RESEARCH METHODS

To meet the research goals of the Autism Research Program, comprehensive scientific research methods are performed. These methods currently include:

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STRUCTURED DIAGNOSTIC INSTRUMENTS

In a research setting, subtle diagnostic distinctions are of critical importance. Research has therefore evolved methods for making fine-grained diagnostic distinctions using what are called structured diagnostic instruments. In autism, these research diagnostic instruments are the Autism Diagnostic Interview-Revised (Lord, Rutter, LeCouteur, 1995) and the Autism Diagnostic Observation Schedule (Lord, Rutter, & DiLavore, 1997). Extensive training is required to administer these instruments and training sessions are typically done by a team of experts from around the world in order maintain uniformity of diagnosis world-wide. These instruments and this training system have been a major contribution to autism research in the past decade. Administration of these instruments is usually audio taped or videotaped for verification of administration and scoring accuracy or to clarify research findings at a later date.

The Autism Diagnostic Interview-Revised or ADI is administered to the parents or care-giver of the person with autism spectrum disorder. The ADI is a semi-structured interview, meaning that the questions are pre-set and the interviewer's main job is to follow the questions and explain what the question is asking until the meaning is clear. The ADI is also structured in the sense that there are set options for scoring the answers to the questions. The ADI requires that the informants (the people being interviewed) report situations or examples of the behavior asked about rather than simply answering yes or no. For example, if the question is about echolalia, then the goal is for the informants to recall one or two specific examples of echolalia. In this way, anyone listening to the tape could confirm that the behavior reported confirmed to the universal understanding of echolalic language. The other basic feature of this interview is that it often asks about current function and about function at age 4 to 5 years. Recalling information from the past is easier if informants first think about specific events, like preschool programs, birthday parties, vacations, or holidays that occurred during the 4 to 5 year age range. This method really increases the amount of information people can recall. To make the interview easier, informants have found it helpful to have baby books, copies of evaluations from the 3-6 year age range, and pictures at age 4 to 5 years on hand during the interview. In addition, we give a copy of this interview to the parents or care givers when they arrive so they will have time to read it while their child is doing the initial testing. We can send the ADI out in advance to parents who would like to think about it at their leisure and are not bothered by having one more packet of material to sort through.

Lord, C., Rutter, M., LeCouteur, A. (1995) Autism Diagnostic Interview-Revised (3rd Ed., Short Form). Chicago: University of Chicago.

The Autism Diagnostic Observation Schedule or ADOS is a set of seven activities completed with the individual who has an autism spectrum disorder. These activities are designed to elicit social, communication, and imaginative play behavior relevant to diagnosis. The activities vary from those with a high degree of structure to those with much less structure in order to determine the dependence of skills on structure provided by the interviewer and the materials. However, even the least structured activities provide more structure than real life situations. For this reasons, observations made during the ADOS are supplemented by observations made by our research personnel across a range of settings. The ADOS is structured in that it uses a standardized set of materials, set questions, and a set scoring system so that all research centers use precisely the same procedures. The ADOS takes approximately 45 minutes to an hour to complete. Together the ADI-R and ADOS give a very comprehensive picture of the individual's current function and developmental history in areas relevant to diagnosis.

Lord, C., Rutter, M., & DiLavore, P.C. (1997) Autism Diagnostic Observation Schedule-Generic. Chicago: University of Chicago.

 

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FAMILY HISTORY INTERVIEW

Family history is critical to research efforts to define subgroups of people who may have different gene abnormalities. At present, it is thought that there will be separate genetic subgroups for: 1) those individuals who have family members with a fragment of the autism syndrome, 2) those who have a family history of depression or anxiety disorder, and 3) those individuals whose autistic disorder presented with loss of skills or regression between 14 and 28 months of age following normal early development. An increase in blood serotonin levels and above average head circumference may also be separate subgroups or may overlap with one of the above subgroups. In our research, family history information will be combined with the cognitive and neural data to identify more sensitive cognitive and brain markers for gene abnormalities that can then be used to accurately classify family members into those that may have some subtle gene abnormality and those that don't. This classification must be extremely accurate for gene searches to be successful.

