| Study summary: |
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Specific Aims:
Aim 1: To recruit 75 children with autism and 75 age- and sex-matched controls ages 6 to 8
years old for an electrophysiological study and to characterize the subjects using
appropriate instruments for autism diagnosis, language functioning and behavior/sensory
profile, and to measure head circumferences Aim 2: To acquire and analyze event-related
potential (ERP) data in the auditory and visual modality.
ERP Hypothesis: Increased amplitude, altered morphology, impaired temporal discrimination
and delayed responsiveness will be found early in the processing hierarchy, and the severity
of these abnormalities will be associated with the severity of dysfunction at higher levels
of cortical processing.
Aim 3: To acquire EEG data and to analyze it quantitatively. Quantitative EEG Hypothesis:
Both interhemispheric and intrahemispheric coherence measures of the EEG will be
significantly deviant from those in the normal sample and predicted by abnormalities of
ERPs. In addition, EEG background alpha activity will show post mature (i.e. higher)
frequencies (Hz) than would be expected for age and focal epileptiform activity and slowing
(i.e. paroxysmal theta) will predict dysfunction on the ERPs.
Rationale:
The goal of this grant is to use electrophysiological measures to characterize abnormalities
in gating and timing in the autistic brain. The motivation for this research project
derives from findings and models in autism of increased excitation/inhibition ratios,
increased brain and white matter volume and altered connectivity. These changes, alone and
in combination, have the potential to alter the intensity, timing and integration of
signaling at multiple stages of processing. These signaling problems can potentially lead
to the autistic behavioral phenotype through cognitive processing abnormalities including
the hyperspecificity/overselectivity of autism, as well as to such features of autism as
sensory processing abnormalities, seizures, and anxiety. We believe that characterizing
abnormalities related to gating and timing phenomena may lead to the development of an
electrophysiological battery that can be utilized for early diagnosis, prognosis and
subtyping of autism, as well as the tracking of treatment efficacy.
Subjects:
Subjects will be recruited from the general population, the Ladders Clinic at MGH/Spaulding
Hospital, where the PI, Dr. Martien, is employed as a clinician, as well as from the
clinical practice of Dr. Herbert at the MGH-Institute of Health Professions preschool
clinic. Flyers will be placed on available bulletin boards at the two clinics and throughout
the greater Boston area, particularly at all Partners, Harvard, MIT, hospital, clinic,
research, and educational settings.
The study will seek to enroll eighty 75, 6 to 8 year olds with autism and 75 age and sex
matched controls. Children will be considered for inclusion in the autism group if:
- English is the primary language in the home
- Experimental group: Child meets criteria for autism on the ADI-R and ADOS evaluation
scales (this inclusion criteria will be explained during the consent process).
They meet non of the Exclusionary criteria, which include:
- Known genetic disorder
- Hearing or gross sensorimotor deficits
- Clinical evidence of progressive encephalopathy
- Asphyxia at birth or any other time
- Frequent seizures or use of anticonvulsant drugs or psychotropic medication
- Known presence of focal brain lesions, brain atrophy or ventriculomegaly. Children will
be considered for the control group if the child meets all of the above criteria except
they do not meet the criteria for autism or close to it on the ADOS and ADI-R
evaluation scales.
Methods:
The child will be seated in a comfortable chair and the physiological assessment will begin
after a head circumference is obtained with a tape measure, an EEG cap is placed on the
child's head and gel is applied to each electrode in the cap. The tasks include 5 minutes
of baseline EEG recording while the child is looking at a design on a monitor placed 2
meters in front of the chair. We then will proceed with a series of auditory and visual
stimuli presented by computer through two speakers placed 1 meter in front of the child
(auditory) and strobe (visual) at 50 cm. The paradigms will include a presentation of pairs
of tones with variable interstimulus intervals presented in random order at 65 dB SPL, a
paradigm with either 1000 Hz or 800 Hz at 65 dB, and a final auditory paradigm with two
different phonemes, presented at 65 dB. The visual tasks will involve the presentation of
flashes of light which vary in frequency and luminance both reflected off a white board one
meter from the child and directly at the child's visual field. In each series, there will be
a 1 minute break between two blocks of 100 trials each for a total of 200 trials. The
experimenter will show the child an interesting toy and talk to the child during the break.
The parent will be asked to complete the Vineland Adaptive Behavior Scales, the
Communication and Symbolic Behavior Scales (CSBS) and the MacArthur Communicative
Development Inventory. In the case that the subjects are recruited from the Ladders infant
sib study, we will use the existing ADI-R and ADOS data because Ladders has authorized the
release of this information.
The total time for the laboratory session will be approximately 1 hour. The full battery of
tasks will be performed on compliant children. For those children whose attention cannot be
maintained for the full battery, the examiner will stop and give breaks as needed. The
examiner will go on to the next task or terminate the session if the subject or parent of
the subject chooses to do so. |