Discovery & Intervention

Brain connected to human body

Cognitive aging is associated with a range of metabolic, physiological, biochemical and genetic variables that offer a wide range of potential neuromodulatory, pharmacological and lifestyle interventions for improving behavioral outcomes in older adults. The Intervention research program is dedicated to discovery, translation and testing of clinical interventions that can improve cognition in older adults. The CAM Center is based on a clinical translational science model, taking science from bench to bedside and back to the bench. Using basic science to discover and understand the mechanisms of action underlying new interventions, we then translate this work into human application in the form of Phase 1, 2 and 3 randomized clinical trials. Data from human study participants is also used to inform targeted investigation into the mechanisms of cognitive decline in preclinical models. Ultimately, our hope is that by combining top-down with bottom-up strategies for identifying and understanding new intervention strategies, we will be able to enhance cognitive function in advanced age. Over the past 10 years, much of our work has focused on methods of non-invasive neuromodulation and lifestyle interventions to improve cognitive outcomes in older adults.

Preclinical

In animal models of cognitive aging and human study participants, CAM Center researchers use a number of experimental approaches from single-cell RNA sequencing to MRI to gain mechanistic insight into the biological factors that confer resilience to functional decline in old age and those factors that are related to the development of cognitive impairment. This information is used to guide the development of new therapeutic strategies for improving behavioral outcomes in older adults. A key feature of the preclinical research at the CAM Center is that basic science experimentation is firmly grounded to the variables that are critical for real world functioning in humans. This “reverse translation” is critical for enhancing the translation potential of findings in model systems to humans.

DEPARTMENT OF NEUROSCIENCE

Preclinical imaging study shows key brain changes in aging; researchers hope findings could be relevant for future Alzheimer’s research

A collaborative study led by UF neuroscientists Sara Burke, Ph.D., and Marcelo Febo, Ph.D., gives insight into why brain networks become vulnerable in old age.

Drs. Sara Burke and Marcelo Febo review images from research

Translational

Translational research at the CAM Center takes advantage of the experimental control that is conferred by animal models as well as discovery research in human study participants to explore metabolic, neuromodulatory and pharmacological variables that can improve cognitive functioning in old age. The goal of the CAM Center translational research program is to inform clinical trials and future implementation of novel interventions that reduce cognitive decline in advanced age.

WOODS LAB

Modeling Transcranial Electrical Stimulation in the Aging Brain

The Woods Lab published a manuscript titled Modeling Transcranial Electrical Stimulation in the Aging Brain in Brain Stimulation. This paper led by Dr. Aprinda Indahlastari represents the largest MRI-derived computational modeling study in history.

Brain model with different areas highlighted

Clinical Trials

Augmenting Cognitive Training in Older Adults (The ACT Study)

Cognitive training for speed of processing and working memory demonstrates promise as an intervention to alter the trajectory of cognitive aging and potentially slow the onset of mild cognitive impairment/dementia.

Neuromodulation of Cognition in Older Adults (The Stimulated Brain Study)

The Stimulated Brain study investigates the effects of different transcranial direct current stimulation (tDCS) and cognitive training doses on cognitive function and brain health in older adults.

The Efficient Brain Study

This study is an industry funded Phase II clinical trial investigating the impact of Fermented Papaya Product (FPP) on brain mitochondrial function, neuroinflammation, and cognitive function in older adults.

Imaging Electrical Current Flow in the Brain

Using Magnetic Resonance Electrical Impedance Topography (MREIT), the team will not only optimize a whole brain sequence across multiple scanner platforms, but also investigate the relationship between objective current flow and change in functional MRI measures from transcranial direct current stimulation (tDCS).

Modifying Working Memory Function with tACS

Transcranial alternating current stimulation (tACS) is a method of safe and non-invasive electrical brain stimulation. This neuromodulation method uses two electrodes to apply a weak electrical current to the scalp and alternate the polarity of current passed between the electrodes.

Transcranial Near Infrared Photobiomodulation and Cognitive Aging

Transcranial near-infrared (NIR) photobiomodulation is a method of non-invasive brain stimulation that uses light in the near-infrared spectrum to the scalp to stimulate underlying brain tissue.

Cognitive Training and Mild Cognitive Impairment

This two-year National Institute on Aging funded U01 (Edwards, PI) will establish the infrastructure necessary to implement a large multisite clinical trial investigating one of the most promising non-invasive approaches for improving MCI outcomes: cognitive training.

Enhancing tES automated models for aging brains

This project will help extend a promising technology to clinical trials in age-related conditions and provide available tools to the aging research community for implementation.

Resources

Research regarding translating basic cognitive neuroscience research to clinical application involves a number of strategies for augmenting cognitive function with non-invasive neuromodulation. The neuromodulation resources in the CAM Center contain state-of-the-art transcranial magnetic stimulation and transcranial electrical stimulation equipment. This includes a Magstim SuperRapid Transcranial Magnetic Stimulation system with BrainSight 2 MRI-guided neuronavigation, Soterix and Neuroconn conventional (1×1) and high-definition (4×1) transcranial direct current stimulation (tDCS) units, as well as transcranial alternating and random noise stimulation systems. In addition, CAM Center labs have an MRI compatible tDCS stimulator in the McKnight Brain Institute Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) 3T human neuroimaging facility. The lab also contains Soterix tDCS and HD-tDCS Explore software for computational modeling of current density and flow to determine optimal electrode locations for study design and implementation, as well as Simpleware and COMSOL software for custom calculation of current flow computational models. The CAM Center is also equipped with transcranial near infrared stimulation equipment and an intermittent hypoxia delivery device. To facilitate large-scale clinical and research trials, the CAM Center maintains access to five clinical testing rooms adjacent to both UF 3T research MRI scanners on the 1st floor of the McKnight Brain Institute with dedicated participant parking as part of the CAM Center.