The family history interview will therefore inquire about family members who have: autism, autism spectrum disorder, impaired social or communication function, odd interest patterns or behavior, developmental language or learning disabilities, depression, anxiety, above average head size, and birth defects. Informants (those being interviewed) may wish to contact family members for more information. Parents may want to review the questions on the structured family history instrument used at other sites to identify partially affected family members for a clearer idea of how to recognize someone who might be "sub-clinically" (would not qualify for a formal diagnosis) affected.

One of the difficulties in accurately identifying mildly and sub-clinically affected family members is that most of these disorders were not clinically diagnosed or recognized in early generations or even earlier in the present generation. Symptoms of depression or anxiety disorder were often viewed as personality traits or the result of stress. Similarly, the recognition of less impaired individuals with autism or autism spectrum disorder is only now improving. When we have finished this stage of our research and have more sensitive markers for classifying family members, we may want to re-contact families in these initial groups for follow-up. Participating families may also re-contact us at any later date to update family history.

 

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NEUROPSYCHOLOGIC TESTS

An extensive battery of neuropsychologic test battery include measures that assess the major cognitive domains of abstract reasoning, problem-solving (executive functioning), memory, language, attention, and various sensory, perceptual, and motor abilities. The purpose of these measures are to:

  • Define intact and deficit abilities across domains within the same subjects using clinically available tests
  • Define the behavioral expression of deficits using ecological tests
  • Investigate specific controversies related to attention, executive function, and memory in detail with specialized laboratory tests


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COGNITIVE STUDIES

These studies were designed to further assess self-initiated conceptual behaviors which are expected to be different in individuals with autism.

  • Computer tasks provide parametric analysis of component cognitive processes used to perform individual tasks.
  • Examines contribution of executive function, working memory, language comprehension, and spatial abilities to tasks.
  • fMRI of cognitive tasks defines brain basis of task performance and how this differs from function of normal brain.

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EYE MOVEMENT STUDIES

  • Defines functional status of cortical & subcortical neural circuitry
  • Provides rigorous laboratory assessment of attention, executive function, and motion processing related to cerebellar, frontal, and parietal lobe circuitry and function
  • fMRI studies of brain while subjects perform eye movement tasks, defines brain regions involved in these tasks and how they are abnormal in autism

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MAGNETIC RESONANCE IMAGING MRI

There are several MR tests, structural MRI, MR Spectroscopy and functional MRI or fMRI. All of these MR tests involve the same equipment but use different computer programs to give the different types of information. Structural MRI is designed to produce very clear and detailed pictures of the brain. Another laboratory will take these pictures and measure the volume of different brain structures. MRS, or magnetic resonance spectroscopy, is designed to provide information about the chemical composition of the brain. 31P MRS measures the amount of brain membrane building block materials and break down products. 1H MRS measures the number of neurons. Functional MRI measures the activity of the brain during a cognitive activity.

During the structural imaging and MRS, volunteers need to hold still while the pictures are being taken but do not need to do anything. They may sleep. During the fMRI, volunteers need to remain awake and alert to read sentences silently or solve puzzles silently. Answers are given by button presses. Although people must read and answer silently, people have a tendency to move while thinking. It is therefore exceedingly important to remember not to move.

Structural MRI

  • Provides volume measurements of brain structures
  • Non-invasive: uses radio waves and magnetic fields

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Functional MRI

  • Defines brain regions active during task performance
  • Non-invasive: uses radio waves and magnetic fields

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MR SPECTROSCOPY

  • 31P Measures the synthesis and turnover of brain membranes, the wiring of circuitry of the brain.
  • H MR Spectroscopy measures the number of neurons.
  • Non-invasive: uses radio waves and magnetic fields

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