap tasks. RESULTS: Compared with the normal subjects, patients with HFA had (1) a significantly higher percentage of directional errors on the anti-saccade task (63.2% versus 26.6%), (2) a significantly higher percentage of response suppression errors on a MGS task (60.3% versus 29.5%) and (3) a significantly lower percentage of predictive eye movements on a predictive saccade task. They also showed longer latencies on a MGS task and for all conditions tested on a gap/null/overlap task (fixation target extinguished before, simultaneously, or after the new peripheral target appeared). When the latencies during the gap condition were subtracted from the latencies in the overlap condition, there was no difference between patients and normals. CONCLUSIONS: Abnormalities in ocular motor function in patients with HFA provide preliminary evidence for involvement of a number of brain regions in HFA including the dorsolateral prefrontal cortex (dlPFC) and the frontal eye fields (FEFs) and possibly the basal ganglia and parietal lobes.

Lamotrigine therapy for autistic disorder: a randomized, double-blind, placebo-controlled trial.

In autism, glutamate may be increased or its receptors up-regulated as part of an excitotoxic process that damages neural networks and subsequently contributes to behavioral and cognitive deficits seen in the disorder. This was a double-blind, placebo-controlled, parallel group study of lamotrigine, an agent that modulates glutamate release. Twenty-eight children (27 boys) ages 3 to 11 years (M = 5.8) with a primary diagnosis of autistic disorder received either placebo or lamotrigine twice daily. In children on lamotrigine, the drug was titrated upward over 8 weeks to reach a mean maintenance dose of 5.0 mg/kg per day. This dose was then maintained for 4 weeks. Following maintenance evaluations, the drug was tapered down over 2 weeks. The trial ended with a 4-week drug-free period. Outcome measures included improvements in severity and behavioral features of autistic disorder (stereotypies, lethargy, irritability, hyperactivity, emotional reciprocity, sharing pleasures) and improvements in language and communication, socialization, and daily living skills noted after 12 weeks (the end of a 4-week maintenance phase). We did not find any significant differences in improvements between lamotrigine or placebo groups on the Autism Behavior Checklist, the Aberrant Behavior Checklist, the Vineland Adaptive Behavior scales, the PL-ADOS, or the CARS. Parent rating scales showed marked improvements, presumably due to expectations of benefits.

Evidence for a deficit in procedural learning in children and adolescents with autism: implications for cerebellar contribution.

To examine the hypothesis that abnormalities in those cognitive functions for which cerebellar components have been implicated contribute to the pathophysiology of autism, tests of judgment of explicit time intervals and procedural learning were administered to 11 participants with autism and 17 age-and-IQ-matched controls. Results indicated that the group with autism demonstrated significant impairments in procedural learning compared with the group of controls. No significant difference in judgment of explicit time intervals was found. The data suggest that deficits in procedural learning may contribute to the cognitive and behavioral phenotype of autism; these deficits may be secondary to abnormalities in cerebellar-frontal circuitry.