Transcranial alternating current stimulation (TACS) non-invasively alters neuroelectric activity in the human brain by applying weak, time-varying electric currents to the scalp. It is increasingly being explored as a therapeutic intervention for various brain disorders by affecting pathological oscillatory neural activity. Despite its increasing popularity and rapidly growing literature, the basic physiological mechanisms of TACS are still not well understood. This has hindered the development of principled TACS protocols with high spatio- temporal precision to affect communication between large-scale brain networks. Here, we propose to develop and validate a new TACS protocol to induce a ?traveling wave? electric field in the brain to manipulate cortico-cortical synchronization. For this, we will leverage single unit recordings in frontal- parietal regions in non-human primates which allow to record and recover neural activity during TACS. We will (1) develop a TACS protocol that can induce precise phase differences across distinct brain regions in a stimulation frequency of interest. We hypothesize that this will lead to a local alignment of spiking with respect to the local electric field phase. Through the simultaneous measurement of TACS electric fields and single-unit activity, we will determine how spike timing is altered across remote brain regions with varying stimulation phase. Accompanying these efforts (2), we will develop computational models to predict the physiological response to our traveling wave TACS protocol. We will combine electric field simulations with realistic neuron models with ongoing synaptic activity to simulate the effect of TACS on connected brain regions. This will allow us to optimize stimulation protocols based on a principled understanding of the underlying biophysics and physiology. Finally (3), in order to translate such novel stimulation protocols into new therapeutic interventions for mental health disorders, we will study the effects of traveling wave TACS on a N-back working memory task. These experiments will be conducted in a population of surgical epilepsy patients allowing the unique possibility to perform invasive electrophysiological recordings during the task and TACS. All these efforts combined will result in a new non-invasive stimulation method to affect the oscillatory coupling of large-scale brain networks, needed for new treatment options for psychiatric disorders.

Public Health Relevance

This research aims to develop and validate a novel transcranial electric stimulation protocol to manipulate large-scale brain networks. This will involve research in non- human primates and surgical epilepsy patients in combination with computational modeling. Such efforts are vital for advancing non-invasive neuromodulation technologies as effective therapeutic approaches for mental health disorders such as schizophrenia.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Multi-Year Funded Research Project Grant (RF1)
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Special Emphasis Panel (ZMH1)
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Mcmullen, David
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University of Minnesota Twin Cities
Biomedical Engineering
Biomed Engr/Col Engr/Engr Sta
United States
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