Probing the Brain in Autism Using fMRI and Diffusion Tensor Imaging

The overall goal of the following experiment is to examine the connections among brain areas that are important for social cognition in autism. Using functional MRI and diffusion tensor imaging of the brain in both children and adults with autism, this is achieved by designing appropriate FMRI experiments, then recruiting autistic participants. The participants must be adequately prepared for the procedure to obtain quality, functional and structural brain images.

The functional experiments are presented to the participant in the MRI scanner while performing a predefined task. The MR Images acquired result in a relatively large amount of data for each experiment. The acquired neuroimaging data are transferred to the lab's computer server, then pre-processed and subjected to statistical analysis by creating models.

In addition to the basic brain activation analysis, the functional and anatomical connectivity is examined in autism and control participants.FMRI. Results are obtained that show reduced activation and weaker functional connectivity during social cognition in autistic subjects. In addition, DTI data analysis indicates abnormal white matter integrity in autism.

This method can answer important questions regarding the brain organization and brain functioning in autism spectrum disorders and potentially one day. This can lead to identifying a neurological marker for autism. The implications of this technique extend toward therapy for autism because identifying altered connectivity among brain regions could lead to developing new therapies that mend those connections.

So though this method can be used to assess the autistic brain, it can also be used in other techniques such as looking at other neurodevelopmental disorders, as well as how the typical brain develops Because it is difficult to introduce the MRI scanner to children with autism as it is a noisy environment, which they're sensitive to. It is a compact and potentially claustrophobic space, and that is a novel environment. Visual demonstration of this method is critical as preparing a child with autism.

For FMRI scanning can be difficult and many people with autism are generally visual thinkers. Demonstrating this procedure will be my grad students from from my lab, Donna Murdo, Lauren Libro, mark Pennick, and Heather Wadsworth. Prior to enrollment in the study, the potential participants and the family in case of child subjects should first be briefed about the study via telephone.

This should also include a screening to assure that the participant meets the inclusion criteria for the study. If eligible, the potential participant should then be recruited For an MRI scan on a day and time that is suitable for the participant as well as for the researchers and the imaging center. Send the subject a copy of the social story about the MRI scan procedure and a CD recording of the scanner noise.

These should be reviewed with parents in the case of children to better understand the study procedures prior to the scan day and to make the subject more comfortable with the MRI environment. When the participant and family arrive at the imaging center, greet them and answer any questions that they may have about the study and experimental procedure. Then review IRB documents before obtaining informed consent.

Next, take the participant to a quiet room for neuropsychological testing, including IQ language ability and handedness. Then have the participant practice short versions of the study paradigms on a laptop computer to become familiar with the experiments. Once all testing and practice is complete, take the participant to a mock MRI scanner and provide a simulated experience of the MRI scanning procedure.

Another preparatory step is to decorate the MRI scanner in the imaging center with easily removable stickers and images of animals and cartoon characters to make the scanning environment more child-friendly. When the participant returns to the imaging center, allow for a short break, then have him or her fill out an MR Safety questionnaire. Before entering the scanning room, put all belongings in a locker and then screen for any metals on the body.

Once the screening is complete, take the participant into the scan room and have him or her sit on the scanner bed, provide earplugs and headphones before having the subject lie down on the scanner bed. Then an MRI technologist should place the multichannel head coil over the participant's head and adjust the attached mirror so that images displayed on the computer screen can be seen. Next, cover the participant with a blanket and provide response boxes for the left and right hand to be used during the FMRI tasks.

Also place the emergency squeeze ball within reach so that the subject can signal if he or she wants to come outta the scanner. Finally, the MRI technologist will advance the scanner bed into the scanner ball and assure that the subject is comfortable before beginning scans. The technologist first starts the scanning session by acquiring Localizers to ensure that the participant's head is correctly positioned.

Then a high resolution structural scan is acquired, which will be used for co-registration and normalization. In subsequent analysis to keep the subject entertained, the researcher can present a movie clip to the participant during this scan. Next, set up the imaging parameters appropriate to the scanner and pulse sequence used.

The researcher should assist the technologist with prescribing the slices for functional imaging. Here, 17 five millimeter slices are prescribed in the oblique axial plane to allow for maximum coverage of the entire brain. Now speak through the microphone to let the subject know that the experiment is about to begin and give instructions for the task that will be run.

Also open the experimental task on the computer, which should be synchronized to start with a trigger from the scanner. The participant should press a button to start the experiment and the scan when he or she's ready to begin experimental tasks, including static and dynamic visual stimuli, as well as auditory stimuli can be seen here displayed and programmed via ePrime software. Be sure to monitor the participant's responses as they're recorded and displayed on the computer screen.

After the first experiment, talk to the participant and provide feedback on task performance and head motion and prepare him or her for the next experiment that will be run. When all FMRI experiments are completed, the researcher should instruct the subject to simply lie still for about 12 minutes, as a DTI scan is acquired, a segment of a movie can a again be shown here for entertainment. Once all scanning is complete, take the participant outta the scanner and allow him or her to retrieve any belongings that may have been placed in the locker.

Then lead him or her to a quiet room for a short debriefing session. During the debriefing session, ask the participant about his or her performance in the scanner, feedback on the difficulty level of the tasks, as well as any problems or concerns that may have arisen. Also, be sure to thank the subject for his or her participation in the study.

Meanwhile, the MR.Technologist should upload all acquired MRI and DTI data onto a HIPAA protected computer network. The researcher can then later log into this network with a password to access and transfer the data onto a research server. Prior to analysis, the acquired data should be anonymized by removing any identifiable information such as name and date of birth from the image header.

Then convert the data to nifty image format to begin functional processing. Both pre and post-processing of the data can be performed via software such as statistical parametric mapping or SPM eight. Functional connectivity for a given task should then be measured by first drawing regions of interest and extracting the FMRI signal time course from each ROI for each participant.

Then correlate the signal from one ROI to the other. Anatomical connectivity can also be examined using the acquired DTI data and FSL software. The preliminary analysis with such software examines the diffusion of water in the brain and uses it as an index of white matter integrity.

Further analysis may involve white matter tractography in which the details about tract orientation and structure are inferred. Here, representative functional maps can be seen with increased activation as seen in a typical language task such as sentence comprehension. Activations appear in the left inferior frontal gyrus and left posterior superior temporal sulcus increased bilateral posterior superior temporal sulci activation can be seen in neurotypical participants during attribution of mental states.

To others, these maps are FWE corrected with a threshold P value less than 0.05. Here we see data from a social cognition task in participants with autism significantly reduced functional connectivity indicating synchronization of brain activation between frontal and temporal regions is demonstrated. Finally, this figure demonstrates DTI tractography results showing a white matter fiber bundle proceeding from the temporal lobe to the temporal parietal junction.

The initial starting point for tractography was an ROI identified by tracked based spatial statistics as having a significantly smaller FA value in young adults with autism when compared to age matched typical control participants. Pediatric neuroimaging can be very difficult, especially with children with autism, but with enough practice and preparation, these scanning techniques can be carried out successfully. While attempting MRI scans with any participant, but particularly with children, it's important to make sure the experience of the lab is a pleasant and positive one.

Data acquired by following this procedure can be used to answer neuroscience related questions. In addition, with the right hypotheses and analyses, one can use this information to learn not only about the brain, but also the relationship between the brain and behavior. Don't forget that the MRI scanning process is extremely sensitive to motion.

In addition, precautions should be taken to remove all metal from participants'pockets and on their body before the procedure is done. After watching this video, you should have a good understanding of how to successfully use neuroimaging to study children in general and children with developmental disorders like autism.