For decades, autism’s brain biology has remained a great mystery. We’ve known that there’s no single gene to point to as the culprit in all cases. We’ve known that autism is a complex disorder that presents differently among individuals. We have also known that most individuals with autism share a number of distinctive aspects of brain anatomy.
Ten years ago, my research team found evidence of brain overgrowth in many toddlers who developed autism. Just last year, we published a study showing that the larger brains of young children with autism have an excess number of brain cells, or neurons, in the part of the brain known as the frontal cortex. In the study we published today, we found clues to how this excess occurs.
Our study found dysfunction in several gene networks that may affect the number of neurons that are generated during the second trimester of pregnancy, when about 40 billion neurons are produced in the developing brain. We also found abnormality in gene networks that affect the number of neurons that survive through the second and third trimesters. Not all early neurons are meant to survive. Some play temporary roles during brain development and are supposed to die off when their job is done. In fact, “apoptosis” or naturally occurring cell death, is a normal and important part of prenatal brain development. By way of analogy, consider the scaffolding set up when constructing a building and then taken down once the building is finished. With autism, one possibility is that some of these “scaffolding” neurons remain. This may contribute to the excess of neurons and abnormal brain wiring.
These findings are exciting. We’ve known that something happens very, very early in the development of the brain: There are too many neurons in frontal brain regions. Now, we also know some of the genetic basis for this: abnormal gene activity in specific networks. This appears to rule out many speculations about post-natal causes of autism. Instead, it points strongly to prenatal events, at least in a majority of cases.
Importantly, this gives us hope that, one day, research will find ways to normalize gene activity and related neural growth and function. Normally frontal brain circuits are not fully formed at birth. They develop slowly across childhood. This provides a wide window of opportunity for intervention.
By knowing which gene networks are not operating correctly at the youngest ages, it may be possible to target these systems with biomedical interventions and improve outcomes. This is my hope and the reason why I pursue this research. But I also recognize this will be a complex and challenging road.
One of the most interesting findings in the study we published a decade ago was that the early brain overgrowth associated with autism was temporary. It involved accelerated brain growth during the first few years of life. Later in childhood, the growth of some brain regions affected by autism appears to slow considerably. What causes this change in brain growth trajectories in children with autism? This important question remains.
We also know that symptoms improve as some children with autism get older. So it is intriguing to see, in our new study, that by adulthood there is clear evidence of gene activity associated with remodeling, repair, immune response and signaling. I wonder if this means that, in children and adolescents who show clear improvement as they mature, there is a second stage of enhanced adaptive connections and a pruning back of earlier maladaptive connections and dysfunctional cells.
I think of this colloquially as a sort of “cleaning house.” The brain is getting rid of connections or cells that impede function. In these individuals, their brains may be able to modify and improve some of these neural pathways.
I do not know if this is the case. But our new evidence opens up this major new opportunity to better understand changes in brain genetic activity at all ages. It holds out promise of discovering age-relevant interventions that help individuals with autism across the lifespan.
This is what I find so exciting. I believe that, eventually, it will be possible to develop ways to foster both the growth of more appropriate cells and connections and a pruning away of unwanted excess. And I believe this may become possible at any age, not just early childhood. In better understanding the development of autism, we may be able to both develop medical interventions and improve our existing behavioral interventions.
What’s encouraging to me is that many excellent researchers in the field are also finding clues that point in the same direction. Together, we may just be able to open up new vistas for children and adults with autism.
Editor’s note: Read more about Dr. Courchesne’s study in our Science News column. Thanks to the families, volunteers and donors who helped make Dr. Courchesne’s research possible with an Autism Speaks research grant. Explore more of the studies we are funding with our website’s Grant Search.