Site-Specific Effects of Online rTMS during a Working Memory Task in Healthy Older Adults.

My research centers around the use of structural and functional imaging measures to study the shifts in network architecture in the aging brain. I am specifically interested in changes in how changes in structural and functional connectivity associated with aging impact the semantic retrieval of word or fact knowledge. Currently this involves asking why older adults have particular difficulty in certain kinds of semantic retrieval, despite the fact that vocabularies and knowledge stores typically improve with age.

A second line of research involves asking questions about how this semantic system is organized in young adults, understanding which helps form a basis for asking questions about older adults. To what degree are these semantic retrieval processes lateralized? What cognitive factors affect this laterality? How are brain structures like the corpus callosum involved in mediating distributed activation patterns associated with semantic retrieval? 

Sarah Hollingsworth “Holly” Lisanby, MD, is an experienced translational researcher and innovator of neuromodulation technologies to study and treat psychiatric disorders. Dr. Lisanby is Director of the Division of Translational Research at NIMH, which funds research on the discovery of preventions, treatments, and cures for mental illness across the lifespan.  She is Founder and Director of the Noninvasive Neuromodulation Unit in the NIMH Intramural Research Program, a multi-disciplinary clinical research program specializing in the innovation of new brain stimulation tools to measure and modulate neuroplasticity to improve mental health.  Dr. Lisanby is former Chair of the Duke Department of Psychiatry & Behavioral Sciences, and JP Gibbons Endowed Professor at Duke University.  She founded and directed both the Duke and the Columbia University Divisions of Brain Stimulation, where she built interdisciplinary research programs specializing in the convergence of Psychiatry, Neuroscience and Engineering. She co-led the NIH BRAIN Initiative Team focused on large-scale neural recording and modulation devices. Dr. Lisanby has been principal investigator on a series of federally funded grants on the development of novel neuromodulation technologies, including the rational design of magnetic and electrical seizure therapies.  Her team pioneered magnetic seizure therapy (MST) as a novel depression treatment from the stages of animal testing, first-in-human, and international clinical trials.  She led a series of studies involving transcranial magnetic stimulation, electroconvulsive therapy (ECT), MST, vagus nerve stimulation, and deep brain stimulation. She has received numerous international recognitions, including the Max Hamilton Memorial Prize of the Collegium Internationale Neuro-Psychopharmacologicum, the Gerald Klerman Award from the National Depression and Manic Depression Association, and the Eva King Killam Research Award from the American College of Neuropsychopharmacology.  She has been a member of the NIMH Board of Scientific Counselors. Dr. Lisanby served on the FDA Neurological Devices Advisory Panel and has held key leadership positions with numerous professional associations, including serving as President for the Association for Convulsive Therapy/International Society of Neurostimulation, and the International Society for Transcranial Stimulation, and Chair of the American Psychiatric Association Task Force to Revise the Practice on ECT. 

I direct the Brain Stimulation Engineering Lab (BSEL) which focuses on the development, modeling, and application of devices and paradigms for transcranial brain stimulation. Transcranial brain stimulation involves non-invasive delivery of fields (e.g., electric and magnetic) to the brain that modulate neural activity. It is widely used as a tool for research and a therapeutic intervention in neurology and psychiatry, including several FDA-cleared indications. BSEL develops novel technology such as devices for transcranial magnetic stimulation (TMS) that leverage design techniques from power electronics and computational electromagnetics to enable more flexible stimulus control, focal stimulation, and quiet operation. We also deploy these devices in experimental studies to characterize and optimize the brain response to TMS. Another line of work is multi-scale computational models that couple simulations of the electromagnetic fields, single neuron responses, and neural population modulation induced by electric and magnetic brain stimulation. These models are calibrated and validated with experimental neural recordings through various collaborations. Apart from understanding of mechanisms, we develop modeling, algorithmic, and targeting tools for response estimation, dose individualization, and precise localization of transcranial brain stimulation using advanced techniques such as artificial neural networks and machine learning. Moreover, BSEL is involved in the integration of transcranial brain stimulation with robotics, neuronavigation, intracranial electrophysiology recordings, and imaging modalities such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), as well as the evaluation of the safety of device–device interactions, for example between transcranial stimulators and implants. Importantly, we collaborate widely with neuroscientists and clinicians within Duke and at other institutions to translate developments from the lab to research and clinical applications. For over 15 years, BSEL has been continuously supported with multiple NIH grants as well as funding by DARPA, NSF, Brain & Behavior Research Foundation, Coulter Foundation, Duke Institute for Brain Sciences, MEDx, Duke University Energy Initiative, and industry. Further, some of our technology has been commercialized, for example as ElevateTMS cTMS, or incorporated in free software packages, such as SimNIBS.

My laboratory investigates the neural correlates of memory and cognition in young and older adults using fMRI. We have three main lines of research: First, we distinguish the neural correlates of various episodic memory processes. For example, we have compared encoding vs. retrieval, item vs. source memory, recall vs. recognition, true vs. false memory, and emotional vs. nonemotional memory. We are particularly interested in the contribution of prefrontal cortex (PFC) and medial temporal lobe (MTL) subregions and their interactions. Second, we investigate similarities and differences between the neural correlates of episodic memory and other memory and cognitive functions (working, semantic, implicit, and procedural memory; attention; perception, etc.). The main goal of this cross-functional approach is to understand the contributions of brain regions shared by different cognitive functions. Finally, in both episodic memory and cross-function studies, we also examine the effects of healthy and pathological aging. Regarding episodic memory, we have linked processes differentially affected by aging (e.g., item vs. source memory, recall vs. recognition) to the effects of aging on specific PFC and MTL subregions. Regarding cross-function comparisons, we identify age-related changes in activity that are common to various functions. For example, we have found an age-related increase in bilaterality that occurs for many functions (memory, attention, language, perception, and motor) and is associated with functional compensation.