Department of
Psychological and Brain Sciences

In the quest to make inroads into Alzheimer’s, PBS Professor Simon Davis studies both healthy and pathological aging.

Shortly into a conversation with newly arrived PBS Professor Simon Davis, he delves into some of the details of his family origins. His parents settled in the city of St. Augustine, Florida before his birth, after traveling around the Arabian Peninsula. His Italian mother worked as a surveyor; his American father was an architect from northeast Florida. Davis spent his childhood in St. Augustine, which has the remarkable distinction of being the nation’s oldest permanent European settlement, founded in 1565. Davis revels in its colorful and contentious mix of Native American, Spanish, British and contemporary American heritage. It was burned to the ground twice, the first time in 1586 by Sir Francis Drake, who, says Davis, “as those of us in St. Augustine know, was a pirate explorer, despite being legitimized with knighthood by Queen Elizabeth.” Davis also has some myths to dispel when it comes to Floridian history. The notion, for example, that Ponce de Leon, the Spanish explorer who in 1513 led the first European expedition to Florida, was looking for the Fountain of Youth and not for gold, he says, “is a modern construct,” promoted in the 1920s to attract people to the city. And if you go to St. Augustine today, you will find “some animatronic conquistadors around a little sulfur spring.”

From the "fountain of youth" to the neuroscience of aging

From St. Augustine, Davis went to the New College of Florida in Sarasota, the honors college of the state university system, where he majored in neurobiology and went on to study neuropsychology at University College London, before attending Duke University for a Ph.D. in psychology. He gained postdoctoral training at the Centre for Speech, Language, and the Brain at the University of Cambridge before returning to Duke as an assistant professor in the Department of Neurology. There he helped to link Psychology, Neurology, and Psychiatry Departments by co-directing the Brain Stimulation Research Center, and serving as a core member of the Center for Cognitive Neuroscience. In the fall of 2025 Davis joined PBS as one of the “Faculty 100” hires for the Aging Research Initiative. He is delighted to be joining what he has always known to be a revered and legendary department and to establish an identity as an IU professor and researcher.

In the same way he celebrates the varied history of his hometown, as a scientist he seems to thrive on adopting a mix of disciplines and methodologies. “I enjoyed being the person in the Neurology Department who studied normative aging,” he says, “in a department that mostly studied its pathology.” Or to be in both Psychiatry and Neurology, he explains, given “that those departments often don’t talk to each other.” Likewise, his lines of research extend into areas that don’t often coincide. He ventures into the area of cognitive computational modeling for which PBS is well-known, to map the cortical networks mediating memory function, while simultaneously working to develop interventions that will improve memory encoding and retention in those with dementia and Alzheimer’s disease. In this way Davis’s Mnemology Lab encompasses multiple approaches to the study of memory, as well as devices or techniques that can help strengthen or improve it.

A spectrum of research

Davis’s early work explored the process of aging in healthy adults, focusing on some of the generalized patterns that occur in such phenomena as PASA (the Posterior-Anterior Shift in Aging) and HAROLD (the Hemispheric Asymmetry Reduction in Older Adults). HAROLD, he explains, refers to the observation that the aging brain tends to use more bilateral regions for tasks that are typically handled by one hemisphere in youth. The reason for this is not precisely known. It may be “a compensatory phenomenon,” he says, “for example, imagine that as you age you need two arms to lift the same dumbbell, or it could, alternatively, be explained by the idea that the aging brain is no longer inhibiting the non-dominant hemisphere. Hemispheric segregation,” he explains, “may allow you to focus on a process. If those connections degrade across the lifespan, then you may see contralateral activity.”  Compensation versus segregation—Davis’s work suggests this effect depends on multiple factors, including the difficulty and modality of the task, and the flexibility of the cortical regions engaging in cross-hemispheric communication. His lab continues to explore the question using Transcranial Magnetic Stimulation, or TMS, to test the process in younger and older subjects.

Another line of Davis’s research uses fMRI brain images to test what models of information are encoding in our memories, using a method called Representational Similarity Analysis (RSA). Study participants are asked to form a connection between two objects for which fMRI brain scans locates the areas of the brain which respond to the shared properties of the two objects. A basketball and an orange for instance have common visual properties which will show up in the fMRI as having similar neural activity patterns in visual processing brain regions. When items are remembered, these specific regions show stronger activation compared to when the items are forgotten. He ultimately seeks to use TMS to target those regions and their extended networks and in this way boost the memory-encoding process in those with pre-Alzheimer’s conditions.

The search for disease modifying therapies

When it comes to Alzheimer’s, Davis observes, “We do not have what people in the field call disease modifying therapies, or DMTs, and right now, neurologists in the AD world more generally are very desperate for effective therapies.” He mentions two current pharmaceutical treatments, which involve an IV infusion, and can last months, and though they can briefly slow the pace of decline and reduce amyloid in the brain, the effects are mild and associated with a significant risk of brain insult. Davis’s NIH-funded projects focus on an alternative approach, seeking to boost the encoding process of memory formation using TMS in people diagnosed with mild cognitive impairment (MCI), a transitional stage that can lead to Alzheimer’s. TMS has been approved for use as an intervention for a host of psychiatric conditions (depression, OCD, anxiety) and is increasingly being explored as an intervention for neurological conditions such as Parkinson’s disease. He believes it might also be used to treat memory loss.

Despite the enormous challenge of overcoming Alzheimer’s, Davis is optimistic. “We are probably going to have an FDA-approved treatment for AD using TMS within six to 10 years,” he says. “I think it’s going to happen, given the amount of time and energy going forth on this both from university researchers and manufacturers and given the number of phase two and three trials.” Among those treatments could be one developed in his lab. And while they may not perform the magic of that mythical Fountain of Youth, such treatments may nonetheless bestow an even greater gift – the ability to grow old with our memory intact. No animatronic conquistadors needed.