A Novel Framework for Impaired Imitation in ASD

Visuo-motor imitation (VMI) impairments are central to the pathogenesis and affect the
treatment of autism spectrum disorders (ASD). Therapies most commonly used to enhance social,
communicative, academic, adaptive and occupational function in individuals with ASD rely on
imitation, and impairments in VMI represent a bottleneck to the efficiency and efficacy of
these therapies. Furthermore, an influential psychological account suggests that imitation
impairments lead to the development of the ASD phenotype. By studying precisely how VMI is
impaired in ASD, it is possible both to enhance widespread therapies and possibly to alter
the course of the disorder itself. Unfortunately, researchers currently know little about the
precise nature of imitation impairments in ASD. Our laboratory has recently identified a
promising specific task parameter that separates preserved from impaired gesture imitation in
ASD: children with ASD have difficulty imitating when the task requires two separate movement
elements be coordinated simultaneously. By contrast, imitation is relatively preserved when
movement elements are performed serially. This finding has been subsequently validated in a
published study and again replicated in preliminary data. Coordination of simultaneous
movements is a hallmark of skills performed in the real world (shoe tying, eating with
knife-and-fork, driving, communicating with simultaneous verbal and gestural language). In
order to optimize common adaptive and social-communicative skill therapies, the next step is
to tease apart where, in the chain from perception to action, the capacity limitation in
simultaneous processing lies. To do this, the investigators propose a rigorous research plan
that encompasses three complementary experimental approaches: systematic psychophysics,
neuropsychological testing and EEG. The goal is to specifically dissect the contribution to
the simultaneity bottleneck in perceptual vs. motor processes using psychophysical control
experiments. Under the hypothesis that some children with ASD may have more perceptual
limitations and others may have more motor limitations, the investigators will assess
heterogeneity explicitly. It is then possible to relate perceptual and motor aspects of
simultaneous gesture VMI to validated neuropsychological tests of known clinical attentional
and perceptual deficits in ASD. Finally, in Aim 3, the investigators will directly
interrogate visual and motor networks. EEG measures of task-related activation are sensitive
to task load and can be differentially assessed in visual and motor networks. By assessing
deficient event-related modulation of EEG activity in visual or motor networks to
simultaneous (high-load) vs. serial (low-load) conditions, the investigators can pinpoint the
bottleneck. In addition to providing an approach that is complementary to the behavioral
measures of Aims 1 and 2, the results of the EEG study can pave the way for future biomarkers
and neurostimulation therapies.

General Inclusion Criteria:

Age 8 years, 0 months to 12 years, 11 months, 30 days

Informed consent is provided by a parent or guardian and assent is provided by the child

Wechsler Intelligence Scale for Children-IV (WISC-IV) Full Scale Intelligence Quotient (IQ)
> than 80, unless there is a 12 point or greater index discrepancy, in which case either
the Verbal Comprehension Index or Perceptual Reasoning Index must be > 80 and the lower of
the two must be > 65

Right-handedness, based on the Physical and Neurological Examination for Subtle Signs
(PANESS) and Edinburgh Handedness Inventory.

General Exclusion Criteria:

Presence or history of a definitive neurologic disorder including seizures (except for
uncomplicated brief febrile seizures), tumor, severe head injury, stroke, lesion, history
of skull surgery or disease (because it affects electroencephalogram [EEG] analysis) or
history of significant EEG abnormality

Presence of a severe chronic medical disorder

Presence of a significant visual impairment (corrected vision at distance worse than 20/40)

History of alcohol/substance abuse or dependency

Excessive tactile sensitivity of the scalp

Contact sensitivity to skin care products or cosmetics (due to possibility for irritation
from the EEG electrodes/paste)

Hair styles that would interfere with contact between the EEG cap and the scalp and cannot
be removed

Chronic tics or other significant movement disorders

Pregnancy (because of potential and unknown effects on brain function with respect to the
measures of this study).

Children will be excluded if they are in foster care. Parents may be the biological or
adoptive parent as long as they are the child's legal guardian.

Parents of children in the study may not have a diagnosis of autism.

Additional eligibility criteria for each group are contained in the following sections:

Specific Inclusion/Exclusion Criteria for ASD Group:

Diagnosis of autism spectrum disorder (ASD) will be made conservatively using the Autism
Diagnostic Interview-Revised (ADI-R), and the Autism Diagnostic Observation Schedule,
Second Edition (ADOS-2). The ADOS-2 will be performed by a psychology associate trained in
its administration and scoring. Children must meet diagnostic thresholds on both of these
instruments, and the diagnosis will be confirmed using Diagnostic and Statistical Manual of
Mental Disorders, fifth edition (DSM-5), by a neurologist.

Children may not have a history of known etiology for autism (e.g., fragile X syndrome,
Tuberous Sclerosis, phenylketonuria, congenital rubella) or history of documented
prenatal/perinatal insult, and they will show no evidence of meeting criteria for
additional psychiatric diagnoses including major depression, bipolar disorder, conduct
disorder, or adjustment disorder, based on maternal and child responses from the Kiddie
Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS).
Subjects with comorbid anxiety disorders, including generalized anxiety disorder,
separation anxiety disorder, simple and social phobias, and obsessive-compulsive disorder
(OCD), will be allowed to participate since anxiety is common in ASD, and similar
repetitive repertoires resembling "obsessive-compulsive behavior" are components of the
diagnostic criteria for ASD.

Children with a comorbid diagnosis of attention-deficit/hyperactivity disorder (ADHD) will
also be included due to the frequent rates of comorbidity with ASD. Children on stimulant
medication will have the medication held on the day of testing.

Specific Inclusion/Exclusion Criteria for Typically Developing (TD) Controls

Children will be included in the typically developing (TD) control group if they: (1) Do
not meet published cutoff criteria for ASD on the Social Responsiveness Scale, second
edition (SRS-2), (2) do not have a history of a developmental disorder or a psychiatric
disorder based on maternal and child responses from the K-SADS (excluding simple or social
phobia); and (3) are free of immediate family members (sibling, parent) with autism or
other pervasive developmental disorder.