Identifying Treatment Targets for the Symptoms of Autism Spectrum Disorder Based on Brain Lesions

Different patients with autism spectrum disorder (ASD) have different symptoms. Some of these symptoms can be disabling and resistant to current treatments. New types of therapies, such as brain stimulation, might be used to improve these symptoms. However, this can’t be done until we know what brain region we need to target to treat specific ASD symptoms. Dr. Fox has recently developed a new method to identify brain regions causing specific symptoms. He can apply this method to identify regions causing symptoms of ASD, regions that can then serve as treatment targets. There have been many experiments using brain imaging to identify differences in the brains of patients with ASD. However, these differences have been poorly reproducible across studies and may not actually cause ASD symptoms.

Patients with brain lesions may represent a new approach for localizing ASD symptoms. Lesions provide a causal link between the lesion location and resulting symptoms. Although lesion patients are very different from those with ASD, lesions can occasionally cause specific symptoms that are similar to those seen in ASD patients. These lesion cases provide a useful starting point for identifying the brain regions causing ASD
symptoms.

These lesions provide a valuable starting point, but not the end point. A complicating factor is that symptoms can come from regions connected to the lesion location, not just from the lesion location itself. As such, identifying the brain region causing a specific symptom requires more than a set of brain lesions, it also requires a map of brain connectivity. Dr. Fox’s new method integrates brain connectivity into lesion analysis, allowing for better localization of symptoms. Using this method, he has identified brain regions causing many different neurological and psychiatric symptoms. In some cases, these symptoms have been very complex, similar to symptoms seen in ASD. In this study, Dr. Fox will apply this same method towards identifying brain regions causing symptoms in ASD. Once he has identified the relevant brain regions and networks based on lesions, he will confirm the importance of these regions in patients with ASD.

The end result of this work will be a set of candidate brain regions causally involved in generating specific ASD symptoms. These brain regions can then be targeted with invasive or noninvasive brain stimulation. This approach should allow for individualized therapy targeted to specific regions based on patient-specific symptom profile.