By Charlene N. Rivera-Bonet | Waisman Science Writer

Memory impairment as a result of a traumatic brain injury (TBI) has long been associated solely with the hippocampus, the brain’s learning and memory center. However, new research published in the journal Brain Imaging and Behavior, reveals that the hippocampus is not acting alone. The study from the University of Wisconsin-Madison’s Waisman Center, indicates a broader network of brain structures is involved in TBI-induced memory impairment in adolescents.
Traumatic brain injuries usually result from a violent bump, blow or jolt to the head or body, or an object going through brain tissue. The hippocampus, found deep in the human brain, is highly vulnerable to TBI regardless of the main site of the initial injury.
The study, led by Peter Ferrazzano, MD, Enid and Jerry Weygandt Professor of Pediatrics and director of the Pediatric Brain Care Clinic at the Waisman Center, found that although the hippocampus has been in the spotlight for leading to impaired memory after a TBI, memory performance in children relates to the integrity of the entire memory network, not just the hippocampus. This is part of a bigger effort to identify markers that can predict outcomes in children with severe TBI. “We designed a prospective study of these children [who experienced a severe TBI] one to two years after their brain injury events to try and understand how the changes in their brain are related to their outcomes,” says Andrew Alexander, PhD, professor of medical physics and psychiatry, and one of the authors of the study. “In this study, we were focused on how the hippocampus and networks associated with the hippocampus are affected, and how that relates to working memory in these kids.”
The researchers did a comprehensive study of the memory network in relation to memory and learning performance in adolescents with a severe TBI, one to two years after their injury. They measured memory and learning performance, and used magnetic resonance imaging (MRI) to look at brain structure and function. In addition to evaluating multiple parts of the memory network – the fornix, thalamus, and the calcarine sulcus – they used multiple measures such as size, structural connectivity and functional connectivity, making it a comprehensive assessment of the brain after injury.
Their results showed the hippocampus was smaller in size in adolescents with traumatic brain injury compared to individuals without injury. This loss of hippocampal volume was consistent with worse performance on memory and learning in individuals with TBI.
Structural connectivity measures look at direct, physical connections between brain regions. It assesses the state or condition of the fibers that act as a bridge to connect the hippocampus to other parts of the brain. Adolescents with TBI, the study shows, have structural abnormalities in prominent fiber bundles that connect the hippocampus to other brain regions, including the fornix. These abnormalities were related to worse performance in the memory and learning tests.

As opposed to structural connectivity, functional connectivity measures the synchrony, or lack thereof, between regions of the brain that do not necessarily have a direct physical connection. Even without a straight, physical connection, regions can share signals through indirect ways, and their ability to signal each other is important for brain function. Results from this study show that the hippocampus was less structurally and functionally connected to other important regions of the memory network – the thalamus and calcarine sulcus, with effects on worse performance of memory and learning.
The thalamus and the calcarine sulcus are involved in sensory processing and vision, respectively. These regions have strong connections to the hippocampus and are involved in guided attention, and may be important for “visualizing” a word when trying to recall it. “That was a very interesting finding. Because when these participants are asked to remember the words on the test, they may be forming mental pictures of this task, or objects that they’re asked about,” explains José Guerrero-Gonzalez, PhD, lead author of the study.
The population with traumatic brain injuries is a heterogeneous one. “There’s really no two cases that are identical,” Alexander says. “So, by taking a more holistic approach to looking at multiple measures we can develop a more comprehensive picture of what’s going on with the hippocampus as well as the network associated with the hippocampus.”

“Those were the main takeaways, that not only the hippocampus, but the network would be altered by the injuries, so there would be effects observed on the whole network,” Guerrero-Gonzalez summarizes.
These effects being measured one to two years post injury means that the association between hippocampal atrophy and memory dysfunction continue in adolescents with severe TBI years after the injury. However, following injury, the hippocampus may have some capacity for reorganization and potential for the formation of new neurons. Broadening research to focus on areas beyond the hippocampus may point to other potential mechanisms that aid or impair recovery after a TBI.
Your support makes a difference. Donate now to advance knowledge about human development, developmental disabilities, and neurodegenerative diseases through research, services, training, and community outreach. | DONATE NOW |