Simultaneously Weaker and Stronger? New Brain Research Begins to Makes Sense of a Longstanding Paradox


For many years, scientists who study brain function in autism and other developmental and behavioral conditions have been challenged by seemingly conflicting results from study after study looking at the strength of brain network connections. Despite sound methodology designed by some of the top researchers in the field, some studies seemed to demonstrate that people diagnosed with autism spectrum disorder (ASD) demonstrated weaker brain network connections than their neurotypical peers, while other studies showed stronger connections.

Recently, scientists who study brain function in autism, including CAR senior scientist Dr. Benjamin Yerys, have begun to shift the way they think about the architecture of the brain. The brain can be thought of as one large integrated network, made up of several smaller specialized networks that are each linked to specific brain functions, such as social cognition or sensory processing. Related brain regions connect, or communicate, as a unit to interpret stimuli or perform tasks. Brain regions in a specialized network also communicate information to brain regions involved in other specialized networks. Together, all of these in-network and out-of-network communications make up the overarching, integrated, large-scale network responsible for all of our conscious and unconscious behaviors, thoughts, and responses.

The rapidly developing field of functional connectivity research provides a nuanced understanding of brain connections, or communications, and suggests that people on the autism spectrum may have simultaneously weaker and stronger brain connections.

How is this possible? A recent study by Dr. Yerys and collaborators from the CHOP and UPenn Lifespan Brain Institute (LiBi) helps to sort out the riddle.

Dr. Yerys and colleagues used resting state-fMRI (functional magnetic resonance imaging) to examine the strength of the connections both within and across specific brain networks in 163 children and adolescents (81 with ASD). Resting state-fMRI measures brain activation, or communication, between two brain regions over time; the more synchronized the communication the “stronger” the connection. They hypothesized that differences in the strength of connections within a single brain network and between separate networks may help explain several key behavioral traits and social differences commonly seen in children with ASD.

Compared to youth with typical development, children with ASD appeared to have weaker brain connections when looking at absolute strength of the connection. However, despite showing weaker connections overall, children with ASD showed relatively stronger connections within brain networks responsible for attention and social cognition compared with other brain networks. Finally, the researchers found that the more these brain network connections varied from typical development, the more severe the child’s ASD symptoms tended to be.

“This study is important because it gives new insights into how the brain is organized and communicates differently in children and teens with ASD. It is also important because it highlights that communication in the brain may appear weaker or stronger in ASD based on how we define functional connectivity,” explained Dr. Yerys. “Scientists have often thought that differences in age, cognitive ability, or how we check the quality of our data explain these differences across studies. However, we show that even when controlling for those factors, the choice of our functional connectivity metric (absolute vs. relative strength of the connection) plays an important role in observing whether children and teens with ASD have stronger or weaker connections compared to those with typical development.”

When considering long-term implications of this research, Dr. Yerys says that this line of work is just the first step. “Studies on functional connectivity give us hints about what is different in the brain networks of children and teens with ASD, but we are still far away from using a brain scan to pick out the right treatment for the right child at the right time. Our goal is to find the best methods that tell us how to treat individuals. To achieve that goal, we will need careful research outlining the wide range of variability across children so we can identify when a child’s brain function or development is significantly off course that it requires intervention.”

The results of this study build on earlier work by Dr. Yerys and his team, which showed several interesting variations in brain connectivity between non-medicated children with ASD, compared with their neurotypical peers. In children with ASD, the default mode network- the region of the brain involved when considering the emotional state of oneself or others- appeared to have a weaker absolute functional connectivity strength (or weaker strength) within itself, and greater connection strength with other networks. This suggested that the network was not as well formed in children with ASD, leading to more severe social symptoms. This difference may contribute to their struggle to understand their own and other people’s emotional states.

Together, these studies point the way toward improving our understanding of how children with ASD interpret and react to the world around them and the basis for some of the most common social, sensory and communication challenges of ASD.

Looking ahead, Dr. Yerys says, “My hope is that this study will push others to examine both absolute and relative strength functional connectivity. This work is also part of a larger effort in our center to understand the contributions of sensory and motor function to social difficulties in children with ASD.”