Adult Neurogenesis Found to Aid Verbal Learning and Memory

Why do adults make new brain cells? A new study published in Cell Stem Cell provides the first cellular evidence that making new brain cells in adults supports verbal learning and memory, which enables people to have conversations and to remember what they hear. This discovery could point to new approaches to restore cognitive function. 

The study, led by scientists from USC Stem Cell and the USC Neurorestoration Center at the Keck School of Medicine of USC, relied on brain tissue from patients with drug-resistant cases of mesial temporal lobe epilepsy (MTLE), which involves seizures as well as accelerated cognitive decline. 

"Treating patients with epilepsy allows us to investigate the purpose of generating new neurons in our brains. We observe that one of reasons is to learn from the conversations we have" said co-corresponding author Michael Bonaguidi, an associate professor of stem cell biology and regenerative medicine, gerontology, biochemistry and molecular medicine, biomedical engineering, and neurological surgery, and assistant director of the USC Neurorestoration Center. 

"These findings are clearly important for all people who suffer from learning and cognitive decline, but they are also specifically relevant to the epilepsy patients who participated in the research," added co-corresponding author Charles Liu, a professor of neurological surgery, neurology, and biomedical engineering, director of the USC Neurorestoration Center, and director of the USC Epilepsy Care Consortium.

In the study, first authors Aswathy Ammothumkandy and Luis Corona from USC and their collaborators investigated how the process of making new brain cells-;called neurogenesis-;affects different types of cognitive decline during the progression of MTLE.

The researchers found that MTLE patients experience cognitive decline in many areas including verbal learning and memory, intelligence, and visuospatial skills. For verbal learning and memory, as well as for intelligence, patients undergo a dramatic decline during the first 20 years of seizures. During those same two decades, neurogenesis slows to the point where immature brain cells became nearly undetectable. 

Based on these observations, the scientists searched for links between the number of immature brain cells and the major areas of MTLE-related cognitive decline. They found the strongest association occurs between the declining number of immature brain cells and verbal learning and memory. 

This is a surprising finding because neurogenesis levels in rodents and other lab animals contribute to a different type of learning and memory using visuospatial skills. The role of neurogenesis in verbal learning and memory highlights the value of studying human brain tissue. These highly valuable surgical specimens were generously donated by patients of the Rancho Los Amigos Epilepsy Center- a unique resource in the public safety-net health system advancing health care and research equity for the underinsured population in the region. During the complex operations, the neurosurgeons carefully removed the affected hippocampus in one piece, curing the majority of the patients of their seizures.

Our study provides the first cellular evidence of how neurogenesis contributes to human cognition-;in this case, verbal learning and memory. This work opens a gateway for future studies exploring ways to improve verbal learning and memory by boosting neurogenesis, possibly through exercise or therapeutic drugs. Those approaches could help not only patients with MTLE, Alzheimer's disease and dementia, but also all of us with aging brains."

Michael Bonaguidi, associate professor of stem cell biology and regenerative medicine, gerontology, biochemistry and molecular medicine, biomedical engineering, and neurological surgery, Keck School of Medicine of USC

Neuropsychologist Jason Smith from the Medical University of South Carolina is also a co-corresponding author. Additional authors are: Kristine Ravina, Victoria Wolseley, Jeremy Nelson, Nadiya Atai, Aidin Abedi, Lina D'Orazio, Alisha Cayce, Carol McClearly, George Nune, Laura Kalayjian, Darrin Lee, Brian Lee, Christianne Heck, Robert Chow, and Jonathan Russin from USC; Nora Jimenez from Los Angeles General Medical Center; Michelle Armacost from USC and Rancho Los Amigos National Rehabilitation Center; and Virginia Zuverza-Chavarria from Rancho Los Amigos National Rehabilitation Center.

Thirty percent of this work was supported by federal funding from the National Institutes of Health (grants R56AG064077, R01AG076956, and U01MH098937). Additional support came from the Donald E. and Delia B.Baxter Foundation, L.K. Whittier Foundation, Simon-Strauss Foundation, Cure Alzheimer's Fund, Eli andEdythe Broad Foundation, USC Neurorestoration Center, Rudi Schulte Research Institute, American Epilepsy Society, and California Institute for Regenerative Medicine.