The Hales Lab Identifies Neuroinflammatory Links to Spatial Navigation Deficits in ADHD Models

Researchers, including neuroscience majors Sophia Skubic and Madeline Kramer, alumna Zoe Wynter ’23 (BA) and Associate Professor of Neuroscience, Cognition and Behavior Jena Hales, PhD, of the Hales Lab at the University of San Diego have published a compelling new study in Frontiers in Cellular Neuroscience, a peer-reviewed journal, exploring the biological underpinnings of Attention-Deficit Hyperactivity Disorder (ADHD).

Led by Dr. Hales, the team utilized a naturalistic foraging task based on the Traveling Salesperson Problem (TSP) to observe how ADHD-like models navigate complex environments. The study focused on TPS or "route optimization" — the ability to find the most efficient path between locations — finding that these models struggled significantly with spatial working memory and the decision-making required for efficient movement.

Beyond behavioral observations, the research highlights a critical link between cognitive impairment and neuroinflammation. Dr. Hales and her team analyzed microglial activation — the brain's immune response — within the hippocampus and prefrontal cortex. They discovered a higher percentage of "hypertrophic" or chronically activated microglia in these areas, suggesting that persistent inflammation may be a key factor in disrupting the neural circuits required for navigation. This suggests that the cognitive difficulties seen in ADHD may be rooted in specific inflammatory responses within the brain's "GPS" system.

Notably, the study also emphasized the importance of considering sex as a biological variable in neuroscience research. The team observed sex-specific differences in inflammatory markers, particularly within the dentate gyrus, suggesting that the physiological manifestation of ADHD may differ between males and females. By bridging the gap between behavioral deficits and cellular-level inflammation, the Hales Lab’s latest work provides a more nuanced understanding of ADHD, opening new doors for investigating how targeted treatments might one day address these specific neurological pathways.

Dr. Hales is particularly proud of her student researchers for their work on the project. She says, “One of the most fulfilling aspects of being a USD professor has been observing my undergraduate students’ passion for neuroscience research grow within my lab.”

Read the entire research publication in Frontiers in Cellular Neuroscience.